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14,000 | 16,437,425 | AUTHORS ' CONCLUSIONS Limited data from small studies using neuroleptic reduction or specific neuroleptic drugs as treatments for TD did not provide any convincing evidence of the value of these approaches . | BACKGROUND Since the 1950s neuroleptic medication has been extensively used to treat people with chronic mental illnesses such as schizophrenia .
These drugs , however , have been also associated with a wide range of adverse effects , including movement disorders such as tardive dyskinesia ( TD ) .
Various strategies have been examined to reduce a person 's cumulative exposure to neuroleptics .
These studies include dose reduction , intermittent dosing strategies such as drug holidays , and neuroleptic cessation .
OBJECTIVES To determine whether a reduction or cessation of neuroleptic drugs is associated with a reduction in TD , for people with schizophrenia ( or other chronic mental illnesses ) who have existing TD .
Our secondary objective was to determine whether the use of specific neuroleptics for similar groups of people could be a treatment for TD that was already established . | Animal data suggest that a D1 antagonistic component in neuroleptic drugs counteracts development of dopamine supersensitivity and of tolerance to cataleptic effect . This has led to the hypothesis that neuroleptics with D1 antagonistic activity should cause a better suppression of tardive dyskinesia ( TD ) and less rebound aggravation after withdrawal than pure D2 antagonists . In this study the effect of zuclopenthixol ( mixed D1/D2 antagonist ) and haloperidol ( D2 antagonist ) was evaluated in chronic psychotic patients with TD . Fifteen patients completed a r and omized crossover study with blind evaluation of TD and parkinsonism . The test medications , haloperidol and zuclopenthixol , caused a significant suppression of TD and a significant increase of parkinsonism . No significant differences between haloperidol and zuclopenthixol were observed . No TD aggravation was seen . The lack of differences between the mixed D1/D2 antagonist and a D2 antagonist suggest that tolerance and DA supersensitivity play no or a minor role for development of TD Eleven patients with tardive dyskinesia were treated with lithium carbonate in a placebo-controlled double-blind crossover study . No significant effect of lithium on either tardive dyskinesia or blood prolactin concentrations was demonstrated , but 5 patients developed pseudo-Parkinsonian features In a double-blind , placebo-controlled study , ten chronic schizophrenic patients with pronounced symptoms of tardive dyskinesia ( TD ) were withdrawn from anticholinergic medication . All patients had previously been under long-term treatment with neuroleptics and anticholinergics for at least two years . The rating-scales used were the AIMS , our own TD Scale , and the Simpson-Angus scale for extra-pyramidal side-effects . The severity of TD decreased significantly in nine patients with in two weeks ; this improvement , most pronounced in the oral region ( P less than .001 ) , persisted during a six-week placebo period . There was a slight increase in parkinsonian symptoms ( P less than .05 ) , which was not a prerequisite for improvement in TD . Hence , discontinuation of anticholinergic medication is a possible therapeutic approach in patients with TD A study was conducted to investigate a novel approach to the prophylaxis of schizophrenic relapse . The treatment strategy comprised brief intermittent courses of neuroleptic agents begun as soon as non-psychotic symptoms believed to be early signs of relapse appeared . Fifty four stable , remitted out patients meeting the American Psychiatric Association 's DSM-III criteria for schizophrenia were r and omised double blind to receive brief intermittent treatment with either active or placebo depot neuroleptic injections . Only three patients given placebo injections and two controls were admitted to hospital during one year of follow up . Eight ( 30 % ) of the patients given placebo injections and only 2 ( 7 % ) of the controls , however , had a recurrence of schizophrenic symptoms . Patients given placebo injections experienced fewer extrapyramidal side effects and showed a trend towards a reduction in tardive dyskinesia . Dysphoric and neurotic symptoms were identified before eight out of 11 relapses , and these symptoms were more frequent in patients given placebo depot injections . These results suggest a viable but not necessarily better alternative to continuous oral or depot treatment for less ill , chronic , stabilised schizophrenics based on the early treatment of putative prodromal symptoms of relapse BACKGROUND While the atypical antipsychotics should ultimately reduce the prevalence of tardive dyskinesia , it is likely to remain a significant clinical problem for a long time to come . No strategy has clearly emerged as the treatment of choice for tardive dyskinesia . Atypical antipsychotics have reduced propensities for producing acute extrapyramidal symptoms ( EPS ) and possibly tardive dyskinesia and may be effective in treating patients with established tardive dyskinesia . METHOD This 12-month , r and omized , investigator-blinded study compared the efficacy of quetiapine ( N = 22 ) and haloperidol ( N = 23 ) in treating patients with DSM-IV schizophrenia or schizoaffective disorder and established tardive dyskinesia . Dyskinesia was assessed using the Extrapyramidal Symptom Rating Scale ( ESRS ) dyskinesia subscale scores and the Clinical Global Impression ( CGI ) dyskinesia scores . Other EPS , weight , serum prolactin level , and glycosylated hemoglobin level were also assessed . Subjects were enrolled in the study between April 2000 and March 2002 . RESULTS Mean endpoint doses were 400 mg/day of quetiapine and 8.5 mg/day of haloperidol . Compared with the haloperidol group , the quetiapine group showed significantly greater improvements in ESRS dyskinesia ( 6 and 9 months [ p < or=.01 ] ) and CGI dyskinesia ( from 6 months onward [ p < .05 ] and with repeated- measures analysis [ p = .002 ] ) . Response rate ( > or= 50 % symptom reduction ) was greater with quetiapine than haloperidol ( 64 % [ 9/14 ] and 37 % [ 6/16 ] at 6 months ; 55 % [ 6/11 ] and 28 % [ 4/14 ] at 12 months ) . Other EPS decreased significantly with quetiapine at 3 ( p = .01 ) , 6 ( p = .01 ) , and 9 ( p = .002 ) months . Serum prolactin levels decreased with quetiapine but increased with haloperidol , differing significantly between the groups at endpoint ( p = .005 ) . No significant changes in weight or glucose metabolism were recorded in either group . CONCLUSION Quetiapine effectively reduces the severity of tardive dyskinesia and is well tolerated in patients with established tardive dyskinesia Clozapine has long been considered a useful treatment in patients who have schizophrenia with the neuroleptic-induced delayed-onset side effect tardive dyskinesia . We present data in support of the clinical impression using both an animal model of the disorder and dyskinetic patients themselves . Clozapine produces a lower rate of oral dyskinesia in laboratory rats after 6 months of chronic treatment than does haloperidol ( 8.6 + /- 1.3 vs. 13.6 + /- 1.4 vacuous chewing movements every 5 minutes , respectively ) , suggesting a lower propensity to cause tardive dyskinesia . In the human , when clozapine was compared with haloperidol in the treatment of patients with tardive dyskinesia , clozapine produced significantly greater benefit for motor symptoms after 12 months of treatment than did haloperidol ( p < .001 ) . Moreover , the dyskinesia rebound , which occurred equally in both drug groups at the beginning of the study , was sustained in the haloperidol group but lost in the clozapine-treated patients . These data suggest that dyskinetic patients lose their symptoms of tardive dyskinesia , along with dopaminergic hypersensitivity , with long-term clozapine treatment A comparison of the features of persistent oral dyskinesia and functional oral movements is made . The literature on the drug control of oral dyskinesia is review ed . In a double-blind interrupted cross-over trial in two established cases of oral dyskinesia , thiopropazate dihydrochloride was found to be highly effective An experimental method was utilized to compare the masking effects of two neuroleptic agents -- molindone and haloperidol -- on 18 neuroleptic-treated schizophrenic patients exhibiting operationally defined withdrawal-exacerbated tardive dyskinesia . After a week on one of these two medications at preestablished doses equivalent to that of the pre- study neuroleptic , molindone-masked total AIMS scores by significantly less ( 12 % ) than haloperidol ( 27 % ) . Similarly , during a second week when the dose of these neuroleptics was equivalent to 200 % that of the pre- study dose , molindone masked the total AIMS score significantly less ( 23 % ) as compared to haloperidol ( 53 % ) . Several interpretations of this finding are considered . This study demonstrates the feasibility of a method that may offer a model for underst and ing pharmacological differences among neuroleptic medications The authors estimated components of variance and intraclass correlation coefficients ( ICCs ) to aid in the design of complex surveys and community intervention studies by analyzing data from the Health Survey for Engl and 1994 . This cross-sectional survey of English adults included data on a range of lifestyle risk factors and health outcomes . For the survey , households were sample d in 720 postal code sectors nested within 177 district health authorities and 14 regional health authorities . Study subjects were adults aged 16 years or more . ICCs and components of variance were estimated from a nested r and om-effects analysis of variance . Results are presented at the district health authority , postal code sector , and household levels . Between-cluster variation was evident at each level of clustering . In these data , ICCs were inversely related to cluster size , but design effects could be substantial when the cluster size was large . Most ICCs were below 0.01 at the district health authority level , and they were mostly below 0.05 at the postal code sector level . At the household level , many ICCs were in the range of 0.0 - 0.3 . These data may provide useful information for the design of epidemiologic studies in which the units sample d or allocated range in size from households to large administrative areas Fluperlapine , a new clozapine-like neuroleptic drug with weak affinity for dopamine receptors , was evaluated in a blind , placebo controlled trial in 11 patients with stable hyperkinesia ( ten with tardive dyskinesia ( TD ) and one with spontaneous dyskinesia ) . Drug effects during active treatment ( 200–600 mg/day ) and during pre- and post-treatment placebo periods were determined by scoring r and omly sequenced videotapes of TD and parkinsonian symptoms recorded weekly during st and ardized examinations . TD score was unchanged , while parkinsonism slightly decreased ( P<0.05 ) and eye-blinking rates increased ( P<0.05 ) . Psychiatric symptoms showed no significant changes , although positive psychotic symptoms diminished in four patients . Side effects included dizziness , sedation and constipation . The effects in movement disorders found in this study may imply that fluperlapine is less liable than traditional neuroleptics to induce acute extrapyramidal side effects and tardive dyskinesia and is particularly beneficial in the treatment of patients vulnerable to neurological side-effects We sought to determine whether such state-related factors as neuroleptic treatment and facio-oral tardive dyskinesia ( TD ) influence smooth-pursuit eye movement ( SPEM ) in chronic schizophrenics . The design involved 100 schizophrenics , 64 of whom showed " abnormal " eye tracking . Experimentally drug-withdrawn patients , some of whom were clinical ly relapsed , were compared with control patients who continued taking medication in prewithdrawal and postwithdrawal SPEM tests . All groups showed a slight worsening in eye-tracking performance on two postwithdrawal tests , but significant group-by-test session " interactions " were not demonstrable . We also determined that patients with TD tend to substitute large , nontracking saccades for SPEM to a significantly greater extent than nondyskinetic patients . Our findings strengthen the supposition that impaired SPEM is a trait in many schizophrenics but suggest that patients with TD be excluded in future studies of SPEM addressed to trait issues Clozapine , which has had limited clinical testing in the U.S.A. , was evaluated in 12 chronic schizophrenic patients with tardive dyskinesia . Its antipsychotic activity was again demonstrated and it suppressed the symptoms of tardive dyskinesia with a marked rebound occurring in these symptoms when it was withdrawn ; there was no rigidity or other Parkinsonian symptoms . However , out of a total of 12 patients , neutropenia ( 800 and 1120 ) occurred in two patients , convulsions in one patient , marked withdrawal effects in three patients , and a hypotensive collapse with atrial fibrillation in one patient . If these adverse effects are confirmed in a larger sample size , then despite the novel desirable effects of clozapine it would seem unlikely that it will gain widespread or routine use1 BACKGROUND Amisulpride is a potent substituted benzamide antipsychotic drug cl aim ed to improve the negative symptoms of schizophrenia , particularly at low dosage . METHOD Sixty long-term in- patients with schizophrenia and selected for predominant negative symptoms were r and omised to receive either haloperidol or amisulpride . Over a year there was systematic dose reduction , as symptoms allowed . RESULTS There were no significant differences between the treatment groups in the proportion receiving low-dose treatment , the control of positive symptoms , or ratings of social behaviour , side-effects or tardive dyskinesia . For negative symptoms , there were consistent but non-significant trends in favour of amisulpride . The amisulpride patients required significantly less anticholinergic medication . CONCLUSIONS In chronically-hospitalised in- patients with schizophrenia characterised by persistent negative symptoms , amisulpride was a well-tolerated maintenance antipsychotic medication . The drug had only a limited effect in reducing negative symptoms , which were relatively stable , enduring phenomena in this sample , despite dosage reduction Eleven patients with Huntington 's disease and nine patients with tardive dyskinesia participated in a r and omised double-blind crossover trial of sulpiride ( as sole antidopaminergic therapy ) versus placebo . Although functional improvement was not seen in Huntington 's disease patients , sulpiride reduced movement count and total dyskinesia score in both conditions . Sulpiride differs pharmacologically in several respects from conventional neuroleptics , and has not been convincingly shown to cause tardive dyskinesia . Among currently available treatments , it may therefore be considered a drug of choice for treatment of tardive dyskinesia The goal of this study was to assess the time course of change in psychopathology and dyskinesia after neuroleptic withdrawal . Fifteen DSM-III schizophrenic patients were abruptly withdrawn in a double-blind fashion from stable haloperidol treatment . Weekly ratings of dyskinesia and psychopathology were performed for 4 weeks post-withdrawal . There was an overall increase in dyskinesia ratings over the 4-week period ( p < 0.05 ) beginning in week 2 , with dyskinetic movements of the fingers showing the most significant increase ( p < 0.001 ) . There were no overall changes in psychopathology , though the group appeared to be bimodal with 6 of the 15 patients showing a significant relapse in psychotic symptoms . Neither baseline TD nor psychotic relapse significantly interacted with change in TD over time . These schizophrenic patients showed an increase in global dyskinesia rating early within four weeks of neuroleptic withdrawal . This time course did not appear to be associated with reemergence of psychopathology which occurred later . A significant minority of patients relapsed within this time period . This suggests the relative safety of brief periods of neuroleptic withdrawal for carefully selected patients in a controlled setting with specific goals ( e.g. , for evaluation or in preparation for clozapine ) and the need to further underst and who is at risk for rapid relapse Of 2,145 residents of a state facility for the mentally retarded , 103 children between ages 11 and 16 were found who were being given phenothiazines and who had been receiving such therapy for a long period of time . Twenty-one of these children , 15 girls and six boys , had mild to moderate tardive dyskinesia as confirmed by two observers ( G.P. , G.C. ) . The movements of the limbs , tongue , and trunk were grade d on a scale of one to four . In a double-blind study , the medication was withdrawn or readjusted and the patients rechecked at two- , four- , and six-week intervals . The patients were seen in each Based on the hypothesis that an enhanced dopaminergic activity in the basal ganglia may play a major role in tardive dyskinesia , the clinical efficacy of two dopamine-blocking agents , haloperidol ( Haldol ) and thiopropazate dihydrochloride ( Dartal ) , for the short-term treatment of tardive dyskinesia was studied on 20 patients for four weeks . Both drugs were shown to have marked antidyskinetic effects in over a half of the patients . Improvements of dyskinesia were not always accompanied by development of reversible extrapyramidal symptoms . These results , together with the findings obtained in the previous study , appear to support the above-mentioned hypothesis , and suggest another approach to the symptomatic control of tardive dyskinesia through neurochemical regulation , although the clinical practicability of these drug regimens over a longer period of time is not established and needs further investigation The effect was measured by a Doppler‐radar device and by counting the number of involuntary movements from video‐recordings . Besides these methods , subjective assessment s were made on analogue scales by family , nurses and attendant doctors Using a blind evaluation of cinematographic films of patients suffering from tardive dyskinesia we found that thiopropazate hydrochloride in a dosage up to 30 mg daily was effective in reducing the severity of the dyskinesia in most patients . The overall improvement in the group of patients studied was not significant after one or three months of therapy but was significant after six months of treatment . The administration of thiopropazate hydrochloride over a six month period did not appear to aggravate the underlying pathophysiology so that the drug could be considered likely to be safe for long-term use . The anticholinergic antiparkinsonism agent benztropine mesylate aggravated the dyskinesia to a significant degree BACKGROUND Previous studies on the use of clozapine in neuroleptic-resistant chronic schizophrenic patients have demonstrated positive effects on tardive dyskinesia but were less conclusive about chronic akathisia and parkinsonism . The aim of the present study was to investigate the short-term ( 18 weeks ) efficacy of clozapine in neuroleptic-resistant chronic schizophrenic patients with coexisting tardive dyskinesia , chronic akathisia , and parkinsonism . METHOD Twenty chronic , neuroleptic-resistant schizophrenic patients with coexisting tardive dyskinesia , parkinsonism , and chronic akathisia were treated with clozapine . Assessment of tardive dyskinesia , parkinsonism , and chronic akathisia was made once weekly for 18 weeks with the Abnormal Involuntary Movement Scale ( AIMS ) , Simpson-Angus Rating Scale for Extrapyramidal Side Effects , and Barnes Rating Scale for Drug-Induced Akathisia ( BAS ) . RESULTS At the end of 18 weeks of clozapine treatment , improvement rates were 74 % for tardive dyskinesia , 69 % for parkinsonism , and 78 % for chronic akathisia . A statistically significant reduction in the scores on the AIMS and Simpson-Angus Scale was achieved at Week 5 and on the BAS at Week 6 ( p < .0001 ) . CONCLUSION Relatively low doses of clozapine are effective for the treatment of neuroleptic-induced extrapyramidal syndromes in neuroleptic-resistant chronic schizophrenic patients . The relief of tardive dyskinesia , parkinsonism , and chronic akathisia in this group of patients occurs more rapidly than the reduction in psychotic symptoms . Disturbing , long-term extrapyramidal syndromes in chronic schizophrenic patients should be considered an indication for clozapine treatment Benztropine mesylate ( intravenous [ IV ] and oral ) challenge was compared with brief neuroleptic withdrawal on dyskinesia ratings and symptom measures . Thirty-six neuroleptic-treated patients underwent a placebo-controlled acute IV challenge with 2 mg benztropine and a placebo-controlled two-week trial of oral benztropine mesylate ( 2 mg three times a day ) , followed by a double-blind placebo-controlled neuroleptic withdrawal involving four weeks of dose tapering and six weeks of placebo treatment . Benztropine given IV had no significant effect . Orally administered benztropine , however , led to statistically significant increases in dyskinesia and dysphoric mood . The brief neuroleptic withdrawal significantly increased dyskinesia scores and dysphoria and result ed in early termination of therapy in 12 of 36 patients ( 33 % ) due to symptom exacerbation . There was a striking absence of correlation between dyskinesia change measures brought about by benztropine and changes following neuroleptic withdrawal . Therefore anticholinergic challenge does not appear to be a fruitful procedure for identifying patients with covert dyskinesia Although it is generally accepted that antipsychotic treatment improves the negative symptoms of schizophrenia in the context of improvement of positive symptoms , exactly how and to what extent they effect “ primary ” negative symptoms remains controversial . Antipsychotic treatment may reduce only those negative symptoms secondary to positive or depressive symptoms , and may have minimal , if any effect , on negative symptoms that represent a primary psychopathological trait manifestation of schizophrenia . In an effort to further examine this issue , we prospect ively assessed negative , positive , depressive , and extrapyramidal symptoms following the discontinuation of antipsychotic medication . Fifty-nine DSM III-R schizophrenic patients underwent a three-week drug wash as part of our neuroimaging protocol s. We assessed psychopathological status and adverse effects utilizing various rating instruments ( i.e. , Scale for Assessment of Positive Symptoms [ SAPS ] , Scale for Assessment of Negative Symptoms [ SANS ] , Hamilton Rating Scale for Depression , and Simpson-Angus Extrapyramidal ) at baseline and weekly during this three-week period . Negative symptoms , as measured by the SANS , worsened significantly during the three-week drug wash . Positive symptoms showed a less consistent change with symptoms of disorganization worsening and with psychotic symptoms remaining the same . The changes in negative symptoms during the drug-free period were correlated with the changes in psychosis and disorganization , but not with changes in depression or extrapyramidal side effects . We were not able to substantiate if the worsening in negative symptoms was a direct result of the worsening of positive symptoms or if they were changing simultaneously , but independent of each other Plasma prolactin concentration ( pPRL ) , plasma homovanillic acid concentration ( pHVA ) , and symptomatology were measured in 24 male subjects with schizophrenia during maintenance haloperidol treatment . Fourteen subjects subsequently underwent 50 percent dose decreases under placebo-controlled , double-blind conditions . At baseline , a significant inverse correlation was found between pPRL and both tardive dyskinesia ( TD ) and " thinking disorder " ; pPRL was directly correlated with negative symptoms . No such relationship was found with pHVA . In the patients who underwent a dose decrease , no relationship was found between baseline pPRL or pHVA and any clinical variable after the decrease . These data do not support the use of baseline pPRL or pHVA as markers of central dopamine function subsequent to a neuroleptic dose decrease We evaluated the effectiveness and the side effects of what we defined as low ( 5-mg ) and conventional ( 25-mg ) doses of fluphenazine decanoate administered every two weeks in a double-blind comparison . Subjects were 66 patients who fulfilled DSM-III criteria for schizophrenic disorder . Evaluation of the survival with each dose revealed no significant difference at one year , but significantly better survival was seen with the 25-mg dose ( 64 % ) than the 5-mg dose ( 31 % ) at two years . There was no significant difference in survival when the clinician was permitted to make a dosage adjustment up to 10 mg in the low-dose group and 50 mg in the higher-dose group when the patient demonstrated evidence of a symptomatic exacerbation . Patients assigned to the higher dose appeared to feel more uncomfortable during the early months of the study , as indicated by significantly higher scores on subscales of the Hopkins Symptom Checklist-90R and higher side effect scores for retardation and akathisia . Implication s for clinical practice are discussed In a double-blind placebo controlled trial of oxypertine in the treatment of tardive dyskinesia , 33 patients with chronic schizophrenia received either oxypertine or placebo . At the end of eight weeks , the results showed that oxypertine was superior to placebo at a statistically significant level OBJECTIVES To describe the incidence of tardive dyskinesia ( TD ) in the Yale TD Study and to identify demographic , treatment , and clinical risk factors for TD occurrence . DESIGN An ongoing prospect i ve cohort study in which subjects have been examined every 6 months since 1985 . SETTING The outpatient division of the Connecticut Mental Health Center in New Haven . SUBJECTS Three hundred ninety-eight adult out patients who had been maintained with neuroleptics for 3 months to 33 years at intake and who were free of persistent TD at intake with no history of persistent TD movements . OUTCOME MEASURE New cases of persistent TD were defined as the presence of mild or more severe dyskinetic movements at two successive follow-up visits , using the Abnormal Involuntary Movement Scale . RESULTS As of July 1 , 1990 , there were 62 new persistent cases of TD , yielding an average incidence rate of 0.053 per year and a 5-year risk of 20 % . The TD rate was positively affected by age , being nonwhite , and neuroleptic dose , and it was inversely affected by years of previous exposure . Little or no effects were found for age at first neuroleptic exposure , type of neuroleptic , use of other psychiatric medications , and psychiatric diagnosis . CONCLUSIONS For out patients maintained for many years with neuroleptics , dose should be minimized to reduce the risk of TD . This strategy does not appear to be negated by prescribing frequent changes in dosage . Although the TD rate is greatest during the first 5 years of neuroleptic treatment , new persistent cases continue to occur many years after first exposure The effect of single intravenous doses of metoclopramide ( 10 mg , 20 mg and 40 mg ) and haloperidol ( 5 mg and 10 mg ) have been compared to placebo ( saline ) in a double blind r and omised study in 8 patients with tardive dyskinesia secondary to neuroleptic therapy . Tardive dyskinesia rating scores were improved significantly ( P less than 0.01 ) 6 hours after dosing by metoclopramide 40 mg , and haloperidol 5 mg and 10 mg , when compared to placebo . Single doses of dopamine receptor blocking agents improve tardive dyskinesia . The dose of metochlopramide required to show a beneficial effect was high , and this therefore suggests that it is unlikely to be of therapeutic value as the incidence of adverse reactions would be greatly increased . By monitoring the effects of single doses of dopamine receptor blocking drugs in patients with tardive dyskinesia it is possible to compare the relative potencies of these drugs on dopaminergic systems in vivo in man OBJECTIVE To study the effects of antipsychotic withdrawal in elderly nursing home residents . DESIGN Longitudinal prospect i ve study . SETTING 12 community nursing homes that participated in a r and omized controlled trial of an educational program design ed to reduce antipsychotic use . SUBJECTS 271 residents receiving antipsychotics at baseline and remaining in the home for approximately 6 months thereafter . These were placed into two groups : those with continued use of antipsychotics at follow-up ( n = 207 ) and those with drug discontinued ( n = 64 ) . MEASUREMENTS Change between baseline and follow-up for several st and ard measurements . These included behavior problems , as reported by both regular care providers ( Nursing Home Behavior Problem Scale ) or a blinded study rater ( items from the Brief Psychiatric Rating Scale ) , observer-rated psychiatric symptoms ( subset of the Brief Psychiatric Rating Scale ) , and other st and ard tests of function ( Activities of Daily Living , Mini-Mental State Examination , Geriatric Depression Scale , and Abnormal Involuntary Movements Scale ) . RESULTS The frequency of behavior problems did not increase in residents with antipsychotics discontinued . For these residents , observer-rated psychiatric symptoms decreased by 21 % ( P = 0.003 ) , which result ed from a 27 % decrease in adverse affective symptoms ( P = 0.0002 ) . Residents with drug discontinued had no deterioration in any of the measures of function . CONCLUSION In this sample , nursing home residents whose antipsychotics were discontinued had significantly improved affect and no discernable adverse effects Tardive dyskinesia can be suppressed by drugs that block dopaminergic receptors , but often at the cost of a concomitant increase in parkinsonism . Sulpiride ( 400–2100 mg/day ) , a selective type-2 dopamine receptor antagonist , was evaluated in a blind , placebo-controlled trial in 11 patients with tardive dyskinesia . It significantly ( P<0.01 ) reduced tardive dyskinesia without significantly affecting parkinsonism , although three patients had an increase in preexisting parkinsonian hypokinesia and tremor , During the placebo phase , the tardive dyskinesia and parkinsonian scores returned to the pretreatment values . There was no relationship between either tardive dyskinesia or parkinsonism and eye blinking rates . These results are consistent with the hypothesis that more than one population of dopamine receptors are involved in controlling extrapyramidal functions . Sulpiride is an important tool for elucidating both the practical and heuristic aspects of subtypes of dopamine receptors and is a lead in the search for compounds that selectively affect dopaminergic mechanisms Tardive dyskinesia ( TD ) may be a clinical manifestation of a relative imbalance between the inversely related dopaminergic ( DA ) and acetylcholinergic ( ACh ) influences in the central nervous system ( CNS ) . Six patients were evaluated with single challenge doses of a DA agonist , levodopa , and antagonist , droperidol , as well as with an ACh agonist , physostigmine , an antagonist , benztropine , and a placebo . A single blind trial with deanol and placebo followed . Responses , measured by an electrophysiological technique , formed two subgroups . The patients who improved with a DA antagonist or an ACh agonist improved while taking deanol . Another group of patients were made worse with a DA antagonist or ACh agonist and were worsened or had no response while taking deanol . While the results add support to the concept of counterbalancing DA-ACh influences in TD , further investigation of TD subtypes and predictors of drug response is warranted In an attempt to prospect ively vali date the existence of supersensitivity psychosis ( SSP ) , five schizophrenic patients meeting Chouinard 's criteria for SSP and five non-SSP schizophrenic controls had neuroleptic treatment withdrawn for 2 weeks under double-blind conditions . The sudden worsening of psychotic symptoms and tardive dyskinesia postulated in the SSP group was not observed on the Brief Psychiatric Rating Scale , the Clinical Global Impressions scale , and the Abbreviated Dyskinesia Rating Scale . In conclusion , the authors ' pilot data do not seem to support the existence of SSP The relative costs and benefits of low- and conventional-dose neuroleptic maintenance therapy were evaluated in a double-blind comparison of 5 and 25 mg of fluphenazine decanoate administered every two weeks . Subjects were 50 patients fulfilling DSM-III criteria for schizophrenic disorder who had been successfully maintained with 25 mg or less of fluphenazine decanoate . A one-year survival analysis disclosed that there were no statistically significant differences between the two doses insofar as preventing relapse . Patients receiving the higher dose appeared to feel more uncomfortable , as indicated by higher scores on subscales of the Hopkins Symptom Checklist-90 . In addition , patients receiving the higher dose had higher side-effect scores . These findings suggest that a substantial proportion of patients who are presently maintained with 25 mg or less of fluphenazine decanoate every two weeks will do just as well with as little as 5 mg Thirty-eight chronically ill psychotic patients were treated with clozapine for indications of tardive dyskinesia , severe extrapyramidal side effects caused by other neuroleptics , or treatment-resistant psychosis . Fifty-five percent of all patients and 40 % of schizophrenics improved with clozapine . Abnormal involuntary movements were suppressed during treatment and , with 1 exception , returned to baseline levels after clozapine was discontinued . Our results support the conclusion that clozapine 's efficacy in refractory cases and its lack of neurological side effects make it a unique neuroleptic with advantages over conventional antipsychotic agents . The drug appears to be safe when treatment is accompanied by frequent clinical and hematologic monitoring Remoxipride in a dose range of 150–600 mg/day was evaluated in a single-blind placebo controlled study in eight patients with persistent tardive dyskinesia ( TD ) . Dyskinesia score was significantly reduced without an increase in parkinsonism . The maximum mean reduction in dyskinesia rating score was 44 % . After withdrawal of remoxipride TD scores returned to baseline levels without rebound deterioration . A negative correlation between remoxipride concentrations and the dyskinesia scores were found . Adverse effects were few and mild and no clinical ly relevant changes were seen in clinical chemistry , haematology or cardiovascular assessment s. It is concluded that remoxipride in the dose range used has anti-dyskinetic effects but does not induce parkinsonism Saccadic distractibility , Stroop color-word scores , and serial dyskinesia assessment s were obtained on 10 schizophrenic patients with tardive dyskinesia during a pharmacologic challenge with placebo or 7 mg muscimol , a potent , direct-acting GABA agonist . Although no significant difference in the measures was evident between conditions , a significant correlation was found between GABA agonist-induced changes in saccadic distractibility and dyskinesia scores where no correlation existed between these measures on placebo . Improvement in saccadic distractibility was also correlated with reduction in attention performance , as measured by Stroop . These effects are not due to sedation . The correlation between dyskinesia and saccadic distractibility is consistent with a model of parallel motor and oculomotor cortico-striatal-thalamic circuits in humans . This work supports the hypothesis that a dysfunction in GABA-mediated neurotransmission may be the basis for tardive dyskinesia In an attempt to begin to establish minimum effective dosage requirements for the maintenance treatment of schizophrenia , we undertook a double-blind comparison of low-dose fluphenazine decanoate ( 1.25 to 5.0 mg/2 wk ) with the st and ard-dose regimen ( 12.5 to 50.0 mg/2 wk ) in outpatient schizophrenics . For the first 126 patients studied , cumulative relapse rates at one year for the low dose were 56 % and for the st and ard dose 7 % , a significant difference . Despite the fact that very little dyskinetic symptomatology developed in the sample as a whole , the low-dose treatment appeared to have a significant advantage in producing fewer early signs of tardive dyskinesia . Severity of relapse and total cumulative dosage were also considered THE FACT that neuroleptic drugs can cause dyskinesias other than parkinsonism or acute dystonia has been well documented by more than 50 papers . I review ed the literature on this subject in 1968 1 ; Schmidt and Jarcho , among others , described the most important manifestations of these abnormalities in an issue of the Archives in 1966 . 2 It suffices to mention here that this type of disorder , also called tardive dyskinesia , is characterized by complex repetitive involuntary motility , localization in the oral region ( bucco-lingual syndrome ) or in the distal parts of the extremities , rocking of the pelvis and shifting of weight from foot to foot , late onset in the course of drug therapy , persistence for months or years after drug withdrawal , and failure to respond to antiparkinsonian drugs . In addition , cases have been reported in which the syndrome resembles Huntington 's chorea , dystonia deformans , choreo-athetosis and various types of tics . The A double-blind withdrawal trial in 41 chronic schizophrenic out patients was carried out over 6 months . Depot neuroleptics ( fluphenazine decanoate or flupenthixol decanoate ) were compared with placebo to evaluate neurological side effects during continued therapy and during withdrawal . The drugs were significantly more effective than placebo in preventing relapse and rehospitalization . In the placebo group 62 % relapsed compared to 27 % in the drug group . A difference was observed in the occurrence of extrapyramidal symtoms ( EPS ) between the neuroleptics in the study .Akathasia was observed in 9/38 ( 23.7 % ) cases , significantly more frequent in the fluphenazine decanoate group . Tardive dyskinesia ( TD ) was observed in six cases ( 15.8 % ) ; four cases existed at the start of the study and two others were observed after 3–6 weeks of withdrawal . There was no relation between TD symptoms and relapse . There was a significant decrease in the EPS scores during the placebo treatment and also a significant weight decrease This is a 2-year , double-blind , placebo-controlled study of 101 patients , evaluating the relative efficacy of intermittent medication ( given only when the patient shows early signs of relapse ) compared with moderate doses of maintenance medication for stable schizophrenic out patients . Patients were dropped from the study if they had three prodromal episodes in 1 year or if an episode lasted more than 9 weeks . Fourteen percent of patients given maintenance treatment were dropped from the study compared with 46 % of intermittently treated patients . Relapse rates were 16 % for patients given maintenance treatment and 30 % for intermittently treated patients , a nonsignificant difference . Intermittently treated patients were receiving significantly less medication , but there were no differences found in drug side effects . There appears to be no advantage in using the intermittent approach , but we found that the use of an early intervention strategy reduced the relapse and rehospitalization rates for these patients OBJECTIVE To report results from a long-term prospect i ve study of safety of haloperidol treatment and prevalence of haloperidol-related dyskinesias . METHOD Subjects were children with autism requiring pharmacotherapy for target symptoms . After baseline assessment s , children received haloperidol treatment ; responders requiring further treatment were considered for enrollment into the present study . Six-month haloperidol treatment periods were followed by a 4-week placebo period . The procedure was repeated if further haloperidol treatment was required . At specified times children were evaluated by using multiple instruments . RESULTS Between 1979 and 1994 , 118 children aged 2.3 to 8.2 years participated in the study . The mean dose of haloperidol was 1.75 mg/day . Mainly withdrawal dyskinesias ( WD ) developed in 40 ( 33.9 % ) children ; 20 had more than one dyskinetic episode . A subgroup that remained significantly longer in the study and had a significantly higher cumulative dose of haloperidol evidence d a significantly higher incidence of WD . Occurrence rates of tardive dyskinesia ( TD ) and multiple episodes of TD/WD were higher among girls . CONCLUSION Female gender and pre- and perinatal complications may be involved in susceptibility to dyskinesias ; greater cumulative haloperidol dose and /or longer exposure to haloperidol may increase the risk The abnormal involuntary movements in tardive dyskinesia can be reduced by the dopamine antagonist drugs , phenothiazines and butyrophenones , but most cause an increase in Parkinsonian signs . Sulpiride , a benzamide derivative , and selective antagonist of D2 receptors had a significantly beneficial effect on most of 15 patients ( p less than 0.01 ) . In 12 patients the improvement was marked . The reduction of abnormal movements was observed even with low doses , and it was not necessary to increase the dose of sulpiride above 600 mg daily . There were no significant side effects during the trial nor during an additional three months of treatment OBJECTIVE Tardive dyskinesia is a serious and common complication of neuroleptic treatment . Olanzapine is a novel antipsychotic agent exhibiting regional mesolimbic dopaminergic selectivity and a broad-based pharmacology encompassing serotonin , dopamine , muscarinic , and adrenergic receptor binding affinities . The authors ' goal was to compare the incidence of tardive dyskinesia among patients receiving olanzapine and those receiving the conventional dopamine 2 antagonist haloperidol . METHOD Data were analyzed from three actively controlled and blind long-term responder studies of subjects meeting DSM-III-R criteria for schizophrenia , schizophreniform disorder , or schizoaffective disorder treated with olanzapine ( N = 707 , up to 20 mg/day , 237 median days of exposure ) or haloperidol ( N = 197 , up to 20 mg/day , 203 median days of exposure ) who did not have evidence of tardive dyskinesia at baseline . All of the subjects had a chronic disease course ( mean greater than 10 years ) , and there were no significant between-treatment group differences in demographic or disease characteristics . The Abnormal Involuntary Movement Scale and research diagnostic criteria for tardive dyskinesia were used to define the comparative incidence rates of long-term treatment-emergent tardive dyskinesia . RESULTS The incidence of newly emergent tardive dyskinesia at any visit after baseline , at the final visit , and at the final two clinical assessment s was statistically significantly lower among olanzapine-treated patients than among haloperidol-treated patients . CONCLUSIONS These findings support an atypical extrapyramidal symptom profile and the potential of a significantly lower risk of tardive dyskinesia with olanzapine than with haloperidol among patients requiring maintenance antipsychotic treatment OBJECTIVE This study evaluated the feasibility and impact of gradually reducing relatively high doses of fluphenazine decanoate by one-half for chronically impaired , poor inner-city patients with schizophrenia . METHOD Forty-three patients currently receiving an average of 23 mg ( 0.3 mg/kg ) of fluphenazine decanoate every 2 weeks were divided alternately into a group to remain at current doses ( control group ) and a group to undergo stepwise 50 % dose reduction over 5 months under double-blind conditions . Clinical status and side effects were assessed quarterly for a year . Relapse was determined clinical ly and by changes in psychopathology ratings . RESULTS Eighty-six percent ( N = 37 ) of the patients ( control group , N = 17 ; reduced-dose group , N = 20 ) completed the study . The groups did not differ at baseline in demographic or clinical variables or neuroleptic dose . In the reduced-dose group , doses were lowered to an average of 11.5 mg every 2 weeks . The two groups did not differ throughout the year in number of relapses , and hospitalization rates fell similarly in both ( overall , by about 67 % ) . Clinical measures changed little . Extrapyramidal symptoms worsened in the control group but improved slightly in the reduced-dose group . Tardive dyskinesia worsened in both groups , but less in the reduced-dose group . CONCLUSIONS Maintenance neuroleptic doses much lower than the conventional ones can be achieved safely in schizophrenic patients by gradual reduction , without clinical worsening and perhaps with fewer extrapyramidal symptoms and less tardive dyskinesia . The two-thirds lower hospitalization rate , with substantial financial savings , apparently was due to nonspecific effects of research intervention We have conducted a 6-wk drug withdrawal study in a group of chronic schizophrenic out patients who had been maintained on injectable fluphenazine decanoate for at least 2 yr prior to the study . After two baseline assessment s , patients were r and omly assigned to two groups . The first group ( holiday ) received a placebo injection from a nurse who was not involved in the assessment ( N = 17 ) . The second group continued on their regular medication ( N = 14 ) . The assessment was done in a double-blind fashion at 3 and 6 wk using the Schedule for Affective Disorders and Schizophrenia ( SADS ) and the Global Assessment Scale ( GAS ) inventories to assess symptom status . Tardive dyskinesia was measured using the Abnormal Involuntary Movement Scale ( AIMS ) . Community adjustment was assessed by means of the self-rated Weissman Social Adjustment Scale . We found that there were no relapses of any kind in either group of patients using the instruments mentioned above . The prevalence of tardive dyskinesia as measured by the AIMS was low , with only one patient having severe tardive dyskinesia . There was no significant worsening of the tardive dyskinesia during the drug holiday . Our study concludes that a 6-wk drug holiday was safe in this group of chronic schizophrenic patients maintained on fluphenazine decanoate . In contrast to other studies , no cases of covert tardive dyskinesia were detected during the drug holiday Preliminary results are described from a study of 11 out patients manifesting exacerbated tardive dyskinesia after tapering and withdrawal of neuroleptic medications . Patients were r and omly assigned to molindone or haloperidol under double-blind placebo-controlled conditions to compare the masking effects of the two drugs . Haloperidol treatment masked withdrawal-exacerbated tardive dyskinesia more than molindone did ; this difference ( measured by percent change in AIMS scores ) was significant ( p = .04 ) when the dose was 200 % but not 100 % of the pre study neuroleptic dose . Despite several limitations to the study , the results suggest that molindone may have less dyskinetogenic potential than haloperidol . Further research in the area of site-specificity of molindone is indicated Issues regarding the side effects of antipsychotic medication and the possible contribution of the environment to dose requirements led to a two-year controlled dosage study of maintenance antipsychotic medication and familial environment among recently discharged schizophrenic patients . Seventy stable patients , living in high- or low-expressed emotion ( EE ) households , were r and omized , double blind , to receive a st and ard dose of fluphenazine decanoate ( average , 25 mg every two weeks ) or a minimal dose representing 20 % of the dose prescribed ( average , 3.8 mg every two weeks ) . No differences in relapse were observed among dose , EE , or dose and EE . Patients in the minimal dose/high-EE condition experienced more minor but aborted episodes in year 2 . Side effects were fewer on the minimal dose after one year , and low-EE patients were better adjusted than high-EE patients . Over time , minimal-dose recipients were significantly more improved in their instrumental and interpersonal role performance than were st and ard-dose recipients & NA ; In the Canadian multicenter , double‐blind clinical trial of risperidone , 135 hospitalized chronic schizophrenic patients were r and omly assigned to one of six parallel treatment groups for 8 weeks : risperidone , 2 , 6 , 10 , or 16 mg/day ; haloperidol , 20 mg/day ; or placebo . Risperidone ( 6 to 16 mg)treated patients showed significantly ( p < 0.05 ) lower dyskinetic scores than those receiving placebo , whereas in haloperidol‐ and placebo‐treated patients , no significant differences for dyskinetic symptoms were noted . To explore the antidyskinetic effect of risperidone , a post hoc analysis was performed on two selected patient sample s : ( 1 ) patients meeting Research Diagnosis Criteria ( RDC ) for tardive dyskinesia ( TD ) at baseline or during double‐blind treatment ( N = 49 ) and ( 2 ) patients with RDC TD and with a Clinical Global Impression ( CGI ) Severity of dyskinesia score ≥ 5 ( at least moderately severe ) ( N = 48 ) . The composition of the two sub sample s was found to be almost identical because all but one of the patients with RDC TD ( N = 49 ) were members of the group with at least moderately severe TD ( N = 48 ) . Analysis of four parameters ( Extrapyramidal Symptom Rating Scale‐dyskinesia total score , CGI severity of dyskinesia , buccolinguomasticatory ? [ BLM ] factor score , and extremities [ choreoathetoid factor ] score confirmed the antidyskinetic effect that was noted in the intent‐to‐treat analysis , which included all patients , whether they had RDC TD or not . Results indicated that risperidone at 6 mg/day had the most beneficial effect on TD , especially on the BLM syndrome , without inducing significant parkinsonism while treating psychotic symptoms . This antidyskinetic effect was greater than with either placebo or haloperidol A study was undertaken to investigate the effects of oxypertine in treating tardive dyskinesia . The design was double-blind , placebo-controlled , between-patient , in 28 patients from whom previous medication was withdrawn , with 14 patients in each group . Treatment was for 4 weeks . Although more oxypertine patients improved than placebo , i.e. 71.4 vs. 50 % , the results did not reach statistically significant difference . A further study is planned to increase the overall number of patients in the study , and to lengthen treatment periods BACKGROUND Risperidone has been reported to alleviate the severity of tardive dyskinesia , but without placebo control , the possibility of spontaneous tardive dyskinesia remission after discontinuing original conventional antipsychotics can not be excluded . This 12-week r and omized , double-blind , placebo-controlled study investigated the effect of risperidone on severe tardive dyskinesia . METHOD Forty-nine DSM-IV schizophrenia patients with severe tardive dyskinesia were enrolled in the study . After a 4-week washout period , the subjects were r and omly assigned to treatment with either risperidone or placebo . The risperidone dose was started at 2 mg/day and gradually increased to 6 mg/day over 6 weeks ; the 6-mg/day dose was maintained for the remaining 6 weeks of the study . The subjects were evaluated every 2 weeks with the Abnormal Involuntary Movement Scale ( AIMS ) and the Extrapyramidal Symptom Rating Scale . The final mental status was assessed with the Brief Psychiatric Rating Scale . RESULTS Twenty-two subjects in the risperidone group and 20 subjects in the placebo group completed the study ; the mean baseline AIMS total score for all subjects was 15.9 + /- 4.6 . At the end of the study , the mean AIMS total score decrease was 1.1 + /- 4.8 in the placebo group and 5.5 + /- 3.8 in the risperidone group ( p < .05 ) . Fifteen subjects ( 68 % ) in the risperidone group and 6 subjects ( 30 % ) in the placebo group were responders ( p < .05 ) . The risperidone responders had a mean AIMS total score decrease of 7.5 + /- 2.1 . More significant tardive dyskinesia improvement among the risperidone group was noted from the eighth week and was mainly demonstrated in the buccolinguomasticatory a rea rather than in choreoathetoid movement of the extremities ( p < .001 ) . CONCLUSIONS Risperidone , 6 mg/day , can improve tardive dyskinesia more significantly than discontinuing antipsychotics in patients with severe tardive dyskinesia , especially in the orofacial areas We examined whether patients exhibiting withdrawal-emergent dyskinesia ( WE-D ) represent a group vulnerable to subsequent development of tardive dyskinesia ( TD ) . WE-D was defined as moderate abnormal movements during antipsychotic withdrawal in persons without persistent TD . We assessed patients with schizophrenia-spectrum illness participating in withdrawal from antipsychotic medication . Patients with WE-D were compared to those without dyskinesia and to those with persistent TD . Clinical measures included duration of illness and antipsychotic exposure , negative symptoms , and neurologic soft signs . We hypothesized that WE-D patients would not differ from persistent-TD patients across the above variables , but would differ from non-TD patients . Patients without TD significantly differed from persistent TD in duration of illness , medication exposure and neurologic soft signs . WE-D did not differ from TD across these measures . No-TD patients also showed less duration of medication exposure and neurologic soft signs than those with Twelve patients with abnormal involuntary movement disorders were treated with clozapine in a double-blind , placebo-controlled trial . The cohort consisted of individuals with Gilles de la Tourette 's syndrome , Huntington 's disease , and atypical persistent dyskinesia that was drug induced . Two subjects were dropped from the protocol due to complications . Two patients with Huntington 's disease showed a marked decrease in movements ; other individuals obtained no significant therapeutic benefits . Seven of the 10 patients completing the trial experienced moderate or marked side effects It has been hypothesized that an association exists between pre- and perinatal complications , central nervous system ( CNS ) dysfunction , and the development of tardive ( TD ) and withdrawal dyskinesias ( WD ) . We assessed the relationship between pre- and perinatal complications and TD/WD in a sample of 118 children with autism who participated in an ongoing long-term prospect i ve study of the efficacy and safety of haloperidol . The mean total Rochester Research Obstetrical Scale ( ROS ) score was significantly higher for children who developed TD/WD compared to those who did not ( p = .007 ) as was the mean score of the ROS Delivery Scale ( p = .002 ) . Anesthesia during delivery was more frequent in children who developed TD/WD ( 25 of 40 , 62.5 % ) than in those who did not ( 30 of 78 , 38.5 % ) ( p = .019 ) . The ROS Not Vertex Presentation item and TD/WD were associated only in females ( p = .019 ) . Six of 7 males with short labor developed TD/WD ( p = .007 ) . ROS scores did not differ significantly as a function of gender or socio-economic status ( SES ) . Pre- and perinatal complications appear to be related to the development of TD/WD in this sample of children ABSTRACT ‐ In a prospect i ve follow‐up the outcome of 60 chronic schizophrenic patients who discontinued neuroleptic therapy after remaining stable 12–48 months was compared with controls continuing medication . Not only did the drug‐discontinued patients have more relapses ( P < 0.001 ) , but the form of relapse was both more severe and acute , result ing in differences of self‐injury ( P < 0.05 ) , anti‐social behaviour ( P < 0.01 ) , inpatient admissions ( P < 0.001 ) , and the use of compulsory powers ( P < 0.01 ) . In patients who relapsed , both social and work function was affected adversely for some months . Patients who remained relapse‐free without drugs ( 20 % ) had a level of work and social function similar to medicated patients . At the end of 18 months the patients who discontinued depot maintenance therapy were found to have been prescribed one‐third more neuroleptic drugs than controls , with a possible increase in the risk of long‐term tardive dyskinesia A double-blind controlled trial of 50 % dose reduction in maintenance treatment in stable out- patients with low BPRS scores and good social function shows a significantly higher relapse rate in the low-dose group at 12 months ( P less than 0.05 ) . After an interval of 24 - 36 months from dose reduction , 56 - 76 % had experienced a relapse and 76 - 79 % had resumed their former dosage . No clear advantage was shown for the lower dose in either a reduction of side-effects or improved social function , but a reduced prevalence or lower rate of symptom emergence for tardive dyskinesia was suggested Sixty-two chronic schizophrenics in hospital were studied . There were 32 male and 30 female patients ; their mean ages were 53.6 years and 60.4 years respectively . They had all been on regular phenothiazines , principally trifluoperazine , for a mean of 9.4 years . Placebo capsules were substituted r and omly for 32 patients . Within the 16 drug-free weeks that followed , 9 ( 28 per cent ) patients relapsed sufficiently to require reinstatement on active phenothiazines . The mean drug-free period for those 9 patients was 5 weeks . They were significantly younger , had consumed larger quantities of phenothiazines over the years , and were originally receiving larger daily doses of trifluoperazine than the 23 patients who did not relapse . The patients were rated for the three main extra-pyramidal syndromes — motor restlessness parkinsonian rigidity and tremor and oral dyskinesia-tremor , before and after trifluoperazine was withdrawn . The mean drug-free period was 16 weeks . Comparisons were made between before and after ratings , as well as between placebo and control trifluoperazine groups . Parkinsonian rigidity and tremor , and oral-dyskinesia-tremor did not appreciably change in the placebo or control groups . Motor restlessness worsened significantly in the placebo , but not the trifluoperazine group . Of the 23 placebo patients who were without trifluoperazine for 16 weeks , 8 remained free from motor restlessness , 1 patient continued unchanged , 3 patients improved , 6 patients became worse , and 5 patients developed the disorder for the first time . There was no significant difference in any of the variables tested between the patients who deteriorated and those who remained the same or improved . Trifluoperazine withdrawal , in this study , was therefore followed by a psychiatric relapse in 28 per cent of the patients , persistence of parkinsonian rigidity and tremor and oral dyskinesia-tremor , and worsening of motor restlessness . The implication s of these findings are discussed |
14,001 | 27,919,293 | No difference in postoperative atrial fibrillation , myocardial infa rct ion , stroke , infections , or mortality was present .
On sensitivity analysis , statin therapy was associated with a slight increase in hospital mortality .
Meta- analysis including also trials with high or unclear risk of bias showed no beneficial effects of statin therapy on any postoperative outcomes .
Conclusions There is no evidence that statin therapy in the days prior to cardiac surgery is beneficial for patients ’ outcomes .
Particularly , statins are not protective against postoperative atrial fibrillation , myocardial infa rct ion , stroke , or infections .
Statins are associated with a possible increased risk of acute kidney injury and a detrimental effect on hospital survival could not be excluded . | Background Several studies suggest beneficial effects of perioperative statin therapy on postoperative outcome after cardiac surgery .
However , recent r and omized controlled trials ( RCTs ) show potential detrimental effects .
The objective of this systematic review is to examine the association between perioperative statin therapy and clinical outcomes in cardiac surgery patients . | The acute administration of atorvastatin has been reported to reduce myocardial infa rct size in animal studies . However , this cardioprotective effect is lost with the chronic administration of atorvastatin , although it can be recaptured by administering an acute high-dose of atorvastatin . We hypothesised that pre-treatment with high-dose atorvastatin , on a background of chronic st and ard ‘ statin ’ therapy , would reduce myocardial injury in patients undergoing elective coronary artery bypass graft ( CABG ) surgery . One hundred and one consenting patients undergoing elective CABG surgery at a single tertiary cardiac centre were recruited into two r and omised controlled , single-blinded clinical studies . Study 1 : 45 patients were r and omised to receive either 160 mg of atorvastatin 2 h preoperatively and 24 h following surgery or their st and ard statin therapy . Study 2 : 56 patients were r and omised to receive either 160 mg of atorvastatin 12 h preoperatively and 24 h following surgery or their st and ard statin therapy . Blood sample s for troponin T and creatine kinase were taken prior to surgery and then at 6 , 12 , 24 , 48 and 72 h post-surgery . Cardiac enzyme levels at each time point and the total area-under curve ( AUC ) were calculated . The group characteristics and surgical methods were well matched . High-dose atorvastatin was not associated with any significant side effects . There was no significant difference in serum troponin T or creatine kinase in either study at each time point or over 72 h. Study 1 : AUC , troponin T : atorvastatin 29.6 ± 34.8 μg/L versus control 25.0 ± 22.0 μg/L : P > 0.05 . Creatine kinase : atorvastatin 33,544 ± 20,063 IU/L versus control 30,620 ± 10,776 IU/L : P > 0.05 . Study 2 : AUC , troponin T : atorvastatin 21.8 ± 14.3 μg/L versus control 20.9 ± 8.7 μg/L : P > 0.05 . Creatine kinase : atorvastatin 36,262 ± 28,821 IU/L versus control 33,448 ± 14,984:P > 0.05 . There were no differences in postoperative outcomes . We report that the administration of high-dose atorvastatin to low risk patients undergoing elective CABG surgery , who are already on st and ard dose ‘ statin ’ therapy is safe , but does not further reduce perioperative myocardial injury Purpose Statins , 3-hydroxy-3-methylglutaryl coenzyme A ( HMG-CoA ) reductase inhibitors have the potential to reduce acute kidney injury ( AKI ) after cardiac surgery through their pleiotropic properties . Here we studied the preventive effect of atorvastatin on AKI after valvular heart surgery . Methods Two-hundred statin-naïve patients were r and omly allocated to receive either statin or placebo . Atorvastatin was administered orally to the statin group according to a dosage schedule ( 80 mg single dose on the evening prior to surgery ; 40 mg on the morning of surgery ; three further doses of 40 mg on the evenings of postoperative days 0 , 1 , and 2 ) . AKI incidence was assessed during the first 48 postoperative hours on the basis of Acute Kidney Injury Network criteria . Results The incidence of AKI was similar in the statin and control groups ( 21 vs. 26 % , respectively , p = 0.404 ) . Biomarkers of renal injury including plasma neutrophil gelatinase-associated lipocalin and interleukin-18 were also similar between the groups . The statin group required significantly less norepinephrine and vasopressin during surgery , and fewer patients in the statin group required vasopressin . There were no significant differences in postoperative outcomes . Conclusions Acute perioperative statin treatment was not associated with a lower incidence of AKI or improved clinical outcome in patients undergoing valvular heart surgery . ( Clinical Trials.gov NCT01909739 ) BACKGROUND Neutrophils play a central role in systemic inflammatory reaction after cardiopulmonary bypass . Apoptosis is significantly delayed , and this might exacerbate systemic and myocardial damage . We tested the hypothesis of whether pretreatment with simvastatin increases the apoptotic rate of neutrophils and hence reduces the entity of inflammatory reaction . METHODS Thirty patients undergoing coronary surgery with cardiopulmonary bypass were r and omized to treatment with either simvastatin ( 40 mg/day ) or placebo for 3 weeks before surgery . A group of 15 patients undergoing off-pump coronary surgery served as controls . Blood sample s for detection of serum cytokine levels were obtained before anesthesia , at the end of surgery , and at 4 , 24 , 48 , and 72 hours postoperatively . Apoptosis and indices of activation were assessed in cultured neutrophils . RESULTS Simvastatin significantly reduced the postoperative peak values of interleukin (IL)-6 and IL-8 . The neutrophil apoptotic rate was significantly higher among neutrophils obtained from patients pretreated with simvastatin ( p < 0.05 at both 8 and 24 hours ) compared with placebo . Neutrophils from the statin group had depressed functional activity , as underscored by significantly lower values of CD11b ( p < 0.01 at 24 hours ) and a significantly less percentage of cells positive for nitro-blue tetrazolium ( p < 0.01 at 12 and 24 hours ) compared with placebo . CONCLUSIONS This r and omized , double-blind study indicates that statin therapy before cardiopulmonary bypass is associated with reduction of circulating markers of inflammation and increased neutrophil apoptosis . These data support a routine inclusion of statins as an adjuvant pharmacologic therapy before cardiopulmonary bypass surgery IMPORTANCE Statins affect several mechanisms underlying acute kidney injury ( AKI ) . OBJECTIVE To test the hypothesis that short-term high-dose perioperative atorvastatin would reduce AKI following cardiac surgery . DESIGN , SETTING , AND PARTICIPANTS Double-blinded , placebo-controlled , r and omized clinical trial of adult cardiac surgery patients conducted from November 2009 to October 2014 at V and erbilt University Medical Center . INTERVENTIONS Patients naive to statin treatment ( n = 199 ) were r and omly assigned 80 mg of atorvastatin the day before surgery , 40 mg of atorvastatin the morning of surgery , and 40 mg of atorvastatin daily following surgery ( n = 102 ) or matching placebo ( n = 97 ) . Patients already taking a statin prior to study enrollment ( n = 416 ) continued taking the preenrollment statin until the day of surgery , were r and omly assigned 80 mg of atorvastatin the morning of surgery and 40 mg of atorvastatin the morning after ( n = 206 ) or matching placebo ( n = 210 ) , and resumed taking the previously prescribed statin on postoperative day 2 . MAIN OUTCOMES AND MEASURES Acute kidney injury defined as an increase of 0.3 mg/dL in serum creatinine concentration within 48 hours of surgery ( Acute Kidney Injury Network criteria ) . RESULTS The data and safety monitoring board recommended stopping the group naive to statin treatment due to increased AKI among these participants with chronic kidney disease ( estimated glomerular filtration rate < 60 mL/min/1.73 m2 ) receiving atorvastatin . The board later recommended stopping for futility after 615 participants ( median age , 67 years ; 188 [ 30.6 % ] were women ; 202 [ 32.8 % ] had diabetes ) completed the study . Among all participants ( n = 615 ) , AKI occurred in 64 of 308 ( 20.8 % ) in the atorvastatin group vs 60 of 307 ( 19.5 % ) in the placebo group ( relative risk [ RR ] , 1.06 [ 95 % CI , 0.78 to 1.46 ] ; P = .75 ) . Among patients naive to statin treatment ( n = 199 ) , AKI occurred in 22 of 102 ( 21.6 % ) in the atorvastatin group vs 13 of 97 ( 13.4 % ) in the placebo group ( RR , 1.61 [ 0.86 to 3.01 ] ; P = .15 ) and serum creatinine concentration increased by a median of 0.11 mg/dL ( 10th-90th percentile , -0.11 to 0.56 mg/dL ) in the atorvastatin group vs by a median of 0.05 mg/dL ( 10th-90th percentile , -0.12 to 0.33 mg/dL ) in the placebo group ( mean difference , 0.08 mg/dL [ 95 % CI , 0.01 to 0.15 mg/dL ] ; P = .007 ) . Among patients already taking a statin ( n = 416 ) , AKI occurred in 42 of 206 ( 20.4 % ) in the atorvastatin group vs 47 of 210 ( 22.4 % ) in the placebo group ( RR , 0.91 [ 0.63 to 1.32 ] ; P = .63 ) . CONCLUSIONS AND RELEVANCE Among patients undergoing cardiac surgery , high-dose perioperative atorvastatin treatment compared with placebo did not reduce the risk of AKI overall , among patients naive to treatment with statins , or in patients already taking a statin . These results do not support the initiation of statin therapy to prevent AKI following cardiac surgery . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00791648 BACKGROUND Acute kidney injury ( AKI ) is a serious complication of cardiac operations for which there remains no specific therapy . Animal data and several observational studies suggest that statins prevent AKI , but the results are not conclusive , and many studies are retrospective in nature . METHODS We conducted a multicenter prospect i ve cohort study of 625 adult patients undergoing elective cardiac operations . All patients were taking statins and were grouped according to whether statins were continued or held in the 24 hours before operation . The primary outcome was AKI as defined by a doubling of serum creatinine or dialysis . The secondary outcome was the peak level of several kidney injury biomarkers . The results were adjusted for demographic and clinical factors . RESULTS Continuing ( vs holding ) a statin before operation was not associated with a lower risk of AKI , as defined by a doubling of serum creatinine or dialysis ( adjusted relative risk [ RR ] 1.09 ; 95 % confidence interval [ CI ] 0.44 , 2.70 ) . However , continuing a statin was associated with a lower risk of elevation of the following AKI biomarkers : urine interleukin-18 , urine neutrophil gelatinase-associated lipocalin , urine kidney injury molecule-1 , and plasma neutrophil gelatinase-associated lipocalin ( adjusted RR 0.34 ; 95 % CI 0.18 , 0.62 ) , ( adjusted RR 0.41 ; 95 % CI 0.22 , 0.76 ) , ( adjusted RR 0.37 ; 95 % CI 0.20 , 0.76 ) , ( adjusted RR 0.62 ; 95 % CI 0.39 , 0.98 ) , respectively . CONCLUSIONS Statins may prevent kidney injury after cardiac operations , as evidence d by lower levels of kidney injury biomarkers OBJECTIVE Endothelial dysfunction represents a critical early component of organ injury following cardiopulmonary bypass . Recent studies demonstrate that the treatment with atorvastatin is associated with a significant improvement of endothelial function independently of its efficacy on cholesterol levels . Therefore , we investigated the effects of preoperative atorvastatin treatment on endothelium function after coronary surgery . METHODS Forty patients undergoing coronary surgery were r and omized to treatment with atorvastatin ( 20 mg/die ; N=20 ) or placebo ( N=20 ) 3 weeks before surgery . Twenty normal patients served as control group . The flow-mediated dilations ( FMD ) of the brachial artery after both reactive hyperemia ( endothelium dependent ) and nitroglycerin administration ( endothelium independent ) were evaluated at baseline , at 48 h , and 5 days postoperatively . RESULTS At baseline , the endothelium-dependent FMD was significantly attenuated in coronary versus normal patients ( normal 10.3+/-1.8 % vs coronary 4.1+/-1.6 % , p<0.01 ) . At 48 h postoperatively all patients exhibited a reduced FMD compared with baseline values : the endothelium-dependent dilatation showed a drop of 60.1 + 15 % in the patients of the placebo group compared with 45.8 + 16.6 % ( p<0.05 ) those in the atorvastatin group . At the univariate analysis , no significant correlation was found between serum levels of either total cholesterol or HDL cholesterol and FMD . The nitroglycerin-induced dilation was not significantly influenced by extracorporeal circulation as well as by atorvastatin treatment . CONCLUSIONS The endothelial dysfunction following cardiopulmonary bypass is improved by the treatment with atorvastatin , by a mechanism unrelated to the drug efficacy of controlling serum cholesterol levels Background — Atrial fibrillation ( AF ) after cardiac surgery is associated with increased risk of complications , length of stay , and cost of care . Observational evidence suggests that patients who have undergone previous statin therapy have a lower incidence of postoperative AF . We tested this observation in a r and omized , controlled trial . Methods and Results — Two hundred patients undergoing elective cardiac surgery with cardiopulmonary bypass , without previous statin treatment or history of AF , were enrolled . Patients were r and omized to atorvastatin ( 40 mg/d , n=101 ) or placebo ( n=99 ) starting 7 days before operation . The primary end point was incidence of postoperative AF ; secondary end points were length of stay , 30-day major adverse cardiac and cerebrovascular events , and postoperative C-reactive protein ( CRP ) variations . Atorvastatin significantly reduced the incidence of AF versus placebo ( 35 % versus 57 % , P=0.003 ) . Accordingly , length of stay was longer in the placebo versus atorvastatin arm ( 6.9±1.4 versus 6.3±1.2 days , P=0.001 ) . Peak CRP levels were lower in patients without AF ( P=0.01 ) , irrespective of r and omization assignment . Multivariable analysis showed that atorvastatin treatment conferred a 61 % reduction in risk of AF ( odds ratio 0.39 , 95 % confidence interval 0.18 to 0.85 , P=0.017 ) , whereas high postoperative CRP levels were associated with increased risk ( odds ratio 2.0 , 95 % confidence interval 1.2 to 7.0 , P=0.01 ) . The incidence of major adverse cardiac and cerebrovascular events at 30 days was similar in the 2 arms . Conclusions — Treatment with atorvastatin 40 mg/d , initiated 7 days before surgery , significantly reduces the incidence of postoperative AF after elective cardiac surgery with cardiopulmonary bypass and shortens hospital stay . These results may influence practice patterns with regard to adjuvant pharmacological therapy before cardiac surgery OBJECTIVE It has earlier been suggested that postoperative thrombocytosis frequently occur after coronary artery bypass grafting ( CABG ) and may be linked to lipid disturbances . A prospect i ve r and omized study was undertaken to evaluate if preoperative lipid-control , using HMG-CoA-reductase inhibitor ( Zocor ) , simvastatin , reduces the risk of postoperative thrombocytosis . METHODS Seventy-seven patients with symptomatic coronary artery disease and hypercholesterolemia ( total cholesterol > or = 6.2 mmol/l ) , planned for CABG where r and omly assigned to ; undergo CABG without preoperation lipid control ( group I , n = 37 ) or undergo simvastatin-treatment ( 20 mg daily ) to control their lipids ( 4 weeks ) prior to CABG ( group II , n = 40 ) . RESULTS Patient characteristics and operation data did not differ between the groups . Serum-cholesterol , cholesterol/HDL-cholesterol , LDL-cholesterol , Apolipoprotein A1 and Plasminogen were all significantly higher in group I patients compared with group II just prior to surgery . Other laboratory parameters did not differ . RESULTS In group II , total cholesterol and cholesterol/HDL-cholesterol quota were significantly lowered by simvaststin ( -2 and -29 % , respectively ) . Postoperative thrombocytosis ( platelet counts > or = 400000/microl ) occurred significantly more frequently in group I 81 % ( 30/37 ) compared with 3 % ( 1/40 ) in group II , P<0.0001 . Myocardial infa rct ion after the 7th postoperative day was more often diagnosed in group I , 14 vs. 0 % in group II . Postoperative transient renal failure occurred also more frequently in group I , 24 % compared with 8 % in group II . Other postoperative complications and laboratory data did not differ . CONCLUSIONS This study once again underlines the importance of lipid control using HMG-CoA-reductase inhibitors ( e.g. Zocor ) in patients with established coronary artery disease . For the first time it is shown that lipid-control with simvastatin prior to CABG reduces the risk of postoperative thrombocytosis , thus lowers the risk for thrombotic complications Background To evaluate the efficacy of perioperative atorvastatin administration for prophylaxis of postoperative atrial fibrillation ( POAF ) after heart valve surgery . Methods Our study included 90 patients with heart valve disease who were scheduled to undergo elective cardiac surgery . Cases with previous AF or preoperative beta-blocker therapy were excluded . Patients were r and omized into the atorvastatin group , which included 47 patients who received 40 mg/day of atorvastatin 7 days before and after the surgery and the control group , which included 43 patients . Primary endpoint was the occurrence of POAF . Secondary endpoints included modifications in the preoperative and postoperative levels of the markers of inflammation ( C-reactive protein [ CRP ] ) , myocardial injury ( ultrasensitive troponin T and creatinine phosphokinase MB [ CPK-MB ] ) , and cardiac dysfunction ( pro-brain natriuretic peptide [ proBNP ] ) related to POAF and changes in the echocardiographic parameters , such as atrial electromechanical interval , A wave , E/A ratio , and Doppler imaging systolic velocity wave amplitude , related to POAF . Results No relationship between atorvastatin administration and reduction in the incidence of POAF was observed ( 42.6 % in the atorvastatin vs. 30.2 % in the control group ) ( p=0.226 ) . No difference in the levels of CPK-MB , ultrasensitive troponin T , CRP , or proBNP and in the analyzed echocardiographic parameter was detected between both groups . Conclusions Atorvastatin in the described dose , was not adequate for the prophylaxis of POAF after heart valve surgery . It was ineffective in controlling the inflammatory phenomena , myocardial injury , and echocardiographic predictors of POAF BACKGROUND In the acute respiratory distress syndrome ( ARDS ) , inflammation in the lungs and other organs can cause life-threatening organ failure . Inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase ( statins ) can modulate inflammatory responses . Previous observational studies suggested that statins improved clinical outcomes in patients with sepsis . We hypothesized that rosuvastatin therapy would improve clinical outcomes in critically ill patients with sepsis-associated ARDS . METHODS We conducted a multicenter trial in which patients with sepsis-associated ARDS were r and omly assigned to receive either enteral rosuvastatin or placebo in a double-blind manner . The primary outcome was mortality before hospital discharge home or until study day 60 if the patient was still in a health care facility . Secondary outcomes included the number of ventilator-free days ( days that patients were alive and breathing spontaneously ) to day 28 and organ-failure-free days to day 14 . RESULTS The study was stopped because of futility after 745 of an estimated 1000 patients had been enrolled . There was no significant difference between study groups in 60-day in-hospital mortality ( 28.5 % with rosuvastatin and 24.9 % with placebo , P=0.21 ) or in mean ( ±SD ) ventilator-free days ( 15.1±10.8 with rosuvastatin and 15.1±11.0 with placebo , P=0.96 ) . The groups were well matched with respect to demographic and key physiological variables . Rosuvastatin therapy , as compared with placebo , was associated with fewer days free of renal failure to day 14 ( 10.1±5.3 vs. 11.0±4.7 , P=0.01 ) and fewer days free of hepatic failure to day 14 ( 10.8±5.0 vs. 11.8±4.3 , P=0.003 ) . Rosuvastatin was not associated with an increased incidence of serum creatine kinase levels that were more than 10 times the upper limit of the normal range . CONCLUSIONS Rosuvastatin therapy did not improve clinical outcomes in patients with sepsis-associated ARDS and may have contributed to hepatic and renal organ dysfunction . ( Funded by the National Heart , Lung , and Blood Institute and the Investigator-Sponsored Study Program of AstraZeneca ; Clinical Trials.gov number , NCT00979121 . ) Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more Acute kidney injury ( AKI ) is a serious complication of cardiovascular surgery . Although some nonexperimental studies suggest that statin use may reduce postsurgical AKI , method ologic differences in study design s leave uncertainty regarding the reality or magnitude of the effect . The aim of this study was to estimate the effect of preoperative statin initiation on AKI after coronary artery bypass grafting ( CABG ) using an epidemiologic approach more closely simulating a r and omized controlled trial in a large CABG patient population . Health care cl aims from large , employer-based and Medicare insurance data bases for 2000 to 2010 were used . To minimize healthy user bias , patients were identified who underwent nonemergent CABG who either newly initiated a statin < 20 days before surgery or were unexposed for ≥200 days before CABG . AKI was identified < 15 days after CABG . Multivariate-adjusted risk ratios ( RRs ) and 95 % confidence intervals ( CIs ) were calculated using Poisson regression . Analyses were repeated using propensity score methods adjusted for clinical and health care utilization variables . A total of 17,077 CABG patients were identified . Post-CABG AKI developed in 3.4 % of statin initiators and 6.2 % of noninitiators . After adjustment , a protective effect of statin initiation on AKI was observed ( RR 0.78 , 95 % CI 0.63 to 0.96 ) . This effect differed by age , with an RR of 0.91 ( 95 % CI 0.68 to 1.20 ) for patients aged ≥65 years and an RR of 0.62 ( 95 % CI 0.45 to 0.86 ) for those aged < 65 years , although AKI was more common in the older group ( 7.7 % vs 4.0 % ) . In conclusion , statin initiation immediately before CABG may modestly reduce the risk for postoperative AKI , particularly in younger CABG patients Objectives We investigated the effects of short-term use of atorvastatin on CD34+/VEGF-R2+/CD133+/CD45- endothelial progenitor cell ( EPC ) count after on-pump coronary artery bypass surgery ( CABG ) . Methods Between Feb-2010 and May-2010 , we r and omly assigned , in a placebo-controlled , double-blind study , 60 consecutive patients who underwent isolated , first-time CABG to receive either 14-day atorvastatin ( 40 mg/day ) or placebo preoperatively . Urgent CABG and recent myocardial infa rct ion were excluded . EPCs were quantified ( cells/μl ) by flow cytometric phenotyping obtained from venous blood sample s collected preoperatively ( T1 ) , 6-hours ( T2 ) , and on the 5th day postoperatively ( T3 ) . Levels of markers of inflammation and serum cardiac troponin I were also measured preoperatively and daily until day-5 after surgery . Results There were no differences in baseline risk factors including cholesterol profiles , and EuroSCORES between the groups . The composite primary end-point , favored statin group with higher amount of circulating , early EPC count ( cells/μl ) at all time points compared with placebo ( T1 , 2.30 ± 0.02 versus 1.58 ± 0.03 , p < 0.001 ; T2 , 5.00 ± 0.06 versus 2.19 ± 0.06 , p < 0.001 ; T3 , 3.03 ± 0.08 versus 1.78 ± 0.02 , p < 0.001 ) . Postoperative hsCRP rise were inversely correlated with EPC count , and were significantly lower in the statin group ( T1 , 0.8 ± 0.1 versus 2.2 ± 1.5 , p < 0.001 ; T2 , 72.9 ± 3.2 versus 96.0 ± 3.6 , p < 0.001 ; T3 , 4.3 ± 1.2 versus 11.4 ± 4.1 , p < 0.001 ) . Furthermore , the incidence of postoperative atrial fibrillation was significantly lower in the statin group compared to placebo ( 3.3 % versus 23 % , p = 0.02 ) . Conclusions Short-term atorvastatin use increases circulating early EPCs both pre- and post-operatively and is associated with better preservation of sinus rhythm and reduced hsCRP levels . ( Clinical Trials.gov number , NCT01096875 Background — Statins improve clinical outcome of patients with atherosclerosis , but their perioperative role in patients undergoing coronary artery bypass grafting ( CABG ) is unclear . We hypothesized that short-term treatment with atorvastatin before CABG would improve the redox state in saphenous vein grafts ( SVGs ) , independently of low-density lipoprotein cholesterol (LDL)-lowering . Methods and Results — In a r and omized , double-blind controlled trial , 42 statin-naïve patients undergoing elective CABG received atorvastatin 40 mg/d or placebo for 3 days before surgery . Circulating inflammatory markers and malondialdehyde ( MDA ) were measured before and after treatment . SVG segments were used to determine vascular superoxide ( O2·− ) and Rac1 activation . For ex vivo studies , SVG segments from 24 patients were incubated for 6 hours with atorvastatin 0 , 5 , or 50 & mgr;mol/L. Oral atorvastatin reduced vascular basal and NADPH-stimulated O2·− in SVGs ( P<0.05 for all versus placebo ) and reduced plasma MDA ( P<0.05 ) , independently of LDL-lowering and of changes in inflammatory markers . In SVGs exposed to atorvastatin ex vivo , without exposure to LDL , basal and NADPH-stimulated O2·− were significantly reduced ( P<0.01 for both concentrations versus 0 & mgr;mol/L ) in association with a striking reduction in Rac1 activation and 1 membrane-bound Rac1 and p67phox subunit . The antioxidant effects of atorvastatin were reversed by mevalonate , implying a dependence on vascular HMG-CoA reductase inhibition . Conclusions — Short-term treatment with atorvastatin 40 mg/d before CABG improves redox state in SVGs , by inhibiting vascular Rac1-mediated activation of NADPH-oxidase . These novel findings suggest that statin therapy should be maintained or initiated in patients undergoing CABG , independently of LDL levels . Clinical Trial Registration — URL : http://www . clinical trials.gov . Unique identifier : NCT01013103 Atrial fibrillation ( AF ) is one of the most common postoperative arrhythmias in patients who undergo coronary artery bypass grafting ( CABG ) . The aim of this study was to evaluate the effect of preoperative atorvastatin on postoperative atrial fibrillation following coronary artery bypass grafting with cardiopulmonary bypass ( CCABG ) . One hundred consecutive patients undergoing elective CCABG , without history of AF or previous statin treatment , were enrolled and r and omly assigned to a statin group ( atorvastatin 20 mg/d , n = 49 ) or a control group ( placebo , n = 51 ) starting 7 days preoperatively . The primary endpoint was the occurrence of postoperative AF . C-reactive protein ( CRP ) levels were assessed in all selected patients before surgery and every 24 hours postoperatively until discharge from hospital . Atorvastatin significantly reduced the incidence of postoperative AF and postoperative peak CRP level versus placebo ( 18 % versus 41 % , P = 0.017 ; 129.3 ± 24.3 mg/L versus 149.3 ± 32.5 mg/L , P < 0.0001 ) . Kaplan-Meier curves confirmed a significantly better postoperative atrial fibrillation-free survival in the statin group ( χ(2 ) = 7.466 , P = 0.006 ) . Logistic regression analysis showed preoperative atorvastatin treatment was an independent factor associated with a significant reduction in postoperative AF ( OR = 0.235 , P = 0.007 ) , whereas high postoperative CRP levels were associated with increased risk ( OR = 2.421 , P = 0.015 ) . Preoperative atorvastatin administration may inhibit inflammatory reactions to prevent atrial fibrillation following coronary artery bypass grafting with cardiopulmonary bypass Background Periprocedural treatment with high-dose statins is known to have cardioprotective and pleiotropic effects , such as anti-thrombotic and anti-inflammatory actions . We aim ed to assess the efficacy of high-dose rosuvastatin loading in patients with stable angina undergoing off-pump coronary artery bypass grafting ( OPCAB ) . Material s and Methods A total of 142 patients with stable angina who were scheduled to undergo surgical myocardial revascularization were r and omized to receive either pre-treatment with 60-mg rosuvastatin ( rosuvastatin group , n=71 ) or no pre-treatment ( control group , n=71 ) before OPCAB . The primary endpoint was the 30-day incidence of major adverse cardiac events ( MACEs ) . The secondary endpoint was the change in the degree of myocardial ischemia as evaluated with creatine kinase-myocardial b and ( CK-MB ) and troponin T ( TnT ) . Results There were no significant intergroup differences in preoperative risk factors or operative strategy . MACEs within 30 days after OPCAB occurred in one patient ( 1.4 % ) in the rosuvastatin group and four patients ( 5.6 % ) in the control group , respectively ( p=0.37 ) . Preoperative CK-MB and TnT were not different between the groups . After OPCAB , the mean maximum CK-MB was significantly higher in the control group ( rosuvastatin group 10.7±9.75 ng/mL , control group 14.6±12.9 ng/mL , p=0.04 ) . Furthermore , the mean levels of maximum TnT were significantly higher in the control group ( rosuvastatin group 0.18±0.16 ng/mL , control group 0.39±0.70 ng/mL , p=0.02 ) . Conclusion Our findings suggest that high-dose rosuvastatin loading before OPCAB surgery did not result in a significant reduction of 30-day MACEs . However , high-dose rosuvastatin reduced myocardial ischemia after OPCAB Endothelial progenitor cells ( EPCs ) are a subtype of hematopoietic stem cells , which contribute to the repair of injured endothelium . Treatment with atorvastatin has been shown to increase EPC count in patients with coronary artery disease . Therefore , we investigated whether atorvastatin augments the number of EPCs after cardiopulmonary bypass ( CPB ) surgery . We conducted a r and omized double-blind , placebo-controlled , 2-way crossover trial in 50 patients undergoing elective coronary surgery . Patients received either 3-week treatment with atorvastatin or placebo . EPCs were quantitated by flow cytometric phenotyping on blood sample s. Levels of interleukin , IL-6 and IL-8 ; tumor necrosis factor α ; SDF-1α ; granulocyte colony-stimulating factor ; and vascular endothelial growth factor were determined at recruitment , preoperatively , post-CPB , and 6 , 12 , and 24 hours postoperatively . The atorvastatin group showed a significantly higher amount of EPCs both pre- and postoperatively compared with the placebo , with a > 4-fold increase compared with the baseline values . CPB induced an increase in all cytokines , but the levels of proinflammatory cytokines were significantly lower in the atorvastatin group ( P < 0.05 ) . Statin did not affect levels of SDF-1α , granulocyte colony-stimulating factor , and vascular endothelial growth factor . However , no correlation was found between plasma levels of any cytokine and number of EPCs , with the exception of SDF-1α . Pretreatment with atorvastatin significantly increases the amount of EPCs after CPB , by a mechanism independent of plasma levels of cytokines and cholesterol BACKGROUND Abnormal erythrocyte deformability can cause severe complications during cardiopulmonary bypass ( CPB ) surgery , including both hemolysis and perfusion abnormalities . OBJECTIVES The goals of this study were to evaluate changes in erythrocyte membrane fluidity and lipid peroxidation during CPB and to examine the effect of simvastatin treatment on these parameters . METHODS Patients undergoing cardiac surgery involving CPB were selected and r and omized to receive either simvastatin 40 mg/d or placebo for 3 weeks before surgery . Three blood sample s were obtained at different times during surgery for analysis of erythrocyte membrane fluidity , anion permeability , and lipid peroxidation . Erythrocyte ghosts were prepared and incubated with a lipophilic fluorescent probe ( diphenyl-hexatriene ) , and fluorescence anisotropy was evaluated by spectrophotofluorimetric assay as a measure of membrane fluidity . Anion permeability was evaluated by the specific absorption of methemoglobin ( CM ) at 590 and 635 nm after treatment of heparinized blood with NaNO2 . The formation of thiobarbituric acid-reactive substances was evaluated as an index of lipid peroxidation . Aspartate transaminase and lactate dehydrogenase were also measured as indices of hemolysis . RESULTS Forty patients met the inclusion criteria ( 20 simvastatin , 20 placebo ) . Their characteristics differed significantly at baseline only in terms of the lipid profile ; the statin group had higher levels of high-density lipoprotein cholesterol ( P = 0.01 ) and lower levels of low-density lipoprotein cholesterol ( P = 0.001 ) than the placebo group . CPB was found to significantly modify characteristics of the erythrocyte membrane . Compared with preoperative values , CPB induced decreases in both mean ( SD ) erythrocyte membrane fluidity and anion permeability ( preoperative CM : 0.69 [ 0.02 ] ; 24-hour postoperative CM : 0.18 [ 0.02 ] ; P < 0.001 ) and an increase in mean ( SD ) membrane lipid peroxidation ( preoperative malonyl dialdehyde [ MDA ] : 0.21 [ 0.01 ] nmol/mL ; postoperative MDA : 0.10 [ 0.02 ] nmol/mL ; P < 0.001 ) . Treatment with simvastatin was associated with a significant reduction in mean ( SD ) membrane lipid peroxidation both preoperatively and at 24 hours postoperatively compared with placebo ( preoperative MDA : 0.07 [ 0.01 ] vs 0.10 [ 0.02 ] nmol/mL , respectively ; P < 0.05 ; postoperative MDA : 0.10 [ 0.04 ] vs 0.21 [ 0.01 ] nmol/mL ; P < 0.05 ) . In addition , statin treatment was associated with significant increases in anion permeability preoperatively and postoperatively compared with placebo ( preoperative CM : 0.79 [ 0.01 ] vs 0.69 [ 0.02 ] ; P < 0.01 ; 24-hour postoperative CM : 0.30 [ 0.01 ] vs 0.18 [ 0.02 ] ; P < 0.01 ) . CONCLUSION The results of this study suggest that among these patients undergoing CPB surgery , use of simvastatin for 3 weeks before the surgery had significant beneficial effects on erythrocyte membrane fluidity , lipid peroxidation , and anion permeability ABSTRACT Purpose : Recent observational studies have suggested that statins can decrease the incidence and severity of various infections including pneumonia and bacteremia . However , the effect of statins on post-cardiac surgery infection has not been adequately evaluated . Therefore we sought to determine whether preoperative statin use result ed in a reduction in infection following cardiac surgery . Methods : This was a cohort evaluation of all consecutive patients who underwent coronary artery bypass graft ( CABG ) and /or valve surgery at our institution between January 1 , 2004 and August 31 , 2006 . Our primary outcome measure was the occurrence of at least one of the following postoperative infectious complications ( pneumonia , bacteremia , sternal wound , leg vein harvest site infection , urinary tract infection , or tracheotomy site infection ) . We used multivariable logistic regression to control for potential confounding and to calculate adjusted odds ratios ( AORs ) and 95 % confidence intervals ( CIs ) . Results : A total of 1934 patients were included in this evaluation of which 1248 received a statin preoperatively and 686 did not . Our study population was 66.3 ± 11.6 years of age , 71.3 % male ; 37.2 % underwent complex surgery , 3.6 % were morbidly obese , and 32.0 % were diabetic ( each being previously identified as an independent predictor of infection following cardiac surgery ) . Patients receiving a statin preoperatively and not receiving a statin preoperatively varied in respect to a number of important pre- and peri- operative characteristics . Patients receiving preoperative statin therapy were more likely to have had a history of diabetes , chronic obstructive pulmonary disease or high cholesterol and to be smokers , but less likely to be undergoing urgent/emergent surgery or surgery utilizing a cardiopulmonary bypass pump ( p < 0.05 for all comparisons ) . In total , 151 ( 7.8 % ) patients developed an infectious complication . Upon multivariable logistic regression , preoperative statin use was associated with a significant reduction in the development of infection ( AOR ; 0.67 ( 95 % CI 0.46–0.99 ) , p = 0.04 ) . The use of a statin was not associated with a statistically significant reduction in any individual infection on its own ( p > 0.08 for all ) . Limitations : Patients were not r and omized to receive statins or not . We did not have adequate power to evaluate individual infections . Conclusions : Preoperative statin use is associated with a reduction in patients ’ odds of developing a postoperative infection following cardiac surgery OBJECTIVE Myocardial disease without evidence of myocardial infa rct ion is a frequent complication after cardiac surgery during cardiopulmonary bypass . Statins might be protective , but their efficacy has not been established in r and omized trials . METHODS Two hundred patients undergoing coronary surgery were enrolled . They were r and omized to rosuvastatin ( 20 mg/d , n = 100 ) or placebo ( n = 100 ) starting 1 week before the operation . Troponin I , myoglobin , creatine kinase-MB mass , and high-sensitivity C-reactive protein were used as markers of myocardial injury , and their values were determined at baseline and at regular intervals after the operation . Electrocardiography and echocardiography were performed before and after the operation . RESULTS Myocardial disease was diagnosed when troponin I , myoglobin , and creatine kinase-MB mass values were above the upper normal limit without evidence of electrocardiographic changes , echocardiographic changes , or both . The percentages of marker level increase indicative of myocardial disease were determined in the placebo versus statin groups and were as follows : troponin I , 35 % versus 65 % ( P < .0001 ) ; myoglobin , 39 % versus 72 % ( P < .0001 ) ; creatine kinase-MB mass , 22 % versus 40 % ( P = .0002 ) . Peak postoperative values of troponin I ( 0.16 + /- 0.15 vs 0.32 + /- 0.26 ng/mL , P = .0008 ) , myoglobin ( 72.25 + /- 25 vs 98.31 + /- 31 ng/mL , P < .0001 ) , and creatine kinase-MB mass ( 3.9 + /- 3.3 vs 9.3 + /- 8.1 ng/mL , P < .0001 ) were significantly higher in the placebo group . High-sensitivity C-reactive protein values were increased in 58 % of pretreated versus 88 % of the control patients ( 15.4 + /- 2.5 vs 17.2 + /- 3.4 mg/L , P < .0001 ) . In high-risk patients myocardial disease was observed more frequently but significantly less in statin-pretreated patients . CONCLUSIONS Statin pretreatment reduces myocardial damage after coronary surgery and could improve both short- and long-term results OBJECTIVES The purpose of this study was to evaluate the role of the myocardial redox state in the development of in-hospital complications after cardiac surgery and the effect of statins on the myocardial redox state . BACKGROUND Statins improve clinical outcome after cardiac surgery , but it is unclear whether they exert their effects by modifying the myocardial redox state . METHODS We quantified myocardial superoxide anion ( O(2)(- ) ) and peroxynitrite ( ONOO(- ) ) and their enzymatic sources in sample s of the right atrial appendage ( RAA ) from 303 patients undergoing cardiac surgery who were followed up until discharge , and in 42 patients who were r and omized to receive 3-day treatment with atorvastatin 40 mg/d or placebo before surgery . The mechanisms by which atorvastatin modifies myocardial redox state were investigated in 26 RAA sample s that were exposed to atorvastatin ex vivo . RESULTS Atrial O(2)(- ) ( derived mainly from nicotinamide adenine dinucleotide phosphate [ NADPH ] oxidases ) and ONOO(- ) were independently associated with increased risk of atrial fibrillation , the need for post-operative inotropic support , and the length of hospital stay . Pre-operative atorvastatin treatment suppressed atrial NADPH oxidase activity and myocardial O(2)(- ) and ONOO(- ) production . Ex vivo incubation of RAA sample s with atorvastatin induced a mevalonate-reversible and Rac1-mediated inhibition of NADPH oxidase . CONCLUSIONS There is a strong independent association between myocardial O(2)(-)/ONOO(- ) and in-hospital complications after cardiac surgery . Both myocardial O(2)(- ) and ONOO(- ) are reduced by pre-operative statin treatment , through a Rac1-mediated suppression of NADPH oxidase activity . These findings suggest that inhibition of myocardial NADPH oxidases may contribute to the beneficial effect of statins in patients undergoing cardiac surgery . ( Effects of Atorvastatin on Endothelial Function , Vascular and Myocardial Redox State in High Cardiovascular Risk Patients ; NCT01013103 ) BACKGROUND Atrial fibrillation ( AF ) after coronary artery bypass grafting ( CABG ) is still the most common postoperative arrhythmic complication . Previous studies report that patients undergoing preoperative statin therapy had a lower incidence of postoperative AF . This study aim ed to assess the effect of preoperative atorvastatin therapy on preventing AF following off-pump CABG in a r and omized , controlled trial . METHODS AND RESULTS The 140 consecutive patients undergoing elective off-pump CABG , without a history of AF or previous statin treatment , were enrolled and r and omly assigned to a statin ( atorvastatin 20 mg/day , n=71 ) or a control group ( placebo , n=69 ) starting 7 days preoperatively . The primary endpoint was the occurrence of postoperative AF ; secondary endpoints were major adverse in-hospital cardiac and cerebrovascular events and identification of variables predicting postoperative AF . Atorvastatin significantly reduced the incidence of postoperative AF and the postoperative peak C-reactive protein ( CRP ) level vs placebo ( 14 % vs 34 % , P=0.009 ; 126.5 + /-22.3 vs 145.2 + /-31.6 mg/L , P<0.0001 ) . Logistic regression analysis showed preoperative atorvastatin treatment was an independent factor associated with a significant reduction in postoperative AF ( odds ratio ( OR ) 0.219 , P=0.005 ) , whereas a high postoperative CRP level was associated with increased risk ( OR 2.011 , P=0.013 ) . CONCLUSIONS Administration of atorvastatin 20 mg/day , initiated 1 week before elective off-pump CABG and continued in the postoperative period , significantly decreases postoperative AF BACKGROUND Acute kidney injury is a frequent postoperative complication that confers increased mortality , morbidity , and costs . The purpose of this study was to evaluate whether preoperative statin use is associated with a decreased risk of postoperative acute kidney injury . METHODS We assembled a retrospective cohort of 98,939 patients who underwent a major open abdominal , cardiac , thoracic , or vascular procedure between 2000 and 2010 . Statin users were pair-matched to nonusers on the basis of surgery type , baseline kidney function , days from admission until surgery , and propensity score based on demographics , comorbid conditions , and concomitant medications . Acute kidney injury was defined based on changes in serum creatinine measurements applying Acute Kidney Injury Network and Risk-Injury-Failure staging systems , and on the need for renal replacement therapy . Associations between statin use and acute kidney injury were estimated by conditional logistic regression . RESULTS Across various acute kidney injury definitions , statin use was consistently associated with a decreased risk : adjusted odds ratios ( 95 % confidence intervals ) varied from 0.74 ( 0.58 - 0.95 ) to 0.80 ( 0.71 - 0.90 ) . Associations were similar among diabetics and nondiabetics , and across strata of baseline kidney function . The protective association of statins was most pronounced among patients undergoing vascular surgery and least among patients undergoing cardiac surgery . CONCLUSIONS Preoperative statin use is associated with a decreased risk of postoperative acute kidney injury . Future r and omized clinical trials are needed to determine causality BACKGROUND While statins are increasingly used in cardiopulmonary bypass ( CPB ) , the anti-inflammatory effects of individual statins , within the context of various treatment regimes , need further examination . The present study evaluates the anti-inflammatory effectiveness of the short-term , preoperative and intensive postoperative use of pravastatin in CPB . METHOD Forty three patients undergoing CPB were enrolled in a r and omized , prospect i ve clinical study . One group ( n = 21 ) , received pravastatin , the other ( n = 22 ) did not . Patients in the pravastatin group received one dose of 40 mg per day for nine days , starting 48 hours before CPB , with an additional dose of 40 mg one hour after surgery . Plasma levels of selected inflammatory mediators were measured at baseline and tracked systematic ally . RESULTS Pravastatin reduced postoperative interleukin-6 ( IL-6 ) levels significantly at 24 and 48 hours , and at seven days . Mean + /- SD values , for treated versus untreated patients were : at 24 hours , 159.5 + /- 58.5 versus 251.2 + /- 53.0 pg/mL ( p < 0.001 ) ; at 48 hours , 81.9 + /- 31.5 versus 194.2 + /- 56.3 pg/mL ( p < 0.001 ) ; and at seven days , 16.4 + /- 7.2 versus 30.8 + /- 12.6 ( p < 0.001 ) . C-reactive protein ( CRP ) decreased significantly on the seventh postoperative day , when plasma levels were 3.6 + /- 1.1 in the treated patients versus 8.2 + /- 2.1 mg/dL in the controls ( p < 0.001 ) . No changes in plasma IL-1 and TNF-alpha were found during entire study . CONCLUSIONS Pravastatin induced a precocious modulation of IL-6 expression and a later reduction of plasma CRP levels . Pravastatin;s effects on the expression of these pivotal inflammatory mediators strongly support its well-timed use in CPB OBJECTIVE The preventative effect of statins on postoperative atrial fibrillation has been hypothesized . However , all studies to date have examined patients who did not receive statins before their further allocation to treatment or no treatment . Because guidelines recommend the routine use of statins in patients with coronary artery disease , we set out to examine the effect of intensive statin pretreatment versus continuation of usual statin dose on atrial fibrillation after cardiac surgery . METHODS Patients receiving routine statin treatment and undergoing coronary artery bypass surgery or aortic valve replacement with no history of atrial fibrillation or antiarrhythmic medication were r and omized to receive atorvastatin 80 mg or atorvastatin 10 mg for 7 days before surgery in a single-blind fashion . The primary end point was the development of postoperative atrial fibrillation during hospital stay . RESULTS A total of 104 consecutive patients were included . Postoperative atrial fibrillation occurred in 33 patients ( 32.4 % ) . No significant differences were found in demographics , medical history , or intraoperative variables between treatment groups , with the exception of higher rate of β-blocker use in the atorvastatin 10 mg group ( 75 % vs 53 % , P = .002 ) and previous myocardial infa rct ion ( 62 % vs 42 % , P = .049 ) . The incidence of postoperative atrial fibrillation was lower in the atorvastatin 80 mg group when compared with the atorvastatin 10 mg group , but this difference did not reach statistical significance ( 29 % vs 36 % , P = .43 ) . CONCLUSIONS High-dose atorvastatin for 7 days before cardiac surgery conferred a nonsignificant reduction in postoperative atrial fibrillation when compared with a low-dose regimen . A larger study would be necessary to confirm the beneficial effect of high-dose statins in this setting OBJECTIVE Recent studies have suggested that statins reduce atrial fibrillation after cardiothoracic surgery , but the use of proven prophylactic strategies such as beta-blockers and amiodarone in these studies was not provided . Therefore , we sought to determine whether preoperative statin use could reduce the incidence of post-cardiothoracic surgery atrial fibrillation in a population who already had a high background use of beta-blockers and appreciable use of prophylactic amiodarone . METHODS Patients undergoing cardiothoracic surgery from the r and omized , controlled Atrial Fibrillation Suppression Trials I , II , and III were evaluated in this nested cohort evaluation . The patients ' demographics , surgical characteristics , medication use , and incidence of post-cardiothoracic surgery atrial fibrillation ( atrial fibrillation > 5 minutes duration ) were uniformly and prospect ively collected as part of Atrial Fibrillation Suppression Trials I , II , and III . Multivariate logistic regression was used to calculate adjusted odds ratios with 95 % confidence intervals . RESULTS Overall , 331 patients ( 59.6 % ) received a statin preoperatively and 224 patients ( 40.4 % ) did not . The study population had an average age of 67.8 + /- 8.6 years , 77.1 % were male , 14.6 % had valve surgery , 6.1 % had a history of atrial fibrillation , 12.6 % had a history of heart failure , 84.0 % received postoperative beta-blockade , and 44.1 % received postoperative prophylactic amiodarone . In total , 174 patients ( 31.4 % ) developed post-cardiothoracic surgery atrial fibrillation . Upon multivariate logistic regression , statin use was associated with a reduction in post-cardiothoracic surgery atrial fibrillation ( adjusted odds ratio : 0.60 ; 95 % confidence interval 0.37 - 0.99 ) . Higher intensity statin dosing ( equivalent of > or = 40 mg of atorvastatin ) seemed to be associated with the greatest reductions in post-cardiothoracic surgery atrial fibrillation ( adjusted odds ratio : 0.45 ; 95 % confidence interval 0.21 - 0.99 ) . CONCLUSIONS In a population with appreciable beta-blocker and amiodarone use , adjunctive preoperative statin use was still associated with a 40 % reduction in patients ' odds of developing post-cardiothoracic surgery atrial fibrillation BACKGROUND Pretreatment with statins reduces early ischemic events after percutaneous coronary interventions , primarily in patients with a high level of inflammation markers . We sought to examine the association between preoperative statin therapy , systemic inflammation , and myocardial ischemia with the occurrence of early cardiac complications after coronary artery bypass grafting surgery . METHODS One hundred forty-one consecutive patients who underwent coronary artery bypass grafting surgery from two university tertiary hospitals were stratified according to their preoperative status of statin therapy ( 87 treated and 54 nontreated ) . Preoperative blood sample s were collected for measurement of lipid parameters , C-reactive protein , interleukin-6 , and troponin T. The evaluated primary endpoint was a composite of death and myocardial infa rct ion at 30 days . RESULTS Patients undergoing preoperative statin therapy showed a reduced incidence of death ( 2.3 % versus 13.0 % , p = 0.012 ) , myocardial infa rct ion ( 5.7 % versus 18.5 % , p = 0.017 ) , and primary combined endpoint ( 8.0 % versus 22.2 % , p = 0.017 ) . In the multivariate model , preoperative troponin T greater than 0.01 ng/mL ( odds ratio 6.85 , p = 0.001 ) and nonstatin therapy ( odds ratio 4.2 , p = 0.01 ) predicted a higher risk of primary endpoint . Statins showed a significant interaction with troponin T status and benefited primarily those patients with positive troponin T. Among 19 patients with troponin T greater than 0.01 ng/mL , the primary endpoint occurred in all 6 nonstatin-treated patients , but it occurred in only 1 of 13 statin-treated patients ( p < 0.001 ) . Neither C-reactive protein nor interleukin-6 predicted early complications , nor did they interact with statin therapy ( p = not significant ) . CONCLUSIONS Preoperative statin therapy reduces early complications and offers additional protection in patients with positive troponin T status , regardless of inflammatory markers AIM Statins exert pleiotropic effects that result in cardioprotective and antiinflammatory properties . There is a lack of information about the effect of preoperative reloading statin administration in surgical coronary patients regarding myocardial protection , systemic inflammatory response ( SIR ) attenuation and nitric oxide ( NO ) metabolism . METHODS Thirty consecutive dyslipidemic patients under chronic treatment with statins were r and omized to orally receive pravastatin 80 mg ( N.=10 ) , 40 mg ( N.=10 ) or placebo ( N.=10 ) two hours before anesthetic induction for non-emergent on-pump coronary artery bypass grafting ( CABG ) procedures . Perioperative peripheral venous and intraoperative CS blood sample s were collected for determination of drug-related adverse effects , NO metabolism and both myocardial damage and SIR biomarkers . RESULTS Pravastatin reloading result ed in a significant and dose-related intense attenuation of SIR , but no differences in cardiac damage biomarker levels were demonstrated . NO release and inducible nitric oxide synthase expression was significantly reduced in both treatment groups . Highest pravastatin doses significantly increased systemic creatine phosphokinase ( CPK ) concentration compared with intermediate doses but no other adverse effects were observed . CONCLUSION Oral pravastatin reloading before non-emergent CABG significantly attenuates postoperative SIR and systemic NO/iNOS concentrations with no effect in perioperative myocardial damage . Highest pravastatin doses increase CPK levels and must be avoided in susceptible patients This study was conducted to compare the effects of atorvastatin plus aspirin combined therapy on inflammatory responses , endothelial cell function , and blood coagulation system in patients undergoing coronary artery bypass grafting ( CABG ) to aspirin monotherapy . The patients were r and omized into atorvastatin plus aspirin combined therapy group and aspirin monotherapy group . Reduced total cholesterol in the combined therapy group was found in a short term of medication for 14 days . On postoperative day (POD)-14 , inhibitory effects of the combined therapy on whole blood aggregation as well as platelet activation assessed by flow cytometry were stronger than those of the monotherapy . Furthermore , cytokine , cytokine receptors , c-reactive protein and alpha1-acid glycoprotein in the combined therapy group were down-regulated on POD-14 . At the same time , circulating levels of thromboxane A(2 ) , vascular endothelial growth factor and thrombin-antithrombin III complex as well as P-selectin , L-selectin and intercellular adhesion molecule-1 were down-regulated , while E-selectin and transforming growth factor-beta1 was up-regulated . Atorvastatin plus aspirin combined therapy may improve inflammatory responses , accelerated platelet function , vascular endothelial cell function , blood coagulation system at the early stage such as 14th day after CABG . In conclusion , atorvastatin and aspirin combined therapy may bring beneficial effects to the patient after CABG Objective —Myocardial injury during cardiac surgery is a major cause of perioperative morbidity and mortality . We determined whether perioperative statin therapy is cardioprotective in patients undergoing noncoronary artery cardiac surgery and the potential mechanisms . Methods and Results —One hundred fifty-one patients undergoing noncoronary artery cardiac surgery were r and omly assigned to either a statin group ( n=77 ) or a control group ( n=74 ) . Simvastatin ( 20 mg ) was administered preoperatively and postoperatively . Plasma were analyzed for troponin T , isoenzyme of creatine kinase , C-reaction protein , interleukin-6 , interleukin-8 , creatinine , and blood urea nitrogen . Cardiac echocardiography was performed . Endothelial nitric oxide synthase ( eNOS ) , Akt , p38 , heat shock protein 90 , caveolin-1 , and nitric oxide ( NO ) in the heart were detected . Simvastatin significantly reduced plasma troponin T , isoenzyme of creatine kinase , C-reaction protein , blood urea nitrogen , creatinine , interleukin-6 , interleukin-8 , and the requirement of inotropic postoperatively . Simvastatin increased NO production , the expression of eNOS and phosphorylation at serine1177 , phosphorylation of Akt , expression of heat shock protein 90 , heat shock protein 90 association with eNOS and decreased eNOS phosphorylation at threonine 495 , phosphorylation of p38 , and expression of caveolin-1 . Simvastatin also improved cardiac function postoperatively . Conclusion —Perioperative statin therapy can improve cardiac function and renal function by reducing myocardial injury and inflammatory response through activating Akt-eNOS and attenuating p38 signaling pathways in patients undergoing noncoronary artery cardiac surgery . Clinical Trial Registration —URL : http://www . clinical trials.gov . Unique identifier : NCT01178710 Abstract Background This r and omized controlled trial aim ed to evaluate the effects of seven-day preoperative treatment with two different dosages of atorvastatin on the incidence of postoperative atrial fibrillation ( POAF ) and release of inflammatory markers such as high-sensitive C-reactive protein ( hsCRP ) and interleukin-6 in patients undergoing elective first-time on-pump coronary artery bypass grafting ( CABG ) . Methods The cohort study comprised 212 consecutive patients , already taking statins , who underwent elective first-time CABG with cardiopulmonary bypass without history of atrial fibrillation ( AF ) . Patients were r and omly divided into two groups : those who received atorvastatin 40 mg ( TOR40 group , 111 patients ) and those who received 80 mg ( TOR80 group , 101 patients ) once a day for 7 days before the planned operation . The primary endpoint was the incidence of AF . The secondary endpoints were the postoperative variations of inflammatory markers , hospital length of stay , and the incidence of major adverse cardiac and clinical events . Results A total of 26 patients ( 23.6 % ) pretreated with atorvastatin 40 mg and 16 ( 15.8 % ) patients pretreated with atorvastatin 80 mg had postoperative AF but the difference did not reach the statistical significance ( p = 0.157 ) . Median values of interleukin-6 and hsCRP at 12 and 24 h did not have differences between the two groups . No statistically significant differences in the other secondary endpoints were detected . Conclusions According to our result , 7-day preoperative treatment with a high dose of atorvastatin is associated with a trend to a decrease in the incidence of POAF compared with treatment at a lower dose , although it does not impact on the level of inflammatory markers . Clinical Trial Registration European Clinical Trials Data base ( EudraCT : 2006 - 005757 - 30 ) Objectives : We explored whether preoperative rosuvastatin could protect the cardiac health of patients with coronary artery disease undergoing emergency , noncardiac surgery . Methods : We r and omized 550 noncardiac emergency surgery patients with stable coronary artery disease on long-term statin therapy to treatment with and without preoperative rosuvastatin . All patients received rosuvastatin after surgery . We evaluated the incidence of myocardial necrosis and major adverse cardiovascular and cerebrovascular events ( MACCE ) 30 days and 6 months after surgery . Results : Creatinine kinase-myocardial b and ( CK-MB ) isoform elevations occurred less frequently 12 and 24 h after noncardiac emergency surgery in the experimental group than in the control group ( p = 0.029 ) . After surgery , the incidence of MACCE was also lower in the experimental group than in the control group ( p = 0.019 ) . The difference was mainly due to the incidence of perioperative myocardial infa rct ion ( p = 0.029 ) . Multivariable analysis found that rosuvastatin reload reduced the incidence of MACCE 52 % 6 months after surgery ( p = 0.03 ) . Conclusions : Preoperative rosuvastatin reload therapy decreases the incidence of myocardial necrosis and MACCE after noncardiac emergency surgery in patients with stable coronary artery disease on long-term statin therapy PURPOSE Cardiopulmonary bypass ( CPB ) is commonly associated with a systemic inflammatory response that may lead to severe complications . Classic signs of systemic inflammatory response syndrome are complement activation and changes in cytokine and acute phase reactant levels . The effects of rosuvastatin after CPB on interleukin-6 ( IL-6 ) , interleukin-10 ( IL-10 ) , interleukin-18 ( IL-18 ) and High Sensitivity C-Reactive Protein ( hs-CRP ) levels were investigated . METHODS Thirty-seven male and thirteen female patients ( total=50 ) aged 42 to 78 years , who had coronary bypass surgery due to coronary artery disease were r and omly divided into two groups . The 25 patients in the control group were administered placebos . The 25 in the treatment group were administered 20 mg rosuvastatin tablets daily between preoperative day 7 and postoperative day 28 . Blood sample s were taken at six time points ; before induction of anesthesia ( T1 ) , during CPB ( T2 ) , five minutes after removal of cross clamp ( T3 ) , after protamine infusion ( T4 ) , postoperative day three ( T5 ) and postoperative day 28 ( T6 ) . Data points were expressed as mean ± st and ard deviation ( SD ) . RESULTS Rosuvastatin lowered IL-6 levels at T4 , T5 and T6 time points ( T4 , T5 , T6 p < 0.05 ) , and elevated IL-10 levels at T3 and T4 ( T3 , T4 p < 0.05 ) . IL-18 levels were also elevated at multiple time points . Rosuvastatin also lowered hs-CRP levels and cholesterol levels at T6 ( p < 0.05 ) . CONCLUSION Administering 20 mg/day of rosuvastatin between preoperative day 7 and postoperative day 28 may result in fewer complications in certain ( especially intraoperative ) cases of systemic inflammatory response caused by the CPB technique used in coronary bypass surgery BACKGROUND Atrial fibrillation ( AF ) after coronary artery bypass graft ( CABG ) surgery is still the most common arrhythmic complication . This study evaluated whether pretreatment with atorvastatin protects against AF after off-pump CABG . METHODS One hundred twenty-four patients without a history of AF or previous statin use , who were scheduled to undergo elective off-pump CABG , were enrolled . Patients were r and omized to control group ( n = 62 ) or to atorvastatin group ( n = 62 ) who were administered atorvastatin 20 mg/d for 3 days before the surgery . Primary outcome was the incidence of postoperative AF . Secondary outcomes were major adverse cardiac and cerebrovascular events , persistent AF at 1 month , and identification of the markers to predict inhospital postoperative AF . RESULTS The incidence of AF was significantly lower in the atorvastatin group than in the control group ( 13 % vs 27 % , P = .04 ) . The incidence of major adverse cardiac and cerebrovascular events and persistent AF at 1 month was similar in comparisons between the groups . Postoperative peak N-terminal pro-brain natriuretic peptide levels were significantly higher in the patients with AF ( P = .03 ) . Multivariate analysis identified pretreatment with atorvastatin as an independent factor associated with a significant reduction in postoperative AF ( odds ratio 0.34 , P = .04 ) . Higher postoperative peak N-terminus pro-B-type natriuretic peptide levels were associated with the development of postoperative AF ( odds ratio 1.02 per 100 pg/mL , P = .03 ) . CONCLUSIONS Pretreatment with atorvastatin significantly reduced the occurrence of postoperative AF after off-pump CABG AIM Cardiopulmonary bypass is associated with a complex systemic inflammatory response and the extent of their increase has been correlated with the development of postoperative complications . Recent studies suggest that treatment with statins is associated with a significant and marked decrease in inflammation-associated variables such as cytokines . Therefore , we investigated the effects of preoperative simvastatin treatment on systemic inflammatory response and perioperative morbidity after cardiopulmonary bypass . METHODS A prospect i ve , r and omized study , was design ed . Forty-four subjects undergoing elective coronary artery bypass grafting who fulfilled the inclusion criteria were r and omized to treatment with simvastatin ( 20 mg/day , group A , N. 22 ) or control ( group B , N. 22 ) before surgery . Plasma levels of interleukins ( IL-6 , IL-8 , TNF-alpha ) , and systemic inflammatory response score ( SIRS ) were measured during the surgical intervention and over the following 48 postoperative hours . Cytokine levels were measured by enzyme-linked assays from plasma sample s obtained at specific time points pre- and post-operation . RESULTS In both groups the serum levels of the proinflammatory cytokines ( IL-6 , IL-8 , TNF-alpha ) , and leukocytes , and the SIRS score increased significantly over the baseline , though no significant differences were observed between the two groups . The preoperative and postoperative course did not differ between both groups . CONCLUSIONS In patients undergoing coronary artery bypass grafting with cardiopulmonary bypass , the administration of simvastatin doses not produce any changes in the inflammatory response as measured by the levels of IL-6 , IL-8 , TNF-alpha and SIRS score , nor does it reduce the complications after cardiac surgery OBJECTIVE P-selectin is an adhesion molecule that plays a role in the pathogenesis of atherosclerosis . The aim of this study was to assess whether or not the treatment with fluvastatin for 3 weeks preoperatively would reduce the levels of circulating P-selectin in patients with coronary heart disease undergoing coronary artery bypass grafting surgery ( CABG ) . MATERIAL S AND METHODS Forty-six patients referred to CABG operation were included in the study . The patients were r and omized into two groups ( 1:1 ) : one treated with fluvastatin ( 80 mg/day , fluvastatin group , n = 23 ) , and the other one treated with placebo ( placebo group , n = 23 ) for three weeks before surgery . All patients underwent CABG using CPB . Blood sample s were collected at baseline ( the day before surgery ) , before and after aortic cross-clamping ( ACC ) , at postoperative 0 h ( the end of surgical intervention ) , and at 4 , 12 , and 24 hours postoperatively . Concentrations of soluble P-selectin ( sP-selectin ) were analyzed . RESULTS The sP-selectin values measured in the fluvastatin group were significantly lower than the values measured in the placebo group . There was less use of intraoperative inotropic agents in the fluvastatin group ( P < 0.015 ) and the difference in the length of ICU and hospital stay showed a significantly shorter stay for the fluvastatin group . CONCLUSIONS Pretreatment with fluvastatin seemed to reduce P-selectin levels compared to patients given placebo , and hence , we think that pretreatment with a statin , fluvastatin in our study , might reduce the perioperative cardiac injury caused by cardiopulmonary bypass-induced inflammatory changes . We believe that routine preoperative use of fluvastatin should be carefully considered AIM To test whether short-term perioperative administration of oral atorvastatin could reduce incidence of postoperative acute kidney injury ( AKI ) in cardiac surgical patients . METHODS We conducted a double-blind , r and omized controlled trial in 100 cardiac surgical patients at increased risk of postoperative AKI . Patients were r and omized to atorvastatin ( 40 mg once daily for 4 days starting preoperatively ) or identical placebo capsule . Primary outcome was to detect a smaller absolute rise in postoperative creatinine with statin therapy . Secondary outcomes included AKI defined by the creatinine criteria of RIFLE consensus classification ( RIFLE R , I or F ) , change in urinary neutrophil gelatinase-associated lipocalin ( NGAL ) concentration , requirement for renal replacement therapy , length of stay in intensive care , length of stay in hospital and hospital mortality . RESULTS Study groups were well matched . For each patient maximal increase in creatinine during the 5 days after surgery was assessed ; median maximal increase was 28 µmol/L in the atorvastatin group and 29.5 µmol/L in the placebo group ( P = 0.62 ) . RIFLE R or greater occurred in 26 % of patients with atorvastatin and 32 % with placebo ( P = 0.65 ) . Postoperatively urine NGAL changes were similar ( median NGAL : creatinine ratio at intensive care unit admission : atorvastatin group 1503 ng/mg , placebo group 1101 ng/mg ; P = 0.22 ) . Treatment was well tolerated and adverse events were similar between groups . CONCLUSION Short-term perioperative atorvastatin use was not associated with a reduced incidence of postoperative AKI or smaller increases in urinary NGAL . ( Clinical Trials.gov NCT00910221 ) BACKGROUND The purpose of this study was to determine the effects of statins on endothelium-derived nitric oxide ( NO ) levels during coronary artery bypass grafting ( CABG ) surgery . METHODS In a prospect i ve study , 130 patients with coronary artery disease were r and omized according to preoperative atorvastatin treatment . The patients in group 1 took 40 mg atorvastatin daily for at least 1 month preoperatively , and those in group 2 took no atorvastatin preoperatively . Plasma nitrite and nitrate were measured at baseline and after inducing reactive hyperemia , both before and after surgery . Reactive hyperemia was induced by placing a blood pressure cuff on the upper forearm , inflating it for 5 minutes at 250 mm Hg , and then rapidly deflating the cuff . Blood was collected from the radial artery on the same side 2 minutes after cuff deflation . Plasma levels of total cholesterol , triglycerides , and high- and low-density lipoproteins were measured and analyzed for correlations with NO . RESULTS The mean ( + /-SD ) baseline plasma NO levels before operation were as follows : group 1 , 33.97 + /- 18.27 nmol/L ; group 2 , 24.24 + /- 8.53 nmol/L ( P < .001 ) . A significant difference between the 2 groups in plasma NO levels was observed after preoperative reactive hyperemia induction : group 1 , 56.43 + /- 15.03 nmol/L ; group 2 , 43.12 + /- 10.67 nmol/L ( P < .001 ) . Two hours after cardiopulmonary bypass ( CPB ) , we observed no significant differences in plasma NO levels , either at baseline ( group 1 , 11 + /- 3.41 nmol/L ; group 2 , 9 + /- 5.51 nmol/L ) or after reactive hyperemia ( group 1 , 17.98 + /- 6.77 nmol/L ; group 2 , 18.00 + /- 6.47 nmol/L ) . A correlation with preoperative nitroglycerine use was observed ( P = .007 ; r = 0.23 ) . Linear regression analysis ( F = 1.463 ; R = 0.314 ; R2 = 0.099 ; P = .16 ) indicated that the only significant correlation was with preoperative nitroglycerine use ( P = .007 ; t = 2.746 ) . CONCLUSIONS Preoperative atorvastatin treatment in patients with coronary artery disease increases plasma NO levels before and after reactive hyperemia prior to surgery . CABG surgery with CPB significantly impairs endothelial-derived NO levels , with or without preoperative atorvastatin treatment . Preoperative nitroglycerine use is correlated with higher NO levels after CABG Objectives : This study compared the anti-inflammatory effects of methylprednisolone ( MP ) and atorvastatin and analysed their influences on clinical variables in patients undergoing coronary revascularization . Methods : Ninety patients with compromised left ventricular ejection fraction ( ≤30 % ) undergoing elective coronary surgery were equally r and omized to one of three groups : statin group , treatment with atorvastatin ( 20 mg/day ) 3 weeks before surgery ; methylprednisolone group , a single shot of methylpredniosolone ( 10mg/kg ) ; and control group . Results : Postoperative IL-6 was higher in the control group when compared to the methylprednisolone and statin groups ( p<0.01 ) . IL-6 was higher in the statin-treated patients ( p<0.05 versus methylprednisolone ) . Administration of methylprednisolone as well as statin treatment increased postoperative cardiac index , left ventricular stroke work index , decreased postoperative atrial fibrilation rate and reduced ICU stay ( p<0.05 versus control ) . The number of patients requiring inotropic support was lower in the methylprednisolone group when compared with the other two groups ( p<0.01 ) . Tracheal intubation time was reduced in patients who received methylprednisolone ( p<0.01 versus control ) . Conclusions : Preoperative administration of either methylprednisolone or atorvastatin reduced pro-inflammatory cytokine release , improved haemodynamics , decreased postoperative atrial fibrilation rate and reduced ICU stay in patients with significantly impaired cardiac function undergoing coronary revascularization . Treatment with methylprednisolone was associated with less inotropic support requirements and reduced mechanical ventilation time BACKGROUND AND OBJECTIVE There is contradictory evidence as to whether the pleiotropic effects of statins improve morbidity/mortality rates in coronary artery bypass grafting with extracorporeal circulation , as they reduce the protein plasma levels in the acute phase . PATIENTS AND METHOD This r and omized prospect i ve study included 44 patients undergoing elective coronary artery bypass grafting with extracorporeal circulation who were allocated to one of 2 groups : group A ( n = 22 ) , patients taking simvastatin , and group B , control ( n = 22 ) . The plasma levels of interleukin-6 , complement 4 and C-reactive protein were determined . RESULTS No significant differences were noted between the 2 groups with respect to the acute-phase protein levels , or the postoperative complications . In both groups , compared with the initial levels , interleukin-6 levels peaked at 6 h after surgery and C-reactive protein at 48 h. Complement 4 levels decreased from the start of the cardiopulmonary bypass and returned progressively toward the baseline value at 48 h after surgery . CONCLUSIONS Simvastatin in patients undergoing coronary artery bypass grafting with cardiopulmonary bypass produces no significant differences in the levels of acute-phase protein BACKGROUND Statins interact with multiple pathways involved in infection . Therefore , we examined the association between preoperative statin therapy and infections after cardiac operations and assessed whether statin therapy was associated with lower infection-related mortality . METHODS From January 2005 to January 2011 , 12,741 patients underwent cardiac operations . Endpoints were ( 1 ) postoperative infections and ( 2 ) mortality after an infectious complication . A propensity score was developed on the probability of patients receiving statin therapy ; patients were matched in part on this score . A multivariable logistic model was developed to examine mortality . Survival of infected patients was estimated using Kaplan-Meier and multiphase hazard function methodology . RESULTS A total of 6,113 patients ( 48 % ) were receiving statins and 6,628 ( 52 % ) were not . Five hundred fifteen patients had postoperative infections-260 ( 4.3 % ) in the statin group and 255 ( 3.8 % ) in the no-statin group . However , patients receiving statins were older with more comorbidities and less favorable operative characteristics . Among propensity-matched groups , postoperative infections were significantly lower in patients receiving statins ( n = 102 [ 3.1 % ] ) than in those who were not ( n = 147 [ 4.5 % ] ; p = 0.004 ) . Among patients in whom infections developed , there was no significant difference in hospital mortality between the statin and no-statin groups either before or after propensity-score matching ( odds ratio , 1.38 ; confidence limit [ CL ] , 0.59 , 3.22 ; p = 0.5 ) . CONCLUSIONS We observed a protective effect of statin therapy against the development of infections after cardiac operations , but not on mortality from these infections . Prospect i ve investigations are needed to determine optimal dose and duration of statin therapy and their relationship to infectious complications Objectives : Systemic inflammatory response occurs frequently after coronary artery bypass surgery , and it is strongly correlated with the risk of postoperative morbidity and mortality . Recent studies demonstrate that treatment with statin is associated with a significant and marked decrease in inflammation-associated variables such as the C-reactive protein , cytokines , and adhesion molecules . Therefore , we investigated the effects of preoperative atorvastatin treatment on systemic inflammatory response and perioperative morbidity after cardiopulmonary bypass . Design : Double-blinded , placebo-controlled , r and omized study . Setting : University hospital . Patients : Forty patients were r and omized to treatment with atorvastatin ( 20 mg/day , group A , n = 20 ) or placebo ( group B , n = 20 ) 3 wks before surgery . Interventions : Three-week treatment by atorvastatin 20 mg/day . Measurement and Main Results : Postoperative serum levels of both interleukin-6 and interleukin-8 increased significantly over baseline , but the peak levels observed 4 hrs postoperatively were significantly lower in the atorvastatin group . In the same fashion , CD11b expression on neutrophils was significantly lower in the statin group at 4 and 24 hrs postoperatively . Finally , neutrophil-endothelial adhesion was significantly reduced in the statin patients compared with controls . The operation time , blood loss , need for inotropic support , intubation time , and length of intensive care unit or hospital stay did not differ significantly between the two groups . The systemic inflammatory response syndrome score on postoperative days 1 and 2 was comparable in both groups . Conclusions : Pretreatment with atorvastatin significantly reduces cytokine release and neutrophil adhesion to the venous endothelium in patients undergoing coronary artery bypass grafting with cardiopulmonary bypass IMPORTANCE Observational studies have reported that statin use may be associated with improved outcomes of various infections . Ventilator-associated pneumonia ( VAP ) is the most common infection in the intensive care unit ( ICU ) and is associated with substantial mortality . OBJECTIVE To determine whether statin therapy can decrease day-28 mortality in patients with VAP . DESIGN , SETTING , AND PARTICIPANTS R and omized , placebo-controlled , double-blind , parallel-group , multicenter trial performed in 26 intensive care units in France from January 2010 to March 2013 . For power to detect an 8 % absolute reduction in the day-28 mortality rate , we planned to enroll 1002 patients requiring invasive mechanical ventilation for more than 2 days and having suspected VAP , defined as a modified Clinical Pulmonary Infection Score of 5 or greater . The futility stopping rules were an absolute increase in day-28 mortality of at least 2.7 % with simvastatin compared with placebo after enrollment of the first 251 patients . INTERVENTIONS Participants were r and omized to receive simvastatin ( 60 mg ) or placebo , started on the same day as antibiotic therapy and given until ICU discharge , death , or day 28 , whichever occurred first . MAIN OUTCOMES AND MEASURES Primary outcome was day-28 mortality . Day-14 , ICU , and hospital mortality rates were determined , as well as duration of mechanical ventilation and Sequential Organ Failure Assessment ( SOFA ) scores on days 3 , 7 , and 14 . RESULTS The study was stopped for futility at the first scheduled interim analysis after enrollment of 300 patients , of whom all but 7 % in the simvastatin group and 11 % in the placebo group were naive to statin therapy at ICU admission . Day-28 mortality was not lower in the simvastatin group ( 21.2 % [ 95 % CI , 15.4 % to 28.6 % ) than in the placebo group ( 15.2 % [ 95 % CI , 10.2 % to 22.1 % ] ; P = .10 ; hazard ratio , 1.45 [ 95 % CI , 0.83 to 2.51 ] ) ; the between-group difference was 6.0 % ( 95 % CI , -3.0 % to 14.9 % ) . In statin-naive patients , day-28 mortality was 21.5 % ( 95 % CI , 15.4 % to 29.1 % ) with simvastatin and 13.8 % ( 95 % CI , 8.8 % to 21.0 % ) with placebo ( P = .054 ) ( between-group difference , 7.7 % [ 95%CI , -1.8 % to 16.8 % ) . There were no significant differences regarding day-14 , ICU , or hospital mortality rates ; duration of mechanical ventilation ; or changes in SOFA score . CONCLUSIONS AND RELEVANCE In adults with suspected VAP , adjunctive simvastatin therapy compared with placebo did not improve day-28 survival . These findings do not support the use of statins with the goal of improving VAP outcomes . TRIAL REGISTRATION clinical trials.gov Identifier : NCT01057758 BACKGROUND Atrial fibrillation after cardiac surgery is associated with increased rates of death , complications , and hospitalizations . In patients with postoperative atrial fibrillation who are in stable condition , the best initial treatment strategy --heart-rate control or rhythm control -- remains controversial . METHODS Patients with new-onset postoperative atrial fibrillation were r and omly assigned to undergo either rate control or rhythm control . The primary end point was the total number of days of hospitalization within 60 days after r and omization , as assessed by the Wilcoxon rank-sum test . RESULTS Postoperative atrial fibrillation occurred in 695 of the 2109 patients ( 33.0 % ) who were enrolled preoperatively ; of these patients , 523 underwent r and omization . The total numbers of hospital days in the rate-control group and the rhythm-control group were similar ( median , 5.1 days and 5.0 days , respectively ; P=0.76 ) . There were no significant between-group differences in the rates of death ( P=0.64 ) or overall serious adverse events ( 24.8 per 100 patient-months in the rate-control group and 26.4 per 100 patient-months in the rhythm-control group , P=0.61 ) , including thromboembolic and bleeding events . About 25 % of the patients in each group deviated from the assigned therapy , mainly because of drug ineffectiveness ( in the rate-control group ) or amiodarone side effects or adverse drug reactions ( in the rhythm-control group ) . At 60 days , 93.8 % of the patients in the rate-control group and 97.9 % of those in the rhythm-control group had had a stable heart rhythm without atrial fibrillation for the previous 30 days ( P=0.02 ) , and 84.2 % and 86.9 % , respectively , had been free from atrial fibrillation from discharge to 60 days ( P=0.41 ) . CONCLUSIONS Strategies for rate control and rhythm control to treat postoperative atrial fibrillation were associated with equal numbers of days of hospitalization , similar complication rates , and similarly low rates of persistent atrial fibrillation 60 days after onset . Neither treatment strategy showed a net clinical advantage over the other . ( Funded by the National Institutes of Health and the Canadian Institutes of Health Research ; Clinical Trials.gov number , NCT02132767 . ) Background : Atorvastatin has been demonstrated to reduce the incidence of postoperative atrial fibrillation ( POAF ) in patients undergoing cardiac surgery , but its effect on isolated heart valve surgery is unknown . Methods : In a r and omized , double-blinded , placebo-controlled trial , 58 patients who underwent isolated heart valve surgery supported by on-pump cardiopulmonary bypass were r and omly assigned to receive either placebo ( n = 29 ) or 40 mg of atorvastatin once daily starting 3 days preoperatively and continuing within 5 days postoperatively ( n = 29 ) . A continuous monitoring tool and an electrocardiographic Holter monitoring were used for detecting the POAF ( Clinical Trial Registration : www . clinical trials.gov ; Unique Identifier : NTC02084069 ) . Results : The patients ’ median age was 49 years , and 67 % were female . In all , 6 ( 21 % ) and 13 ( 45 % ) cases of POAF were observed in the atorvastatin and placebo groups , respectively ( P = .050 ) . The duration of AF before re-establishment of sinus rhythm was significantly lower in the atorvastatin group than in the placebo group ( median of 70 vs 132 minutes , P = .026 ) . The lengths of intensive care unit and hospital stay were comparable between the groups . The increase in postoperative white blood cell count was significantly lower in the atorvastatin group than in the placebo group ( median of 1.5 vs 2.3 × 103/µL , respectively , P = .019 ) . After adjustment , the atorvastatin treatment was associated with a decrease in the risk of developing POAF ( odds ratio 0.122 , 95 % confidence interval 0.027 - 0.548 , P = .006 ) . Conclusion : Perioperative treatment with 40 mg of atorvastatin is useful to decrease the incidence of POAF in the statin-naive patients undergoing isolated heart valve surgery Background — Treatment with statins improves clinical outcome , but the exact mechanisms of pleiotropic statin effects on vascular function in human atherosclerosis remain unclear . We examined the direct effects of atorvastatin on tetrahydrobiopterin-mediated endothelial nitric oxide ( NO ) synthase coupling in patients with coronary artery disease . Methods and Results — We first examined the association of statin treatment with vascular NO bioavailability and arterial superoxide ( O2·− ) in 492 patients undergoing coronary artery bypass graft surgery . Then , 42 statin-naïve patients undergoing elective coronary artery bypass graft surgery were r and omized to atorvastatin 40 mg/d or placebo for 3 days before surgery to examine the impact of atorvastatin on endothelial function and O2·− generation in internal mammary arteries . Finally , segments of internal mammary arteries from 26 patients were used in ex vivo experiments to evaluate the statin-dependent mechanisms regulating the vascular redox state . Statin treatment was associated with improved vascular NO bioavailability and reduced O2·− generation in internal mammary arteries . Oral atorvastatin increased vascular tetrahydrobiopterin bioavailability and reduced basal and N-nitro-L-arginine methyl ester – inhibitable O2·− in internal mammary arteries independently of low-density lipoprotein lowering . In ex vivo experiments , atorvastatin rapidly improved vascular tetrahydrobiopterin bioavailability by upregulating GTP-cyclohydrolase I gene expression and activity , result ing in improved endothelial NO synthase coupling and reduced vascular O2·−. These effects were reversed by mevalonate , indicating a direct effect of vascular hydroxymethylglutaryl-coenzyme A reductase inhibition . Conclusions — This study demonstrates for the first time in humans the direct effects of statin treatment on the vascular wall , supporting the notion that this effect is independent of low-density lipoprotein lowering . Atorvastatin directly improves vascular NO bioavailability and reduces vascular O2·− through tetrahydrobiopterin-mediated endothelial NO synthase coupling . These findings provide new insights into the mechanisms mediating the beneficial vascular effects of statins in humans . Clinical Trial Registration — URL : http://www . clinical trials.gov . Unique identifier : NCT01013103 |
14,002 | 17,092,344 | Results The 12 studies included in this review describe evaluations of a wide range of interventions , across different diseases in different setting s. However the stepped wedge design appears to have found a niche for evaluating interventions in developing countries , specifically those concerned with HIV . | Background Stepped wedge r and omised trial design s involve sequential roll-out of an intervention to participants ( individuals or clusters ) over a number of time periods .
By the end of the study , all participants will have received the intervention , although the order in which participants receive the intervention is determined at r and om .
The design is particularly relevant where it is predicted that the intervention will do more good than harm ( making a parallel design , in which certain participants do not receive the intervention unethical ) and /or where , for logistical , practical or financial reasons , it is impossible to deliver the intervention simultaneously to all participants .
Stepped wedge design s offer a number of opportunities for data analysis , particularly for modelling the effect of time on the effectiveness of an intervention .
One aim of the review is to highlight the potential for the stepped wedge design , given its infrequent use to date . | To comprehend the results of a r and omised controlled trial ( RCT ) , readers must underst and its design , conduct , analysis , and interpretation . That goal can be achieved only through total transparency from authors . Despite several decades of educational efforts , the reporting of RCTs needs improvement . Investigators and editors developed the original CONSORT ( Consoli date d St and ards of Reporting Trials ) statement to help authors improve reporting by use of a checklist and flow diagram . The revised CONSORT statement presented here incorporates new evidence and addresses some criticisms of the original statement . The checklist items pertain to the content of the Title , Abstract , Introduction , Methods , Results , and Discussion . The revised checklist includes 22 items selected because empirical evidence indicates that not reporting this information is associated with biased estimates of treatment effect , or because the information is essential to judge the reliability or relevance of the findings . We intended the flow diagram to depict the passage of participants through an RCT . The revised flow diagram depicts information from four stages of a trial ( enrolment , intervention allocation , follow- up , and analysis ) . The diagram explicitly shows the number of participants , for each intervention group , included in the primary data analysis . Inclusion of these numbers allows the reader to judge whether the authors have done an intention- to-treat analysis . In sum , the CONSORT statement is intended to improve the reporting of an RCT , enabling readers to underst and a trial 's conduct and to assess the validity of its results Reports of cluster r and omised trials require additional information to allow readers to interpret them accurately The effective reporting of r and omised controlled trials has received useful attention in recent years . Many journals now require that reports conform to the guidelines in the Consoli date d St and ards of Reporting Trials ( CONSORT ) statement , first published in 1996 and revised in 2001 . The statement includes a checklist of items that should be included in the trial report . These items are evidence based whenever possible and are regularly review ed . The statement also recommends including a flow diagram to show the flow of participants from group assignment through to the final analysis . The CONSORT statement focused on reporting parallel group r and omised trials in which individual participants are r and omly assigned to study groups . However , in some situations it is preferable to r and omly assign groups of individuals ( such as families or medical practice s ) rather than individuals . Reasons include the threat of contamination of some interventions ( such as dietary interventions ) if individual r and omisation is used . 5 Also , in certain setting s r and omisation by group may be the only feasible method of conducting a trial . Trials with this design are variously known as field trials , community based trials , place based trials , or ( as in this paper ) cluster r and omised trials . In an earlier discussion paper we considered the implication s of the CONSORT statement for the reporting of cluster r and omised trials . Here we present up date d guidance , based on the 2001 revision of the CONSORT statement BACKGROUND Childhood malnutrition is common in Malawi , and the st and ard treatment , which follows international guidelines , results in poor recovery rates . Higher recovery rates have been seen in pilot studies of home-based therapy with ready-to-use therapeutic food ( RUTF ) . OBJECTIVE The objective was to compare the recovery rates among children with moderate and severe wasting , kwashiorkor , or both receiving either home-based therapy with RUTF or st and ard inpatient therapy . DESIGN A controlled , comparative , clinical effectiveness trial was conducted in southern Malawi with 1178 malnourished children . Children were systematic ally allocated to either st and ard therapy ( 186 children ) or home-based therapy with RUTF ( 992 children ) according to a stepped wedge design to control for bias introduced by the season of the year . Recovery , defined as reaching a weight-for-height z score > -2 , and relapse or death were the primary outcomes . The rate of weight gain and the prevalence of fever , cough , and diarrhea were the secondary outcomes . RESULTS Children who received home-based therapy with RUTF were more likely to achieve a weight-for-height z score > -2 than were those who received st and ard therapy ( 79 % compared with 46 % ; P < 0.001 ) and were less likely to relapse or die ( 8.7 % compared with 16.7 % ; P < 0.001 ) . Children who received home-based therapy with RUTF had greater rates of weight gain ( 3.5 compared with 2.0 g . kg(-1 ) . d(-1 ) ; difference : 1.5 ; 95 % CI : 1.0 , 2.0 g . kg(-1 ) . d(-1 ) ) and a lower prevalence of fever , cough , and diarrhea than did children who received st and ard therapy . CONCLUSION Home-based therapy with RUTF is associated with better outcomes for childhood malnutrition than is st and ard therapy Maintaining greater than 95 % adherence to antiretroviral medication is necessary in order to have the greatest therapeutic impact on HIV infection . Furthermore , evidence suggests that adherence rates of between 70 % and 89 % are significantly associated with viral rebound and the development of drug resistance . Adherence rates at and above the 95 % level are difficult for patients to achieve and maintain . Our aim was to determine if an adherence intervention could improve adherence among patients attending an ambulatory care clinic at a large public hospital . The intervention was delivered by a multidisciplinary team of health care professionals and consisted of education coupled with the provision of devices design ed to assist patient memory and adherence . A crucial component of the intervention consisted of the identification of patient specific barriers to adherence and the development of strategies to circumvent these problems . Adherence was assessed using patient self-report over the past 4 , 7 , and 28 days and by calculation of the Morisky score . The study was conducted as a r and omised controlled trial using the stepped wedge design with a total of 68 subjects r and omised to receive the intervention over a 20-week period . Adherence before and after the intervention formed the analysis . There was a significant decrease in the number of missed doses over the past 4 ( 1.9 to 1.0 , p < 0.001 ) , 7 ( 3.0 to 1.8 , p < 0.001 ) and 28 ( 7.4 to 4.2 , p < 0.001 ) days and a decrease in the Morisky score , indicating an improvement in medication taking behaviour ( 1.3 to 0.5 p < 0.001 ) BACKGROUND A r and omized study of the effect on people 's health of improving their housing is underway in Torbay . The link between poor health , particularly respiratory health , and poor housing conditions has been recognized for a long time , but there have been few intervention studies to demonstrate that improving housing can improve health . In 1994 , South and West Devon Health Authority set up a community development project in a deprived area of Torbay , in response to the concerns of local primary health-care workers . A community development worker helped local residents survey their homes for dampness and record their respiratory symptoms . The survey reported high levels of condensation/dampness and respiratory illness and the Council agreed to direct the majority of their housing improvement funds to the estate over the next 3 years . The Health Authority , University of Plymouth and Torbay Council were successful in obtaining funding to evaluate the housing improvements from the NHS R & D programme . PARTICIPANTS AND METHODS Of 119 houses eligible for the study , 50 were chosen at r and om and improved in the first year . The rest were improved the following year . Question naires screening for health problems were sent to all 580 residents and baseline surveys of the indoor environment were also carried out . More detailed health surveys were completed by community nurses visiting residents in their homes . All adults were asked to complete SF-36 and GHQ 12 question naires , as well as disease-specific question naires if appropriate . PROGRESS All houses in the study have now been improved , including insulation , double-glazing , re-roofing , heating , ventilation and electrical rewiring . Follow-up surveys are underway Our aim was to determine if a comprehensive adherence package improved self reported adherence to antiretroviral therapy . The adherence package included an education programme , individualized planning of regimens , and the opportunity for a patient to choose from a number of adherence aids and reminder devices . A r and omized step wedge design was used . Forty-three individuals were r and omized to begin the intervention over a five-month period . There was a substantial fall in the number of missed doses reported for the last four days ( 0.76 to 0.38 , P = 0.03 ) and last seven days ( 1.5 to 0.74 , P = 0.005 ) but not for the last 28 days ( 2.5 to 2.5 , P = 0.63 ) . There was no statistical difference in the viral load or CD4 lymphocyte count in the period before or after the intervention . The Morisky score during the pre and post intervention periods was significantly different ( P = 0.006 ) , 2.9 ( SD 0.9 ) and 3.3 ( SD 0.8 ) respectively . This adherence package improved self reported adherence during the last four and seven days Objective The purpose of the study was to investigate the effects of introducing a critical care outreach service on in-hospital mortality and length of stay in a general acute hospital . Design A pragmatic ward-r and omised trial design was used , with intervention introduced to all wards in sequence . No blinding was possible . Setting Sixteen adult wards in an 800-bed general hospital in the north of Engl and . Patients and participants All admissions to the 16 surgical , medical and elderly care wards during 32-week study period were included ( 7450 patients in total , of whom 2903 were eligible for the primary comparison ) . Interventions Essential elements of the Critical Care Outreach service introduced during the study were a nurse-led team of nurses and doctors experienced in critical care , a 24-h service , emphasis on education , support and practical help for ward staff . Measurements and results The main outcome measures were in-hospital mortality and length of stay . Outreach intervention reduced in-hospital mortality compared with control ( two-level odds ratio : 0.52 ( 95 % CI 0.32–0.85 ) . A possible increased length of stay associated with outreach was not fully supported by confirmatory and sensitivity analyses . Conclusions The study suggests outreach reduces mortality in general hospital wards . It may also increase length of stay , but our findings on this are equivocal |
14,003 | 24,636,238 | There was no evidence that other programme characteristics were associated with programme effectiveness .
Most but not all behavioural weight management programmes are effective . | A systematic review , meta- analysis and meta-regression were conducted to evaluate the effectiveness of behavioural weight management programmes and examine how programme characteristics affect mean weight loss . | Abstract Background Diabetes prevalence is increasing . The Finnish Diabetes Prevention Study ( DPS ) showed a 58 % reduction in Type 2 Diabetes ( T2D ) incidence in adults with impaired glucose tolerance ( IGT ) . The European Diabetes Prevention Study ( EDIPS ) extends the DPS to different European population s , using the same study design . In the Newcastle arm of this study ( EDIPS-Newcastle ) , we tested the hypothesis that T2D can be prevented by lifestyle intervention and explored secondary outcomes in relation to diabetes incidence . Methods We recruited 102 participants ( 42 men and 60 women , mean age 57 years , mean BMI 34 kgm-2 ) with IGT to EDIPS-Newcastle and r and omised to Intervention and usual care Control groups . The intervention included individual motivational interviewing aim ed at : weight reduction , increase in physical activity , fibre and carbohydrate intake and reduction of fat intake ( secondary outcomes ) . The primary outcome was diagnosis of T2D . Results Mean duration of follow-up was 3.1 years . T2D was diagnosed in 16 participants ( I = 5 , C = 11 ) . Absolute incidence of T2D was 32.7 per 1000 person-years in the Intervention-group and 67.1 per 1000 person-years in the Control-group . The overall incidence of diabetes was reduced by 55 % in the Intervention-group , compared with the Control-group : RR 0.45 ( 95%CI 0.2 to 1.2).Explanatory survival analysis of secondary outcomes showed that those who sustained beneficial changes for two or more years reduced their risk of developing T2D . Conclusion Our results are consistent with other diabetes prevention trials . This study was design ed as part of a larger study and although the sample size limits statistical significance , the results contribute to the evidence that T2D can be prevented by lifestyle changes in adults with IGT . In explanatory analysis small sustained beneficial changes in weight , physical activity or dietary factors were associated with reduction in T2D incidence . Trial Registration International St and ard R and omised Controlled Trial Number registry ( IS RCT N)Registry number : IS RCT N 15670600 http://www.controlled-trials.com/is rct n/ search .html?srch=15670600%26sort=3%26dir = BACKGROUND Obesity exacerbates the age-related decline in physical function and causes frailty in older adults ; however , the appropriate treatment for obese older adults is controversial . METHODS In this 1-year , r and omized , controlled trial , we evaluated the independent and combined effects of weight loss and exercise in 107 adults who were 65 years of age or older and obese . Participants were r and omly assigned to a control group , a weight-management ( diet ) group , an exercise group , or a weight-management-plus-exercise ( diet-exercise ) group . The primary outcome was the change in score on the modified Physical Performance Test . Secondary outcomes included other measures of frailty , body composition , bone mineral density , specific physical functions , and quality of life . RESULTS A total of 93 participants ( 87 % ) completed the study . In the intention-to-treat analysis , the score on the Physical Performance Test , in which higher scores indicate better physical status , increased more in the diet-exercise group than in the diet group or the exercise group ( increases from baseline of 21 % vs. 12 % and 15 % , respectively ) ; the scores in all three of those groups increased more than the scores in the control group ( in which the score increased by 1 % ) ( P<0.001 for the between-group differences ) . Moreover , the peak oxygen consumption improved more in the diet-exercise group than in the diet group or the exercise group ( increases of 17 % vs. 10 % and 8 % , respectively ; P<0.001 ) ; the score on the Functional Status Question naire , in which higher scores indicate better physical function , increased more in the diet-exercise group than in the diet group ( increase of 10 % vs. 4 % , P<0.001 ) . Body weight decreased by 10 % in the diet group and by 9 % in the diet-exercise group , but did not decrease in the exercise group or the control group ( P<0.001 ) . Lean body mass and bone mineral density at the hip decreased less in the diet-exercise group than in the diet group ( reductions of 3 % and 1 % , respectively , in the diet-exercise group vs. reductions of 5 % and 3 % , respectively , in the diet group ; P<0.05 for both comparisons ) . Strength , balance , and gait improved consistently in the diet-exercise group ( P<0.05 for all comparisons ) . Adverse events included a small number of exercise-associated musculoskeletal injuries . CONCLUSIONS These findings suggest that a combination of weight loss and exercise provides greater improvement in physical function than either intervention alone . ( Funded by the National Institutes of Health ; Clinical Trials.gov number , NCT00146107 . ) OBJECTIVE To study the overall effect of the Active Prevention in High-Risk Individuals of Diabetes Type 2 in and Around Eindhoven ( APHRODITE ) lifestyle intervention on type 2 diabetes risk reduction in Dutch primary care after 0.5 and 1.5 years and to evaluate the variability between general practice s. RESEARCH DESIGN AND METHODS Individuals at high risk for type 2 diabetes ( Finnish Diabetes Risk Score ≥13 ) were r and omly assigned into an intervention group ( n = 479 ) or a usual-care group ( n = 446 ) . Comparisons were made between study groups and between general practice s regarding changes in clinical and lifestyle measures over 1.5 years . Participant , general practitioner , and nurse practitioner characteristics were compared between individuals who lost weight or maintained a stable weight and individuals who gained weight . RESULTS Both groups showed modest changes in glucose values , weight measures , physical activity , energy intake , and fiber intake . Differences between groups were significant only for total physical activity , saturated fat intake , and fiber intake . Differences between general practice s were significant for BMI and 2-h glucose but not for energy intake and physical activity . In the intervention group , the nurse practitioners ’ mean years of work experience was significantly longer in individuals who were successful at losing weight or maintaining a stable weight compared with unsuccessful individuals . Furthermore , successful individuals more often had a partner . CONCLUSIONS Risk factors for type 2 diabetes could be significantly reduced by lifestyle counseling in Dutch primary care . The small differences in changes over time between the two study groups suggest that additional intervention effects are modest . In particular , the level of experience of the nurse practitioner and the availability of partner support seem to facilitate intervention success OBJECTIVE Changing dietary and physical activity habits has the potential to postpone or prevent the development of type 2 diabetes . However , it needs to be assessed whether moderate interventions , in agreement with current guidelines for the general population , are effective . We evaluated the impact of a 2-year combined diet and physical activity intervention program on glucose tolerance in Dutch subjects at increased risk for developing diabetes . RESEARCH METHODS AND PROCEDURES Subjects with glucose intolerance were r and omly assigned to either the lifestyle intervention group ( INT ) or control group ( CON ) . The INT received regular dietary advice and was stimulated to increase their physical activity . The CON received a brief leaflet about healthy diet and increased physical activity . Primary outcome measure was the change in glucose tolerance . RESULTS In total , 88 subjects completed 2 years of intervention ( 40 subjects in the INT , 48 subjects in the CON , mean BMI 29.4 kg/m2 ) . Subjects in the INT reduced their body weight , waist circumference , and ( saturated ) fat intake and improved their aerobic capacity . Two-hour plasma glucose concentration declined from 8.7 to 8.0 mM in the INT and rose from 8.6 to 9.4 mM in the CON ( p < 0.01 ) . Subjects adherent to both the diet and exercise intervention showed the largest reduction in 2-hour glucose levels . DISCUSSION Our results showed that a lifestyle intervention program according to general recommendations improves glucose tolerance , even in a less obese and more physical active population . Furthermore , our results underscore the importance of combining diet and physical activity to improve glucose tolerance and insulin resistance Exercise is the best predictor of long-term weight loss . This study evaluated two strategies for improving exercise adherence and long-term weight loss in obese out patients . Obese men and women ( N = 193 ) were r and omized to 1 of 5 treatment groups for 18 months : st and ard behavior therapy ( SBT ) ; SBT with supervised walks ( SW ) 3 times per week ; SBT + SW with personal trainers ( PT ) , who walked with participants , made phone reminders , and did make-up SW ; SBT + SW with monetary incentives ( I ) for completing SW ; and SBT + SW + PT + I. Both PT and I enhanced attendance at SWs , the combination producing the best adherence . Increased walk attendance did not result in higher overall energy expenditure , however , and long-term weight loss was also not improved . Post hoc analyses suggest that the level of exercise needed for successful long-term weight loss is much higher than that usually recommended in behavioral treatment programs Summary Background The increasing prevalence of overweight and obesity needs effective approaches for weight loss in primary care and community setting s. We compared weight loss with st and ard treatment in primary care with that achieved after referral by the primary care team to a commercial provider in the community . Methods In this parallel group , non-blinded , r and omised controlled trial , 772 overweight and obese adults were recruited by primary care practice s in Australia , Germany , and the UK . Participants were r and omly assigned with a computer-generated simple r and omisation sequence to receive either 12 months of st and ard care as defined by national treatment guidelines , or 12 months of free membership to a commercial programme ( Weight Watchers ) , and followed up for 12 months . The primary outcome was weight change over 12 months . Analysis was by intention to treat ( last observation carried forward [ LOCF ] and baseline observation carried forward [ BOCF ] ) and in the population who completed the 12-month assessment . This trial is registered , number IS RCT N85485463 . Findings 377 participants were assigned to the commercial programme , of whom 230 ( 61 % ) completed the 12-month assessment ; and 395 were assigned to st and ard care , of whom 214 ( 54 % ) completed the 12-month assessment . In all analyses , participants in the commercial programme group lost twice as much weight as did those in the st and ard care group . Mean weight change at 12 months was −5·06 kg ( SE 0·31 ) for those in the commercial programme versus −2·25 kg ( 0·21 ) for those receiving st and ard care ( adjusted difference −2·77 kg , 95 % CI −3·50 to −2·03 ) with LOCF ; −4·06 kg ( 0·31 ) versus −1·77 kg ( 0·19 ; adjusted difference −2·29 kg , −2·99 to −1·58 ) with BOCF ; and −6·65 kg ( 0·43 ) versus −3·26 kg ( 0·33 ; adjusted difference −3·16 kg , −4·23 to −2·11 ) for those who completed the 12-month assessment . Participants reported no adverse events related to trial participation . Interpretation Referral by a primary health-care professional to a commercial weight loss programme that provides regular weighing , advice about diet and physical activity , motivation , and group support can offer a clinical ly useful early intervention for weight management in overweight and obese people that can be delivered at large scale . Funding Weight Watchers International , through a grant to the UK Medical Research Council Developing more effective behavioural interventions requires an underst and ing of the mechanisms of behaviour change , and methods to rigorously test their theoretical basis . The delivery and theoretical basis of an intervention protocol were assessed in ProActive , a UK trial of an intervention to increase the physical activity of those at risk of Type 2 diabetes ( N = 365 ) . In 108 intervention sessions , behaviours of facilitators were mapped to four theories that informed intervention development and behaviours of participants were mapped to 17 theoretical components of these four theories . The theory base of the intervention specified by the protocol was different than that delivered by facilitators , and that received by participants . Of the intervention techniques delivered , 25 % were associated with theory of planned behaviour ( TPB ) , 42 % with self-regulation theory ( SRT ) , 24 % with operant learning theory ( OLT ) and 9 % with relapse prevention theory ( RPT ) . The theoretical classification of participant talk showed a different pattern , with twice the proportion associated with OLT ( 48 % ) , 21 % associated with TPB , 31 % with SRT and no talk associated with RPT . This study demonstrates one approach to assessing the extent to which the theories used to guide intervention development account for any changes observed Background This study assessed the effect of a 1-year internet-based weight loss intervention for men . Methods Four hundred forty-one overweight and obese men were r and omized to intervention or delayed treatment . Participants completed a Web-based assessment of diet and physical activity behaviors and weekly tailored Web modules addressing weight-related behaviors . Results At 12 months compared to controls , intervention men decreased percent of energy from saturated fat and increased grams of fiber and fruit/vegetable servings per 1.000 kcal ( p values < 0.001 ) and walked 16 min more per day ( p < 0.05 ) . No between-group differences in body mass index ( BMI ) , weight , or waist circumference were seen , but among completers , men in the highest tertile of intervention participation had lower weight ( 98.74 vs. 102.37 kg ) , BMI ( 32.38 vs. 33.46 ) , and waist circumference ( 42.17 vs. 43.47 cm ) compared to men who participated less often . Conclusions The intervention improved diet and activity behaviors , but weight loss occurred only for those with the highest adherence Background : Internet-based weight-loss programs appear promising in the short-term but , to data , have not been able to produce the level of weight loss seen in traditional in-person treatment ; thus , novel approaches are necessary . Using a combination of interactive technology and in-person support has been beneficial in other areas of medicine . Purpose : The aim of this study is to compare 12-month weight-loss outcomes of an Internet-only behavioral weight-loss treatment with the same program supplemented with monthly in-person meetings . Methods : One hundred and twenty-three participants were r and omized to an Internet-only ( n=62 ) or an Internet + in-person treatment ( I+IPS ; n=61 ) . All participants then participated in a 12-month behavioral weight-loss program conducted over the Internet . The groups met online weekly for the first 6 months and biweekly for the second half of the intervention . The I+IPS group had access to the same Web site as the Internet-only group but , once a month , attended an in-person meeting in place of an online chat . Assessment s included body weight , program adherence , and social support measures . Results : An intent-to-treat analysis ( n=123 ) revealed there were no significant Group x Time differences ( p=.15 ) in weight loss at either 6 ( −6.8±7.8 vs. −5.1±4.8 , p=.15 ) or 12 months ( −5.1±7.1 kg vs. −3.5±5.1 kg , p=.17 , for Internet-only and I+IPS , respectively ) . Differences between groups for those completing all measures ( n=77 ) also revealed no significant differences at 6 months ( −9.2±7.0 kg vs. −6.9±4.2 kg , p=.08 ) or 12 months ( −8.0±7.5 kg vs. −5.6±5.5 kg , p=.10 for the Internet-only and I+IPS conditions , respectively ) . Conclusions : Supplementation of an Internet weight-loss treatment with monthly in-person meetings did not result in greater weight losses over 12 months . Dynamic , socially supportive , and interactive elements of the Web site may have obviated the need for further interpersonal behavioral counseling Background Successfully transferring the findings of expensive and tightly controlled programmes of intensive lifestyle modification to the primary care setting is necessary if such knowledge is to be of clinical utility . The objective of this study was to test whether intensive lifestyle modification , shown previously in tightly-controlled clinical trials to be efficacious for diabetes risk-reduction among high-risk individuals , can reduce cardiovascular risk factor levels in the primary care setting . Methodology / Principal Findings The Swedish Björknäs study was a r and omized controlled trial conducted from 2003 to 2006 with follow-up on cardiovascular risk factors at 3 , 12 , 24 and 36 months . A total of 151 middle-aged men and women at moderate- to high-risk of cardiovascular disease from northern Sweden were r and omly assigned to either an intensive lifestyle intervention ( n = 75 ) or control ( n = 76 ) group . The intervention was based broadly on the protocol of the Diabetes Prevention Program . The three-month intervention period was administered in the primary care setting and consisted of supervised exercise sessions and diet counselling , followed by regular group meetings during three years . The control group was given general advice about diet and exercise and received st and ard clinical care . Outcomes were changes in anthropometrics , aerobic fitness , self-reported physical activity , blood pressure , and metabolic traits . At 36 months post-r and omisation , intensive lifestyle modification reduced waist circumference ( −2.2 cm : p = 0.001 ) , waist-hip ratio ( −0.02 : p<0.0001 ) , systolic blood pressure ( −4.9 mmHg : p = 0.036 ) , and diastolic blood pressure ( −1.6 mmHg : p = 0.005 ) , and improved aerobic fitness ( 5 % ; p = 0.038 ) . Changes in lipid or glucose values did not differ statistically between groups . At 36 months , self-reported time spent exercising and total physical activity had increased more in the intervention group than in the control group ( p<0.001 ) . Conclusion / Significance A program of intensive lifestyle modification undertaken in the primary health care setting can favourably influence cardiovascular risk-factor profiles in high-risk individuals . Trial Registration Clinical Trials.gov BACKGROUND High levels of exercise may be necessary for long-term maintenance of weight loss . OBJECTIVE We aim ed to determine in a r and omized prospect i ve design whether encouraging 2500 kcal physical activity/wk produced greater 30-mo weight losses than did the st and ard 1000 kcal physical activity/wk prescription . DESIGN Overweight adults ( n = 202 ) were r and omly assigned to either 18 mo of st and ard behavioral treatment ( SBT ) with an exercise goal of 1000 kcal/wk or a high physical activity ( HPA ) treatment with a goal of 2500 kcal/wk . The HPA treatment included all procedures in the SBT plus encouragement to recruit 1 - 3 exercise partners and small-group counseling with an exercise coach . Participants were followed for 30 mo . RESULTS The HPA group achieved significantly greater exercise levels and weight losses than did the SBT group at 12 and 18 mo ( P < 0.01 ) . Weight losses did not differ significantly at 30 mo : 0.90 + /- 8.9 and 2.86 + /- 8.6 kg for the SBT and HPA groups , respectively ( P = 0.16 ) . At 30 mo , average exercise levels no longer differed significantly between groups ( 1390 and 1696 kcal/wk , respectively ; P > 0.10 ) . Participants sustaining high exercise levels ( > 2500 kcal/wk ) for 30 mo had significantly ( P < 0.001 ) greater 30-mo weight loss than did those exercising less ( 12 + /- 8.8 and 0.8 + /- 8.1 kg , respectively ) . CONCLUSIONS Although participants in the HPA group sustained the 2500-kcal activity goal during the 18-mo treatment , activity declined once treatment ended , which result ed in no between-group differences in activity or weight loss at 2.5 y. Participants who reported continuing to engage in high levels of exercise maintained a significantly larger weight loss BACKGROUND Limitations in mobility are common among older adults with cardiovascular and cardiometabolic disorders and have profound effects on health and well-being . With the growing population of older adults in the United States , effective and scalable public health approaches are needed to address this problem . Our goal was to determine the effects of a physical activity and weight loss intervention on 18-month change in mobility among overweight or obese older adults in poor cardiovascular health . METHODS The study design was a translational , r and omized controlled trial of physical activity ( PA ) and weight loss ( WL ) on mobility in overweight or obese older adults with cardiovascular disease ( CVD ) or at risk for CVD . The study was conducted within the community infrastructure of Cooperative Extension Centers . Participants were r and omized to 1 of 3 interventions : PA , WL + PA , or a successful aging ( SA ) education control arm . The primary outcome was time to complete a 400-m walk in seconds ( 400MWT ) . RESULTS A significant treatment effect ( P = .002 ) and follow-up testing revealed that the WL + PA group improved their 400MWT ( adjusted mean [ SE ] , 323.3 [ 3.7 ] seconds ) compared with both PA ( 336.3 [ 3.9 ] seconds ; P = .02 ) and SA ( 341.3 [ 3.9 ] seconds ; P < .001 ) . Participants with poorer mobility at baseline benefited the most ( P < .001 ) . CONCLUSION Existing community infrastructures can be effective in delivering lifestyle interventions to enhance mobility in older adults in poor cardiovascular health with deficits in mobility ; attention should be given to intervening on both weight and sedentary behavior since weight loss is critical to long-term improvement in mobility . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00119795 The Women on the Move through Activity and Nutrition ( WOMAN ) study was design ed to test whether a nonpharmacological intervention including qualitative and quantitative dietary changes to induce weight loss and increased physical activity levels would reduce blood triglyceride levels and number of low-density lipoprotein particles ( LDL-P ) . Such decreases in lipoproteins and other risk factors could reduce or slow progression of sub clinical cardiovascular disease ( CVD ) . Study participants were r and omized to either the intervention ( Lifestyle Change ) or assessment ( Health Education ) group . Most of the intervention ended at the 30-month visit . The last 48-month examination was completed in 9/2008 . There was very substantial weight loss and increased exercise during the first 30 months of the trial result ing in significant decreases in CV risk factors . Most of the intervention effect was lost through 48 months . Weight loss was 3.4 kg in Lifestyle Intervention and 0.2 kg in the Health Education at 48 months ( P = 0.000 ) . There were no significant changes at 48 months in lipid levels , blood pressure ( BP ) , glucose , insulin , or in the sub clinical measures of coronary calcium , carotid intima media thickness , or plaque . There was a significant decrease in long-distance corridor walk time in the Lifestyle vs. Health Education groups . Significant lifestyle changes can be achieved that result in decreases in CV risk factors . Whether such changes reduce CV outcomes is still untested in clinical trials of weight loss or exercise . Long-term maintenance of successful lifestyle changes , weight loss and reduced risk factors is the hurdle for lifestyle interventions attempting to prevent CV and other chronic diseases CONTEXT The prevalence of overweight and obesity in the United States remains high . Commercial weight loss programs may contribute to efforts to reduce the prevalence of overweight and obesity , although few studies have examined their efficacy in controlled trials . OBJECTIVE To test whether a free prepared meal and incentivized structured weight loss program promotes greater weight loss and weight loss maintenance at 2 years compared with usual care . DESIGN , SETTING , AND PARTICIPANTS A r and omized controlled trial of weight loss and weight loss maintenance in 442 overweight or obese women ( body mass index , 25 - 40 ) aged 18 to 69 years ( mean age , 44 years ) conducted at US institutions over 2 years with follow-up between November 2007 and April 2010 . INTERVENTION The program , which involves in-person center-based or telephone-based one-to-one weight loss counseling , was available over a 2-year period . Behavioral goals were an energy-reduced , nutritionally adequate diet , facilitated by the inclusion of prepackaged food items in a planned menu during the initial weight loss phase , and increased physical activity . Participants assigned to usual care received 2 individualized weight loss counseling sessions with a dietetics professional and monthly contacts . MAIN OUTCOME MEASURES Weight loss and weight loss maintenance . RESULTS Weight data were available at 24 months for 407 women ( 92.1 % of the study sample ) . In an intent-to-treat analysis with baseline value substitution , mean weight loss was 7.4 kg ( 95 % confidence interval [ CI ] , 6.1 - 8.7 kg ) or 7.9 % ( 95 % CI , 6.5%-9.3 % ) of initial weight at 24 months for the center-based group , 6.2 kg ( 95 % CI , 4.9 - 7.6 kg ) or 6.8 % ( 95 % CI , 5.2%-8.4 % ) for the telephone-based group , and 2.0 kg ( 95 % CI , 0.6 - 3.3 kg ) or 2.1 % ( 95 % CI , 0.7%-3.5 % ) for the usual care control group after 24 months ( P < .001 for intervention effect ) . CONCLUSION Compared with usual care , this structured weight loss program result ed in greater weight loss over 2 years . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00640900 This article reports the 12-month follow-up results and process evaluation of the SHED-IT ( Self-Help , Exercise , and Diet using Information Technology ) trial , an Internet-based weight loss program exclusively for men . Sixty-five overweight/obese male staff and students at the University of Newcastle ( Callaghan , Australia ) ( mean ( s.d . ) age = 35.9 ( 11.1 ) years ; BMI = 30.6 ( 2.8 ) ) were r and omly assigned to either ( i ) Internet group ( n = 34 ) or ( ii ) Information only control group ( n = 31 ) . Both received one face-to-face information session and a program booklet . Internet group participants were instructed to use the study website for 3 months . Participants were assessed at baseline , 3- , 6- , and 12-month follow-up for weight , waist circumference , BMI , blood pressure , and resting heart rate . Retention at 3- and 12-months was 85 % and 71 % , respectively . Intention-to-treat ( ITT ) analysis using linear mixed models revealed significant and sustained weight loss of -5.3 kg ( 95 % confidence interval ( CI ) : -7.5 , -3.0 ) at 12 months for the Internet group and -3.1 kg ( 95 % CI : -5.4 , -0.7 ) for the control group with no group difference . A significant time effect was found for all outcomes ( P < 0.001 ) . Per- protocol analysis revealed a significant group-by-time interaction for weight , waist circumference , BMI , and systolic blood pressure . Internet group compliers ( who self-monitored as instructed ) maintained greater weight loss at 12 months ( -8.8 kg ; 95 % CI -11.8 , -5.9 ) than noncompliers ( -1.9 kg ; 95 % CI -4.8 , 1.0 ) and controls ( -3.0 kg ; 95 % CI -5.2 , -0.9 ) . Qualitative analysis by question naire and interview highlighted the acceptability and satisfaction with SHED-IT . Low-dose approaches to weight loss are feasible , acceptable , and can achieve clinical ly important weight loss in men after 1-year follow-up Objectives To evaluate effectiveness of a structured one-to-one behaviour change programme on weight loss in obese and overweight individuals . Design R and omised controlled trial . Setting 23 general practice s in Camden , London . Participants 381 adults with body mass index ≥25 kg/m2 r and omly assigned to intervention ( n=191 ) or control ( n=190 ) group . Interventions A structured one-to-one programme , delivered over 14 visits during 12 months by trained advisors in three primary care centres compared with usual care in general practice . Outcome measures Changes in weight , per cent body fat , waist circumference , blood pressure and heart rate between baseline and 12 months . Results 217/381 ( 57.0 % ) participants were assessed at 12 months : missing values were imputed . The difference in mean weight change between the intervention and control groups was not statistically significant ( 0.70 kg ( 0.67 to 2.17 , p=0.35 ) ) , although a higher proportion of the intervention group ( 32.7 % ) than the control group ( 20.4 % ) lost 5 % or more of their baseline weight ( OR : 1.80 ( 1.02 to 3.18 , p=0.04 ) ) . The intervention group achieved a lower mean heart rate ( mean difference 3.68 beats per minute ( 0.31 to 7.04 , p=0.03 ) ) than the control group . Participants in the intervention group reported higher satisfaction and more positive experiences of their care compared with the control group . Conclusions Although there is no significant difference in mean weight loss between the intervention and control groups , trained non-specialist advisors can deliver a structured programme and achieve clinical ly beneficial weight loss in some patients in primary care . The intervention group also reported a higher level of satisfaction with the support received . Primary care interventions are unlikely to be sufficient to tackle the obesity epidemic and effective population -wide measures are also necessary . Clinical trial registration number Trial registration Clincaltrials.gov NCT00891943 Objective To assess the effectiveness of a range of weight management programmes in terms of weight loss . Design Eight arm r and omised controlled trial . Setting Primary care trust in Birmingham , Engl and . Participants 740 obese or overweight men and women with a comorbid disorder identified from general practice records . Interventions Weight loss programmes of 12 weeks ’ duration : Weight Watchers ; Slimming World ; Rosemary Conley ; group based , dietetics led programme ; general practice one to one counselling ; pharmacy led one to one counselling ; choice of any of the six programmes . The comparator group was provided with 12 vouchers enabling free entrance to a local leisure ( fitness ) centre . Main outcome measures The primary outcome was weight loss at programme end ( 12 weeks ) . Secondary outcomes were weight loss at one year , self reported physical activity , and percentage weight loss at programme end and one year . Results Follow-up data were available for 658 ( 88.9 % ) participants at programme end and 522 ( 70.5 % ) at one year . All programmes achieved significant weight loss from baseline to programme end ( range 1.37 kg ( general practice ) to 4.43 kg ( Weight Watchers ) ) , and all except general practice and pharmacy provision result ed in significant weight loss at one year . At one year , only the Weight Watchers group had significantly greater weight loss than did the comparator group ( 2.5 ( 95 % confidence interval 0.8 to 4.2 ) kg greater loss , ) . The commercial programmes achieved significantly greater weight loss than did the primary care programmes at programme end ( mean difference 2.3 ( 1.3 to 3.4 ) kg ) . The primary care programmes were the most costly to provide . Participants allocated to the choice arm did not have better outcomes than those r and omly allocated to a programme . Conclusions Commercially provided weight management services are more effective and cheaper than primary care based services led by specially trained staff , which are ineffective . Trial registration Current Controlled Trials IS RCT N25072883 CONTEXT Although commercial weight loss programs provide treatment to millions of clients , their efficacy has not been evaluated in rigorous long-term trials . OBJECTIVE To compare weight loss and health benefits achieved and maintained through self-help weight loss vs with a structured commercial program . DESIGN AND SETTING A 2-year , multicenter r and omized clinical trial with clinic visits at 12 , 26 , 52 , 78 , and 104 weeks conducted at 6 academic research centers in the United States between January 1998 and January 2001 . PARTICIPANTS Overweight and obese men ( n = 65 ) and women ( n = 358 ) ( body mass index , 27 - 40 ) aged 18 to 65 years . INTERVENTION R and om assignment to either a self-help program ( n = 212 ) consisting of two 20-minute counseling sessions with a nutritionist and provision of self-help re sources or to a commercial weight loss program ( n = 211 ) consisting of a food plan , an activity plan , and a cognitive restructuring behavior modification plan , delivered at weekly meetings . MAIN OUTCOME MEASURES Weight change was the primary outcome measure . Secondary outcomes included waist circumference , body mass index , blood pressure , serum lipids , glucose , and insulin levels . RESULTS At 2 years , 150 participants ( 71 % ) in the commercial group and 159 ( 75 % ) in the self-help group completed the study . In the intent-to-treat analysis , mean ( SD ) weight loss of participants in the commercial group was greater than in the self-help group at 1 year ( -4.3 [ 6.1 ] kg vs -1.3 [ 6.1 ] kg , respectively ; P<.001 ) and at 2 years ( -2.9 [ 6.5 ] kg vs -0.2 [ 6.5 ] kg , respectively ; P<.001 ) . Waist circumference ( P = .003 ) and body mass index ( P<.001 ) decreased more in the commercial group . Changes in blood pressure , lipids , glucose , and insulin levels were related to changes in weight in both groups , but between-group differences in biological parameters were mainly nonsignificant by year 2 . CONCLUSION The structured commercial weight loss program provided modest weight loss but more than self-help over a 2-year period OBJECTIVE To compare health benefits achieved in a transtheoretical model-chronic disease ( TM-CD ) minimal intervention for obesity vs. augmented usual care ( AUC ) . RESEARCH METHOD AND PROCEDURES This was a 2-year , r and omized clinical trial with overweight or obese men and women from 15 primary care sites . AUC ( n = 336 ) included dietary and exercise advice , prescriptions , and three 24-hour dietary recalls every 6 months . TM-CD care ( n = 329 ) included AUC elements plus " stage of change " ( SOC ) assessment s for five target behaviors every other month , mailed SOC and target behavior-matched workbooks , and monthly telephone calls from a weight-loss advisor . Weight change was the primary outcome . RESULTS Repeated measures models under the missing at r and om assumption yielded nonsignificant adjusted differences between the AUC and TM-CD groups for weight change , waist circumference , energy intake or expenditure , blood pressure , and blood lipids . The pattern of change over time suggested that TM-CD participants were trying harder to impact target behaviors during the first 6 to 12 months of the trial but relapsed afterward . Sixty percent of trial participants maintained their baseline weights for 18 to 24 months . DISCUSSION A combination of mailed patient material s and monthly telephone calls based on the transtheoretical model and some elements of chronic disease care is not powerful enough , relative to AUC , to alter target behaviors among overweight primary care patients in an obesogenic environment . AUC may be sufficient to maintain weights among at-risk primary care patients OBJECTIVE To describe the 1 ) lifestyle intervention used in the Finnish Diabetes Prevention Study , 2 ) short- and long-term changes in diet and exercise behavior , and 3 ) effect of the intervention on glucose and lipid metabolism . RESEARCH DESIGN AND METHODS There were 522 middle-aged , overweight subjects with impaired glucose tolerance who were r and omized to either a usual care control group or an intensive lifestyle intervention group . The control group received general dietary and exercise advice at baseline and had an annual physician 's examination . The subjects in the intervention group received additional individualized dietary counseling from a nutritionist . They were also offered circuit-type resistance training sessions and advised to increase overall physical activity . The intervention was the most intensive during the first year , followed by a maintenance period . The intervention goals were to reduce body weight , reduce dietary and saturated fat , and increase physical activity and dietary fiber . RESULTS The intervention group showed significantly greater improvement in each intervention goal . After 1 and 3 years , weight reductions were 4.5 and 3.5 kg in the intervention group and 1.0 and 0.9 kg in the control group , respectively . Measures of glycemia and lipemia improved more in the intervention group . CONCLUSIONS The intensive lifestyle intervention produced long-term beneficial changes in diet , physical activity , and clinical and biochemical parameters and reduced diabetes risk . This type of intervention is a feasible option to prevent type 2 diabetes and should be implemented in the primary health care system Aim : To determine the effect of whole body vibration ( WBV ) , combined with caloric restriction , on weight , body composition and metabolic risk factors in overweight and obese adults . Methods : A r and omized , controlled study with a 6-month intervention period and a 6-month ‘ no intervention ’ follow-up . 61 of the 79 participants completed the study . Data were collected at baseline and at 3 , 6 and 12 months in the control group ( CONTROL ) , the diet only group ( DIET ) , the diet plus fitness group ( FITNESS ) and the diet plus WBV group ( VIBRATION ) . Results : Weight decreased significantly in all three intervention groups . Only FITNESS and VIBRATION managed to maintain a weight loss of 5 % or more in the long term . Visceral adipose tissue ( VAT ) changed most in VIBRATION : –47.8 ± 41.2 and –47.7 ± 45.7 cm2 after 6 and 12 months respectively compared to CONTROL ( –3.6 ± 20.5 or + 26.3 ± 30.6 cm2 ) , DIET ( –24.3 ± 29.8 or –7.5 ± 28.3 cm2 ) and FITNESS ( –17.6 ± 36.6 or –1.6 ± 33.3 cm2 ) ( p < 0.001 ) . Conclusions : Combining aerobic exercise or WBV training with caloric restriction can help to achieve a sustained long-term weight loss of 5–10 % . These preliminary data show that WBV training may have the potential to reduce VAT more than aerobic exercise in obese adults , possibly making it a meaningful addition to future weight loss programs BACKGROUND The efficacy of physical activity with a healthful diet to reduce obesity is established ; however , little is known about the translation of effective lifestyle strategies for obesity reduction in primary care setting s. METHODS We assessed the effectiveness of a 2-year behaviorally based physical activity and diet program implemented entirely within clinical practice s to reduce obesity . A total of 490 sedentary , obese adults were r and omized to usual care ( n = 241 ) or to the behavioral intervention ( n = 249 ) . The usual care group received advice from their physicians about lifestyle as a strategy for obesity reduction . The behavioral intervention included individual counseling from health educators to promote physical activity with a healthful diet . The primary outcome was change in waist circumference ( WC ) . RESULTS A total of 396 participants completed the trial ( 80.8 % ) . A significant main effect was observed for WC change within the intervention compared with usual care ( P < .001 ) that was sustained at 24 months ( mean [ SE ] , -0.9 [ 0.4 ] vs 0.2 [ 0.4 ] cm ; P = .05 ) . Secondary analyses revealed significant main effects for change in WC in men ( P = .009 ) and women ( P = .02 ) . In men , the mean ( SE ) reduction in WC at 24 months was greater with behavioral intervention compared with usual care ( -1.6 [ 0.6 ] vs 0.1 [ 0.6 ] cm ; P = .049 ) . In women , the behavioral intervention was associated with differences in WC compared with usual care at 6 and 12 months ( P ≤ .01 ) but not at 24 months ( P = .10 ) . CONCLUSIONS Behavioral intervention in clinical setting s is associated with modest reductions in WC during a 2-year study in obese patients . However , the effectiveness of the intervention is restricted to men . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00665158 Lifestyle interventions for weight loss are the cornerstone of obesity therapy , yet their optimal design is debated . This is particularly true for postmenopausal women ; a population with a high prevalence of obesity yet toward whom fewer studies are targeted . We conducted a year-long , 4-arm r and omized trial among 439 overweight-to-obese postmenopausal sedentary women to determine the effects of a calorie-reduced , low-fat diet ( D ) , a moderate-intensity , facility-based aerobic exercise program ( E ) , or the combination of both interventions ( D+E ) , vs. a no-lifestyle-change control ( C ) on change in body weight and composition . The group-based dietary intervention had a weight-reduction goal of ≥10 % , and the exercise intervention consisted of a gradual escalation to 45-min aerobic exercise 5 day/week . Participants were predominantly non-Hispanic whites ( 85 % ) with a mean age of 58.0 ± 5.0 years , a mean BMI of 30.9 ± 4.0 kg/m(2 ) and an average of 47.8 ± 4.4 % body fat . Baseline and 12-month weight and adiposity measures were obtained by staff blinded to participants ' intervention assignment . Three hundred and ninety nine women completed the trial ( 91 % retention ) . Using an intention-to-treat analysis , average weight loss at 12 months was -8.5 % for the D group ( P < 0.0001 vs. C ) , -2.4 % for the E group ( P = 0.03 vs. C ) , and -10.8 % for the D+E group ( P < 0.0001 vs. C ) , whereas the C group experienced a nonsignificant -0.8 % decrease . BMI , waist circumference , and % body fat were also similarly reduced . Among postmenopausal women , lifestyle-change involving diet , exercise , or both combined over 1 year improves body weight and adiposity , with the greatest change arising from the combined intervention Approximately one fourth of the U.S. adult population nearly 50 million peoplehas hypertension ( 1 , 2 ) . Taking a broader perspective , more than half of the adult population has higher than optimal blood pressure ( 1 ) , defined as systolic blood pressure greater than 120 mm Hg and diastolic blood pressure greater than 80 mm Hg ( 2 ) . These persons are at significantly increased risk for cardiovascular disease and stroke ( 3 ) . Although pharmacologic treatment for hypertension significantly reduces morbidity and mortality from cardiovascular diseases ( 4 , 5 ) , long-term pharmacologic therapy can have undesirable side effects and requires the expense of continuing medical supervision . Furthermore , pharmacologic therapy is not usually initiated when blood pressure is higher than optimal yet below diagnostic thresholds for hypertension . Thus , lifestyle interventions for primary prevention and initial treatment of high blood pressure remain a vital strategy for controlling this highly prevalent condition ( 2 ) . Weight loss has been shown to reduce blood pressure in overweight hypertensive patients ( 6 - 9 ) and in overweight persons with high-normal blood pressure ( 10 - 12 ) . Two review s of r and omized trials of weight reduction to reduce blood pressure examined the results of nine studies ( 13 , 14 ) . Most of these trials were small , only one had more than 500 participants ( 11 ) , and most had short-term follow-up ( 1 year or less ) . Only three studies had follow-up of 3 to 5 years ( 8 , 10 , 11 ) . Compared with controls , weight loss averaged nearly 7 kg in the short-term trials and approximately 3 kg in the three longer-term trials . In almost all trials , systolic blood pressure and diastolic blood pressure were reduced in the intervention groups . Since these review s were published , the Trials of Hypertension Prevention ( TOHP ) Phase I reported mean weight reduction of 3.9 kg at 18 months in 564 overweight participants with high-normal blood pressure , result ing in significant decreases in systolic blood pressure and diastolic blood pressure compared with a usual care control group ( 12 , 15 ) . To investigate whether nonpharmacologic interventions can prevent hypertension over the long term , TOHP II was initiated . This was a r and omized , controlled trial examining the effects of weight loss and dietary sodium reduction , alone and in combination , in reducing blood pressure in overweight adults with high-normal diastolic blood pressure ( 16 ) . This target population is at high risk for hypertension as they age . The primary outcome paper from this trial ( 17 ) provided only a brief overview of the effects of weight loss on blood pressure . Here , we provide more detailed analysis of weight loss and blood pressure in TOHP II . Of special interest are the long-term effects of weight loss on blood pressure , the magnitude of the doseresponse relationship at 36 months , the effect of patterns of weight loss on blood pressure , and the predictors of weight loss and blood pressure response . Methods Participants Participants in TOHP II were overweight adults with nonmedicated diastolic blood pressure of 83 to 89 mm Hg and systolic blood pressure less than 140 mm Hg . Other eligibility criteria included age 30 to 54 years and a body mass index of 26.1 to 37.4 kg/m2 for men and 24.4 to 37.4 kg/m2 for women , approximately 110 % to 165 % of ideal weight ( 18 ) . Principal exclusion criteria were current treatment with medications that might affect blood pressure , clinical or laboratory evidence of cardiovascular disease , diabetes mellitus , renal insufficiency ( serum creatinine concentration 150 mol/L [ 1.7 mg/dL ] for men and 132 mol/L [ 1.5 mg/dL ] for women ) , and current or planned pregnancy . Detailed descriptions of recruitment and participant characteristics have been published elsewhere ( 19 , 20 ) . The study was review ed and approved by the institutional review boards at all nine TOHP centers and the coordinating center , and all participants signed informed consent forms . Design Eligible participants were r and omly assigned with equal probability to one of four groups : weight loss only , sodium reduction only , combined weight loss and sodium reduction , or usual care ( controls ) . Measurements Age , sex , ethnicity , and years of education were obtained by question naire . Baseline blood pressure measurements were taken at three screening visits , each separated by 7 to 45 days . At each visit , three readings of systolic blood pressure and diastolic blood pressure were obtained and averaged . Certified staff obtained measurements in seated participants by using a Hawksley r and om-zero sphygmomanometer ( 21 ) . Body weight was measured to the nearest 0.2 kg ( 0.5 lb ) by using a calibrated balance-beam scale ; participants wore indoor clothing ( without shoes ) . Blood pressure and weight were measured every 6 months after r and omization to the end of follow-up at 36 , 42 , or 48 months , depending on r and omization date . Clinic staff who were blinded to study group assignment made these assessment s. Blood pressure measurements were obtained during a single visit at all follow-up points except for 18 and 36 months , when measurements were taken at a series of three visits approximately 1 week apart . Multiple measurements were taken at 18 and 36 months to provide a more precise assessment of average blood pressures at these primary outcome points . Dietary intake was assessed by 24-hour recall , and physical activity was assessed by question naire . Intervention Participants assigned to the weight loss intervention group sought to lose at least 4.5 kg ( 10 lb ) during the first 6 months of the intervention and to maintain their weight loss for the remainder of the trial . A brief description of the intervention methods is presented here ; a more detailed description has been published elsewhere ( 22 ) . The intervention started with an individual counseling session , followed by 14 weekly group meetings led by dietitians or health educators . After this 14-week intensive phase , participants attended six biweekly group meetings and then monthly group meetings . Beginning in the 18th month , participants were offered a variety of options to keep them involved in the intervention , including individual counseling sessions and special group sessions focused on selected weight loss topics . The intervention focused on self-directed behavior change ( behavioral self-management ) , nutrition education , information on physical activity , and social support for making and maintaining behavior changes . Specific behavior change techniques included self-monitoring ( food diaries and graphs of minutes of physical activity per day ) , setting explicit short-term goals and developing specific action plans to achieve those objectives , and developing alternative strategies for situations that trigger problem eating . The dietary intervention focused on reducing caloric intake by decreasing consumption of excess fat , sugar , and alcohol . Keeping daily food diaries was emphasized for monitoring intake and assessing progress . With experience , the participants determined the caloric intake that produced moderate weight loss for them . It was suggested that men not consume less than 1500 kcal/d and women not less than 1200 kcal/d . Weight loss of more than 0.9 kg ( 2 lb ) per week was discouraged . The physical activity goal was to gradually increase activity to 30 to 45 minutes per day , four to five days per week . Exercise intensity was moderate , approximately 40 % to 55 % of heart rate reserve , and consisted primarily of brisk walking . Statistical Analysis Baseline characteristics of the weight loss and usual care groups were compared overall and by sex by using t-tests for means and chi-square tests for proportions . Although weight and blood pressure data were collected every 6 months , special efforts were made to achieve high follow-up rates at 18 and 36 months ; at each of these two time points , nine blood pressure readings were collected over three visits and were averaged . For participants prescribed antihypertensive medication , follow-up blood pressure for all subsequent visits was taken to be the last study blood pressure before therapy was started . Participants receiving medications that affect blood pressure for reasons other than hypertension or who became pregnant were treated as missing at that visit . We used two- sample t-tests to compare changes in weight and blood pressure from baseline in the weight loss intervention and usual care groups overall , by sex , by ethnicity , and by sex and ethnicity . The effects of the intervention in terms of changes in weight and blood pressure were examined overall and in subgroups defined by sex , ethnicity , and sex and ethnicity . Subgroup differences were tested by using terms for the interaction of treatment group with sex and with ethnicity in multiple linear regression models . Regression analyses were also used to analyze the doseresponse relationship between change in weight and change in blood pressure , overall and within sex and ethnicity subgroups . Differences in dose response were tested by using interaction terms in linear regression models . All regressions were adjusted for age and baseline weight . We also adjusted for baseline blood pressure in the blood pressure regression models . Change in blood pressure was also examined in relation to quintile of weight loss . Quintiles were computed by using the distribution of weight change in the weight loss intervention group . Additional multiple regression analyses were performed in which weight loss participants were categorized according to patterns of weight loss at 6 and 36 months . The PROC MIXED function of SAS software ( SAS Institute , Inc. , Cary , North Carolina ) was used to perform repeated- measures analyses that tested differences over time by pattern of weight loss . Cox proportional-hazards models were used for survival analyses , with onset of hypertension as the outcome . Results Baseline Findings The baseline characteristics of participants assigned to The Think Health ! study evaluated a behavioral weight loss program adapted from the Diabetes Prevention Program ( DPP ) lifestyle intervention to assist primary care providers ( PCPs ) and auxiliary staff acting as lifestyle coaches ( LCs ) in offering weight loss counseling to their patients . In a r and omized trial conducted at five clinical sites , study participants were r and omly assigned in a 1:1 ratio within each site to either " Basic Plus " ( n = 137 ) , which offered PCP counseling every 4 months plus monthly LC visits during the first year of treatment , or " Basic " ( n = 124 ) , which offered only PCP counseling every 4 months . Participants were primarily ( 84 % ) female , 65 % African American , 16 % Hispanic American , and 19 % white . In the 72 % of participants in each treatment group with a 12-month weight measurement , mean ( 95 % CI ) 1-year weight changes ( kg ) were -1.61 ( -2.68 , -0.53 ) in Basic Plus and -0.62 ( -1.45 , 0.20 ) in Basic ( difference : 0.98 ( -0.36 , 2.33 ) ; P = 0.15 ) . Results were similar in model-based estimates using all available weight data for r and omized participants , adjusting for potential confounders . More Basic Plus ( 22.5 % ) than Basic ( 10.2 % ) participants lost ≥ 5 % of their baseline weight ( P = 0.022 ) . In a descriptive , nonr and omized analysis that also considered incomplete visit attendance , mean weight change was -3.3 kg in Basic Plus participants who attended ≥ 5 LC visits vs. + 0.53 kg in those attending < 5 LC visits . We conclude that the Basic Plus approach of moderate-intensity counseling by PCPs and their staff can facilitate modest weight loss , with clinical ly significant weight loss in high program attenders Objective : R and omized controlled trials ( RCTs ) in obesity are plagued by missing data due to participant dropouts . Most method ologists and regulatory bodies agree that the primary analysis of such RCTs should be based on the intent-to-treat ( ITT ) principle , such that all r and omized subjects are included in the analysis , even those who dropped out . Unfortunately , some authors do not include an ITT analysis in their published reports . Here we show that one form of ITT analysis , baseline observation carried forward ( BOCF ) , can be performed utilizing only information available in a published complete-case ( CC ) analysis , permitting readers , editors , meta-analysts and regulators to easily conduct their own ITT analyses when the original authors do not report one . Method : We mathematically derive a simple method for estimating and testing treatment effects using the BOCF to allow a more conservative comparison of treatment effects when there are dropouts in a clinical trial . We provide two examples of this method using available CC analysis data from reported obesity trials to illustrate the application for readers who wish to determine a range of treatment effects based on published summary statistics . Conclusion : Commonly used CC analyses may lead to inflated type I error rates and /or treatment effect estimates . The method described herein can be useful for research ers who wish to estimate a conservative range of plausible treatment effects based on limited reported data . Limitations of this method are discussed BACKGROUND Obesity and its cardiovascular complications are extremely common medical problems , but evidence on how to accomplish weight loss in clinical practice is sparse . METHODS We conducted a r and omized , controlled trial to examine the effects of two behavioral weight-loss interventions in 415 obese patients with at least one cardiovascular risk factor . Participants were recruited from six primary care practice s ; 63.6 % were women , 41.0 % were black , and the mean age was 54.0 years . One intervention provided patients with weight-loss support remotely -- through the telephone , a study -specific Web site , and e-mail . The other intervention provided in-person support during group and individual sessions , along with the three remote means of support . There was also a control group in which weight loss was self-directed . Outcomes were compared between each intervention group and the control group and between the two intervention groups . For both interventions , primary care providers reinforced participation at routinely scheduled visits . The trial duration was 24 months . RESULTS At baseline , the mean body-mass index ( the weight in kilograms divided by the square of the height in meters ) for all participants was 36.6 , and the mean weight was 103.8 kg . At 24 months , the mean change in weight from baseline was -0.8 kg in the control group , -4.6 kg in the group receiving remote support only ( P<0.001 for the comparison with the control group ) , and -5.1 kg in the group receiving in-person support ( P<0.001 for the comparison with the control group ) . The percentage of participants who lost 5 % or more of their initial weight was 18.8 % in the control group , 38.2 % in the group receiving remote support only , and 41.4 % in the group receiving in-person support . The change in weight from baseline did not differ significantly between the two intervention groups . CONCLUSIONS In two behavioral interventions , one delivered with in-person support and the other delivered remotely , without face-to-face contact between participants and weight-loss coaches , obese patients achieved and sustained clinical ly significant weight loss over a period of 24 months . ( Funded by the National Heart , Lung , and Blood Institute and others ; Clinical Trials.gov number , NCT00783315 . ) BACKGROUND Current evidence suggests a combined treatment of postpartum weight loss of diet and exercise . However , to our knowledge , neither their separate and interactive effects nor long-term outcomes have been evaluated . OBJECTIVE We evaluated whether a 12-wk dietary behavior modification ( D ) treatment to decrease energy intake , physical exercise behavior modification ( E ) treatment to implement moderate aerobic exercise , or combined dietary and physical exercise behavior modification ( DE ) treatment compared with control ( usual care ) ( C ) reduces body weight in lactating women measured at the end of treatment and at a 1-y follow-up 9 mo after treatment termination . DESIGN At 10 - 14 wk postpartum , 68 lactating Swedish women with a prepregnancy BMI ( in kg/m² ) of 25 - 35 were r and omly assigned to D , E , DE , or C groups . Measurements were made at baseline , after the intervention , and again at a 1-y follow-up 9 mo later . A 2 × 2 factorial approach was used to analyze main and interaction effects of treatments . RESULTS Weight changes after the intervention and 1-y follow-up were -8.3 ± 4.2 and -10.2 ± 5.7 kg , respectively , in the D group ; -2.4 ± 3.2 and -2.7 ± 5.9 kg , respectively , in the E group ; -6.9 ± 3.0 and -7.3 ± 6.3 kg , respectively , in the DE group ; and -0.8 ± 3.0 and -0.9 ± 6.6 kg , respectively , in the C group . The main effects of D treatment , but not of E treatment , on weight were significant at both times ( P < 0.001 ) . CONCLUSIONS Dietary treatment provided clinical ly relevant weight loss in lactating postpartum women , which was sustained at 9 mo after treatment . The combined treatment did not yield significant weight or body-composition changes beyond those of dietary treatment alone The objective of this study was to determine whether overweight insulin resistant individuals who lost weight and improved cardiovascular risk factors during a 4-month lifestyle intervention could sustain these lifestyle changes in the long-term . Seventy-nine insulin resistant adults were r and omised to a control group or either a modest or intensive lifestyle intervention group for 4-months . Thereafter the two intervention groups were combined and all participants were followed-up at 8 , 12 and 24 months . Anthropometry , blood pressure , fasting glucose , lipids , insulin and aerobic fitness were measured and dietary intake was assessed . An interview was conducted to determine factors which participants perceived facilitated or hindered maintenance of healthy lifestyle habits . Seventy-two ( 91.1 % ) , sixty-nine ( 87.3 % ) and sixty-two ( 78.5 % ) participants were retained at 8 , 12 and 24-month respectively . At 4-months the adjusted difference in weight between the modest and control groups was -3.4 kg ( 95 % CI -5.4 , -1.3 ) p=0.002 and intensive and control groups was -4.7 kg ( -6.9 , -2.4 ) p=0.0001 respectively . At 2-years there were no significant differences for weight when the initial 3 groups were compared or when the combined intervention group was compared with the control group . At 2-years , 64 % of participants reported that more frequent follow-up would have helped them to maintain healthy lifestyle habits . Even intensive counselling for 4-months with 4-monthly and then yearly monitoring were not enough for maintaining lifestyle changes sufficient to sustain weight loss . More frequent monitoring for an indefinite period was perceived by two-thirds of participants as necessary for them to maintain their initial lifestyle changes PURPOSE The study investigated the efficacy and cost-effectiveness of a cognitive-behavioral weight management program , complemented by an interactive Web site and brief telephone/e-mail coaching . METHODS In 2006 - 2007 , 1755 overweight , non-active-duty TRICARE beneficiaries were r and omized to one of three conditions with increasing intervention intensity : written material s and basic Web access ( RCT 1 ) , plus an interactive Web site ( RCT 2 ) , plus brief telephone/e-mail coaching support ( RCT 3 ) . The study assessed changes in weight , blood pressure , and physical activity from baseline to 6 , 12 , and 15 - 18 months . ( Study retention was 31 % at 12 months . ) Average and incremental cost-effectiveness and cost-offset analyses were conducted . RESULTS Participants experienced significant weight loss ( -4.0 % , -4.0 % , and -5.3 % , respectively , in each RCT group after 12 months and -3.5 % , -3.8 % , and -5.1 % , respectively , after 15 to 18 months ) , increased physical activity , and decreased blood pressure . Cost-effectiveness ratios were $ 900 to $ 1100/ quality -adjusted life year ( QALY ) for RCT 1 and RCT 2 and $ 1900/QALY for RCT 3 . The cost recovery period to the government was 3 years for RCTs 1 and 2 and 6 years for RCT 3 . CONCLUSION A relatively inexpensive cognitive-behavioral weight management intervention improved patient outcomes . Extrapolation of savings for the entire TRICARE population would significantly reduce direct medical costs BACKGROUND Type 2 diabetes affects approximately 8 percent of adults in the United States . Some risk factors -- elevated plasma glucose concentrations in the fasting state and after an oral glucose load , overweight , and a sedentary lifestyle -- are potentially reversible . We hypothesized that modifying these factors with a lifestyle-intervention program or the administration of metformin would prevent or delay the development of diabetes . METHODS We r and omly assigned 3234 nondiabetic persons with elevated fasting and post-load plasma glucose concentrations to placebo , metformin ( 850 mg twice daily ) , or a lifestyle-modification program with the goals of at least a 7 percent weight loss and at least 150 minutes of physical activity per week . The mean age of the participants was 51 years , and the mean body-mass index ( the weight in kilograms divided by the square of the height in meters ) was 34.0 ; 68 percent were women , and 45 percent were members of minority groups . RESULTS The average follow-up was 2.8 years . The incidence of diabetes was 11.0 , 7.8 , and 4.8 cases per 100 person-years in the placebo , metformin , and lifestyle groups , respectively . The lifestyle intervention reduced the incidence by 58 percent ( 95 percent confidence interval , 48 to 66 percent ) and metformin by 31 percent ( 95 percent confidence interval , 17 to 43 percent ) , as compared with placebo ; the lifestyle intervention was significantly more effective than metformin . To prevent one case of diabetes during a period of three years , 6.9 persons would have to participate in the lifestyle-intervention program , and 13.9 would have to receive metformin . CONCLUSIONS Lifestyle changes and treatment with metformin both reduced the incidence of diabetes in persons at high risk . The lifestyle intervention was more effective than metformin In order to evaluate the effectiveness of a cognitive behavioural group therapy programme for the treatment of obesity in clinical practice , 122 patients from 14 general practice s ( n = 70 ) were r and omised into either a treatment or a control arm with a ratio of 3 to 2 . The group treatment programme was also assessed in a clinical centre ( n = 52 ; University Hospital Basel ) . Before therapy , a clinical interview and a mental disorder examination were carried out on all patients . The instructors of the programme ( practitioners ; clinic physicians ) were trained during two afternoon meetings to supervise the group sessions . The treatment programme consisted of 16 group sessions of 90 min each , and contained psycho-educational elements concerning a balanced diet , instruction for the integration of more activity in everyday life ( lifestyle activity ) , problemsolving strategies , and the cognitive restructuring of dysfunctional cognition regarding the own body . All the patients who were treated in the various setting s demonstrated a benefit from therapy . Compared to the control groups which received usual medical care , they were able to reduce their starting weight by around 5 % ( p < 0.001 for the group treated by practitioners ) at the end of treatment and stabilise it until follow up after one year . In regard to psychological factors the treatment groups showed an increased sense of control over eating behaviour , and feelings of distractibility and hunger were reduced after treatment and at follow up ( p < 0.05 ) . All treatment groups showed statistically relevant increases in feelings of attractiveness regarding their body and shape ( p < 0.05 ) . These results support the effectiveness of the integrated cognitive behavioural treatment programme in clinical practice over a duration of 12 months Obesity is a chronic condition that is prevalent in black women . The Obesity Reduction Black Intervention Trial ( ORBIT ) was a r and omized controlled weight loss and weight-loss maintenance ( WLM ) trial . Participants ( N = 213 ) were r and omized to the intervention or control groups in August 2005 and September 2006 . Follow-up data were collected 6 and 18 months after r and omization . The main outcome was change in weight and BMI from baseline to 18 months . The mean weight at baseline was 104.9 kg , and the mean weight loss in the intervention group at 6 months was 3.0 kg and a gain of 0.2 kg in the control group ( mean difference between groups in weight change at 6 months , adjusting for baseline weight and cohort , -3.27 kg ; 95 % confidence interval ( CI ) , -4.50 to -2.05 kg ; P < 0.001 ) . Both groups gained weight between 6 and 18 months ( mean 1.0 kg in the intervention group and 0.1 kg in the control group ) . However , intervention participants lost significantly more weight than control participants during the 18-month intervention ( adjusted mean difference between groups at 18 months , -2.83 kg ; 95 % CI , -4.71 to -0.95 ; P = 0.003 ) . At 18 months , intervention participants were more likely than control participants to have lost at least 5 % of baseline weight ( 24 % vs. 12 % , P < 0.04 ) . Our results indicate that the ORBIT program did promote weight loss and weight-loss maintenance . However , the results also clearly illustrate there is more to learn about what will contribute to meaningful weight loss and maintenance in this population One hundred seventy-seven men and women who had participated in an 18-month trial of behavioral interventions involving food provision and financial incentives were examined 12 months later . Food provision , but not financial incentives , led to better weight loss than st and ard behavioral treatment during the 18-month trial , but over 12 additional months of no-treatment follow-up , all treated groups gained weight , maintained only slightly better weight losses than a no-treatment control group , and did not differ from each other . Weight loss success during both active treatment and maintenance was associated with increase in exercise , decrease in percentage of energy from fat , increase in nutrition knowledge , and decrease in perceived barriers to adherence . Obesity treatment research should focus on developing better ways to maintain changes in the diet and exercise behaviors needed for sustained weight loss BACKGROUND Previous studies demonstrated that intensive lifestyle modification can prevent type 2 diabetes mellitus among those with impaired glucose tolerance , but similar beneficial results have not been proved among those with impaired fasting glucose levels . We investigated the efficacy of lifestyle modification on type 2 diabetes incidence among those with impaired fasting glucose levels . METHODS The present study was an unmasked , multicenter , r and omized , controlled trial . A total of 641 overweight Japanese ( aged 30 - 60 years ) with impaired fasting glucose levels were recruited nationwide in Japan and r and omly assigned to a frequent intervention group ( n = 311 ) or a control group ( n = 330 ) . For 36 months after r and omization , the frequent intervention group received individual instructions and follow-up support for lifestyle modification from the medical staff 9 times . The control group received similar individual instructions 4 times at 12-month intervals during the same period . The primary outcome was type 2 diabetes incidence in annual 75-g oral glucose tolerance tests , diagnosed according to World Health Organization criteria . RESULTS There were no significant differences between the allocation groups in baseline characteristics and dropout rates . Estimated cumulative incidences of type 2 diabetes were 12.2 % in the frequent intervention group and 16.6 % in the control group . Overall , the adjusted hazard ratio in the frequent intervention group was 0.56 ( 95 % confidence interval , 0.36 - 0.87 ) . In the post hoc subgroup analyses , the hazard ratio reduced to 0.41 ( 95 % confidence interval , 0.24 - 0.69 ) among participants with impaired glucose tolerance at baseline , and to 0.24 ( 0.12 - 0.48 ) among those with baseline hemoglobin A(1c ) levels of 5.6 % or more ( the Japan Diabetes Society method ) . Such risk reduction was not observed among those with isolated impaired fasting glucose findings or baseline hemoglobin A(1c ) levels of less than 5.6 % . CONCLUSIONS Lifestyle modifications can prevent type 2 diabetes among overweight Japanese with impaired fasting glucose levels . In addition , identifying individuals with more deteriorated glycemic status by using 75-g oral glucose tolerance test findings or , especially , measurement of hemoglobin A(1c ) levels , could enhance the efficacy of lifestyle modifications . TRIAL REGISTRATION umin.ac.jp/ctr Identifier : UMIN000001959 |
14,004 | 21,520,208 | The use of IL-2Ra was also associated with a lower incidence of posttransplant diabetes mellitus , whereas the incidence of other adverse events was similar .
The use of IL-2Ra is associated with a lower incidence of acute rejection after transplantation . | UNLABELLED Interleukin 2 receptor antagonists ( IL-2Ra ) are frequently used as induction therapy in liver transplant recipients to decrease the risk of acute rejection while allowing the reduction of concomitant immunosuppression .
We conducted a systematic review of prospect i ve , controlled studies to test the hypothesis that the use of IL-2Ra is associated with a decrease in acute rejection and /or a decrease in the side effects of concomitant medication . | The glomerular filtration rate ( GFR ) is traditionally considered the best overall index of renal function in health and disease ( 1 ) . Because GFR is difficult to measure in clinical practice , most clinicians estimate the GFR from the serum creatinine concentration . However , the accuracy of this estimate is limited because the serum creatinine concentration is affected by factors other than creatinine filtration ( 2 , 3 ) . To circumvent these limitations , several formulas have been developed to estimate creatinine clearance from serum creatinine concentration , age , sex , and body size ( 4 - 12 ) . Despite more recent studies that have related serum creatinine concentration to GFR ( 13 - 24 ) , no formula is more widely used to predict creatinine clearance than that proposed by Cockcroft and Gault ( 4 ) . This formula is used to detect the onset of renal insufficiency , to adjust the dose of drugs excreted by the kidney , and to evaluate the effectiveness of therapy for progressive renal disease . More recently , it has been used to document eligibility for reimbursement from the Medicare End Stage Renal Disease Program ( 25 ) and for accrual of points for patients on the waiting list for cadaveric renal transplantation ( 26 ) . Major clinical decisions in general medicine , geriatrics , and oncology ( as well as nephrology ) are made by using the Cockcroft-Gault formula and other formulas to predict the level of renal function . Therefore , these formulas must predict GFR as accurately as possible . The Modification of Diet in Renal Disease ( MDRD ) Study , a multicenter , controlled trial , evaluated the effect of dietary protein restriction and strict blood pressure control on the progression of renal disease ( 27 - 30 ) . During the baseline period , GFR , serum creatinine , and several variables that affect the relation between them were measured in patients with chronic renal disease . The purpose of our study was to develop an equation from MDRD Study data that could improve the prediction of GFR from serum creatinine concentration . Methods Baseline Cohort and Measurement Methods in the Modification of Diet in Renal Disease Study The overall study design and methods of recruitment for the MDRD Study have been described elsewhere ( 31 , 32 ) . A total of 1785 patients entered the baseline period . Of these patients , 1628 ( 91 % ) also underwent measurement of GFR and the other variables described below ; these patients constitute the study group for these analyses . Glomerular filtration rate was measured as the renal clearance of 125I-iothalamate ( 33 , 34 ) . Creatinine clearance was computed from creatinine excretion in a 24-hour urine collection and a single measurement of serum creatinine . Serum and urine creatinine were measured by using a kinetic alkaline picrate assay with a normal range in serum of 62 to 124 mol/L ( 0.7 to 1.4 mg/dL ) ( 35 ) . Glomerular filtration rate and creatinine clearance were expressed per 1.73 m2 of body surface area by multiplying measured values by 1.73/body surface area ( 36 ) . The serum and urine specimens were also used for other measurements , including serum albumin ( bromcresol green method [ 35 ] ) , serum urea nitrogen ( urease method [ 35 ] ) , and urine urea nitrogen ( urease method [ 35 ] ) . Protein intake ( g/d ) was estimated as 6.25 [ UUN ( g/d ) + 0.031 ( g/kg per day ) SBW ( kg ) ] , where UUN is urine urea nitrogen , SBW is st and ard body weight , and 0.031 g/kg per day is a constant reflecting the rate of excretion of nitrogen in compounds other than urine urea ( 37 , 38 ) . The diagnosis of diabetes and the cause of renal disease were assigned on the basis of chart review at the clinical center ( 39 ) . Statistical Analysis Descriptive Statistics The relation of renal function measurements to other baseline characteristics was assessed by using contingency tables , t-tests , analysis of variance , and linear regression , as appropriate . Nonparametric tests ( Wilcoxon rank-sum tests and Kruskal-Wallis tests ) gave consistent results . A P value less than 0.01 was considered statistically significant . Multivariable Analysis of Glomerular Filtration Rate We used stepwise multiple regression to determine a set of variables that jointly predicted GFR . The stepwise regression models were developed by using a training sample consisting of a r and om sample of 1070 of the 1628 patients . We found that the variability of the difference between the observed and predicted GFR values was greater for higher GFR values . This increase was eliminated by performing multiple regressions on log-transformed data . To facilitate clinical interpretation , the results were re-expressed in terms of the original units . Consequently , the prediction equation is a multiplicative model ; regression coefficients refer to the change in geometric mean GFR associated with unit changes in the independent variable . Predicted GFR is expressed in mL/min per 1.73 m2 . The following variables were considered for possible inclusion in the regression model : weight , height , sex , ethnicity , age , diagnosis of diabetes , serum creatinine concentration , serum urea nitrogen level , serum albumin level , serum phosphorus level , serum calcium level , mean arterial pressure , urine creatinine level , urine urea nitrogen level , urine protein level , and urine phosphorus level . The cause of renal disease was not included because in clinical practice , the cause may be unknown or clinicians may not use the same classification method as the investigators in the MDRD Study . A P value less than 0.001 was used as the criterion for entry of a variable into the model . Because of the difficulty in collecting complete 24-hour urine sample s in clinical practice , an additional stepwise regression was performed to develop a prediction model that did not include urine biochemistry variables . Finally , because of the interest in developing a prediction equation to assess eligibility for Medicare reimbursement and listing for cadaveric renal transplantation , we repeated the analysis restricting the population to the subgroup of patients with higher serum creatinine concentrations ( > 221 mol/L [ 2.5 mg/dL ] ; n=509 in the training sample ) . Methods for Comparing Equations To Predict Glomerular Filtration Rate We first developed coefficients for each prediction equation ( including the selection of the predictor variables for the stepwise regressions ) using the data from the training sample to predict log GFR . Each prediction equation also included a multiplicative constant to account for any consistent bias in the application of that equation in the MDRD Study Group . This was particularly important for equations that are intended to estimate creatinine clearance , which is known to be higher than GFR . The regression coefficients determined in the training sample were then applied to obtain predicted GFRs in a separate validation sample consisting of the remaining 558 patients ( 172 patients with serum creatinine concentration>221 mol/L [ 2.5 mg/dL ] ) . These predicted GFR values were compared with the actual GFRs in the validation sample to evaluate the performance of each prediction equation . In this way , separate data sets were used to construct the equations and assess their accuracy after removal of systematic bias . For each equation , we computed overall R 2 ( percentage of variability in log GFR explained by the regression model ) and the 50th , 75th , and 90th percentiles of the distribution of the percentage absolute difference between measured and predicted GFRs in the validation sample . The 50th percentiles indicate the typical size of the errors in prediction of GFR , and the 75th and 90th percentiles assess the sizes of the larger errors that occurred for each model . Development of Final Prediction Equations To improve the accuracy of the final MDRD Study prediction equations , the regression coefficients derived from the training sample were up date d on the basis of data from all 1628 patients . As a result , the st and ard errors of the regression coefficients in the final MDRD Study prediction equations are slightly smaller than those derived from the training sample ; thus , the accuracy of the final prediction equations may be slightly better ( by about 0.1 % to 0.2 % ) than their accuracy as assessed in the validation sample . Results Demographic and Clinical Characteristics The mean age ( SD ) of the cohort was 50.6 12.7 years . Sixty percent of patients were male , 88 % were white , and 6 % were diabetic . Causes of renal disease were glomerular disease ( 32 % ) , polycystic kidney disease ( 22 % ) , tubulointerstitial disease ( 7 % ) , and other or unknown renal diseases ( 40 % ) . Mean protein intake was 0.99 0.24 g/kg of body weight per day and mean arterial pressure was 99.4 12.2 mm Hg . Mean weight was 79.6 16.8 kg , body surface area was 1.91 0.23 m2 , serum urea nitrogen concentration was 11.4 5.7 mmol/L [ 32 16 mg/dL ] , and serum albumin concentration was 40.0 4.0 g/L [ 4.0 0.4 g/dL ] , respectively . Glomerular Filtration Rate , Creatinine Clearance , and Serum Creatinine Concentration Renal function measurements for the study group and for various subgroups are shown in Table 1 . Mean GFR for the population was 0.38 mL s 2 m 2 ( 39.8 mL/min per 1.73 m2 ) , with lower values in patients with lower protein intake , white patients compared with black patients , and older patients ( 55 years ) compared with younger patients ( P<0.01 ) . The mean value of creatinine clearance was 0.81 mL s 2 m 2 ( 48.6 mL/min per 1.73 m2 ) and was lower in older patients and patients with lower protein intake ( P 0.01 ) . The mean serum creatinine concentration was 203 mol/L ( 2.3 mg/dL ) and was higher in men , patients with lower protein intake , and patients with higher mean arterial pressure ( P 0.01 ) . Figure 1 shows the well-known reciprocal relation of serum creatinine concentration to GFR for subgroups based on sex and ethnicity . At any given GFR , the serum creatinine concentration is significantly higher in men than in women and in black persons than in white persons ( P<0.001 ) . Table 1 . Association of Renal Basiliximab , a high-affinity chimeric monoclonal antibody , is effective in reducing acute rejection episodes in renal allograft recipients . We assessed the ability of this antibody to similarly improve the outcome in liver transplant recipients . Adult recipients of a primary cadaveric liver transplant were r and omized to treatment , stratified by hepatitis C virus ( HCV ) seropositivity . Patients were administered 40 mg of basiliximab ( n = 188 ) or placebo ( n = 193 ) as two 20-mg bolus injections days 0 and 4 , plus cyclosporine and steroids . Primary efficacy variables were biopsy-confirmed acute rejection and its composite end point , including death or graft loss , and were assessed at 6 and 12 months and by HCV cohort . Because of differential efficacy responses between HCV-positive and HCV-negative cohorts , an additional analysis incorporating HCV recurrence as a component of treatment failure , termed problem-free transplant , was introduced . Safety and tolerability were monitored over the 12 months of the study . All 381 patients were assessable , and no meaningful differences in background characteristics were apparent between treatment groups . Biopsy-confirmed acute rejection rates 6 months after transplantation were 35.1 % in the basiliximab group versus 43.5 % in the placebo group . For death , graft loss , or first biopsy-confirmed acute rejection , rates were 44.1 % versus 52.8 % , respectively . The reduction in rejection episodes was concentrated in the HCV-negative cohort ( 14.5 % relative to placebo ; P = .034 ) , with a much smaller difference ( 2.9 % ) in the HCV-positive cohort . For HCV-positive patients , problem-free transplant was shown at 12 months in 26.6 % of the basiliximab group versus 11.6 % in the placebo group ( P = .020 ) and for all patients at 12 months in 39.7 % of the basiliximab group versus 30.1 % in the placebo group ( P = .035 ) . The incidence of infection and other adverse events was similar across the two treatment groups . There were 56 deaths ( 25 deaths , basiliximab group ; 31 deaths , placebo group ) over the 12-month study . The intravenous bolus injection was well tolerated . Immunoprophylaxis with 40 mg of basiliximab , in combination with cyclosporine and steroids , reduces the incidence of acute rejection episodes with no clinical ly relevant safety or tolerability concerns . The influence of HCV recurrence on efficacy results can be accounted for in future trials by using the concept of problem-free transplant , incorporating recurrence as a component of treatment failure Background . Calcineurin inhibitor-induced renal dysfunction is a major problem in liver transplantation . Interleukin-2 receptor antagonist induction followed by delayed tacrolimus ( Tac ) administration may minimize the renal insult without compromising immunoprotection . Methods . This open , r and omized , multicenter trial evaluated the benefit of daclizumab induction with delayed Tac on renal function at 6 months ; an observational study was continued for 18 months . Liver transplant patients with a 12-hr serum creatinine ( SrC ) level less than 180 & mgr;mol/L received either delayed Tac with daclizumab induction ( n=98 ) or st and ard Tac ( n=101 ) both combined with mycophenolate mofetil and steroids . The primary endpoint was the incidence of SrC level more than 130 & mgr;mmol/L at 6 months . Results . The incidence was 22.4 % with delayed Tac and 29.7 % with st and ard Tac ( P = ns ) , which remained unchanged at 12 months ( 21.6 % and 23.9 % ) but increasing slightly at 24 months ( 29.0 % and 32.9 % ) , respectively . A post hoc analysis of renal function was done based on patients stratification by SrC at 12 hr ( ≤100&mgr;mol/L or > 100 & mgr;mol/L ) showing no difference in SrC values at 6 months regardless of the 12-hr values despite a trend toward better estimated glomerular filtration rate for patients with 12-hr value less than 100 & mgr;mol/L in the delayed Tac group . Biopsy-proven acute rejection was similar at 6 months ( 17.5 % and 18.75 % ) , 12 months ( 23.5 % and 23.8 % ) , and 24 months ( 24.5 % and 25.7 % ) , respectively . Patient and graft survival in both groups were comparable and good . Similar types and incidences of adverse events were reported in both groups at all time . Conclusions . Delay of Tac does not benefit renal function in liver transplant recipients with a good renal function at baseline We report a multicenter , prospect i ve , r and omized , open‐label trial investigating the effect of lower levels and delayed introduction of tacrolimus on renal function in liver transplant recipients . Adult patients with good renal function undergoing primary liver transplant were r and omized to either : group A ( st and ard‐dose tacrolimus [ target trough levels > 10 ng/mL ] and corticosteroids ; n = 183 ) ; group B ( mycophenolate mofetil [ MMF ] 2g/day , reduced‐dose tacrolimus [ target trough levels ≤8 ng/mL ] , and corticosteroids ; n = 170 ) ; group C ( daclizumab induction , MMF , reduced‐dose tacrolimus delayed until the fifth day posttransplant and corticosteroids , n = 172 ) . The primary endpoint was change from baseline in estimated glomerular filtration rate ( eGFR ) at 52 weeks . The eGFR decreased by 23.61 , 21.22 and 13.63 mL/min in groups A , B and C , respectively ( A vs C , p = 0.012 ; A vs B , p = 0.199 ) . Renal dialysis was required less frequently in group C versus group A ( 4.2 % vs. 9.9 % ; p = 0.037 ) . Biopsy‐proven acute rejection rates were 27.6 % , 29.2 % and 19.0 % , respectively . Patient and graft survival was similar . In conclusion , daclizumab induction , MMF , corticosteroids and delayed reduced‐dose tacrolimus was associated with less nephrotoxicity than therapy with st and ard‐dose tacrolimus and corticosteroids without compromising efficacy or tolerability This open , r and omized ( 1 : 1 ) , multicenter , 3-month study compared a dual tacrolimus plus steroids ( Tac / steroids ) regimen with a steroid-free immunosuppressive regimen of tacrolimus following daclizumab induction therapy ( Tac / Dac ) in adult liver transplant recipients . The full analysis set comprised 347 patients in the Tac / steroids group and 351 in the Tac / Dac group . Mean tacrolimus dose during month 3 was 0.11 mg/kg/day in both groups ; mean whole-blood trough levels during month 3 were 10.9 ng/mL ( Tac / steroids ) and 10.6 ng/mL ( Tac / Dac ) . The incidence of biopsy-confirmed acute rejection that required treatment was similar in both groups : 26.5 % in the Tac / steroids group and 25.4 % in the Tac / Dac group ( P = .727 ) . However , the incidence of biopsy-confirmed corticosteroid-resistant acute rejection was higher in the Tac / steroids group than in the Tac / Dac group ( 6.3 vs. 2.8 % ; P = .027 ) . Kaplan-Meier estimates of graft survival ( 92.2 vs. 90.5 % ) and patient survival ( 94.5 vs. 93.7 % ) were similar in both groups . While also the overall adverse event profiles were similar , the incidences of diabetes mellitus ( 15.3 vs. 5.7 % , respectively ; P < .001 ) and cytomegalovirus infection ( 11.5 vs. 5.1 % , respectively ; P = .002 ) were higher in the Tac / steroids group compared with the Tac / Dac group . Mean cholesterol levels increased by 16 % in the Tac / steroids group , but were unchanged in the Tac / Dac group during the study . In conclusion , tacrolimus monotherapy following daclizumab induction is an effective and safe regimen , with an advantage over concomitant steroid-maintenance therapy in terms of a lower incidence of diabetes and viral infection , and a lower incidence of steroid-resistant acute rejection BACKGROUND Monoclonal antibodies that block the high-affinity interleukin-2 receptor expressed on alloantigen-reactive T lymphocytes may cause selective immunosuppression . Daclizumab is a genetically engineered human IgG1 monoclonal antibody that binds specifically to the alpha chain of the interleukin-2 receptor and may thus reduce the risk of rejection after renal transplantation . METHODS We administered daclizumab ( 1.0 mg per kilogram of body weight ) or placebo intravenously before transplantation and once every other week afterward , for a total of five doses , to 260 patients receiving first cadaveric kidney grafts and immunosuppressive therapy with cyclosporine , azathioprine , and prednisone . The patients were followed at regular intervals for 12 months . The primary end point was the incidence of biopsy-confirmed acute rejection within six months after transplantation . RESULTS Of the 126 patients given daclizumab , 28 ( 22 percent ) had biopsy-confirmed episodes of acute rejection , as compared with 47 of the 134 patients ( 35 percent ) who received placebo ( P=0.03 ) . Graft survival at 12 months was 95 percent in the daclizumab-treated patients , as compared with 90 percent in the patients given placebo ( P=0.08 ) . The patients given daclizumab did not have any adverse reactions to the drug , and at six months , there were no significant differences between the two groups with respect to infectious complications or cancers . The serum half-life of daclizumab was 20 days , and its administration result ed in prolonged saturation of interleukin-2alpha receptors on circulating lymphocytes . CONCLUSIONS Daclizumab reduces the frequency of acute rejection in kidney-transplant recipients UNLABELLED Monoclonal antibodies against the interleukin 2 receptor have been developed in an effort to decrease rejection rates and spare calcineurin inhibitors when renal dysfunction occurs after transplant . While success has been reported in kidney transplantation , its effectiveness in liver transplantation is less clear . METHODS This prospect i ve nonr and omized study including adult patients was performed between October 2000 and April 2003 . Two groups of immunosuppressive regimens were compared : group A received 2 g of methylprednisolone intraoperatively followed by a rapid reduction with intention to withdraw by month 4 , continuing on Neoral monotherapy . Cellcept was also given for 2 months in the absence or for up to 4 months in the presence of rejection . Group B received the same immunosuppressive regimen but , in addition , daclizumab 1 to 1.5 mg/kg on day 1 and day 5 posttransplant . Rejection diagnosis is made on histology basis . Protocol biopsies were performed in all the patients on day 7 and if indicated by biochemistry thereafter . RESULTS Both groups were similar in terms of preoperative CHILD score , serum creatinine , incidence of status I , donor and recipient age and ischemia times . The mean follow-up time was 20 months for Group B ( n = 24 ) and 7 months for Group A ( n = 10 ) . The 1-month and 1-year rejection rates are 29.1 % and 41 % in Group A versus 20 % and 30 % in group B. Rejection severity was similar between both groups . One-year patient and graft survival rates were 96 % and 92 % in group A and 100 % for both in Group B. CONCLUSIONS In this series , daclizumab induction therapy seems to display a trend toward a lower rejection rate without increasing infectious complications nor affecting graft survival rates BACKGROUND Currently available immunosuppressive regimens for cadaver-kidney recipients are far from ideal because acute-rejection episodes occur in about 30 % to 50 % of these patients . In the phase III study described here we assessed the ability of basiliximab , a chimeric interleukin (IL)-2 receptor monoclonal antibody , to prevent acute-rejection episodes in renal allograft recipients . METHODS 380 adult recipients of a primary cadaveric kidney transplant were r and omly allocated , in this double-blind trial , to receive a 20 mg infusion of basiliximab on day 0 ( day of surgery ) and on day 4 , to provide IL-2-receptor suppression for 4 - 6 weeks ( n=193 ) , or to receive placebo ( n=187 ) . Both groups received baseline dual immunosuppressive therapy with cyclosporin and steroids throughout the study . The primary outcome measure was incidence of acute-rejection episodes during the 6 months after transplantation . Safety and tolerability were monitored over the 12 months of the study . FINDINGS 376 patients were eligible for intention-to-treat analysis ( basiliximab , n=190 ; placebo , n=186 ) . No significant differences in patient characteristics were apparent . The incidence of biopsy-confirmed acute rejection 6 months after transplantation was 51 ( 29.8 % ) of 171 in the basiliximab group compared with 73 ( 44.0 % ) of 166 in the placebo group ( 32 % reduction ; 14.2 % difference [ 95 % Kaplan-Meier CIs 3 % to 24 % ] , p=0.012 ) . The incidence of steroid-resistant first rejection episodes that required antibody therapy was significantly lower in the basiliximab group ( 10 % vs 23.1 % , 13.1 % difference [ 5.4 % to 20.8 % ] , p<0.001 ) . At weeks 2 and 4 post-transplantation , the mean daily dose of steroids was significantly higher in the placebo group ( p<0.001 with one-way analysis of variance ) . The incidence of graft loss at 12 months post-transplantation was 23 ( 12.1 % ) of 190 in the basiliximab group and 25 ( 13.4 % ) of 186 in the placebo group ( 1.3 % difference [ -5 % to 9 % ] , p=0.591 ) . The incidence of infection and other adverse events was similar in the two treatment groups . The acute tolerability of basiliximab was excellent , with no evidence of cytokine-release syndrome . 14 deaths ( basiliximab n=9 ; placebo n=5 ; -2.0 % difference [ -6 % to 2 % ] , p=0.293 ) occurred during the 12-month study and a further three deaths ( basiliximab n=1 ; placebo n=2 ) occurred within the 380-day cut-off period . One post-transplantation lymphoproliferative disorder was recorded in each group . INTERPRETATION Prophylaxis with 40 mg basiliximab reduces the incidence of acute rejection episodes significantly , with no clinical ly relevant safety or tolerability concerns Background . Basiliximab ( B ) , an anti-CD25 monoclonal antibody , may represent an alternative to steroids ( S ) in immunosuppression after liver transplantation ( LTx ) . The aim of this prospect i ve r and omized clinical trial was to compare B with S in a cyclosporin A (CsA)-based immunosuppression regimen in primary LTx . Methods . Forty-seven adult recipients of LTx were r and omly assigned to receive B or S. CsA was administered at the initial dose of 10 mg/kg/day and adjusted to the target C2 level of 800 to 1000 ng/mL by day 7 . Clinical ly suspected acute cellular rejection ( ACR ) was histologically confirmed . Endpoints include ACR , survival , and disease-free survival . Results . In group B ( 26 patients ) , there were seven biopsy-confirmed ACR with an ACR rate of 15.4 % ; in group S ( 21 patients ) , 8 ACR with an ACR rate of 28.6 % ( P = n.s . ) . Cumulative survival at 36 months after transplantation was 84.3 % for group B and 61.0 % for group S. In hepatitis C virus patients ( n=20 : 12 in group B , 8 in group S ) , the ACR rate was 25 % in group B and 50 % in group S. The incidence of infection and other adverse events was similar in the two treatment groups . Conclusions . B may represent a valid alternative to S in the induction of immunosuppression in LTx . Further studies of basiliximab in a large cohort are needed Background . Due to the known high recurrence rate of hepatitis C virus ( HCV ) among orthotopic liver transplant ( OLT ) recipients who receive tacrolimus+corticosteroid maintenance , use of steroid-free induction was considered . Methods . OLT recipients with HCV were r and omized to receive tacrolimus+daclizumab ( steroid-free ) vs. tacrolimus+corticosteroids during 1999–2001 and then tacrolimus+mycophenolate mofetil (MMF)+daclizumab ( steroid-free ) vs. tacrolimus+MMF+corticosteroids during 2002–2005 . Patients in the steroid-free arm of both periods received no steroids except for treating biopsy-proven rejection . Primary objective was to compare mean fibrosis stage at the 1-year protocol biopsy , between the steroid-free and corticosteroid arms , stratifying by period . Results . No noticeable differences in mean fibrosis stage between the two treatment arms , either averaging across periods ( P=0.99 ) or during either period ( P>0.35 ) were found . Occurrence of acute rejection during the first year was the only factor associated with a significantly increased fibrosis stage at 1 year ( P=0.0003 ) ; stage ≥2 was seen in 63 % ( 17 of 27 ) vs. 19 % ( 8 of 43 ) of those with vs. without rejection . In addition , MMF use was associated with significantly fewer patients experiencing acute rejection during the first 6 and 12 months posttransplant ( P=0.006 and 0.046 ) . Regarding steroid-related side effects , posttransplant diabetes mellitus occurred in 10 % vs. 45 % , and wound infection in 6 % vs. 31 % of steroid-free vs. corticosteroid patients ( P=0.003 and 0.01 ) . Conclusions . OLT recipients with HCV tolerated the steroid-free protocol with fewer side effects ; however , its use had no apparent impact on hepatic fibrosis progression . Occurrence of acute rejection was strongly associated with increased hepatic fibrosis at 1 year , and MMF use appears to have significantly reduced the rejection rate BACKGROUND In OLT induction therapy with interleukin-2-receptor antibodies is often applied as part of the st and ard immunosuppression protocol . It was the aim of this study to determine if Basilixirnab mduction therapy serves to reduce the incidence of acute rejection episodes and improves graft function and survival in the long term after OLT . MATERIAL / METHODS We prospect ively analysed 99 patients transplanted at our institution ( 1997 - 2000 ) . Patients were r and omised to two study groups : 51 patients received Basiliximab induction combined with Calcineurin inhibitors and steroids , 48 patients received CNIs and steroids only . Incidence and severity of rejection , graft and patient survival and intensity of long-term immunosuppression were analysed . Frequency of CNI and steroid induced adverse effects were recorded . RESULTS In our patient collective we could not detect a significant impact of Basiliximab induction therapy on the fre queny of acute or chronic rejection . CNI levels were almost identical in both groups ; graft and patient survival rates were not influenced by the application of induction therapy . CONCLUSIONS In our patient collective induction therapy does not have a general positive influence on the post transplant course . A slight improvement in long term renal function could be detected for Basiliximab treated patients Posttransplant chronic renal failure , secondary to calcineurin inhibitor agents , is emerging as a major problem in liver transplantation . We report a r and omized clinical trial comparing daclizumab , delayed low-dose tacrolimus ( target trough level 4 - 8 ng/mL , starting day 4 - 6 ) , Investigational Arm ( n = 72 ) , to st and ard tacrolimus induction/maintenance dosing , St and ard Arm ( n = 76 ) , with mycophenolate mofetil and tapering corticosteroids in both study arms . The end-points were renal function indicated by the Modification of Diet in Renal Disease ( MDRD ) . There was no significant difference in patient survival ( 86.6 % Investigational Arm vs. 92.9 % St and ard Arm ; P = 0.21 ) or acute rejection ( 23.2 % vs. 27.7 % , respectively ; P = 0.68 ) . Statistically significant differences in median glomerular filtration rate ( GFR ) were found in favor of the Investigational Arm . With the CG equation , the GFR at the end of the first week was 110.7 vs. 89.6 mL/min ( P = 0.019 ) without significant differences thereafter . With the MDRD , statistically significant differences extended to the first posttransplant month ( 86.8 vs. 70.1 mL/min/1.73 m(2 ) ; P < 0.001 ) with and was seen at month 6 ( 75.4 vs. 69.5 mL/min/1.73 m(2 ) ; P = 0.038 ) . In conclusion , delayed low-dose tacrolimus , in combination with daclizumab and mycophenolate mofetil , preserves early renal function post-liver transplantation without the cost of increased acute rejection This work is a 1-yr interim analysis of a prospect i ve , r and omized , multicenter trial evaluating the effect of corticosteroid-free immunosuppression on hepatitis C virus-positive ( HCV(+ ) ) liver transplant recipients following liver transplantation ( LT ) . Patients received tacrolimus and corticosteroids ( Arm 1 ; n = 80 ) ; tacrolimus , corticosteroids , and mycophenolate mofetil ( MMF ) ( Arm 2 ; n = 79 ) ; or daclizumab induction , tacrolimus , and MMF ( Arm 3 ; n = 153 ) . At 1 yr , 64.1 % , 63.4 % , and 69.4 % of patients achieved the composite primary endpoint of freedom from rejection , freedom from HCV recurrence , and freedom from treatment failure , respectively . Excellent patient and graft survival did not differ significantly among treatment arms . Freedom from HCV recurrence at 1 yr was 61.8 + /- 6.2 % , 60.1 + /- 6.1 % , and 67.0 + /- 4.3 % in Arms 1 , 2 , and 3 , respectively ( P = not significant ) . Freedom from rejection was significantly higher in Arm 3 compared to Arm 1 ( 93.0 + /- 2.2 % vs. 81.9 + /- 4.4 % ; P = 0.011 ) . Multivariate analysis identified acute rejection ( hazard ratio = 2.692 ; P = 0.001 ) and donor age ( hazard ratio = 1.015 ; P = 0.001 ) as significant risk factors for HCV recurrence . HCV recurrence was not influenced by recipient demographics , HCV genotype , or immunosuppression . In conclusion , these results suggest that a corticosteroid-free regimen of tacrolimus and MMF following daclizumab induction is safe and effective in HCV(+ ) liver transplant recipients OBJECTIVE To investigate the effects of tacrolimus-based immunosuppression regimens after orthotopic liver transplantation and search a reasonable regimen of combination therapy and suitable blood concentration of tacrolimus . METHODS Ninety-four adult recipients of cadaveric livers were r and omly divided into 3 groups to undergo different tacrolimus-based immunosuppression regimens : dual ( tacrolimus + glucocorticoid ) , triple [ tacrolimus + mycophenolate mofetil ( MMF ) + glucocorticoid ] ; quadruple [ tacrolimus + MMF + glucocorticoid in addition of induction treatment by daclizumab ] . The efficacy and safety of the 3 groups 6 months after the transplantation were compared . RESULTS The frequencies of acute rejection were 25.9 % , 11.1 % , and 7.5 % for the dual , triple , and quadruple therapy groups , that of the quadruple therapy group being significantly lower than that of the dual therapy group ( P = 0.038 ) . There were no significant differences in the rates Three months after transplantation , the levels of ALT and total cholesterol of the dual therapy groups were significantly higher than those of the quadruple therapy group ( P(ALT ) = 0.011 , P(Tch ) = 0.002 ) . Within the first month post-operatively the concentration of tacrolimus of the triple therapy group could be controlled at the level 8 ng x ml(-1)-13 ng x ml(-1 ) . CONCLUSIONS Quadruple tacrolimus-based immunosuppression regimen is the most effective and safest , followed by the triple therapy and dual therapy . Low-dose tacrolimus combination therapy provides an effective protection to the liver graft with mild drug toxicity to the patient The purpose of this study is to find out whether basiliximab administration will improve postoperative renal function by delaying the start of tacrolimus and decreasing of dosage requirement for tacrolimus in adult living donor liver transplantation ( LDLT ) . Forty-five adult LDLT recipients were enrolled in the study . The induction group ( n = 27 ) was given basiliximab 20 mg on days 0 and 4 ; tacrolimus administration was delayed until renal function improved . The control group ( n = 18 ) did not receive basiliximab ; tacrolimus was given on the first postoperative day . Trough levels of tacrolimus in the induction and control groups were aim ed to be maintained at 5 - 10 ng/ml and 10 - 15 ng/ml during the first week after transplant , respectively . The median follow-up was 22 months ( range 10 - 34 months ) . The preoperative conditions were poorer in the induction group ( Child C , 56 % vs. 33 % , P = 0.01 ; UNOS 2a , 15 % vs. 0 % , P = 0.02 ) . The intraoperative blood loss was also higher in the induction group than in the control group ( median 2,180 ml vs. 495 ml , P < 0.01 ) . The median delay in tacrolimus administration in the induction group was 36 hours ( range 24 - 108 hours ) . Serum creatinine levels at second and third postoperative months were significantly lower in the induction group . The creatinine clearance rate in the induction group was higher at the third month posttransplant ( median 72 vs. 57 ml/minute , P = 0.04 ) . The incidence of renal insufficiency was significantly lower in the induction group at the third month posttransplant ( 26 % vs. 67 % , P < 0.01 ) . Blood cholesterol level at the sixth month posttransplant was lower in the induction group ( median 152 vs. 196 mg/dl P = 0.03 ) . The incidences of acute cellular rejection , bacteremia , and cytomegalovirus ( CMV ) infection were similar in both groups . In conclusion , for pretransplant critical patients with more intraoperative blood loss , basiliximab induction could prevent early renal dysfunction by delaying the start of tacrolimus and reducing the dose requirement of tacrolimus without increasing graft rejection and infection . Furthermore , it also improved renal function as well as lowered cholesterol levels within 6 months after transplantation BACKGROUND Corticosteroids have long been a cornerstone of orthotopic liver transplant ( OLTx ) immunosuppression . Newer , more potent , agents have successfully allowed for more rapid tapering and discontinuation of corticosteroids in OLTx recipients . We hypothesize that corticosteroids can be safely avoided after the first postoperative day ( POD ) using these newer agents . METHODS Thirty adult OLTx recipients were prospect ively enrolled in a r and omized open-label , institutional review board-approved protocol . Fifteen patients ( group A ) received our st and ard regimen of tacrolimus , mycophenolate mofetil , and corticosteroids , and 15 patients ( group B ) received daclizumab , 2 mg/kg on POD 0 and 14 , with tacrolimus , mycophenolate mofetil , and corticosteroids on POD 0 and 1 and then discontinuation . In both groups , mycophenolate mofetil was tapered off between 3 and 4 months after OLTx . Bone mineral densitometry was performed at 1 , 3 , and 6 months after OLTx . Quantitative hepatitis C virus ( HCV ) polymerase chain reaction was obtained at days 0 , 7 , 14 , 21 , and 28 . Retransplant recipients , patients with autoimmune hepatitis , or status 1 or 2A patients were excluded . RESULTS Patient and graft survival rates were 93 % ( group A ) and 100 % ( group B ) with mean follow-up of 18 months . Patients in group B had more rejection diagnosed ( 25 % ) compared with group A ( 6.7 % ) . Yet , the incidence of biopsy-proven acute rejection requiring steroid therapy was 6.7 % in both groups . Hispanic race was common in groups A and B ( 87 % and 74 % ) . A total of six biopsies were performed in group B , with three patients having mild rejection responding to an increase in tacrolimus without the need for corticosteroids . One patient in group B was switched to cyclosporine for severe neurotoxicity and remains on monotherapy with normal graft function . No patient in either group developed a requirement for additional antihypertensive medication . Likewise , there were no patients with new-onset diabetes . The bone mineral densitometry was higher in group B at every time point but did not reach statistical significance . Serum cholesterol level was significantly ( P=0.03 ) lower in group B at 6 months after OLTx . Serum triglycerides were also lower , but the difference was not significant . Quantitative polymerase chain reaction for HCV-positive patients ( group A , n=7 ; group B , n=8 ) frequently increased after OLTx . There was no correlative decrease associated with daclizumab . At present , two patients in group A have documented HCV recurrence . CONCLUSION Corticosteroids can be safely avoided after POD 1 with the current regimen . With early follow-up , there is no difference in hypertension or diabetes or bone density . Lipid panels tended to be lower in patients who were not on corticosteroids . Longer term follow-up will be needed to demonstrate the potential advantage of corticosteroid avoidance in regard to hypertension , diabetes , and possibly HCV recurrence |
14,005 | 17,130,383 | The addition of brief psychotherapy did not substantially improve outcome , nor did increased numbers of sessions .
Cumulative meta- analysis showed that sufficient evidence had emerged by 2000 to demonstrate the statistically significant benefit of collaborative care .
CONCLUSIONS Collaborative care is more effective than st and ard care in improving depression outcomes in the short and longer terms . | BACKGROUND Depression is common in primary care but is suboptimally managed .
Collaborative care , that is , structured care involving a greater role of nonmedical specialists to augment primary care , has emerged as a potentially effective c and i date intervention to improve quality of primary care and patient outcomes . | BACKGROUND Quality improvement ( QI ) programs for depressed primary care patients can improve health outcomes for 6 to 28 months ; effects for longer than 28 months are unknown . OBJECTIVE To assess how QI for depression affects health outcomes , quality of care , and health outcome disparities at 57-month follow-up . DESIGN A group-level r and omized controlled trial . SETTING Forty-six primary care practice s in 6 managed care organizations . PATIENTS Of 1356 primary care patients who screened positive for depression and enrolled in the trial , 991 ( 73 % , including 451 Latinos and African Americans ) completed 57-month telephone follow-up . INTERVENTIONS Clinics were r and omly assigned to usual care or to 1 of 2 QI programs supporting QI teams , provider training , nurse assessment , and patient education , plus re sources to support medication management ( QI-meds ) or psychotherapy ( QI-therapy ) for 6 to 12 months . MAIN OUTCOME MEASURES Probable depressive disorder in the previous 6 months , mental health-related quality of life in the previous 30 days , primary care or mental health specialty visits , counseling or antidepressant medications in the previous 6 months , and unmet need , defined as depressed but not receiving appropriate care . RESULTS Combined QI-meds and QI-therapy , relative to usual care , reduced the percentage of participants with probable disorder at 5 years by 6.6 percentage points ( P = .04 ) . QI-therapy improved health outcomes and reduced unmet need for appropriate care among Latinos and African Americans combined but provided few long-term benefits among whites , reducing outcome disparities related to usual care ( P = .04 for QI-ethnicity interaction for probable depressive disorder ) . CONCLUSIONS Programs for QI for depressed primary care patients implemented by managed care practice s can improve health outcomes 5 years after implementation and reduce health outcome disparities by markedly improving health outcomes and unmet need for appropriate care among Latinos and African Americans relative to whites ; thus , equity was improved in the long run OBJECTIVE To determine whether a new model of primary care , Chronic Care Clinics , can improve outcomes of common geriatric syndromes ( urinary incontinence , falls , depressive symptoms , high risk medications , functional impairment ) in frail older adults . DESIGN R and omized controlled trial with 24 months of follow-up . Physician practice s were r and omized either to the Chronic Care Clinics intervention or to usual care . SETTING Nine primary care physician practice s that comprise an ambulatory clinic in a large staff-model HMO in western Washington State . PARTICIPANTS Those patients aged 65 and older in each practice with the highest risk for being hospitalized or experiencing functional decline . INTERVENTION Intervention practice s ( 5 physicians , 96 patients ) held half-day Chronic Care Clinics every 3 to 4 months . These clinics included an extended visit with the physician and nurse dedicated to planning chronic disease management ; a pharmacist visit that emphasized reduction of polypharmacy and high-risk medications ; and a patient self-management/support group . Control practice s ( 4 physicians , 73 patients ) received usual care . MEASUREMENTS Changes in self-reported urinary incontinence , frequency of falls , depressive symptoms , physical function , and satisfaction were analyzed using an intention-to-treat analysis adjusted for baseline differences , covariates , and practice -level variation . Prescriptions for high-risk medications and cost/utilization data obtained from administrative data were similarly analyzed . RESULTS After 24 months , no significant improvements in frequency of incontinence , proportion with falls , depression scores , physical function scores , or prescriptions for high risk medications were demonstrated . Costs of medical care including frequency of hospitalization , hospital days , emergency and ambulatory visits , and total costs of care were not significantly different between intervention and control groups . A higher proportion of intervention patients rated the overall quality of their medical care as excellent compared with control patients ( 40.0 % vs 25.3 % , P = .10 ) . CONCLUSIONS Although intervention patients expressed high levels of satisfaction with Chronic Care Clinics , improved outcomes for selected geriatric syndromes were not demonstrated . These findings suggest the need for developing greater system-wide support for managing geriatric syndromes in primary care and illustrate the challenges of conducting practice improvement research in a rapidly changing delivery system The object of the study was to evaluate outcomes of a r and omized clinical trial ( RCT ) of a pharmacist intervention for depressed patients in primary care ( PC ) . We report antidepressant ( AD ) use and depression severity outcomes at 6-months . The RCT was conducted between 1998 and 2000 in 9 eastern Massachusetts PC practice s. We studied 533 patients with major depression and /or dysthymia as determined by a screening test done at the time of a routine PC office visit . The majority of participants had recurrent depressive episodes ( 63.5 % with > /=4 lifetime episodes ) , and 49.5 % were taking AD medications at enrollment . Consultation in person and by telephone was performed by a clinical pharmacist who assisted the primary care practitioner ( PCP ) and patient in medication choice , dose , and regimen , in accordance with AHCPR depression guidelines . Six-month AD use rates for intervention patients exceeded controls ( 57.5 % vs. 46.2 % , P = .03 ) . Furthermore , the intervention was effective in improving AD use rates for patients not on ADs at enrollment ( 32.3 % vs. 10.9 % , P = .001 ) . The pharmacist intervention proved equally effective in subgroups traditionally considered difficult to treat : those with chronic depression and dysthymia . Patients taking ADs had better modified Beck Depression Inventory ( mBDI ) outcomes than patients not taking ADs , ( -6.3 points change , vs. -2.8 , P = .01 ) but the outcome differences between intervention and control patients were not statistically significant ( 17.7 BDI points vs. 19.4 BDI points , P = .16 ) . Pharmacists significantly improved rates of AD use in PC patients , especially for those not on ADs at enrollment , but outcome differences were too small to be statistically significant . Difficult-to-treat subgroups may benefit from pharmacists ' care BACKGROUND Depression in women is one of the commonest problems encountered in primary care . We aim ed to compare the effectiveness of a stepped-care programme with usual care in primary -care management of depression in low-income women in Santiago , Chile . METHODS In a r and omised controlled trial , in three primary -care clinics in Chile , 240 adult female primary -care patients with major depression were allocated stepped care or usual care . Stepped care was a 3-month , multicomponent intervention led by a non-medical health worker , which included a psychoeducational group intervention , structured and systematic follow-up , and drug treatment for patients with severe depression . Data were analysed on an intention-to-treat basis . The primary outcome measure was the Hamilton depression rating scale ( HDRS ) administered at baseline and at 3 and 6 months after r and omisation . FINDINGS About 90 % of r and omised patients completed outcome assessment s. There was a substantial between-group difference in all outcome measures in favour of the stepped-care programme . The adjusted difference in mean HDRS score between the groups was -8.89 ( 95 % CI -11.15 to -6.76 ; p<0.0001 ) . At 6-months ' follow-up , 70 % ( 60 - 79 ) of the stepped-care compared with 30 % ( 21 - 40 ) of the usual-care group had recovered ( HDRS score < 8) . INTERPRETATION Despite few re sources and marked deprivation , women with major depression responded well to a structured , stepped-care treatment programme , which is being introduced across Chile . Socially disadvantaged patients might gain the most from systematic improvements in treatment of depression BACKGROUND This study augments a r and omized controlled trial to analyze the cost-effectiveness of 2 st and ardized treatments for major depression relative to each other and to the " usual care " provided by primary care physicians . METHODS A r and omized controlled trial was conducted in which primary care patients meeting DSM-III-R criteria for current major depression were assigned to pharmacotherapy ( where nortriptyline hydrochloride was given ) or interpersonal psychotherapy provided in a st and ardized framework or a primary physician 's usual care . Two outcome measures , depression-free days and quality -adjusted days , were developed using information on depressive symptoms over time . The costs of care were calculated . Cost-effectiveness ratios comparing the incremental outcomes with the incremental costs for the different treatments were estimated . Sensitivity analyses were performed . RESULTS In terms of both economic costs and quality -of-life outcomes , patients assigned to the pharmacotherapy group did slightly better than those assigned to interpersonal psychotherapy . Both st and ardized therapies provided better outcomes than primary physician 's usual care , but each consumed more re sources . No meaningful cost-offsets were found . The incremental direct cost per additional depression-free day for pharmacotherapy relative to usual care ranges from $ 12.66 to $ 16.87 which translates to direct cost per quality -adjusted year gained from $ 11270 to $ 19510 . CONCLUSIONS St and ardized treatments for depression lead to better outcomes than usual care but also lead to higher costs . However , the estimates of the cost per quality -of-life year gained for st and ardized pharmacotherapy are comparable with those found for other treatments provided in routine practice Abstract Objectives : To evaluate the long term effect of ongoing intervention to improve treatment of depression in primary care . Design : R and omised controlled trial . Setting : Twelve primary care practice s across the United States . Participants : 211 adults beginning a new treatment episode for major depression ; 94 % of patients assigned to ongoing intervention participated . Intervention : Practice s assigned to ongoing intervention encouraged participating patients to engage in active treatment , using practice nurses to provide care management over 24 months . Main outcome measures : Patients ' report of remission and functioning . Results : Ongoing intervention significantly improved both symptoms and functioning at 24 months , increasing remission by 33 percentage points ( 95 % confidence interval 7 % to 46 % ) , improving emotional functioning by 24 points ( 11 to 38 ) and physical functioning by 17 points ( 6 to 28 ) . By 24 months , 74 % of patients in enhanced care reported remission , with emotional functioning exceeding 90 % of population norms and physical functioning approaching 75 % of population norms . Conclusions : Ongoing intervention increased remission rates and improved indicators of emotional and physical functioning . Studies are needed to compare the cost effectiveness of ongoing depression management with other chronic disease treatment routinely undertaken by primary care BACKGROUND This article addresses whether dissemination of short-term quality improvement ( QI ) interventions for depression to primary care practice s improves patients ' clinical outcomes and health-related quality of life ( HRQOL ) over 2 years , relative to usual care ( UC ) . METHODS The sample included 1299 patients with current depressive symptoms and 12-month , lifetime , or no depressive disorder from 46 primary care practice s in 6 managed care organizations . Clinics were r and omized to UC or 1 of 2 QI programs that included training local experts and nurse specialists to provide clinician and patient education , assessment , and treatment planning , plus either nurse care managers for medication follow-up ( QI-meds ) or access to trained psychotherapists ( QI-therapy ) . Outcomes were assessed every 6 months for 2 years . RESULTS For most outcomes , differences between intervention and UC patients were not sustained for the full 2 years . However , QI-therapy reduced overall poor outcomes compared with UC by about 8 percentage points throughout 2 years , and by 10 percentage points compared with QI-meds at 24 months . Both interventions improved patients ' clinical and role outcomes , relative to UC , over 12 months ( eg , a 10 - 11 and 6 - 7 percentage point difference in probable depression at 6 and 12 months , respectively ) . CONCLUSIONS While most outcome improvements were not sustained over the full 2 study years , findings suggest that flexible dissemination of short-term , QI programs in managed primary care can improve patient outcomes well after program termination . Models that support integrated psychotherapy and medication-based treatment strategies in primary care have the potential for relatively long-term patient benefits BACKGROUND The diagnosis and treatment of depression constitutes a significant component of a general practitioner 's workload . A pilot study has suggested that the practice nurse may have an important contribution to make in the care of patients with depression . AIM To evaluate an extended role for practice nurses in improving the outcome of depression through two specially- design ed interviews running in parallel . METHOD Two naturalistic , r and om allocation studies took place concurrently over four months . Study 1 evaluated the effectiveness of st and ardized psychiatric assessment by a practice nurse and feedback of information to the general practitioner ( GP ) . Study 2 evaluated the above assessment and feedback combined with nurse-assisted follow-up care . Twenty general practice s participating in the Medical Research Council General Practice Research Framework took part in the study . Subjects included general practice attenders identified as depressed by their GP . The main outcome measures were a change in Beck Depression Inventory ( BDI ) scores and in the proportion of patients fulfilling DSM-III criteria for major depression . RESULTS A total of 577 patients were recruited ; 516 [ 89 % ( 95 % CI = 86 - 92 % ) ] were rated as depressed on the BDI and 474 [ 82 % ( 95 % CI = 79 - 85 % ) ] met criteria for DSM-III major depression . Altogether , 524 ( 91 % ) patients completed follow-up at four months . All groups of patients showed improvement , but no difference in the rate of improvement was shown for the nurse intervention groups . BDI mean scores fell from 18.54 ( 95 % CI = 17.53 - 20.06 ) to 11.53 ( 95 % CI = 10.02 - 13.04 ) in Study 1 , and from 21.01 ( 95 % = CI 20.26 - 21.86 ) to 10.62 ( 95 % CI = 9.73 - 11.51 ) in Study 2 . The proportion of patients fulfilling criteria for DSM-III major depression in Study 1 fell from 80 % ( 95 % CI = 73 - 87 % ) to 30 % ( 95 % CI = 22 - 38 % ) , and in Study 2 from 80 % ( 95 % CI = 76 - 84 % ) to 27 % ( 95 % CI = 23 - 31 % ) . Prescription rates of antidepressant medication were higher than expected , ranging between 63 % and 76 % in the two studies . CONCLUSION There was an increase in the rate of antidepressant prescription , but no additional benefit could be adduced for patients who received a nurse intervention BACKGROUND Despite improvements in the accuracy of diagnosing depression and use of medications with fewer side effects , many patients treated with antidepressant medications by primary care physicians have persistent symptoms . METHODS A group of 228 patients recognized as depressed by their primary care physicians and given antidepressant medication who had either 4 or more persistent major depressive symptoms or a score of 1.5 or more on the Hopkins Symptom Checklist depression items at 6 to 8 weeks were r and omized to a collaborative care intervention ( n = 114 ) or usual care ( n = 114 ) by the primary care physician . Patients in the intervention group received enhanced education and increased frequency of visits by a psychiatrist working with the primary care physician to improve pharmacologic treatment . Follow-up assessment s were completed at 1 , 3 , and 6 months by a telephone survey team blinded to r and omization status . RESULTS Those in the intervention group had significantly greater adherence to adequate dosage of medication for 90 days or more and were more likely to rate the quality of care they received for depression as good to excellent compared with usual care controls . Intervention patients showed a significantly greater decrease compared with usual care controls in severity of depressive symptoms over time and were more likely to have fully recovered at 3 and 6 months . CONCLUSIONS A multifaceted program targeted to patients whose depressive symptoms persisted 6 to 8 weeks after initiation of antidepressant medication by their primary care physician was found to significantly improve adherence to antidepressants , satisfaction with care , and depressive outcomes compared with usual care Abstract Objective To determine the long term effectiveness of collaborative care management for depression in late life . Design Two arm , r and omised , clinical trial ; intervention one year and follow-up two years . Setting 18 primary care clinics in eight US healthcare organisations . Patients 1801 primary care patients aged 60 and older with major depression , dysthymia , or both . Intervention Patients were r and omly assigned to a 12 month collaborative care intervention ( IMPACT ) or usual care for depression . Teams including a depression care manager , primary care doctor , and psychiatrist offered education , behavioural activation , antidepressants , a brief , behaviour based psychotherapy ( problem solving treatment ) , and relapse prevention geared to each patient 's needs and preferences . Main outcome measures Interviewers , blinded to treatment assignment , conducted interviews in person at baseline and by telephone at each subsequent follow up . They measured depression ( SCL-20 ) , overall functional impairment and quality of life ( SF-12 ) , physical functioning ( PCS-12 ) , depression treatment , and satisfaction with care . Results IMPACT patients fared significantly ( P < 0.05 ) better than controls regarding continuation of antidepressant treatment , depressive symptoms , remission of depression , physical functioning , quality of life , self efficacy , and satisfaction with care at 18 and 24 months . One year after IMPACT re sources were withdrawn , a significant difference in SCL-20 scores ( 0.23 , P < 0.0001 ) favouring IMPACT patients remained . Conclusions Tailored collaborative care actively engages older adults in treatment for depression and delivers substantial and persistent long term benefits . Benefits include less depression , better physical functioning , and an enhanced quality of life . The IMPACT model may show the way to less depression and healthier lives for older adults Abstract OBJECTIVE : A previous study described the effect of a collaborative care intervention on improving adherence to antidepressant medications and depressive and functional outcomes of patients with persistent depressive symptoms 8 weeks after the primary care physician initiated treatment . This paper examined the 28-month effect of this intervention on adherence , depressive symptoms , functioning , and health care costs . DESIGN : R and omized trial of stepped collaborative care intervention versus usual care . SETTING : HMO in Seattle , Wash. PATIENTS : Patients with major depression were stratified into severe and moderate depression groups prior to r and omization . INTERVENTIONS : A multifaceted intervention targeting patient , physician , and process of care , using collaborative management by a psychiatrist and a primary care physician . MEASURES AND MAIN RESULTS : The collaborative care intervention was associated with continued improvement in depressive symptoms at 28 months in patients in the moderate-severity group ( F1,87=8.65 ; P=.004 ) , but not in patients in the high-severity group ( F1,51=0.02 ; P=.88 ) Improvements in the intervention group in antidepressant adherence were found to occur for the first 6 months ( χ2(1)=8.23 ; P<.01 ) and second 6-month period ( χ2(1)=5.98 ; P<.05 ) after r and omization in the high-severity group and for 6 months after r and omization in the moderate-severity group(χ2(1)=6.10 ; P<.05 ) . There were no significant differences in total ambulatory costs between intervention and control patients over the 28-month period ( F1,180=0.77 ; P=.40 ) . CONCLUSIONS : A collaborative care intervention was associated with sustained improvement in depressive outcomes without additional health care costs in approximately two thirds of primary care patients with persistent depressive symptoms Objectives The purpose of this study was to explore the efficacy in a primary care setting of a telephone-based disease management program for the acute management of depression and /or at-risk drinking . Material s and Methods Veterans ( N = 97 ) with depression and /or at-risk drinking were identified by systematic screening and assessment . Eligible subjects received either telephone disease management ( TDM ) program or usual care based on r and om assignment of their clinician . The TDM program consisted of regular contacts with each subject by a behavioral health specialist ( BHS ) to assist in assessment , education , support , and treatment planning . Symptomatic outcomes were assessed at 4 months . Results Overall response rates favored those assigned to TDM compared with those assigned to usual care ( 39.1 % responded vs. 17.6 % , p = 0.022 ) . Response rates within the separate diagnostic groups also favored TDM , but this was only significant for depressive disorders . Conclusions Although the sample size was modest and the sample was limited to veterans , findings strongly suggest that a telephone-based disease management program can improve outcomes for patients with a behavioral health problem . Findings also suggest that a health specialist can focus and manage patients with different diagnoses , thus exp and ing the role beyond just depression care . TDM may be a viable , low-cost , model for primary care clinicians to deliver manual guideline -adherent behavioral health care , especially in a VA clinical setting Most depressed patients are seen and treated exclusively by primary care clinicians . However , primary care patients with depression are often not adequately treated . The aims of this pilot study were to measure the impact of a telephone disease management program on patient outcome and clinician adherence to practice guidelines , measure the relationship of clinician adherence to patient outcome , and explore the measurement of patient adherence to clinician recommendations and its impact on patient outcomes . Thirty-five primary care practice s in the University of Pennsylvania Health System were r and omized to telephone disease management ( TDM ) or " usual care " ( UC ) . All patients received a baseline and a 16-week follow-up clinical evaluation performed over the telephone . Those from TDM practice s also received follow-up contact at least every 3 weeks , with formal evaluations at weeks 6 and 12 . These interval contacts were design ed to facilitate patient and clinician adherence to a treatment algorithm based on the Agency for Health Research and Quality ( AHRQ ) practice guidelines . Depressive symptoms evaluated with the Community Epidemiologic Survey of Depression ( CES-D ) scale as well as guideline adherence were the primary outcome measures . Sixty-one patients were enrolled in this pilot project . The overall effect for CES-D scores over time was significant , ( P < .001 ) , indicating that those participating in the trial ( both TDM and UC groups ) showed significant improvement . The interaction between intervention condition and time was also significant ( P < .05 ) , indicating that TDM patients improved significantly more over time than did UC patients . A greater proportion of TDM patients had CES-D scores < 16 by Week 16 ( 66.7 versus 33.3 % ; chi(2 ) , P < .05 ) . The improvement in depression outcome for the TDM group was related to its impact on improving clinician adherence to depression treatment algorithms . The TDM pilot did not show a statistically significant effect on improving patient adherence to clinician recommendations , however . This preliminary data suggests that TDM for depression improves both clinician guideline adherence and patient outcomes in the acute phase of depression . The effect on patient outcome is at least partially explained by the effect of TDM on clinician adherence to depression treatment algorithms CONTEXT Suicide rates are highest in late life ; the majority of older adults who die by suicide have seen a primary care physician in preceding months . Depression is the strongest risk factor for late-life suicide and for suicide 's precursor , suicidal ideation . OBJECTIVE To determine the effect of a primary care intervention on suicidal ideation and depression in older patients . DESIGN AND SETTING R and omized controlled trial known as PROSPECT ( Prevention of Suicide in Primary Care Elderly : Collaborative Trial ) with patient recruitment from 20 primary care practice s in New York City , Philadelphia , and Pittsburgh regions , May 1999 through August 2001 . PARTICIPANTS Two-stage , age-stratified ( 60 - 74 , > or = 75 years ) depression screening of r and omly sample d patients ; enrollment included patients who screened positive and a r and om sample of screened negative patients . This analysis included patients with a depression diagnosis ( N = 598 ) . INTERVENTION Treatment guidelines tailored for the elderly with care management compared with usual care . MAIN OUTCOME MEASURES Assessment of suicidal ideation and depression severity at baseline , 4 months , 8 months , and 12 months . RESULTS Rates of suicidal ideation declined faster ( P = .01 ) in intervention patients compared with usual care patients ; at 4 months , in the intervention group , raw rates of suicidal ideation declined 12.9 % points ( 29.4 % to 16.5 % ) compared with 3.0 % points ( 20.1 % to 17.1 % in usual care [ P = .01 ] ) . Among patients reporting suicidal ideation , resolution of ideation was faster among intervention patients ( P = .03 ) ; differences peaked at 8 months ( 70.7 % vs 43.9 % resolution ; P = .005 ) . Intervention patients had a more favorable course of depression in both degree and speed of symptom reduction ; group difference peaked at 4 months . The effects on depression were not significant among patients with minor depression unless suicidal ideation was present . CONCLUSIONS Evidence of the intervention 's effectiveness in community-based primary care with a heterogeneous sample of depressed patients introduces new challenges related to its sustainability and dissemination . The intervention 's effectiveness in reducing suicidal ideation , regardless of depression severity , reinforces its role as a prevention strategy to reduce risk factors for suicide in late life BACKGROUND This research study evaluates the effectiveness of a multifaceted intervention program to improve the management of depression in primary care . METHODS One hundred fifty-three primary care patients with current depression were entered into a r and omized controlled trial . Intervention patients received a structured depression treatment program in the primary care setting that included both behavioral treatment to increase use of adaptive coping strategies and counseling to improve medication adherence . Control patients received " usual " care by their primary care physicians . Outcome measures included adherence to antidepressant medication , satisfaction with care of depression and with antidepressant treatment , and reduction of depressive symptoms over time . RESULTS At 4-month follow-up , significantly more intervention patients with major and minor depression than usual care patients adhered to antidepressant medication and rated the quality of care they received for depression as good to excellent . Intervention patients with major depression demonstrated a significantly greater decrease in depression severity over time compared with usual care patients on all 4 outcome analyses . Intervention patients with minor depression were found to have a significant decrease over time in depression severity on only 1 of 4 study outcome analyses compared with usual care patients . CONCLUSION A multifaceted primary care intervention improved adherence to antidepressant regimens and satisfaction with care in patients with major and minor depression . The intervention consistently result ed in more favorable depression outcomes among patients with major depression , while outcome effects were ambiguous among patients with minor depression OBJECTIVE The authors ' goal was to determine whether improved outcomes from enhanced acute-phase ( 3-month ) treatment for depression in primary care persisted . METHOD They conducted a 19-month follow-up assessment of 156 patients with major depression in the Collaborative Care intervention trials , which had found greater improvements in treatment adherence and depressive symptoms at 4 and 7 months for patients given enhanced acute-phase treatment than for patients given routine treatment in a primary care setting . Sixty-three of the 116 patients who completed the follow-up assessment had received enhanced treatment , and 53 had received routine treatment in primary care . The Inventory for Depressive Symptomatology and the Hopkins Symptom Checklist were used to measure depressive symptoms . Automated pharmacy data and self-reports were used to assess adherence to and adequacy of pharmacotherapy . RESULTS At 19 months , the patients who had received enhanced acute-phase treatment did not differ from those who had received routine primary care treatment in clinical outcomes or quality of pharmacotherapy . CONCLUSIONS Even though enhanced acute-phase treatment of depression in primary care result ed in better treatment adherence and better clinical outcomes at 4 and 7 months , these improvements failed to persist over the following year . Continued enhancement of depression treatment may be needed to ensure better long-term results Background .Late life depression can be successfully treated with antidepressant medications or psychotherapy , but few depressed older adults receive effective treatment . Research Design . A r and omized controlled trial of a disease management program for late life depression . Subjects . Approximately 1,750 older adults with major depression or dysthymia are recruited from seven national study sites . Intervention . Half of the subjects are r and omly assigned to a collaborative care program where a depression clinical specialist supervised by a psychiatrist and a primary care expert supports the patient ’s regular primary care provider to treat depression . Intervention services are provided for 12 months using antidepressant medications and Problem Solving Treatment in Primary Care according to a stepped care protocol that varies intervention intensity according to clinical needs . The other half of the subjects are assigned to care as usual . Evaluation . Subjects are independently assessed at baseline , 3 months , 6 months , 12 months , 18 months , and 24 months . The evaluation assesses the incremental cost-effectiveness of the intervention compared with care as usual . Specific outcomes examined include care for depression , depressive symptoms , health-related quality of life , satisfaction with depression care , health care costs , patient time costs , market and nonmarket productivity , and household income . Conclusions .The study blends methods from health services and clinical research in an effort to protect internal validity while maximizing the generalizability of results to diverse health care systems . We hope that this study will show the cost-effectiveness of a new model of care for late life depression that can be applied in a range of primary care setting PURPOSE The impact of pharmacist interventions on the care and outcomes of patients with depression in a primary care setting was evaluated . METHODS Patients diagnosed with a new episode of depression and started on anti-depressant medications were r and omized to enhanced care ( EC ) or usual care ( UC ) for one year . EC consisted of a pharmacist collaborating with primary care providers to facilitate patient education , the initiation and adjustment of antidepressant dosages , the monitoring of patient adherence to the regimen , the management of adverse reactions , and the prevention of relapse . The patients in the UC group served as controls . Outcomes were measured by the Hopkins Symptom Checklist , Diagnostic and Statistical Manual of Mental Disorders , Fourth Edition , criteria for major depression , health-related quality of life , medication adherence , patient satisfaction , and use of depression-related health care services . An intent-to-treat analysis was used . RESULTS Seventy-four patients were r and omized to EC or UC . At baseline , the EC group included more patients diagnosed with major depression than did the UC group ( p = 0.04 ) . All analyses were adjusted for this difference . In both groups , mean scores significantly improved from baseline for symptoms of depression and quality of life at three months and were maintained for one year . There were no statistically significant differences between treatment groups in depression symptoms , quality of life , medication adherence , provider visits , or patient satisfaction . CONCLUSION Frequent telephone contacts and interventions by pharmacists and UC in a primary care setting result ed in similar rates of adherence to antidepressant regimens and improvements in the outcomes of depression at one year Objective : To examine the effectiveness of integrating generalist and specialist care for veterans with depression . Method : We conducted a r and omized trial of patients screening positive for depression at two Veterans Affairs Medical Center general medicine clinic firms . Control firm physicians were notified prior to the encounter when eligible patients had PRIME-MD depression diagnoses . In the intervention firm , a mental health clinical nurse specialist ( CNS ) was to : design a treatment plan ; implement that plan with the primary care physician ; and monitor patients via telephone or visits at two weeks , one month and two months . Primary outcomes ( depressive symptoms , patient satisfaction with health care ) were collected at 3 and 12 months . Results : Of 268 r and omized patients , 246 ( 92 % ) and 222 ( 83 % ) completed 3- and 12-month follow-up interviews . There were no between-group differences in depressive symptoms or satisfaction at 3 or 12 months . The intervention group had greater chart documentation of depression at baseline ( 63 % versus 33 % , p = 0.003 ) and a higher referral rate to mental health services at 3 months ( 27 % versus 9 % , p = 0.019 ) . There was no difference in the rate of new prescriptions for , or adequate dosing of , anti-depressant medications . In 40 % of patients , CNSs disagreed with the PRIME-MD depression diagnosis , and their rates of watchful waiting were correspondingly high . Conclusions : Implementing an integrated care model did not occur as intended . Experienced CNSs often did not see the need for treatment in many primary care patients identified by the PRIME-MD . Integrating integrated care models in actual practice may prove challenging Abstract OBJECTIVE : To determine the effectiveness of screening and treatment for depression among ambulatory indigent patients visiting resident physicians . DESIGN : Two-group r and omized trial ( N=33 intervention , N=28 usual care ) with baseline , 6-month , and 12-month outcome measurements . SETTING : Internal Medicine Residency Clinic . PATIENTS : Clinic patients over 18 years of age who screened positive for depression on the PRIME-MD during a visit to their resident physician . Patients were not receiving treatment nor seeking care for any emotional problems . All patients were either enrolled in Medicaid or had income below the poverty line . INTERVENTION : Resident physicians were educated to follow AHCPR ( AHRQ ; Agency for Healthcare Research and Quality ) guidelines for diagnosis and treatment of depression in a primary care setting . For the intervention group patients , a screening nurse advised residents regarding the positive screen , h and ed them a st and ardized protocol outline , and attempted to arrange behavioral care . The patients in the usual care group were provided the results of the screen by the screening nurse before their visit with the resident , and advised to seek care for their symptoms . MAIN RESULTS : Results for the primary outcome of depression symptoms measured with the Beck Depression Inventory ( BDI ) demonstrated that intervention was successful in reducing symptoms relative to usual care ( difference=−4.9 BDI points , P=.05 , 95 % confidence interval [ CI ] , −9.8 to −0.005 effect size=−0.41 ) . During the 12-month follow-up , 70 % of intervention patients were treated for depression ( of these , 91 % with antidepressants ) , while 15 % of usual care patients were treated with antidepressants for depression . Another 18 % of the usual care group had depression noted , but no treatment was identified . BDI differences between intervention and control groups were similar at the 6- and 12-month measures . Quality of life and costs were also measured , but differences between the groups were not significant in this regard . CONCLUSION : Screening and treatment for depression by resident physicians was successful in reducing symptoms relative to usual care in an indigent population . Almost twice as many intervention patients as usual care controls demonstrated a substantial reduction ( 10 BDI points ) in symptoms related to depression OBJECTIVE : To determine the effect of case-finding for depression on frequency of depression diagnoses , prescriptions for antidepressant medications , prevalence of depression , and health care utilization during 2 years of follow-up in elderly primary care patients . DESIGN : R and omized controlled trial . SETTING : Thirteen primary care medical clinics at the Kaiser Permanente Medical Center , an HMO in Oakl and , Calif , were r and omly assigned to intervention conditions ( 7 clinics ) or control conditions ( 6 clinics ) . PARTICIPANTS : A total of 2,346 patients aged 65 years or older who were attending appointments at these clinics and completed the 15-item Geriatric Depression Scale ( GDS ) . GDS scores of 6 or more were considered suggestive of depression . INTERVENTIONS : Primary care physicians in the intervention clinics were notified of their patients ’ GDS scores . We suggested that participants with severe depressive symptoms ( GDS score ≥ 11 ) be referred to the Psychiatry Department and participants with mild to moderate depressive symptoms ( GDS score of 6–10 ) be evaluated and treated by the primary care physician . Intervention group participants with GDS scores suggestive of depression were also offered a series of organized educational group sessions on coping with depression led by a psychiatric nurse . Primary care physicians in the control clinics were not notified of their patients ’ GDS scores or advised of the availability of the patient education program ( usual care ) . Participants were followed for 2 years . MEASUREMENTS AND MAIN RESULTS : Physician diagnosis of depression , prescriptions for antidepressant medications , prevalence of depression as measured by the GDS at 2-year follow-up , and health care utilization were determined . A total of 331 participants ( 14 % ) had GDS scores suggestive of depression ( GDS ≥ 6 ) at baseline , including 162 in the intervention group and 169 in the control group . During the 2-year follow-up period , 56 ( 35 % ) of the intervention participants and 58 ( 34 % ) of the control participants received a physician diagnosis of depression ( odds ratio [ OR ] , 1.0 ; 95 % confidence interval [ CI ] , 0.6 to 1.6 ; P=.96 ) . Prescriptions for antidepressants were received by 59 ( 36 % ) of the intervention participants and 72 ( 43 % ) of the control participants ( OR , 0.8 ; 95 % CI , 0.5 to 1.2 ; P=.3 ) . Two-year follow-up GDS scores were available for 206 participants ( 69 % of survivors ) : at that time , 41 ( 42 % ) of the 97 intervention participants and 54 ( 50 % ) of the 109 control participants had GDS scores suggestive of depression ( OR , 0.7 ; 95 % CI , 0.4 to 1.3 ; P=.3 ) . Comparing participants in the intervention and control groups , there were no significant differences in mean GDS change scores ( −2.4±SD 3.7 vs −2.1 SD±3.6 ; P=.5 ) at the 2-year follow-up , nor were there significant differences in mean number of clinic visits ( 1.8±SD 3.1 vs 1.6±SD 2.8 ; P=.5 ) or mean number of hospitalizations ( 1.1±SD 1.6 vs 1.0±SD 1.4 ; P=.8 ) during the 2-year period . In participants with initial GDS scores > 11 , there was a mean change in GDS score of −5.6±SD 3.9 for intervention participants ( n=13 ) and −3.4±SD 4.5 for control participants ( n=21 ) . Adjusting for differences in baseline characteristics between groups did not affect results . CONCLUSIONS : We were unable to demonstrate any benefit from case-finding for depression during 2 years of follow-up in elderly primary care patients . Studies are needed to determine whether case-finding combined with more intensive patient education and follow-up will improve outcomes of primary care patients with depression BACKGROUND High utilizers of nonpsychiatric health care services have disproportionally high rates of undiagnosed or undertreated depression . OBJECTIVE To determine the impact of offering a systematic primary care-based depression treatment program to depressed " high utilizers " not in active treatment . DESIGN R and omized clinical trial . SETTING One hundred sixty-three primary care practice s in 3 health maintenance organizations located in different geographic regions of the United States . PATIENTS A group of 1465 health maintenance organization members were identified as depressed high utilizers using a 2-stage telephone screening process . Eligibility criteria were met by 410 patients and 407 agreed to enroll : 218 in the depression management program ( DMP ) practice s and 189 in the usual care ( UC ) group . INTERVENTION The DMP included patient education material s , physician education programs , telephone-based treatment coordination , and antidepressant pharmacotherapy initiated and managed by patients ' primary care physicians . MAIN OUTCOME MEASURES Depression severity was measured using the Hamilton Depression Rating Scale ( Ham-D ) and functional status using the Medical Outcomes Study 20-item short form ( SF-20 ) subscales . Outpatient visit and hospitalization rates were measured using the health plan 's encounter data . RESULTS Based on an intent-to-treat analysis , at least 3 antidepressant prescriptions were filled in the first 6 months by 151 ( 69.3 % ) of 218 of DMP patients vs 35 ( 18.5 % ) of 189 in UC ( P < .001 ) . Improvements in Ham-D scores were significantly greater in the intervention group at 6 weeks ( P = .04 ) , 3 months ( P = .02 ) , 6 months ( P < .001 ) , and 12 months ( P < .001 ) . At 12 months , DMP intervention patients were more improved than UC patients on the mental health , social functioning , and general health perceptions scales of the SF-20 ( P < .05 for all ) . CONCLUSION In depressed high utilizers not already in active treatment , a systematic primary care-based treatment program can substantially increase adequate antidepressant treatment , decrease depression severity , and improve general health status compared with usual care Abstract OBJECTIVE : To determine whether redefining primary care team roles would improve outcomes for patients beginning a new treatment episode for major depression . DESIGN : Following stratification , 6 of 12 practice s were r and omly assigned to the intervention condition . Intervention effectiveness was evaluated by patient reports of 6-month change in 100-point depression symptom and functional status scales . SETTING : Twelve community primary care practice s across the country employing no onsite mental health professional . PATIENTS : Using two-stage screening , practice s enrolled 479 depressed adult patients ( 73.4 % of those eligible ) ; 90.2 % completed six-month follow-up . INTERVENTION : Two primary care physicians , one nurse , and one administrative staff member in each intervention practice received brief training to improve the detection and management of major depression . MAIN RESULTS : In patients beginning a new treatment episode , the intervention improved depression symptoms by 8.2 points ( 95 % confidence interval [ CI ] , 0.2 to 16.1 ; P=.04 ) . Within this group , the intervention improved depression symptoms by 16.2 points ( 95 % CI , 4.5 to 27.9 ; P=.007 ) , physical role functioning by 14.1 points ( 95 % CI , 1.1 to 29.2 ; P=.07 ) , and satisfaction with care ( P=.02 ) for patients who reported antidepressant medication was an acceptable treatment at baseline . Patients already in treatment at enrollment did not benefit from the intervention . CONCLUSIONS : In practice s without onsite mental health professionals , brief interventions training primary care teams to assume redefined roles can significantly improve depression outcomes in patients beginning a new treatment episode . Such interventions should target patients who report that antidepressant medication is an acceptable treatment for their condition . More research is needed to determine how primary care teams can best sustain these redefined roles over time BACKGROUND There is a high prevalence of depression in patients with diabetes mellitus . Depression has been shown to be associated with poor self-management ( adherence to diet , exercise , checking blood glucose levels ) and high hemoglobin A1c ( HbA1c ) levels in patients with diabetes . OBJECTIVE To determine whether enhancing quality of care for depression improves both depression and diabetes outcomes in patients with depression and diabetes . DESIGN R and omized controlled trial with recruitment from March 1 , 2001 , to May 31 , 2002 . SETTING Nine primary care clinics from a large health maintenance organization . PARTICIPANTS A total of 329 patients with diabetes mellitus and comorbid major depression and /or dysthymia . Intervention Patients were r and omly assigned to the Pathways case management intervention ( n = 164 ) or usual care ( n = 165 ) . The intervention provided enhanced education and support of antidepressant medication treatment prescribed by the primary care physician or problem-solving therapy delivered in primary care . MAIN OUTCOME MEASURES Independent blinded assessment s at baseline and 3 , 6 , and 12 months of depression ( Hopkins Symptom Checklist 90 ) , global improvement , and satisfaction with care . Automated clinical data were used to evaluate adherence to antidepressant regimens , percentage receiving specialty mental health visits , and HbA1c levels . RESULTS When compared with usual care patients , intervention patients showed greater improvement in adequacy of dosage of antidepressant medication treatment in the first 6-month period ( odds ratio [ OR ] , 4.15 ; 95 % confidence interval [ CI ] , 2.28 - 7.55 ) and the second 6-month period ( OR , 2.90 ; 95 % CI , 1.69 - 4.98 ) , less depression severity over time ( z = 2.84 , P = .004 ) , a higher rating of patient-rated global improvement at 6 months ( intervention 69.4 % vs usual care 39.3 % ; OR , 3.50 ; 95 % CI , 2.16 - 5.68 ) and 12 months ( intervention 71.9 % vs usual care 42.3 % ; OR , 3.50 ; 95 % CI , 2.14 - 5.72 ) , and higher satisfaction with care at 6 months ( OR , 2.01 ; 95 % CI , 1.18 - 3.43 ) and 12 months ( OR , 2.88 ; 95 % CI , 1.67 - 4.97 ) . Although depressive outcomes were improved , no differences in HbA1c outcomes were observed . CONCLUSION The Pathways collaborative care model improved depression care and outcomes in patients with comorbid major depression and /or dysthymia and diabetes mellitus , but improved depression care alone did not result in improved glycemic control Abstract This paper describes a study design that blends health services and clinical research approaches to examine the cost-effectiveness of treatments and of quality improvement for depression in primary care , managed care practice s. Six managed care organizations in Los Angeles ( Calif. ) , San Antonio ( Tex . ) , San Luis Valley ( Colo. ) , Twin Cities ( Minn. ) , and Columbia ( Md. ) participated . Primary care clinics were r and omized to one of two quality improvement interventions or care as usual . Interventions included patient and provider education , nurse-assisted patient assessment , and re sources to support appropriate medication management or access to cognitive behavioral therapy . Practice s implemented the interventions with study support . Providers and patients selected treatment . Patients with depressive symptoms regardless of comorbidities were eligible . Over 27,000 primary care patients visiting the practice s of 181 primary care clinicians were screened for depression , 14 % were potentially eligible , and 1356 enrolled into the 2-year longitudinal study . Enrollees were similar to eligibles , but usual care clinic patients tended to be less severely depressed than intervention clinic patients , partly due to clinic staff enthusiasm . The result of the study showed that study ing treatment effects and quality improvement in nonacademic setting s is feasible , but requires relaxation of design features of experiments that protect internal validity . The trade-off between certainty of causal inference and generalizability to usual care conditions is discussed . The strengths and limitations of this study design are compared to those of clinical trials and recent clinical effectiveness studies BACKGROUND Recent trials have shown improved depression outcomes with chronic care models . We report the methods of a project that assesses the sustainability and transportability of a chronic care model for depression and change strategy . METHODS In a r and omized controlled trial ( RCT ) , a clinical model for depression was implemented through a strategy supporting practice change . The clinical model is evidence based . The change strategy relies on established quality improvement programs and is informed by diffusion of innovations theory . Evaluation will address patient outcomes , as well as process of care and process of change . RESULTS Five medical groups and health plans are participating in the trial . The RCT involves 180 clinicians in 60 practice s. All practice s assigned to the clinical model have implemented it . Participating organizations have the potential to disseminate this clinical model of care to 700 practice s and 1,700 clinicians . CONCLUSIONS It is feasible to implement the clinical model and change strategy in diverse practice s. Follow-up evaluation will determine the impact , sustainability , and potential for dissemination . Material s are available through http://www.depression- primary care.org ; more in-depth descriptions of the clinical model and change strategy are available in the online-only appendixes to this article BACKGROUND Many patients with major depression are non-adherent to antidepressant medication and do not receive care according to current guidelines . There is increasing evidence that treatment of depression in primary care can be improved . Comparison between effective interventions may help to establish the active ingredients of such interventions . METHOD In a r and omized trial two interventions to improve treatment of major depression in primary care were compared ( 1 ) a depression care programme , targeting general practitioners ( GPs ) , patients , and systematic follow-up , and ( 2 ) a systematic follow-up programme . Thirty GPs were r and omized and 211 primary -care patients with current major depression were included . All patients were prescribed a selective serotonin reuptake inhibitor . Outcome measures included adherence to antidepressant medication , and depression outcome . RESULTS No significant differences in adherence rates and treatment outcome measures were demonstrated between interventions at week 10 or week 26 . Adherence rates were high and treatment outcome was favourable . CONCLUSIONS The depression care programme was not superior to the systematic follow-up programme . Systematic follow-up in depression treatment in primary care seems to be an intervention per se , having the potential to improve adherence and treatment outcome Abstract Objectives : To evaluate two different methods of improving adherence to antidepressant drugs . Design : Factorial r and omised controlled single blind trial of treatment leaflet , drug counselling , both , or treatment as usual . Setting : Primary care in Wessex Participants : 250 patients starting treatment with tricyclic antidepressants . Main outcome measures : Adherence to drug treatment ( by confidential self report and electronic monitor ) ; depressive symptoms and health status . Results : 66 ( 63 % ) patients continued with drugs to 12 weeks in the counselled group compared with 42 ( 39 % ) of those who did not receiving counselling ( odds ratio 2.7 , 95 % confidence interval 1.6 to 4.8 ; number needed to treat=4 ) Treatment leaflets had no significant effect on adherence . No differences in depressive symptoms were found between treatment groups overall , although a significant improvement was found in patients with major depressive disorder receiving drug doses of at least 75 mg ( depression score 4 ( SD 3.7 ) counselling v 5.9 ( SD 5.0 ) no counselling , P=0.038 ) . Conclusions : Counselling about drug treatment significantly improved adherence , but clinical benefit was seen only in patients with major depressive disorder receiving doses ≥75 mg . Further research is required to evaluate the effect of this approach in combination with appropriate targeting of treatment and advice about dosage . Key messages Non-adherence is a serious problem in the treatment of depression by general practitioners In this study a brief psychosocial intervention delivered by a nurse greatly improved adherence Clinical benefit was apparent only in patients with major depressive episodes on higher doses of drugs Counselling should be targeted at patients with symptoms of at least moderate severity and combined with therapeutic drug CONTEXT Both antidepressant medication and structured psychotherapy have been proven efficacious , but less than one third of people with depressive disorders receive effective levels of either treatment . OBJECTIVE To compare usual primary care for depression with 2 intervention programs : telephone care management and telephone care management plus telephone psychotherapy . DESIGN Three-group r and omized controlled trial with allocation concealment and blinded outcome assessment conducted between November 2000 and May 2002 . SETTING AND PARTICIPANTS A total of 600 patients beginning antidepressant treatment for depression were systematic ally sample d from 7 group-model primary care clinics ; patients already receiving psychotherapy were excluded . INTERVENTIONS Usual primary care ; usual care plus a telephone care management program including at least 3 outreach calls , feedback to the treating physician , and care coordination ; usual care plus care management integrated with a structured 8-session cognitive-behavioral psychotherapy program delivered by telephone . MAIN OUTCOME MEASURES Blinded telephone interviews at 6 weeks , 3 months , and 6 months assessed depression severity ( Hopkins Symptom Checklist Depression Scale and the Patient Health Question naire ) , patient-rated improvement , and satisfaction with treatment . Computerized administrative data examined use of antidepressant medication and outpatient visits . RESULTS Treatment participation rates were 97 % for telephone care management and 93 % for telephone care management plus psychotherapy . Compared with usual care , the telephone psychotherapy intervention led to lower mean Hopkins Symptom Checklist Depression Scale depression scores ( P = .02 ) , a higher proportion of patients reporting that depression was " much improved " ( 80 % vs 55 % , P<.001 ) , and a higher proportion of patients " very satisfied " with depression treatment ( 59 % vs 29 % , P<.001 ) . The telephone care management program had smaller effects on patient-rated improvement ( 66 % vs 55 % , P = .04 ) and satisfaction ( 47 % vs 29 % , P = .001 ) ; effects on mean depression scores were not statistically significant . CONCLUSIONS For primary care patients beginning antidepressant treatment , a telephone program integrating care management and structured cognitive-behavioral psychotherapy can significantly improve satisfaction and clinical outcomes . These findings suggest a new public health model of psychotherapy for depression including active outreach and vigorous efforts to improve access to and motivation for treatment Medication non-adherence is a major obstacle in the treatment of affective disorders . The primary objective of this study was to evaluate two different interventions to improve adherence to antidepressant drugs . Secondary objectives included response to treatment , relation between adherence and response , patient satisfaction and tolerability . A r and omized controlled design was used to assess the effect of a patient educational compliance enhancing programme ( CP ) and therapeutic drug monitoring in 1031 major depressed patients treated with sertraline for 24 weeks and managed by their general practitioner . Adherence was measured by question ing , measurable serum levels of sertraline and desmethylsertraline , appointments kept and a composite index including all three methods . Treatment adherence was found in 37–70 % of patients , depending on the method used . Neither of the interventions result ed in a significant increase in adherence rate . However , significantly more patients in the CP group had responded at week 24 compared to patients in the control group . Overall , significantly more adherent patients responded to treatment compared to non-adherent patients , regardless of method used to determine adherence . This large study demonstrates that treatment response increases when using an educational compliance programme and that a strong relationship between treatment adherence and response exists OBJECTIVE To investigate whether an intervention by Dutch community pharmacists improves the drug attitude of depressive patients , who are prescribed a nontricyclic antidepressant by their general practitioner ( GP ) . METHOD A r and omized controlled trial with a 3-month follow-up was conducted among consecutive general practice patients who go to 19 pharmacists for antidepressants . The trial consisted of a control group ( n=79 ) that received usual care and an intervention group ( n=69 ) that received three drug coaching contacts at the pharmacy and a 25-min take-home video on the background of depression and the effects of medication . OUTCOME MEASURE Drug attitude ( DAI ) . RESULTS At the baseline measurement there were no significant differences between the intervention and control group on any demographic and health status variables or on clinical symptoms . At the 3-month follow-up intervention patients had a better drug attitude ( P=0.03 ) than their controls and evaluated the coaching of their pharmacist as more positive . They also felt the video to be useful . It had changed their ideas about medication . CONCLUSIONS Coaching by community pharmacists is an effective way to improve drug attitude of depressive primary care patients and it is acceptable to them BACKGROUND Despite high rates of relapse and recurrence , few primary care patients with recurrent or chronic depression are receiving continuation and maintenance-phase treatment . We hypothesized that a relapse prevention intervention would improve adherence to antidepressant medication and improve depression outcomes in high-risk patients compared with usual primary care . METHODS Three hundred eighty-six patients with recurrent major depression or dysthymia who had largely recovered after 8 weeks of antidepressant treatment by their primary care physicians were r and omized to a relapse prevention program ( n = 194 ) or usual primary care ( n = 192 ) . Patients in the intervention group received 2 primary care visits with a depression specialist and 3 telephone visits over a 1-year period aim ed at enhancing adherence to antidepressant medication , recognition of prodromal symptoms , monitoring of symptoms , and development of a written relapse prevention plan . Follow-up assessment s were completed at 3 , 6 , 9 , and 12 months by a telephone survey team blinded to r and omization status . RESULTS Those in the intervention group had significantly greater adherence to adequate dosage of antidepressant medication for 90 days or more within the first and second 6-month periods and were significantly more likely to refill medication prescriptions during the 12-month follow-up compared with usual care controls . Intervention patients had significantly fewer depressive symptoms , but not fewer episodes of relapse/recurrence over the 12-month follow-up period . CONCLUSIONS A relapse prevention program targeted to primary care patients with a high risk of relapse/recurrence who had largely recovered after antidepressant treatment significantly improved antidepressant adherence and depressive symptom outcomes OBJECTIVE Facilitate primary care physicians ' compliance with recommended st and ards of care for late life depression by reducing barriers to recognition and treatment . DESIGN R and omized controlled clinical trial of physician-targeted interventions . SETTING Academic primary care group practice caring for an urban , medically indigent patient population . PATIENTS / PARTICIPANTS Patients aged 60 and older who exceeded the threshold on the Centers for Epidemiologic Studies Depression Scale ( CES-D ) and the Hamilton Depression Rating Scale ( HAM-D ) and their primary care physicians . INTERVENTION Physicians of intervention patients were provided with patient-specific treatment recommendations during 3 special visits scheduled specifically to address the patient 's symptoms of depression . In general , physicians were encouraged to establish a diagnosis of depression and educate their patient about the diagnosis , discontinue medications that can cause or exacerbate depressive symptoms , initiate antidepressants when appropriate , and consider referral to psychiatry . Guidelines for prescribing antidepressants were provided . Control physicians received no intervention , and control patients received usual care . MAIN OUTCOME MEASURES Frequency of recording a depression diagnosis , stopping medications associated with depression , initiating antidepressant medication , and psychiatry referral ; mean changes in HAM-D and Sickness Impact Profile ( SIP ) scores . RESULTS One hundred three physicians and 175 patients were involved in the clinical trial . Physicians of intervention patients were more likely to diagnose depression and prescribe antidepressants ( P < 0.01 ) . There were no differences between the groups in the frequency of stopping medications associated with depression or referrals to psychiatry . Medications with the strongest cause and effect relationship to depression were infrequently used in this cohort of patients . Although both groups showed improvement in HAM-D and SIP scores , we were unable to demonstrate significant differences in HAM-D or SIP scores between the 2 groups . CONCLUSIONS Intensive screening and feedback of patient-specific treatment recommendations increased the recognition and treatment of late life depression by primary care physicians . However , we were unable to demonstrate significant improvement in depression or disability severity among intervention patients despite the informational support provided to their physicians . Efforts to improve the functional status of these patients may require more integrated interventions and more aggressive attempts to target psychosocial stressors traditionally outside the purview of primary care This pilot study demonstrated the feasibility of providing practice nurse support as an adjunct to st and ard general practitioner treatment to patients with depressive disorders prescribed antidepressant medication . With respect to the measures used and pilot study objectives identified , there were no statistically significant differences between the study groups in treatment adherence to the prescription of antidepressant medication or in the incidence and severity of adverse events to medication . Large-scale r and omized controlled trials are in progress to assess the effectiveness of practice nurse interventions in the management of depressive illness in general practice OBJECTIVE To explore the impact of telephone-based education and monitoring by community pharmacists on multiple outcomes of pharmacist-patient collaboration . DESIGN A r and omized , controlled , unblinded , mixed experimental design . SETTING Eight Wisconsin community pharmacies within a large managed care organization . PATIENTS A total of 63 patients presenting new antidepressant prescriptions to their community pharmacies . INTERVENTIONS Patients were r and omized to receive either three monthly telephone calls from pharmacists providing pharmacist-guided education and monitoring ( PGEM ) or usual pharmacist 's care . Usual care is defined as that education and monitoring which pharmacists may typically provide patients at the study pharmacies . MAIN OUTCOME MEASURES Patient 's frequency of feedback with the pharmacist , antidepressant knowledge , antidepressant beliefs , antidepressant adherence at 3 and 6 months , improvement in depression symptoms , and orientation toward treatment progress . RESULTS Of the 60 patients who completed the study , 28 received PGEM and 32 received usual pharmacist 's care . Results showed that PGEM had a significant and positive effect on patient feedback , knowledge , medication beliefs , and perceptions of progress . There were no significant group differences in patient adherence or symptoms at 3 months ; however , PGEM patients who completed the protocol missed fewer doses than did the usual care group at 6 months ( P < or = .05 ) . CONCLUSION Antidepressant telemonitoring by community pharmacists can significantly and positively affect patient feedback and collaboration with pharmacists . Longer-term studies with larger sample s are needed to assess the generalizability of findings . Future research also needs to explore additional ways to improve clinical outcomes |
14,006 | 15,186,569 | Limited evidence suggests that antihistamines might have a faster therapeutic effect compared to mast cell stabilisers .
Overall , these findings confirm the benefit of topical mast cell stabilisers and antihistamines over placebo for the treatment of allergic conjunctivitis .
There is , however , insufficient evidence to recommend the use of one type of medication over another . | BACKGROUND Evidence for the effectiveness of topical treatments , in providing symptomatic relief from ocular allergy , remains uncertain .
AIMS To assess the effectiveness and relative efficacy of topical treatments for the management of seasonal allergic conjunctivitis . | The objective of this study was to evaluate the efficacy of 0.05 % levocabastine , a new antihistamine formulated for ophthalmic use , compared with the placebo vehicle for the treatment of allergic conjunctivitis induced by ocular allergen challenge . Subjects who reacted . positively in both eyes on two separate occasions to ocular allergen challenge with grass , ragweed , or cat d and er ( N = 47 ) received one dose of 1 to 2 drops of 0.05 % levocabastine in one eye and its vehicle in the other eye . After 10 minutes , the predetermined dose of allergen was instilled in both eyes . Signs and symptoms of allergic conjunctivitis were evaluated with biomicroscopy and subjective evaluation of itching after 3 , 5 , and 10 minutes . Four hours after drug administration , subjects were rechallenged and reevaluated to determine levocabastine 's duration of action . Results showed that levocabastine was significantly more effective than placebo in inhibiting itching , hyperemia , eyelid swelling , chemosis , and tearing after the initial challenge and in inhibiting all parameters except eyelid swelling after the rechallenge 4 hours later ( p < 0.05 ) . These results demonstrate that levocabastine , currently the only ophthalmic antihistamine available that is not combined with a vasoconstrictor , is efficacious in the inhibition of itching , as well as all of the allergic signs of a vascular origin , with a duration of action of at least 4 hours . Because of its strong effects on itching and hyperemia , chemosis , lid swelling , and tearing , levocabastine would be a valuable therapeutic agent to add to the heterogeneous family of antiallergic compounds presently available for the treatment of seasonal allergic conjunctivitis Levocabastine is a recently developed , potent H1‐receptor blocker intended for topical application . Seventeen healthy non‐atopic volunteers participated in this r and omized , double‐blind , placebo‐controlled study undertaken to investigate the speed of onset of action , efficacy and tolerability of levocabastine eye‐drops after a histamine challenge . The degree of histamine‐induced ocular inflammation was found to be significantly less after administration of levocabastine compared with placebo . Furthermore , levocabastine was shown to be rapidly effective with an onset of action within 10 min . Levocabastine eye‐drops were well‐tolerated and no adverse reactions to the study drug were reported . Levocabastine eye‐drops appear to be a valuable therapeutic approach for the treatment of histamine‐mediated ocular allergies A double blind group comparative trial comparing 2 % nedocromil sodium with placebo in treating seasonal allergic conjunctivitis over a four week period is reported . Sixty-four patients were analysed . During the period of peak pollen challenge , statistically significant differences in favour of nedocromil sodium for itching and soreness were demonstrated . During a longer period of a less high pollen count , a significant difference in favour of nedocromil sodium was shown only for the symptom of soreness Forty patients suffering from allergic conjunctivitis , due to birch pollen , participated in a double‐blind parallel group comparison between levocabastine ( a potent new specific histamine ( H1 ) antagonist ) and placebo , both given as eye drops . Symptom scores were recorded during a 4‐week period . A 1‐week run‐in period was followed by a 3‐week treatment period . To enable a fair evaluation of the treatment effect on the ocular symptoms only , all patients were treated with topical nasal glucocorticoids for possible rhinitis symptoms during the whole study period . Plasma levels of levocabastine were determined in all subjects at the end of the 3 weeks ' treatment period . Pollen counts for birch pollen were followed simultaneously . The evaluation of the symptom score cards revealed a significant reduction of ocular symptoms following use of the active compound . The resorption of the active substance through the conjunctiva was low . In accordance with the present trend of more topical treatment for allergic rhinitis , levocabastine may constitute a valuable compound for the topical treatment of allergic conjunctivitis Previous studies have shown the effectiveness of topical cromolyn solution in the treatment of allergic conjunctivitis . However , the preservative , phenylethanol , produces an immediate burning or stinging sensation when the drops are first instilled in the eye . A double-blind , crossover , placebo controlled study using 2 % cromolyn solution was conducted , without the preservative and supplied in unit doses . Twenty six patients took part in the trial . They had ragweed pollen-induced conjunctivitis . The results of the trial indicate that the active drug was effective in controlling the signs and symptoms of allergic conjunctivitis in 22 of the 26 patients , i.e. , 84.6 % ( p less than 0.001 ) . Two patients preferred the placebo . There were no complaints of stinging or burning sensation after the instillation of the drops in the eyes . There were no cases of infection of the eye . Without the preservative , the cromolyn solution does not damage the soft contact lens This multicenter , double-masked , r and omized , parallel-group study compared the efficacy and safety of ketorolac tromethamine 0.5 % ophthalmic solution with levocabastine 0.05 % and ketorolac tromethamine vehicle in patients with seasonal allergic conjunctivitis . One drop of ketorolac , levocabastine , or vehicle was instilled in each eye four times daily for 6 weeks . In the majority of efficacy variables , ketorolac produced the greatest improvements , followed by levocabastine and vehicle . Ketorolac was significantly more effective ( P<.05 ) than vehicle in reducing mean itching scores , palpebral hyperemia , bulbar hyperemia , and edema . Patients treated with ketorolac reported significant improvements ( P<.05 ) in their ability to sleep and to concentrate on work , compared with those who received vehicle . No significant differences were noted among the treatment groups in safety or tolerability . Ketorolac tromethamine 0.5 % ophthalmic solution instilled four times daily is effective and safe in reducing the signs and symptoms of seasonal allergic conjunctivitis PURPOSE This study was conducted to evaluate the efficacy of 0.05 % levocabastine compared with 4 % cromolyn for treating allergic conjunctivitis induced by ocular allergen challenge . METHODS Subjects who met all entry criteria and reacted positively to ocular allergen challenge at two previous visits ( n = 50 ) received placebo in one eye and cromolyn in the fellow eye , four times daily for 2 weeks . On day 18 , subjects received the final dose of cromolyn in the pretreated eye and one drop of levocabastine in the fellow eye . Subjects were challenged and evaluated after 3 , 5 , and 10 minutes . Four hours after drug administration , subjects were rechallenged and evaluated after 3 , 5 , and 10 minutes . RESULTS Levocabastine was significantly more effective than cromolyn in inhibiting itching , hyperemia , eyelid swelling , chemosis , and tearing after the initial challenge and 4-hour rechallenge ( P < 0.05 ) . CONCLUSION These results suggest that levocabastine is superior to cromolyn for treating allergen-induced conjunctivitis and has a duration of action of at least 4 hours A controlled , double-blind comparison of naphalzoline hydrochloride 0.05 % , antazoline phosphate 0.5 % , a combination of both components and a placebo was performed on 51 ragweed sensitive patients presenting allergic conjunctivitis . Evaluation of response at various times after instillation of medication for lacrimation , conjunctival inflammation , pruritus , photophobia and pain showed naphazoline hydrochloride , antazoline phosphate and the combination product superior to placebo . The combination product was statistically significantly superior for conjunctival inflammation and photophobia . The need for post-challenge treatment with epinephrine hydrochloride was significantly less in those eyes treated with the combination product . demonstrating prophylactic efficacy During peak ragweed season , 86 patients with seasonal allergic conjunctivitis participated in a 9-week , multicenter , double-masked , placebo-controlled , group-comparative study testing the efficacy and safety of bid nedocromil sodium , 2 % ophthalmic solution . The clinical effectiveness of nedocromil sodium was measured by analyzing the means of patient daily symptom scores and eye examinations after 1 , 3 , 5 , and 8 weeks of treatment . The use of nedocromil sodium during peak ragweed pollen season reduced symptom scores with statistically significant treatment differences as compared with the placebo for itchy eyes , tearing , overall eye condition , and symptom summary score . Clinician assessment s also favored the use of nedocromil sodium as indicated by significant improvements in tearing , conjunctival injection , and conjunctival edema . No significant side effects were reported by the patients , allergists , or ophthalmologists . We conclude that nedocromil sodium , 2 % ophthalmic solution , administered bid is more effective in the relief of symptoms of seasonal allergic conjunctivitis than placebo and causes no major side effects Purpose The aim of the study was to assess the efficacy and safety of 0.05 % levocabastine eyedrops ( H1 receptor blocker given BID + vehicle BID ) compared with 0.1 % lodoxamide ophthalmic solution ( mast-cell stabilizer instilled QID ) in reducing ocular signs and symptoms of allergic conjunctivitis . Methods A r and omized , double-masked , parallel-group study was conducted in seven centres in France , in which 93 patients suffering from seasonal or perennial allergic conjunctivitis were r and omly allocated to either 0.05 % levocabastine ( n = 47 ) or 0.1 % lodoxamide ( n = 46 ) in both eyes for a 14-day period . Efficacy was evaluated by subjective ( prickling , burning , photophobia , itching ) and objective ( redness , chemosis , eyelid edema , tearing ) sign scores at visits on days 7 and 14 , and from data noted daily by the patient in a self-evaluation form . Safety was assessed as tolerance upon instillation and adverse event reports . Results The ocular allergy symptom and sign scores were comparable in the two treatment groups at baseline . With time , statistically and clinical ly significant reductions ( p < 0.001 ) from baseline were observed for the subjective and objective scores , with no difference between the treatment groups . After the first instillation , signs were alleviated more rapidly in levocabastine-treated patients than in the lodoxamide group ( p < 0.001 ) . Overall assessment s by the patient and investigator were similar in both groups . No serious adverse events were reported . Conclusions Levocabastine ophthalmic suspension 0.05 % ( BID ) appears to be as effective and safe as lodoxamide 0.1 % ( QID ) in the management of allergic conjunctivitis Lodoxamide is an antiallergic compound . The present study evaluated the efficacy on clinical and cytological parameters and safety of topical lodoxamide compared to placebo in the treatment of allergic conjunctivitis . The trial , design ed as double-blind , r and omized , placebo-controlled and parallel group treatment , was carried out in 30 patients , suffering from seasonal allergic conjunctivitis due to grass pollen , during the pollen season . Patients received lodoxamide tromethamine 0.1 % eye drops or placebo eye drops , one drop in each eye t.i.d . for 4 weeks . The clinical and cytological evidence was investigated by clinicians on admission and after 4 weeks ' treatment . At the end of the trial , only the lodoxamide-treated group showed a significant clinical improvement , associated with a reduction of inflammatory cells . No serious side effects were observed . The results show the clinical efficacy of lodoxamide in the treatment of pollen-induced allergic conjunctivitis . In addition , lodoxamide exerts its antiallergic activity by reducing inflammatory infiltrate ( mainly eosinophils ) Levocabastine is a new , highly potent , and specific H1 antagonist . The effects of this drug , administered topically , were evaluated in a conjunctival provocation test ( CPT ) with allergens . CPT was performed by the instillation of one drop of allergen at increasing concentrations in the inferior conjunctival sac of each eye , alternatively , and stopped when both itching and redness of the conjunctiva were present . The concentration of allergen at this step was considered as the reaction threshold . Eleven patients , allergic to grass pollen , underwent , in winter , a first CPT without pretreatment ( screening test ) ; the CPT was then repeated twice after a 24-hour treatment , once , with a placebo , and once , with levocabastine ( one drop twice a day , 0.5 mg/ml ) , administered in a double-blind fashion and in r and om order . The minimal interval between the two tests was 1 week . There was no significant difference between the thresholds determined in the two CPTs performed without medication ( screening test and placebo ) , whereas the threshold was significantly increased ( p less than 0.001 ) after pretreatment with levocabastine . Individually , the threshold increased in 10/11 patients ( p less than 0.01 ) . Levocabastine prevented both redness and itching . A late allergic reaction was observed by the patient in 6/11 CPTs performed after placebo treatment and 8/11 after levocabastine treatment . We conclude that , in this model of allergic conjunctivitis , levocabastine increased the conjunctival tolerance to an allergen . Further studies should help to determine the true place of this H1 antagonist in the treatment of allergic conjunctivitis This study evaluated the effectiviness and the onset of action of levocabastine ( CAS 79547 - 78 - 7 ) nasal spray and eyedrops as well as of nedocromil ( CAS 69049 - 74 - 7 ) nasal spray and eyedrops in practical relevant circumstances . The study was design ed as an open observational study with parallel groups in 10 centres and comprised 102 patients . All patients presented with seasonal allergic rhinitis and evidence d conjunctival symptoms requiring therapy . The patients as well as the investigators were required to rate the symptoms using symptom scores in order to evaluate the effectiveness of the used drugs . The effectiveness according to symptom scores did not differ significantly between investigator 's and patient 's judgment . Onset of action was within the first hour in 81.6 % of the patients treated with levocabastine and in 82.9 % of the patients treated with nedocromil . Symptoms were evaluated on a visual analogue scale ranging from 0 to 100 . The use of both substances reduced the severity of the reported symptoms by 50 % within the first hour . Thus , no significant difference in the onset of action could be observed even though a later onset of action was expected of the stabiliser of mast cell membranes . Both drugs were tolerated well To assess the efficacy and safety of twice-daily administration of nedocromil sodium 2 % ophthalmic solution , we performed a multicenter study involving 140 patients with seasonal allergic conjunctivitis . Subjects had a history of seasonal allergic conjunctivitis and positive results of a skin test to ragweed . The trial coincided with the peak ragweed pollen season at five treatment centers . Patients treated with nedocromil sodium had improvements in symptoms with statistically significant reductions recorded for eye itching ( P less than or equal to .04 ) , conjunctival injection ( P less than or equal to .001 ) , and overall disease severity ( P less than or equal to .001 ) as compared to the placebo-treated group . Adverse events were minor and transient . We concluded that nedocromil sodium 2 % ophthalmic solution administered twice daily is effective in relieving major symptoms associated with seasonal allergic conjunctivitis This was a multicentre , double‐blind , r and omized group comparative study in which 77 children , aged 6–16 years , received 2 % nedocromil sodium eye drops and 72 received placebo , one drop into each eye twice daily . The treatment period was 4 weeks , covering the peak birch pollen season . Prior to the start or the season , patients who had mended the clinic the previous 2 years because of seasonal allergic conjunctivitis ( SAC ) to birch pollen , entered a one week baseline period during which symptoms were assessed , diary cards completed , and routine sampling of blood and urine earned out . The double‐blind treatment period then commenced at the onset of the birch pollen season . Patients parents kept daily diary record cards of eye symptom severity and concomitant therapy . Conjunctivitis was mild in both treatment groups but nedocromil sodium was more effective than placebo in controlling symptoms . During the 2–3 weeks of peak pollen counts , this therapeutic effect was statistically significant for itching ( P < 0–01 ) , watering ( P < 0.05 ) and total symptom score ( P < 0.01 ) , but was not significant for grittiness ( P= 0.08 ) or redness ( P = 0.06 ) . Global opinions of efficacy showed no difference between treatments , due to a high placebo effect ( however , the diary card data indicated a significant improvement with nedocromil sodium ) . We therefore conclude that nedocromil sodium 2 % eye drops , administered twice daily , is an effective treatment for SAC in children A double‐blind group comparative trial comparing Opticrom with a matching placebo , over a four‐week period , in seasonal allergic conjunctivitis is reported . Overall assessment of treatment benefit made at the end of the trial by the patients and the clinician showed a statistically significant difference in favour of Opticrom . Of the patients on Opticrom , eighteen ( 90 % ) said they improved while in the clinicians opinion , seventeen ( 85 % ) improved A total of 71 patients with documented birch and grass pollen allergy participated in this r and omized , double‐blind , parallel‐group study initiated to compare the long‐term therapeutic efficacy of twice daily levocabastine , a new topical H1‐receptor blocker , with that of sodium cromoglycate four times daily in the treatment of pollen‐provoked conjunctivitis . There was no statistically significant difference in therapeutic efficacy between the two treatment groups , although a positive trend in favour of levocabastine was observed . Global evaluations of therapeutic efficacy were similar in both treatment groups . A total of 94 % of levocabastine‐treated patients rated treatment to be excellent or good compared with 86 % of patients in the sodium cromoglycate group . Moreover , there were no significant differences in the severity of allergic symptoms reported on the patient diary cards . Patients were permitted to use rescue medication ( oral terfenadine and betamethasone nasal spray ) if symptoms became severe . The use of rescue medication was lower in the levocabastine group than in the sodium cromoglycate group . The mean number of days on which rescue medication was used was 12.8 and 26.9 in the two groups , respectively . The incidence , and type , of adverse reactions was similar in both patient groups . Levocabastine is well‐tolerated and at least as effective as sodium cromoglycate in the treatment of pollen‐provoked conjunctivitis PURPOSE To compare the clinical efficacy of emedastine ophthalmic solution to that of ketorolac ophthalmic solution using a conjunctival allergen challenge model . METHODS The conjunctival allergen challenge model was used in this r and omized , double-masked , single center , crossover study . The titer of allergen that elicited a positive allergic reaction was selected . After at least 14 days , 36 subjects were r and omized into two groups of 18 to receive either emedastine in one eye and placebo in the contralateral eye , or ketorolac in one eye and placebo in the contralateral eye . Ten minutes after drug instillation , subjects were challenged with antigen . At 3 , 10 and 20 minutes following challenge subjects grade d ocular itching and were assessed for hyperemia in conjunctival , ciliary , and episcleral vessel beds . Approximately 14 days later , subjects received the alternate treatment in one eye and placebo in the contralateral eye . They were again challenged with allergen and their responses were rated in the same manner . Ocular discomfort was assessed by the subjects after administration of each study drug . RESULTS Emedastine significantly ( p < 0.05 ) inhibited ocular itching and redness in vascular beds following topical ocular administration . In contrast , ketorolac failed to significantly inhibit ocular itching or redness in this study . Patient assessment of comfort indicated emedastine was significantly ( p < 0.05 ) more comfortable than ketorolac upon topical ocular administration . CONCLUSION Emedastine is superior to ketorolac in controlling itching and redness , the cardinal symptom and sign of allergic conjunctivitis Children ( n = 110 ) with seasonal allergic rhinoconjunctivitis were r and omized to receive either twice daily 0.05 % levocabastine eye drops and nasal spray plus twice daily topical placebos or 2 % sodium cromoglycate eye drops and nasal spray four times daily for a period of 4 weeks . Patients were required to use the nasal sprays as directed and the eye drops only when required . The results obtained suggest that topical levocabastine is at least as effective as sodium cromoglycate for the treatment of this condition . After 2 weeks treatment the effect of therapy on nasal symptoms was considered to be excellent or good in 72 % of levocabastine-treated patients and 54 % of patients on sodium cromoglycate ( p = 0.009 ) , with corresponding values for ocular symptoms of 81 % and 57 % in the two groups , respectively ( p < 0.05 ) . Investigator assessment s also revealed that the severity of sneezing and lacrimation were significantly lower in the levocabastine group at this time ( p < 0.05 ) . After 4 weeks of treatment , patient diary data revealed that levocabastine was at least as effective as sodium cromoglycate with intergroup differences attaining statistical significance in favor of the topical antihistamine for nasal congestion ( p < 0.05 ) . Both agents were well-tolerated with no significant differences in the incidence or type of adverse reactions in the two treatment groups Background Levocabastine is a selective topical H1 antagonist , effective in the treatment of seasonal allergic rhinitis and conjunctivitis We treated 31 patients with ragweed conjunctivitis in an eight-week , double-masked parallel-group study with cromolyn sodium 4 % ophthalmic solution . Analysis of data showed preseason serum IgE antibody to ragweed level was a significant predictor of drug response . Of 16 patients with ragweed IgE values of less than 100 ng/ml , the nine treated with cromolyn had significantly fewer symptoms during the course of treatment than the seven in the placebo group . Of the 15 remaining patients , who had IgE levels of more than 100 ng/ml , the eight treated with cromolyn improved but the difference between their symptom scores and those of the seven patients treated with placebo was not statistically significant A 4 week , multicentre , double‐blind , double dummy , placebo controlled group comparative study was carried out during the birch pollen season to compare the efficacy and tolerability of 2 % nedocromil sodium eye drops ( twice daily ) and 2 % sodium cromoglycate eye drops ( four times daily ) . Participants with a history of seasonal allergic conjunctivitis ( SAC ) were r and omized to receive nedocromil sodium ( 60 ) , sodium cromoglycate ( 61 ) or placebo ( 64 ) . Clinical assessment of SAC showed improvement with both active treatments compared to placebo but symptomatology was low and only changes in photophobia and grittiness reached significance ( P < 0.05 ) . Patient diaries showed significant control of itching by both active treatments , compared to placebo , with no differences between the active preparations . Patients ’ opinions indicated a marked placebo effect : 73 % of this group reported full or moderate control of symptoms , compared with 75 % in sodium cromoglycate and 80 % in the nedocromil sodium group . Unusual symptoms were most common ( 27 patients ) with nedocromil sodium eye drops : P < 0.05 vs. placebo ( 15 patients ) . There were no serious adverse events . Nedocromil sodium eye drops ( b.d . ) and sodium cromoglycate eye drops ( q.i.d . ) were both considered clinical ly more effective than placebo in controlling symptoms of SAC due to birch pollen The aim of this study was to evaluate the effect of levocabastine , a new H1‐blocking antihistamine for topical use , in comparison with sodium cromoglycate on conjunctival symptoms of birch pollinosis . The two drugs were compared in a r and omized double‐blind comparative study over 5 weeks in 37 children and adolescents ( 6–19 years of age ) with birch pollen conjuncitivitis . Nasal symptoms occurred in 31 of the children and were treated with beclomethasone dipropionate nasal spray . An oral antihistamine was offered as rescue medication for eye symptoms . Initially , the patients received placebo four times a day for a 7‐day run‐in period . Conjunctival symptoms were recorded daily on diary cards on a 100 mm visual analogue scale . The pollen counts indicated a short but intensive birch pollen season . There was no statistically significant difference between the two treatment groups with regard to eye symptom scores before and during active treatment . However , the patients ' evaluation of the efficacy of the therapy was in favour of levocabastine ( P < 0.01 ) . Topical levocabastine , an H1‐blocker , applied twice daily , seems to protect from symptoms of allergic conjunctivities as favourably as sodium cromoglycate applied four times a day . There was no difference in number or character of reported adverse reactions between the two treatment groups BACKGROUND Multiple ocular challenges or seasonal trials have demonstrated the efficacy of levocabastine and nedocromil sodium in the treatment of allergic conjunctivitis . OBJECTIVE This study was design ed to compare the protective effect of levocabastine eye drops with that of nedocromil in a conjunctival provocation test with allergen . METHODS Twenty-four patients with allergic conjunctivitis to grass pollen were recruited . After a preliminary provocation to determine conjunctival reaction threshold ( erythema of at least 50 % of the conjunctiva with ocular itching ) , patients were r and omized to receive either topical levocabastine ( 0.05 % ) or nedocromil ( 2 % ) 15 minutes before provocation . Erythema and pruritus intensity were recorded at each concentration of allergen up to the reaction threshold . RESULTS The allergen concentration level necessary to reach reaction threshold was increased ( p < 0.001 ) after treatment with both drugs . Comparison between screening and each treatment indicated that the shift in allergen concentration was significantly greater after levocabastine treatment than after nedocromil treatment ( p = 0.019 ) . Conjunctival itching ( symptom score ) and erythema ( percent conjunctival surface ) were also better controlled by levocabastine than by nedocromil during provocation ( p < 0.05 ) . CONCLUSION In a provocation test with allergen , levocabastine and nedocromil were both effective in increasing the conjunctival tolerance to allergen , with better protection provided by levocabastine Sodium cromoglycate ( SCG ) , in a 4 % solution instilled into each eye 4 times daily , was compared with placebo in a double-blind , noncrossover trial in 30 matched patients with troublesome ragweed pollen-induced conjunctivitis . In the SCG group , eye symptom scores were significantly less ( p = 0.05 ) , and all patients judged that their symptoms were improved over the previous year ( p less than 0.05 ) . Less antihistamine was used by the SCG group but the difference was not significant . It was concluded that SCG was effective in the treatment of ragweed-induced seasonal allergic conjunctivitis In a group of 33 typical hay fever patients with apparent conjunctivitis a double-blind clinical trial was carried out during the summer of 1978 . One group of patients used 2 % cromoglycate eye drops and the other group used placebo eye drops , both in sterile unit-dose packages without benzalconium hydrochloride . Symptoms and use of other symptomatic treatment were recorded daily . The mean daily scores were compared with the daily pollen counts . The daily records of symptoms were somewhat lower in the cromoglycate than in the placebo group , though not significantly so . Mean daily scores of symptoms correlated with the pollen counts fairly well . Need of symptomatic medication did not differ in either groups and had no relation to the pollen counts . Although a beneficial effect had been expected , cromoglycate eye drops were considered ineffective in this study Thirty-one patients with allergic eye diseases were treated three times daily for 4 weeks in a double-blind trial comparing sodium cromoglycate eye ointment with placebo . Patients ' and clinician 's assessment of symptoms and overall opinions of treatment showed sodium cromoglycate was significantly better than placebo and was well tolerated A multicenter double-blind group comparative study was carried out in 126 patients , 64 of whom received 2 % nedocromil sodium eye drops , and 62 placebo eyedrops twice each day for the treatment of seasonal allergic conjunctivitis to birch pollen . The patients were evaluated at 2 week intervals for clinical signs of conjunctivitis and kept daily diary records of eye symptoms ( 0 - 4 severity scales ) and concomitant therapy . Diary trends favored active treatment , and reached significance for excessive lacrimation ( P less than .05 ) during peak pollen challenge . Clinic assessment s showed the same directional trend and final opinions of treatment efficacy were significantly in favor of nedocromil sodium ( P = .003 , patients ; P = .006 , clinicians ) . In addition , the placebo group used significantly more topical ( P less than .05 ) and oral ( P less than .01 ) concomitant antihistamine therapy . Nedocromil sodium and placebo treatments were equally acceptable and well tolerated . The results show that 2 % nedocromil sodium used topically twice each day is an effective therapy for seasonal allergic conjunctivitis BACKGROUND No objective evaluation of the conjunctival provocation test ( CPT ) was possible until now . OBJECTIVE The aim of this study was to develop a tool that would enable us to monitor conjunctival allergic inflammation by objective measurements . METHODS Twenty-four patients allergic to grass pollen were challenged by a CPT with grass pollen and genuine grass pollen in the " Vienna Challenge Chamber . " Patients were r and omized to treatment with placebo or topical application of an H1-receptor antagonist ( azelastine ) . Vascular reaction of the conjunctiva was repeatedly monitored by special video equipment . The signal was sent to a digital frame grabber , and digital image analysis was done with the aid of the WCUE-3 program ( Olympus Optical Co. , Hamburg , Germany ) . RESULTS The CPT led to an immediate increase of the red density . This extension was linear within the first 15 minutes . During the long-term challenge , the increasing vascular effect lasted 2 hours . During active treatment a consistent reaction pattern was obvious ; however , the corresponding levels were statistically lower ( p = 0.022 ) . CONCLUSION The calculation of red density of the conjunctiva by digital analysis proved to be a sensitive tool for measuring the conjunctival allergic reaction . It is possible to overcome the insufficient subjective evaluation of the CPT by objective measurements of the vascular reaction Montan P , Zetterström O , Eliasson E , Strömquist L‐H. Topical sodium cromoglycate ( Opticrom ® ) relieves ongoing symptoms of allergic conjunctivitis within 2 minutes In a placebo controlled double-blind crossover study , 60 patients with chronic non-infections conjunctivitis were treated for 4 weeks with either sodium cromoglycate eye drops or with placebo followed by 4 weeks on the alternative treatment . The dose was one drop into each eye 4 times daily . The scores for a number of symptoms and signs were significantly lower after 4 weeks sodium cromoglycate treatment than after similar placebo treatment . In both the patients ' and clinician 's opinion significantly more patients responded to the active treatment than to the placebo treatment . At the end of the trial clinician recorded more preferences for sodium cromoglycate ( 27 ) than for placebo ( 9 ) , and the difference was highly significant ( P less than 0.01 ) . No side effects were reported during the trial |
14,007 | 25,955,963 | The masseter muscle seemed to be more sensitive than the other 2 muscles , in both females ( healthy : masseter 194.1 ± 62.7 kPa < frontalis 277.5 ± 51.1 kPa < temporalis 282.1 ± 70.8 kPa ) and males ( healthy : masseter 248.2 ± 48.4 kPa < temporalis 314.8 ± 63.3 < frontalis 388 kPa ) .
Females had lower PPT values than those of males in temporalis , masseter , and frontalis muscles . | null | null |
14,008 | 25,910,573 | An antiviral/TACE combination shows promise as an effective and tolerable treatment strategy for intermediate-stage HCC .
The reported efficacy and toxicity of the antiviral/TACE combination appears to compare favorably with TACE monotherapy , the most commonly implemented strategy for intermediate-stage HCC . | BACKGROUND Hepatocellular carcinoma ( HCC ) is the most frequently occurring liver neoplasm and the fifth most common cancer worldwide .
Intermediate-stage HCC is a distinct disease entity that is traditionally treated with transarterial chemoembolisation ( TACE ) .
However , the risk of viral reactivation and subsequent hepatic decompensation is considerable .
Therefore , in this systematic review , we explore the evidence surrounding the benefits of using TACE/antiviral combination in this subset of HCC . | Reactivation of hepatitis B virus ( HBV ) during chemotherapy is well documented . However , there are limited data on this complication in patients with hepatocellular carcinoma ( HCC ) undergoing transarterial chemotherapy . The aim of this study was to evaluate the efficacy of preemptive lamivudine therapy in reducing hepatitis due to HBV reactivation in patients with HCC undergoing transarterial chemo-lipiodolization ( TACL ) and to seek predictors of this event . A total of 73 consecutive HCC patients undergoing TACL using epirubicin 50 mg/m2 and cisplatin 60 mg/m2 at monthly intervals were prospect ively and r and omly assigned to receive lamivudine 100 mg daily from the start of TACL ( preemptive group ) or not ( control group ) . During the study , 11 ( 29.7 % ) of 37 patients in the control group and 1 ( 2.8 % ) of 36 patients in the preemptive group developed hepatitis due to HBV reactivation ( P = .002 ) . In addition , there were significantly more incidences of overall hepatitis ( P = .021 ) and severe grade of hepatitis ( P = .035 ) in the control group . With multivariate Cox regression model , a baseline HBV DNA level of more than 10(4 ) copies/mL was the only independent predictor of hepatitis due to HBV reactivation during chemo-lipiodolization ( P = .046 ) . In conclusion , preemptive lamivudine therapy demonstrated excellent efficacy in reducing hepatitis due to HBV reactivation and hepatic morbidity during TACL . Preemptive therapy should be considered in HCC patients with an HBV DNA level of more than 10(4 ) copies/mL. Further studies are needed to confirm the value of this approach in patients with low-level viremia BACKGROUND According to the results of a number of phase 3 r and omized studies , sorafenib is the only approved systemic therapy for advanced HCC ; however the issue of high economic cost remains challenging ; thus we have conducted this retrospective analysis of our HCC patients treated with sorafenib . METHODS HCC patients treated at Ain Shams University Hospitals , in the period between 2010 and 2012 were review ed . Eligible patients were those who had received sorafenib for advanced HCC not eligible for or progressed after surgery or locoregional therapy . We investigated the impact of baseline clinicopathological factors ( age , gender , child status , performance score , BCLC tumor stage , cause of chronic liver disease , median baseline alpha fetoprotein level and previous treatment received for HCC ) on overall survival ( OS ) in an adjusted Cox regression model . RESULTS 41 patients were included in the analysis fulfilling the inclusion criteria . At a median follow up period of 13 months , the median PFS for the whole group was 4 months ; the median OS for the whole group is 6.25 months . Multivariate analysis identified three baseline characteristics that were prognostic indicators for overall survival : ECOG performance status ( median OS for ECOG 1=7.01 months and for ECOG 2=3.03 months ) , Child-Pugh status ( median OS for child A=12.04 months and for child B=5.23 months ) , and median baseline levels of alpha-fetoprotein . CONCLUSIONS In limited re source countries like Egypt , we suggest that the use of sorafenib for the treatment of advanced HCC cases should be restricted to a highly selected subgroup of patients with good performance and child The only approved systemic therapy for patients with advanced hepatocellular carcinoma ( HCC ) till now is sorafenib . A preliminary study suggested that capecitabine , an oral fluoropyrimidine , may be effective in advanced HCC . We have tested this hypothesis in this phase 2 study . In this single-center , phase 2 , open-label trial , we r and omly assigned 52 patients with advanced HCC who had not received previous systemic treatment to receive either sorafenib ( at a dose of 400 mg twice daily ) or capecitabine ( 1,000 mg/m2 twice daily ) ( day 1–day 14 ) . Primary outcome was progression-free survival . Secondary outcomes included the overall survival and safety . Median overall survival was 7.05 months in the sorafenib group and 5.07 months in the capecitabine group ( hazard ratio in the capecitabine group 2.36 ; 95 % confidence interval 1.174–4.74 ; P < 0.016 ) . The median progression-free survival was 6 months in the sorafenib group and 4 months in the capecitabine group ( P < 0.005 ) . Three patients in the sorafenib group ( 11.5 % ) and one patient in the capecitabine group ( 3 % ) had a partial response ; one patient ( 3 % ) had a complete response in the sorafenib group . H and –foot skin reaction was more frequent in the sorafenib group , hyperbilirubinemia was more common in the capecitabine group , and diarrhea was equivalent between both groups . In patients with advanced HCC , capecitabine is inferior to sorafenib in terms of median progression-free survival and overall survival , and it should not be used alone for the treatment of advanced HCC , but rather , combination therapy with sorafenib should be considered BACKGROUND AND AIMS The present study was carried out to test the hypothesis that interferon-alpha ( IFN-alpha ) treatment would reduce or postpone the recurrence rate and improve the overall survival rate in patients after transarterial chemoembolization ( TACE ) treatment of hepatitis B virus ( HBV ) related unresectable hepatocellular carcinoma ( HCC ) . METHODS 216 patients with unresectable HBV-related HCC were r and omized into a TACE group and a TACE-IFN group , each group had 108 patients . In the TACE-IFN group , patients received IFN-alpha1b at a dose of 3 million units ( mu ) three times a week by intramuscular injection one week after/before TACE treatment , for 48 weeks . RESULTS The median disease-free survival in the TACE-IFN treatment group was 23.6 months ( 95 % CI : 21.4 - 25.8 ) and 20.3 months ( 95 % CI : 15.8 - 24.8 ) in the TACE group ( P = 0.027 ) . The disease free rate at 24 months in the TACE group was lower than in the TACE-IFN group ( 39.8 % vs 59.3 % , P = 0.004 ) . The median overall survival was 29 months ( 95 % CI : 27.5 - 32.1 ) in the TACE-IFN group and 26 months ( 95 % CI : 20.1 - 31.9 ) in the TACE group ( P = 0.003 ) . The 2-year overall survival in the TACE-IFN group was higher than in the TACE group ( 72.2 % vs 52.8 % , P = 0.003 ) . CONCLUSIONS IFN-alpha treatment reduced recurrence and improved the survival of patients after TACE treatment of HBV-related HCC , with acceptable toxicities OBJECTIVE To evaluate the therapeutic effect of interferon therapy after transcatheter arterial chemoembolization ( TACE ) in patients with hepatocellular carcinoma associated with hepatitis B virus . METHODS Sixty-two patients with advanced primary hepatocellular carcinoma associated with hepatitis B virus was r and omly divided into 2 groups . Thirty-one cases were treated with TACE and Interferon . Thirty-one cases with TACE only . HBV DNA , clinical effect , intrahepatic tumor recurrence rate and survival rate were studied . RESULTS Of the 31 patients in TACE+IFN group , 17 ( 54.8 % ) were negative for HBV DNA at the end of treatment . None of TACE group was negative for HBV DNA . The intrahepatic tumor recurrence rate at 1 year and 2 years in TACE+IFN group was 16.1 % , 29.0 % , compared with 38.7 % , 61.3 % in TACE group ( chi-square = 3.97 , chi-square 6.51 , P < 0.05 ) . The survival rate in the former was 83.9 % and 74.2 % respectively , compared with that of 61.3 % and 38.7 % in the latter ( chi-square = 3.97 , chi-square = 7.94 , P < 0.05 ) . CONCLUSION Interferon therapy after transcatheter arterial chemoembolization result ed low recurrence and long survival in patients with hepatocellular carcinoma associated with hepatitis B virus . This method showed fewer side effects and should be recommended UNLABELLED Fatal hepatitis B virus ( HBV ) reactivation in lymphoma patients with " resolved " HBV infection ( hepatitis B surface antigen [ HBsAg ] negative and hepatitis B core antibody [ anti-HBc ] positive ) can occur , but the true incidence and severity remain unclear . From June 2009 to December 2011 , 150 newly diagnosed lymphoma patients with resolved HBV infection who were to receive rituximab-CHOP ( cyclophosphamide , doxorubicin , vincristine , prednisolone)-based chemotherapy were prospect ively followed . HBV DNA was checked at baseline , at the start of each cycle of chemotherapy , and every 4 weeks for 1 year after completion of rituximab-CHOP chemotherapy . Patients with documented HBV reactivation were treated with entecavir at a dosage of 0.5 mg/day for 48 weeks . HBV reactivation was defined as a greater than 10-fold increase in HBV DNA , compared with previous nadir levels , and hepatitis flare was defined as a greater than 3-fold increase in alanine aminotransferase ( ALT ) that exceeded 100 IU/L. Incidence of HBV reactivation and HBV-related hepatitis flares was 10.4 and 6.4 per 100 person-year , respectively . Severe HBV-related hepatitis ( ALT > 10-fold of upper limit of normal ) occurred in 4 patients , despite entecavir treatment . Patients with hepatitis flare exhibited significantly higher incidence of reappearance of HBsAg after HBV reactivation ( 100 % vs. 28.5 % ; P=0.003 ) . CONCLUSION In lymphoma patients with resolved HBV infections , chemotherapy-induced HBV reactivation is not uncommon , but can be managed with regular monitoring of HBV DNA and prompt antiviral therapy . Serological breakthrough ( i.e. , reappearance of HBsAg ) is the most important predictor of HBV-related hepatitis flare . ( Hepatology 2014;59:2092 - 2100 ) |
14,009 | 12,492,100 | A systematic review of case-series reports shows imatinib , when indirectly compared to conventional therapy , improves overall 12-month survival , but not surrogate outcomes , in individuals with Philadelphia chromosome-positive chronic myeloid leukemia ( Ph+ CML ) in myeloid-blast crisis , and accelerated phase .
Surrogate outcomes , but not overall survival , were improved in chronic phase disease .
Preliminary data from one r and omized controlled trial suggest imatinib has a greater impact on surrogate outcomes compared to the combination of interferonalpha and cytarabine in patients undergoing treatment for chronic phase Ph+CML , however , it is not yet known whether it prolongs or improves quality of life | Imatinib mesylate ( GleevecTM ) is a tyrosine kinase inhibitor , one of a new class of anticancer drugs called signal transduction inhibitors . | Blast crisis is the most advanced stage of chronic myelogenous leukemia ( CML ) and is highly refractory to therapy . CML is caused by expression of the chimeric BCR-ABL tyrosine kinase oncogene , the product of the t(9;22 ) Philadelphia translocation . Imatinib ( Glivec , formerly STI571 ) is a rationally developed , orally administered inhibitor of the Bcr-Abl tyrosine kinase . A total of 260 patients with CML were enrolled in a phase II trial , of whom 229 had a confirmed diagnosis of CML in blast crisis . Patients were treated with imatinib in daily oral doses of 400 mg or 600 mg . Imatinib induced hematologic responses in 52 % of patients and sustained hematologic responses lasting at least 4 weeks in 31 % of patients , including complete hematologic responses in 8 % . For patients with a sustained response , the estimated median response duration was 10 months . Imatinib induced major cytogenetic responses in 16 % of patients , with 7 % of the responses being complete . Median survival time was 6.9 months . Nonhematologic adverse reactions were frequent but generally mild or moderate . Episodes of severe cytopenia were also frequent and were attributable to the underlying condition and treatment with imatinib . Drug-related adverse events led to discontinuation of therapy in 5 % of patients , most often because of cytopenia , skin disorders , or gastrointestinal reactions . These results demonstrate that imatinib has substantial activity and a favorable safety profile when used as a single agent in patients with CML in blast crisis . Additional clinical studies are warranted to explore the efficacy and feasibility of imatinib used in combination with other antileukemic drugs BACKGROUND BCR-ABL is a constitutively activated tyrosine kinase that causes chronic myeloid leukemia ( CML ) . Since tyrosine kinase activity is essential to the transforming function of BCR-ABL , an inhibitor of the kinase could be an effective treatment for CML . METHODS We conducted a phase 1 , dose-escalating trial of STI571 ( formerly known as CGP 57148B ) , a specific inhibitor of the BCR-ABL tyrosine kinase . STI571 was administered orally to 83 patients with CML in the chronic phase in whom treatment with interferon alfa had failed . Patients were successively assigned to 1 of 14 doses ranging from 25 to 1000 mg per day . RESULTS Adverse effects of STI571 were minimal ; the most common were nausea , myalgias , edema , and diarrhea . A maximal tolerated dose was not identified . Complete hematologic responses were observed in 53 of 54 patients treated with daily doses of 300 mg or more and typically occurred in the first four weeks of therapy . Of the 54 patients treated with doses of 300 mg or more , cytogenetic responses occurred in 29 , including 17 ( 31 percent of the 54 patients who received this dose ) with major responses ( 0 to 35 percent of cells in metaphase positive for the Philadelphia chromosome ) ; 7 of these patients had complete cytogenetic remissions . CONCLUSIONS STI571 is well tolerated and has significant antileukemic activity in patients with CML in whom treatment with interferon alfa had failed . Our results provide evidence of the essential role of BCR-ABL tyrosine kinase activity in CML and demonstrate the potential for the development of anticancer drugs based on the specific molecular abnormality present in a human cancer BACKGROUND BCR-ABL , a constitutively activated tyrosine kinase , is the product of the Philadelphia chromosome . This enzyme is present in virtually all cases of chronic myeloid leukemia ( CML ) throughout the course of the disease , and in 20 percent of cases of acute lymphoblastic leukemia ( ALL ) . On the basis of the substantial activity of the inhibitor in patients in the chronic phase , we evaluated STI571 ( formerly known as CGP 57148B ) , a specific inhibitor of the BCR-ABL tyrosine kinase , in patients who had CML in blast crisis and in patients with ALL who had the Ph chromosome . METHODS In this dose-escalating pilot study , 58 patients were treated with STI571 ; 38 patients had a myeloid blast crisis and 20 had ALL or a lymphoid blast crisis . Treatment was given orally at daily doses ranging from 300 to 1000 mg . RESULTS Responses occurred in 21 of 38 patients ( 55 percent ) with a myeloid-blast-crisis phenotype ; 4 of these 21 patients had a complete hematologic response . Of 20 patients with a lymphoid blast crisis or ALL , 14 ( 70 percent ) had a response , including 4 who had complete responses . Seven patients with a myeloid blast crisis continue to receive treatment and remain in remission from 101 to 349 days after starting the treatment . All but one patient with a lymphoid blast crisis or ALL has relapsed . The most frequent adverse effects were nausea , vomiting , edema , thrombocytopenia , and neutropenia . CONCLUSIONS The BCR-ABL tyrosine kinase inhibitor STI571 is well tolerated and has substantial activity in the blast crises of CML and in Ph-positive ALL Chronic myelogenous leukemia ( CML ) is caused by expression of the BCR-ABL tyrosine kinase oncogene , the product of the t(9;22 ) Philadelphia translocation . Patients with CML in accelerated phase have rapidly progressive disease and are characteristically unresponsive to existing therapies . Imatinib ( formerly STI571 ) is a rationally developed , orally administered inhibitor of the Bcr-Abl kinase . A total of 235 CML patients were enrolled in this study , of whom 181 had a confirmed diagnosis of accelerated phase . Patients were treated with imatinib at 400 or 600 mg/d and were evaluated for hematologic and cytogenetic response , time to progression , survival , and toxicity . Imatinib induced hematologic response in 82 % of patients and sustained hematologic responses lasting at least 4 weeks in 69 % ( complete in 34 % ) . The rate of major cytogenetic response was 24 % ( complete in 17 % ) . Estimated 12-month progression-free and overall survival rates were 59 % and 74 % , respectively . Nonhematologic toxicity was usually mild or moderate , and hematologic toxicity was manageable . In comparison to 400 mg , imatinib doses of 600 mg/d led to more cytogenetic responses ( 28 % compared to 16 % ) , longer duration of response ( 79 % compared to 57 % at 12 months ) , time to disease progression ( 67 % compared to 44 % at 12 months ) , and overall survival ( 78 % compared to 65 % at 12 months ) , with no clinical ly relevant increase in toxicity . Orally administered imatinib is an effective and well-tolerated treatment for patients with CML in accelerated phase . A daily dose of 600 mg is more effective than 400 mg , with similar toxicity BACKGROUND Treatment with interferon prolongs survival in chronic myelogenous leukemia . We conducted a clinical trial to assess the efficacy of treatment with a combination of interferon and cytarabine . METHODS Previously untreated patients with chronic myelogenous leukemia were r and omly assigned to receive either hydroxyurea ( 50 mg per kilogram of body weight per day ) and interferon alfa-2b ( 5 million units per square meter of body-surface area per day ) , or hydroxyurea and interferon in the same dosages plus monthly courses of cytarabine ( 20 mg per square meter per day , for 10 days ) . The end points were overall survival , complete hematologic remission at 6 months , and major cytogenetic response ( less than 35 percent Philadelphia chromosome-positive cells in the bone marrow ) at 12 months . RESULTS The trial was stopped when a sequential analysis showed a benefit of interferon and cytarabine . A significant improvement in survival was observed in the interferon-cytarabine group ( 360 patients ) as compared with the interferon group ( 361 patients ) ( P=0.02 ; relative risk of death , 0.64 ; 95 percent confidence interval , 0.44 to 0.93 ) . After three years , the survival rate was 85.7 percent with interferon and cytarabine and 79.1 percent with interferon alone . The rate of hematologic response was higher in the interferon-cytarabine group than in the interferon group ( P=0.003 ) . Major cytogenetic responses were observed 12 months after r and omization in 126 of 311 patients treated with interferon and cytarabine ( 41 percent ) and in 75 of 314 patients treated with interferon only ( 24 percent , P<0.001 ) . CONCLUSIONS The combination of interferon and cytarabine , as compared with interferon alone , increases the rate of major cytogenetic response and prolongs survival in patients with the chronic phase of chronic myelogenous leukemia |
14,010 | 26,501,851 | Sensitivity and specificity of qualitative NMP22 . | Bladder cancer is the fourth most commonly diagnosed cancer in U.S. men and the 10th most commonly diagnosed cancer in U.S. women ( 1 ) .
St and ard methods for diagnosis of bladder cancer involve cytologic evaluation of urine , imaging tests , and cystoscopy ( 2 , 3 ) .
Because cystoscopy is uncomfortable and costly , alternative diagnostic methods have been sought .
Urine-based biomarkers have been developed as potential alternatives or adjuncts to st and ard tests for the initial diagnosis of bladder cancer or identification of recurrent disease ( 4 ) .
The purpose of this study was to systematic ally review the evidence on the comparative accuracy of urinary biomarkers for diagnosis of bladder cancer .
This article focuses on the accuracy of urinary biomarkers for initial diagnosis of bladder cancer or for diagnosis of recurrent disease , including any variance in diagnostic accuracy based on tumor characteristics , patient characteristics , or the nature of presenting signs or symptoms . | To evaluate , in a prospect i ve study , the role of immunocytology in assessing patients with gross haematuria . Due to the high prevalence of urothelial cancer in this population , a thorough assessment is m and atory to identify all patients with tumours Objective : To compare the BTA statTM test ( BTA stat ) , a new one-step immunochromatographic assay that can be performed in the urologist ’s office or in the laboratory , to voided urine cytology and bladder wash cytology ( cytology ) in the diagnosis and monitoring of cancer of the bladder ( BC ) . Methods : BTA stat and cytology were performed in a double-blinded , prospect i ve , clinical study on specimens from 240 subjects ( 68 females ; mean age of subjects : 64 years ) suspected of having BC . Results : In 107 subjects with final diagnoses of BC confirmed by cystoscopy or cystoscopy and biopsy , the overall sensitivities of BTA stat and cytology were 65 and 33 % , respectively . For tumor grade s I , II , and III , the sensitivities of BTA stat were 39 , 67 and 83 % , respectively . Those of cytology were 4 , 20 and 69 % . Nine subjects had a diagnosis of ‘ suspicious for bladder cancer ’ . The specificities of BTA stat and cytology in the 124 subjects without BC were 64 and 99 % , respectively . In the subjects with a history of BC ( n = 74 ) , the specificities of BTA stat and cytology were 72 and 99 % , respectively . The specificity of BTA stat was lower in subjects with benign or malignant genitourinary disease other than BC ( 46 % ) than in subjects without genitourinary disease ( 71 % ) . Conclusions : The BTA stat test is considerably more sensitive than cytology in the detection of BC and can replace cytology as an adjunct to cystoscopy in the diagnosis and follow-up of patients with BC . However , due to low specificity , BTA stat should not be used without first ruling out potential interferences such as infections , renal disease and cancer , or genitourinary trauma PURPOSE While detecting bladder cancer , bladder tumor markers demonstrate improved sensitivity compared with urinary cytology but the current limitation is the low specificity and positive predictive value , that is high false-positive rate . We examined the clinical categories of the false-positive results , established relative exclusion criteria , and recalculated the specificity and positive predictive value of this assay with these criteria . MATERIAL S AND METHODS A total of 608 patients considered at risk for bladder cancer presented to a urology clinic and su bmi tted a single urine sample . Of the 608 patients 529 ( 87 % ) presented with de novo hematuria or chronic voiding symptoms without a diagnosis of bladder cancer . There were 79 ( 13.0 % ) patients being monitored with a known history of bladder cancer . Each urine sample was examined via cytology , urinalysis , culture and NMP22 protein assay . All patients underwent office cystoscopy , and transurethral resection and /or biopsy if a bladder tumor was suspected . RESULTS Of the 608 patients 226 ( 37.2 % ) presented with microscopic hematuria , 143 ( 23.5 % ) with gross hematuria and 239 ( 39.3 % ) had chronic symptoms of urinary frequency or dysuria . There were 52 ( 8.6 % ) patients who had histologically confirmed bladder cancer . Of these 52 cancers NMP22 detected 46 ( 88.5 % ) , whereas cytology identified only 16 ( 30.8 % ) . When atypical cytology was considered positive , cytology detected 32 ( 61.5 % ) cases . In the 135 patients with increased NMP22 values the 46 identified tumors were accompanied by 89 false-positive values yielding a specificity of 83.9 % and a positive predictive value of 34.1 % . These false-positive results were divided into 6 clinical categories . Exclusion of these categories improved the specificity and positive predictive value of NMP22 to 99.2 % and 92.0 % , respectively , yielding results similar to urinary cytology ( 99.8 % and 94.1 % ) . CONCLUSIONS Awareness and exclusion of the categories of false-positive results can increase the specificity and positive predictive value of NMP22 , enhancing the clinical use of this urinary tumor marker BACKGROUND Human complement factor H-related protein ( hCFHrp ) is produced by several bladder cancer cell lines and may be useful as a cancer marker . The aim of this study was to compare urinary hCFHrp and cytology for the detection of bladder cancer found by cystoscopy in patients with suggestive signs , symptoms , or preliminary test results . METHODS The BTA TRAK assay , a quantitative enzyme immunoassay for the bladder tumor-associated antigen in urine , was compared with exfoliative cytology in 220 patients ( 155 men , 65 women ; mean age , 64.2 years ) presenting with signs , symptoms , or preliminary diagnostic results suggestive of this disease . Cystoscopy was the st and ard of detection . RESULTS In the 100 patients found to have bladder cancer , the overall sensitivities of the BTA TRAK assay ( at a previously determined decision threshold of 14 kilounits/L ) and cytology were 66 % ( 66 of 100 ) and 33 % ( 33 of 100 ) , respectively ( P < 0.001 ) . The BTA TRAK assay proved to be statistically more sensitive than cytology for tumor grade s I and II and for stage Ta and T1 tumors . In contrast , the overall specificity of the BTA TRAK assay in the 120 patients without cystoscopically confirmed bladder cancer was 69 % ( 83 of 120 ) and that of cytology was 99 % ( 119 of 120 ; P < 0.001 ) . The specificity of the BTA TRAK assay was higher in patients without benign or malignant genitourinary disease other than bladder cancer ( 76 % ; n = 89 ) than in patients with these conditions . When the BTA TRAK assay and cytology were used together such that a positive result in either test was scored as positive and the results compared with those of the BTA TRAK assay alone , increases in overall sensitivity and equivalent specificity were observed . CONCLUSION Because of its relatively high sensitivity , the BTA TRAK assay could complement cytology as an adjunct to cystoscopy in the diagnosis and follow-up of most patients with bladder cancer PURPOSE The limitations of cytology and the invasiveness of cystoscopy for detecting bladder cancer generate increasing interest in noninvasive , urine bound diagnostic tools . We assessed the diagnostic value of the newly developed immunocytochemical test , Immunocyt , which detects cellular markers specific for transitional cell cancer in the voided urine of patients with bladder cancer . MATERIAL S AND METHODS Participating in our prospect i ve study were 264 consecutive patients with a mean age of 65.9 years , including 114 in whom symptoms were suggestive of bladder cancer and 150 who were being followed after complete transurethral resection of superficial transitional cell carcinoma . Voided urine specimens were evaluated by st and ard cytology and the Immunocyt test , which traces the monoclonal antibodies M344 , LDQ10 and 19A211 against transitional cell carcinoma in exfoliated urothelial cells . In all cases cystoscopy was subsequently performed and any suspicious lesion was evaluated by biopsy . RESULTS Histologically proved transitional cell carcinoma was found in 79 patients . Immunocyt with cytology had 89.9 % sensitivity overall ( 84 , 88 and 96.5 % in grade s 1 to 3 disease , respectively ) . A total of 34 ( 43 % ) , 3 ( 3.8 % ) and 34 ( 43 % ) cases were positive on Immunocyt only , cytology only and both evaluations , respectively . In 8 cases ( 10.1 % ) both tests were negative . Overall Immunocyt only was 86.1 % sensitive ( 84 , 84 and 89.6 % in grade s 1 to 3 disease , respectively ) and 79.4 % specific . Overall cytology only was 46.8 % sensitive ( 4 , 52 and 79.3 % in grade s 1 to 3 disease , respectively ) and 98.2 % specific . CONCLUSIONS Immunocyt is a noninvasive , highly sensitive test for detecting transitional cell carcinoma of all grade s and stages . When combined with conventional urinary cytology , it may replace cystoscopy in select patients , especially in followup protocol s of low grade transitional cell carcinoma PURPOSE The limitations of urinary cytology and the invasiveness of cystoscopy generate an increasing interest in noninvasive diagnostic tools for the management of transitional cell carcinoma . We assess the clinical performance of ImmunoCyt ( DiagnoCure , Inc. , Saint-Foy , Canada ) in the detection of bladder cancer in a 10-center French trial . MATERIAL S AND METHODS From October 2000 to April 2001 , 694 patients undergoing cystoscopy were prospect ively included in the study . Of the patients 458 ( 66 % ) had been previously treated for superficial transitional cell carcinoma and 236 ( 34 % ) were referred for symptoms suggestive of bladder cancer . All patients underwent ImmunoCyt test and st and ard urinary cytology from voided urine as well as a complete evaluation including cystoscopy and transurethral resection or biopsy of suspicious lesions . Sensitivity and specificity values of urinary cytology and ImmunoCyt whether or not combined were calculated using cystoscopy as the gold st and ard and histopathology when available . RESULTS A total of 85 recurrent and 58 newly diagnosed bladder tumors were diagnosed by cystoscopy and histologicaly confirmed . Overall sensitivity of urinary cytology was 17.9 % , 46.3 % and 63.8 % respectively , for G1 , G2 and G3 transitional cell carcinoma , whereas that of ImmunoCyt was 60.7 % , 75.6 % and 76.8 % . Sensitivity of the combined tests was 66.7 % , 78 % and 87 % , respectively . Moreover , 10 of 55 ( 18.2 % ) new pT1 and pT2 or greater tumors were diagnosed by ImmunoCyt alone . Specificity of urinary cytology was 94.5 % , whereas that of ImmunoCyt was 84.2 % . Specificity of the combined tests was 80.7 % . Marked variations in urinary cytology sensitivity were observed among the different centers ( 27.3 % to 66.7 % ) , whereas combined assays ( urinary cytology and ImmunoCyt ) enhanced the overall sensitivity in the 80 % range at most centers . CONCLUSIONS This prospect i ve multicenter series confirmed a marked increase in sensitivity without significant loss in specificity when including ImmunoCyt in st and ard urinary cytology protocol . This increased sensitivity was observed in high grade lesions ( with 100 % sensitivity for carcinoma in situ ) as well in low grade , low stage tumors BACKGROUND AND AIMS Cystoscopy and urine cytology are the st and ard tools for monitoring superficial bladder cancer . The sensitivity of cystoscopy is , however , limited to the tumours that can be visualised , and the sensitivity of cytology is relatively low in low-stage/low- grade tumours . Therefore , new tumour markers have been developed . BTA stat has been reported to have high sensitivity in detecting both primary and recurrent bladder tumours , and may have the potential to detect tumours that can not be visualised by routine cystoscopy including recurrences in upper tract . The objective of the study was to analyse the reliability of routine follow-up cystoscopy by further investigating patients with positive marker status , BTA stat Test and urine cytology , but negative cystoscopy . MATERIAL AND METHODS 446 consecutive patients being followed for bladder cancer were analysed in a prospect i ve multicenter study . A voided urine sample was obtained prior to cystoscopy and split for culture , cytology and BTA stat testing . In the case of positive marker status , BTA stat Test or urine cytology , but negative cystoscopy patients were further investigated by i.v . urography or renal ultrasound and r and om biopsies . The sensitivity of routine follow-up cystoscopy is reported . RESULTS Of 446 patients 131 ( 29.4 % ) had a bladder cancer recurrence at routine cystoscopy . Of the remaining 315 patients not having recurrent tumour at cystoscopy , 56 patients ( 17.8 % ) had positive BTA stat Test result , 6 ( 1.9 % ) had positive cytology and 5 were positive by both tests . Nine recurrences that were missed at routine follow-up cystoscopy were detected by further investigations making the total number of bladder confined recurrent tumours 140 ( 140/446 , 31.4 % ) . Five of these 9 recurrences were high grade lesions ( 1 T1G3 , 4 CIS ) , of which 4 were detected by positive cytology . The overall sensitivity of cystoscopy was 93.6 % . CONCLUSIONS We found that routine follow-up cystoscopy may miss over five percent of the recurrent tumours . Although cystoscopy remains the gold st and ard for bladder cancer follow-up , it is suggested that even with negative cystoscopy patients with positive marker status , BTA stat Test and especially urine cytology , should be considered at risk for coexisting , and in some case even high grade recurrence OBJECTIVES To test the clinical value and role of uCyt+ as a noninvasive tool for the detection and surveillance of urothelial carcinoma . METHODS Included in this prospect i ve study were 235 patients ( mean age 71.5 years , range 32 to 86 ) . Of these , 98 patients had signs and symptoms suggestive of bladder cancer and 137 patients were being followed up after complete transurethral resection of superficial urothelial cancer ( UC ) . All patients underwent urinary cytology and the uCyt+ test performed on ThinPrep ( thin layer ) . All underwent subsequent cystoscopy and evaluation of any suspicious lesion by biopsy . RESULTS A total of 102 patients had histologically proven UC . In the group of patients with signs and symptoms suspicious of UC , the sensitivity of cytology increased from 5 % for G1 to 84.6 % for G3 tumors ; for uCyt+ , it was 85 % for G1 , 100 % for G2 , and 92.3 % for G3 tumors . Combining cytology and uCyt+ , the sensitivity was 85 % for G1 and 100 % for G2 and G3 . In the group of follow-up patients , the sensitivity of cytology increased from 4.3 % for G1 to 94.4 % for G3 tumors ; for uCyt+ , it was 78.2 % for G1 , 70 % for G2 , and 94.4 % for G3 tumors . Combining both tests , the sensitivity was 78.2 % for G1 , 90 % for G2 , and 100 % for G3 . CONCLUSIONS The uCyt+ is a valid test in the detection of UC of all grade s and stages . It improves the sensitivity of cytology in low- grade tumors . The two tests combined may be a highly sensitive method to detect UC early in detection and surveillance Purpose : To prospect ively evaluate the clinical role of urinary NMP22 as a marker for transitional cell carcinoma of the urinary bladder in screening and surveillance setting s. Patients and Methods : Single voided specimens were obtained from 211 consecutive patients who presented for flexible cystoscopy . Of these , 96 patients presented with haematuria or irritative symptoms ( screening ) , the remaining 115 were patients with known transitional cell carcinoma on follow – up ( surveillance ) . The urine sample was used for urine microscopy , cytology and for measuring NMP22 levels . Results : Bladder tumours were found in 16 of 96 ( 16.6 % ) patients in the screening group and 17 of 115 ( 15.6 % ) patients on surveillance . The NMP22 levels were significantly lower in patients with lower stage ( Ta vs. T1–3 ) , low grade ( G1 , G2 vs. G3 , CIS ) and papillary morphology . The optimum threshold for NMP22 obtained from the ROC curve was 4.75 U/ml , providing a sensitivity , specificity , positive predictive value and negative predictive value of 42.4 , 85 , 38.5 and 88.6 % , respectively . Sensitivity and specificity were better in patients being screened than in those on surveillance . In both groups , urinary NMP22 had similar diagnostic characteristics as urinary cytology . Conclusions : Urinary NMP22 levels are significantly higher in patients with bladder tumour than in those negative for tumours , and test predictability improves with increasing stage and grade . The overall sensitivity for urinary NMP22 is similar to , but not superior to urine cytology . Our study suggests that the clinical role of urinary NMP22 as a diagnostic marker can be at best supportive only OBJECTIVES To evaluate the clinical utility of a Multi-color FISH ( fluorescence in situ hybridization ) assay in voided urine specimens for the detection of bladder cancer and its recurrences , comparing the results with those afforded by urinary cytology . METHODS Voided urine sample s from 86 patients were obtained for urine cytology and FISH analysis . The latter was performed using a mixture of fluorescent labeled DNA probes for the centromeric regions of chromosomes 3 , 7 and 17 , and the 9p21 region . Cystoscopy with biopsy or tumor resection was performed in all patients , comparing the pathological results with the cytological and FISH findings . RESULTS Urinary cytology affords an overall sensitivity of 63.8 % , the figure being 25 % for grade 1 , 66.6 % for grade 2 and 94.7 % for grade 3 tumors . The sensitivities for FISH were 53.3 % for grade 1 , 83.3 % for grade 2 and 100 % for grade 3 tumors , with an overall sensitivity of 80.4 % . The specificities of urinary cytology and FISH were 86.1 and 85.3 % , respectively . CONCLUSIONS FISH improves the sensitivity rates obtained with urine cytology for bladder cancer detection in all tumor grade s and stages , and offers similar specificity . FISH doubles the accuracy of urinary cytology in application to low grade -stage tumors , and detects all high grade infiltrating tumors The combination of a noninvasive , quantitative immunoassay , NMP22 , with voided urinary cytology prior to cystoscopy was evaluated in patients with urothelial transitional cell carcinoma . Fifty-six patients with a history of transitional cell carcinoma were evaluated . Voided urine was obtained for NMP22 and cytology prior to cystoscopy . One hundred and twenty-three NMP22 assays , 124 cytologies , and 124 cystoscopies were performed . The type of anesthesia used for cystoscopic evaluation was determined by the NMP22 value in 30 patients . Cystoscopy results were considered positive on biopsy-confirmed malignancy . The reference value used for NMP22 was 10.0 U/ml . NMP22 , cytology , and the combination of NMP22 and cytology were compared to cystoscopy and to pathologic grading and staging . Thirty-four recurrent transitional cell carcinoma episodes occurred ; 22 were low- grade ( I-II ) , and 12 were high- grade ( III-IV ) . Twenty-seven were stage Ta ; four were T1 ; and three were T3b or 4 . Within this group , NMP22 detected low- and high- grade tumors equally , as compared to cytology , which was sensitive only to high- grade tumors . Nineteen patients were NMP22-negative and underwent cystoscopy under topical anesthesia ; 17 were tumor-free . Eleven patients were NMP22-positive and had anesthesia , and all had visible lesions , which were subjected to biopsy and were resected . Six lesions were tumors , five were inflammatory . Overall sensitivity of combined NMP22 and cytology was 70 % ; specificity was 72 % ; positive predictive value was 54 % ; and negative predictive value was 77 % . An accurate assessment of the risk of a bladder cancer can be obtained with NMP22 , cytology , and cystoscopy in patients with a history of bladder cancer . NMP22 values can be used to determine the level of anesthesia for cystoscopy in patients with a history of bladder cancer OBJECTIVES To evaluate the sensitivity and specificity of the Bard BTA test compared with bladder washing cytology in patients with a history of transitional cell bladder cancer undergoing routine follow-up cystoscopy . METHODS During routine follow-up for transitional cell bladder cancer , 75 patients underwent cystoscopy , bladder washing cytology , and the Bard BTA test , a latex agglutination test that qualitatively detects basement membrane complexes in voided urine . From October 1994 to October 1995 , a total of 104 Bard BTA test examinations were performed . The results of the Bard BTA test were compared with those attained with cystoscopy and bladder washing cytology . RESULTS Cystoscopy found tumors in 13 cases . The Bard BTA test was diagnostic in 7 ( 54 % ) cases ; it was more sensitive than bladder washing cytology , which was positive in only 3 ( 23 % ) cases . However , the specificity of the Bard BTA was lower ( 9 % clinical ly unconfirmed positive tests ) than that attained with cytology . In 2 patients ( 2 % ) in whom the cystoscopy was negative , the Bard BTA test was predictive for a positive cystoscopy 3 and 5 months later . CONCLUSIONS The Bard BTA test is a noninvasive test that may be an important addition to cystoscopy and cytology in the routine surveillance of patients with a history of transitional cell cancer of the bladder PURPOSE The noninvasive detection of urothelial carcinoma remains challenging . We prospect ively evaluated urine markers for bladder carcinoma . We compared the NMP22 ( Matritech , Cambridge , Massachusetts ) and BTA Stat ( Bard Diagnostics , Redmond , Washington ) tests with immunocytology using mAbs 486p3/12 and BG7 against Lewis X antigen . MATERIAL S AND METHODS The NMP22 and BTA Stat tests were performed in urine sample s and immunocytology with mAbs 486p3/12 and BG7 staining were performed in bladder washing specimens in 146 sample s of 115 patients undergoing transurethral resection for suspected bladder carcinoma ( 70 ) or 45 undergoing followup cystoscopy for a history of bladder carcinoma ( 76 ) . Bladder carcinoma was detected in 54 patients , including stages pTa in 25 , pT1 in 20 , pT2 in 8 and carcinoma in situ in 1 , while 61 had no evidence of bladder carcinoma . The cutoff was 10 units per ml . for the NMP22 , 30 % positive cells for 486p3/12 and 5 % positive cells for the Lewis X tests . RESULTS BTA Stat was positive in 65 sample s ( 44.5 % ) and NMP22 was positive in 69 ( 47.3 % ) . Immunocytology with mAbs 486p3/12 and BG7 against Lewis X was positive in 52 ( 35.6 % ) and 109 ( 74.7 % ) sample s , respectively . Sensitivity was 70.3 % for BTA Stat , 68.5 % for NMP22 , 68.5 % for 486p3/12 and 94.4 % for Lewis X. Specificity was 70.6 % for BTA Stat , 65.2 % for NMP22 , 83.6 % for 486p3/12 and 36.9 % for Lewis X. Area under the receiver operating characteristics curve was 0.6804 for NMP22 , 0.7226 for Lewis X and 0.8002 for 486p3/12 . False-positive results on BTA Stat in 2 of 22 patients ( 9 % ) , on NMP22 in 2 of 25 ( 8 % ) , on 486p3/12 in 3 of 11 ( 27 % ) and on Lewis X in 4 of 43 ( 9.3 % ) were associated with tumor recurrence . Furthermore , negative results on BTA Stat in 2 of 39 patients ( 2 % ) , on NMP22 in 2 of 36 ( 0.5 % ) , on Lewis X in 0 of 18 ( 0 % ) and on 486p3/12 in 1 of 50 ( 2 % ) was associated with tumor recurrence during followup . CONCLUSIONS Immunocytology with mAbs against Lewis X showed higher sensitivity than all commercially available tests evaluated . Because of its high sensitivity and high negative predictive value , it may be useful for screening in a high risk population . Patients with a false-positive 486p3/12 test results are at increased risk for tumor recurrence compared with those with negative results OBJECTIVES To evaluate the nuclear matrix protein 22 ( NMP22 ) test in the management of patients after transurethral resection ( TUR ) of recurrent transitional cell carcinoma of the bladder . METHODS The NMP22 test was performed in 137 patients : in 42 patients , a bladder recurrence was detected by cystoscopy and histologically confirmed ; 95 patients were recurrence-free at cytology and cystoscopy performed at least 3 months after TUR . RESULTS In patients with tumoral recurrence , the mean NMP22 value was 54.8 U/mL. The false-negative rate was 28.5 % . In recurrence-free patients , the mean NMP22 value was 22.8 U/mL. The specificity of the NMP22 test was 61 % . Higher NMP22 mean values ( 29.6 versus 15.8 U/mL ) were found in patients who underwent intravesical chemotherapy or immunotherapy . CONCLUSIONS Despite its good sensitivity , the NMP22 test can not be adopted as a routine tool in the surveillance after TUR of patients with superficial bladder cancer because of its low specificity PURPOSE We assess the sensitivity and specificity of the noninvasive BTA stat urine test for detection of primary and recurrent bladder cancer with special reference to the size , grade and stage of the tumors , and examine the effect of intravesical bacillus Calmette-Guerin treatment on the results . MATERIAL S AND METHODS A total of 250 patients recruited from 3 medical centers provided voided urine sample s for the BTA stat test and cytopathological study . Of these patients 162 were monitored following resection of bladder tumors and 88 were evaluated for the first time for hematuria or irritative voiding symptoms . Each patient underwent cystoscopy . Biopsies were obtained when a bladder tumor was seen or if carcinoma in situ was suspected . The sensitivity , specificity and accuracy of the BTA stat test were compared to st and ard voided urine cytology . RESULTS No tumor was found in 122 patients , primary transitional cell carcinoma was found in 71 and cystoscopy revealed recurrent tumors in 57 . Overall sensitivity of the BTA stat test was 82.8 % and specificity was 68.9 % . Sensitivity of urine cytology was 39.8 % and specificity was 95.1 % . The BTA stat test detected 90.1 % of the primary and 73.7 % of the recurrent tumors . All patients with carcinoma in situ , high grade tumors , muscle invasive cancer and tumors larger than 2 cm . were diagnosed by the BTA stat test . CONCLUSIONS The BTA stat test can be used as a screening test for bladder cancer in patients with hematuria or irritative voiding symptoms and for surveillance of those who have not been treated with intravesical bacillus Calmette-Guerin INTRODUCTION Discrimination between malignant and nonmalignant conditions remains the key problem in assessing microhaematuria . This prospect i ve study investigated the role of immunocytology in the evaluation of patients with microhaematuria . METHODS uCyt+ is a commercially available immunocytologic assay based on microscopic detection of tumour-associated antigens on the membrane of urothelial cells by immunofluorescence . Between October 2000 and August 2005 , 189 consecutive patients with newly diagnosed painless microhaematuria without prior transitional cell carcinoma were included . All urine sample s were examined cytologically and immunocytologically . Of the 189 sample s , 178 ( 94 % ) were assessable . RESULTS Clinical assessment by physical examination , laboratory tests , endoscopy , and imaging modalities found bladder cancer in 8 patients ( 4 % ) . Further diagnoses were benign prostatic hyperplasia ( 54 cases , 29 % ) , cystitis ( including interstitial cystitis ; 20 cases , 11 % ) , urolithiasis ( 18 cases , 9 % ) , tumours of other origin ( 6 cases , 2 % ) , and " further conditions " ( 26 cases , 13 % ) . In 57 patients ( 30 % ) the reasons for haematuria were not disclosed . Immunocytology was positive in 7 of 8 bladder tumours ( 87 % ) and negative in 154 of 170 patients with haematuria for other reasons ( 91 % ) . CONCLUSIONS The high sensitivity and good specificity of immunocytology in the diagnosis of bladder cancer was confirmed in this population with a low disease prevalence . Only one tumour of low malignant potential was missed by immunocytology . If assessment of these patients would have been based only on immunocytology , 154 costly and invasive diagnostic procedures could have been avoided , with only 16 of 170 individuals ( 9 % ) undergoing these examinations unnecessarily . The findings justify a prospect i ve investigation of this issue You are back where we put you in the previous article1 on diagnostic tests in this series on how to use the medical literature : in the library study ing an article that will guide you in interpreting ventilation-perfusion ( V/Q ) lung scans . Using the criteria in Table 1 , you have decided that the Prospect i ve Investigation of Pulmonary Diagnosis ( PIOPED ) study 2 will provide you with valid information . Just then , another Objectives : Application of immunocytology directed against antigens of urothelial tumor cells or tumor-associated breakdown products intends to improve the sensitivity of the diagnosis of superficial transitional cell carcinoma ( TCC ) of the urinary bladder . In this study , the mode of action , sensitivity and specificity of the Bard ® BTA test , detecting a tumor-associated release of a basement membrane complex , was addressed and compared with voided urine cytology ( VUC ) . Results : Contrary to grade , a significant ( p = 0.003 ) relationship between tumor stage and BTA test sensitivity was observed , being 23.8 , 33.3 to 100 % for Ta ( n = 42 ) , T1 ( n = 6 ) to ≥T2 ( n = 5 ) , respectively . These data suggest an association between an increase of the BTA test sensitivity with an increase of basement membrane degradation or interruption . With regard to this mechanism , the BTA test may be of special importance for monitoring tumor progression or increase in tumor invasiveness . Detection of low-stage , low- grade tumors by noninvasive techniques remains a challenge . The sensitivity of the BTA test for the presence of TCC was 32.3 % , while that of VUC was 17.7 % , but in this study the difference was not statistically significant . Furthermore , the BTA test was not more effective in identifying the various tumor grade s , stages or stage/ grade groupings . However , dividing the patients in two groups of low risk ( TaG1/TaG2 ) and high risk ( TaG3 to ≥T2 ) leads to a significant ( p = 0.008 ) increased sensitivity of the BTA test ( 27.3 % ) in detecting patients with low-risk tumors compared to VUC ( 3.0 % ) . The specificity of the BTA test in patients with a history of TCC was 81.6 % , while that of VUC was 98.9 % . Conclusion : The sensitivity of the BTA test is at least equivalent to VUC and may be suited to monitor increase in stage in patients suffering from bladder carcinoma , but can not replace cystoscopy in patients suspected for a bladder tumor PURPOSE The UroVysion fluorescence in situ hybridization assay ( UroVysion Bladder Cancer Recurrence Kit , Vysis , Inc. , Downers Grove , Illinois ) is a multi-target assay that detects aneuploidy of chromosomes 3 , 7 and 17 , and loss of the 9p21 b and in exfoliated cells in urine from patients with transitional cell carcinoma . We performed 2 multicenter trials . In 1 trial we compared the sensitivity of the FISH assay to the BTA Stat test ( Bion Scientific , Redmond , Washington ) and voided cytology in the detection of transitional cell carcinoma . In a separate study of healthy volunteers and patients with other ( nontransitional cell carcinoma ) conditions we determined the specificity of the FISH assay . MATERIAL S AND METHODS A total of 176 patients with transitional cell carcinoma in the previous 9 months provided voided urine before cystoscopy . Each specimen was split , preserved and shipped to a central laboratory where all 3 tests were performed . All sites were blinded to results . Sensitivity calculations were based on central pathology review of resected tissue . Specificity was determined by testing 275 volunteers who were healthy and with nontransitional cell carcinoma conditions . RESULTS The 21 sites enrolled 176 patients with a history of transitional cell carcinoma , with 62 recurrences while undergoing surveillance . Overall sensitivities ( with 95 % CI ) were FISH 71 % ( 95 % CI 58 to 82 ) , BTA Stat test 50 % ( 37 to 63 ) and cytology 26 % ( 16 to 39 ) . FISH was negative in 260 of the 275 healthy volunteers or patients with no history of transitional cell carcinoma ( specificity 94.5 % ) . CONCLUSIONS Sensitivity of the FISH assay is superior to that of cytology and at least equivalent to the BTA Stat test in detecting recurrent transitional cell carcinoma . Its specificity approaches that of cytology . Further testing of its clinical use is warranted PURPOSE We compare the diagnostic value of NMP22 and BTA stat testing , and QUANTICYT computer assisted dual parameter image analysis to cytology and cystoscopy in patients who had symptoms suggestive of transitional cell cancer or were being followed after treatment for that disease . MATERIAL S AND METHODS We prospect ively evaluated voided urine and /or barbotage specimens from 291 patients a mean of 65.2 years old . All voided urine sample s were evaluated by quick staining and st and ard cytology , the BTA stat 1-step qualitative assay ( which detects a bladder tumor associated antigen ) and the NMP22 test ( which detects a nuclear mitotic apparatus protein ) . In addition , barbotage specimens were evaluated by QUANTICYT computer assisted dual parameter image analysis . All patients underwent subsequent cystoscopy and biopsy evaluation of any suspicious lesion . Sensitivity , specificity , and the predictive value of positive and negative results were determined in correlation with endoscopic and histological findings . RESULTS In 91 patients with histologically proved transitional cell carcinoma overall sensitivity was 48 , 57 , 58 , 59 and 59 % for the NMP22 test , the BTA stat test , rapid staining cytology of barbotage sample s , rapid staining cytology of voided urine specimens and image analysis , respectively . For histological grade s 1 to 3 underlying transitional cell carcinoma sensitivity was 17 , 61 and 90 % for urinary cytology , 48 , 58 and 63 % for the BTA stat test , and 52 , 45 and 50 % for the NMP22 test , respectively . Specificity was 100 % for cytology , 93 % for image analysis , 70 % for the NMP22 test and 68 % for the BTA stat test . CONCLUSIONS Immunological markers are superior to cytological evaluation and image analysis for detecting low grade transitional cell carcinoma but they have low specificity and sensitivity in grade 3 transitional cell carcinoma . Urine bound diagnostic tools can not replace cystoscopy PURPOSE We investigated whether the RNA assay uRNA ® and its derivative Cxbladder ® have greater sensitivity for the detection of bladder cancer than cytology , NMP22 ™ BladderChek ™ and NMP22 ™ ELISA , and whether they are useful in risk stratification . MATERIAL S AND METHODS A total of 485 patients presenting with gross hematuria but without a history of urothelial cancer were recruited prospect ively from 11 urology clinics in Australasia . Voided urine sample s were obtained before cystoscopy . The sensitivity and specificity of the RNA tests were compared to cytology and the NMP22 assays using cystoscopy as the reference . The ability of Cxbladder to distinguish between low grade , stage Ta urothelial carcinoma and more advanced urothelial carcinoma was also determined . RESULTS uRNA detected 41 of 66 urothelial carcinoma cases ( 62.1 % sensitivity , 95 % CI 49.3 - 73.8 ) compared with NMP22 ELISA ( 50.0 % , 95 % CI 37.4 - 62.6 ) , BladderChek ( 37.9 % , 95 % CI 26.2 - 50.7 ) and cytology ( 56.1 % , 95 % CI 43.8 - 68.3 ) . Cxbladder , which was developed on the study data , detected 82 % , including 97 % of the high grade tumors and 100 % of tumors stage 1 or greater . The cutoffs for uRNA and Cxbladder were prespecified to give a specificity of 85 % . The specificity of cytology was 94.5 % ( 95 % CI 91.9 - 96.5 ) , NMP22 ELISA 88.0 % , ( 95 % CI 84.6 - 91.0 ) and BladderChek 96.4 % ( 95 % CI 94.2 - 98.0 ) . Cxbladder distinguished between low grade Ta tumors and other detected urothelial carcinoma with a sensitivity of 91 % and a specificity of 90 % . CONCLUSIONS uRNA and Cxbladder showed improved sensitivity for the detection of urothelial carcinoma compared to the NMP22 assays . Stratification with Cxbladder provides a potential method to prioritize patients for the management of waiting lists OBJECTIVE BTA stat is a rapid , urine-based test for bladder cancer that detects human complement factor H related protein ( HCFHrp ) by monoclonal assay . This aim of this study was to assess the efficacy of BTA stat as a diagnostic tool for bladder cancer in symptomatic patients suspected of bladder cancer and in the surveillance of patients with a history of treated bladder cancer . PATIENTS AND METHODS One hundred and six patients presenting with haematuria ( gross or microscopic ) or irritative bladder symptoms presenting to the urology outpatient clinic of Changi General Hospital and 13 patients under bladder cancer surveillance were recruited for this prospect i ve study . All underwent voided urine cytology ( VUC ) , urine culture , urine BTA stat , intravenous urogram and cystoscopy . Sensitivity , specificity , positive and negative predictive values were calculated for both tests . The stage and grade of bladder tumours detected were also correlated with both test results . Causes of false positives and specificity in different patient groups were analysed . RESULTS BTA stat is more sensitive than VUC in detecting primary and recurrent bladder tumours ( 85 % versus 55 % ) but is less specific ( 62.6 % versus 100 % ) . Urinary tract infections and urinary calculi accounted for 62 % of false positives with BTA stat . When patients with positive urine cultures and benign IVU abnormalities were excluded , specificity of BTA stat improved ( 93.9 % cf . 62.6 % ) . BTA stat was highly specific ( 100 % ) and more sensitive than VUC ( 75 % versus 25 % ) in detecting recurrent tumours in asymptomatic patients on cancer surveillance . CONCLUSION A high false positive rate and low predictive value limits the use BTA stat in screening symptomatic patients . However , it has a role in cancer surveillance and in the screening of high-risk asymptomatic individuals . Further prospect i ve trials should be performed to better assess its role in this respect BACKGROUND Among urinary tumor markers we studied the utility of the BTA TRAK assay to diagnose transitional cell carcinoma of the bladder in highly suspiscious patients , in comparison to urine cytology . MATERIAL S AND METHODS A preliminary study of 65 patients was made ( 21 transitional cell carcinoma ( TCC ) , 36 without TCC and 8 excluded patients who received BCG therapy , endocavitary mytomicin or radiotherapy ) , using the BTA TRAK , cytology and cystoscopy . RESULTS 12 out of the 21 selected patients were pTa ( 9 G1 and 3 G2 ) , 2 carcinoma in situ ( CIS ) , 2pT1 ( 1 G2 and 1 G3 ) and 5 muscle invasive tumors ( all of them G3 ) . Setting our cut-off at 18 U/ml , a sensitivity of 52.3 % and a specificity of 88.9 % was reached . BTA TRAK detected 11 out of 21 of the tumors as well as urine cytology . However , BTA TRAK was more sensitive in the detection of low grade tumors ( p<0.05 ) . When considering both tests as complementary , a combined sensitivity of 80.9 % and specificity of 88.5 % were obtained . CONCLUSION BTA TRAK is a valid test for the diagnosis of TCC of the bladder , which is not superior to urine cytology but complementary . More extensive prospect i ve studies are required to vali date this application and others of the BTA TRAK assay used either alone or in combination with urinary cytology in the management of bladder cancer patients OBJECTIVES To study the diagnostic performance of the ImmunoCyt test in patients in follow-up for superficial urothelial cell carcinoma ( UCC ) of the bladder . METHODS Voided urine sample s were collected from all included patients . Sample s were processed with the ImmunoCyt test . The ImmunoCyt slides were scored under a fluorescence microscope by 3 observers . The ImmunoCyt test was considered positive if one or more observers scored the test positive . Urethrocystoscopy ( and additional histologic examination in the case of suspicious cystoscopic findings ) was used as the reference st and ard . To investigate the validity of ImmunoCyt , sensitivity , specificity , positive predictive value , negative predictive value , area under the receiver operating characteristic curve , and diagnostic odds ratios were determined . To investigate the reproducibility of ImmunoCyt , kappa values ( measure of agreement ) were computed . The observers ' findings were analyzed in pairs . RESULTS One hundred four patients in follow-up after primary superficial UCC of the bladder were included . Sample s of 18 patients had to be excluded because of low cellularity ( ie , insufficient assessable urothelial cells ) . Tumor recurrence was found in 22 of the remaining 86 patients ( 17 pTa , 3 pT1 , 1 carcinoma in situ , 1 pT2 or higher ) . The test had a sensitivity of 50 % , specificity of 73 % , positive predictive value of 39 % , and negative predictive value of 81 % . The diagnostic odds ratio was 2.8 ( 95 % confidence interval 1.0 to 7.5 ) . The area under the curve for the different observers varied between 0.54 and 0.60 . The kappa values were low ( 0.05 to 0.45 ) , representing high interobserver variability . CONCLUSIONS The promising results from other studies could not be confirmed in this specific group of patients in follow-up for superficial UCC of the bladder . The validity of ImmunoCyt was insufficient to justify the omission of cystoscopy in patients in follow-up for superficial UCC OBJECTIVES To assess the efficacy of nuclear matrix protein 22 ( NMP-22 ) in the diagnosis of recurrent , superficial bladder cancer and whether it can predict for future recurrence . METHODS Patients with diagnosed and treated superficial transitional cell carcinoma urinary bladder ( Stage Ta , T1 , Tis , Nx , and M0 ) presenting for surveillance follow-up were prospect ively enrolled in this study from February 2004 to August 2005 . These patients underwent urine cytology , NMP-22 testing , and cystopanendoscopy on enrollment in the study . For the next year , these patients underwent cystopanendoscopy and cytology at 3-month intervals . The ability of NMP-22 to predict for recurrence was determined using the cystoscopy findings as the reference st and ard . RESULTS A total of 145 patients were included in the study . Of these , 56 had recurrence at enrollment . Of the 56 patients , 48 had positive NMP-22 findings and 22 had positive urine cytology findings . The sensitivity , specificity , positive predictive value , and negative predictive value was 85.7 % , 77.5 % , 70.6 % , and 89.6 % , respectively , for NMP-22 alone and 92.9 % , 75.3 % , 70.3 % , and 94.4 % , respectively , when the cytology and NMP-22 findings were combined . During the subsequent follow-up of 1 year , 61 recurrences developed in 47 patients . Cox regression analysis showed that those with positive NMP-22 had a 9.57 times greater risk of recurrence during 1 year compared with those with negative NMP-22 . CONCLUSIONS The results of our study have shown that the addition of NMP-22 testing to cytology increases the sensitivity for recurrence detection in patients with superficial transitional cell bladder cancer . Patients with positive NMP-22 findings developed significantly more recurrences compared with those with negative NMP-22 findings BACKGROUND Systematic review s that " compare " the accuracy of 2 or more tests often include different sets of studies for each test . PURPOSE To investigate the availability of direct comparative studies of test accuracy and to assess whether summary estimates of accuracy differ between meta-analyses of noncomparative and comparative studies . DATA SOURCES Systematic review s in any language from the Data base of Abstract s of Review s of Effects and the Cochrane Data base of Systematic Review s from 1994 to October 2012 . STUDY SELECTION 1 of 2 assessors selected review s that evaluated at least 2 tests and identified meta-analyses that included both noncomparative studies and comparative studies . DATA EXTRACTION 1 of 3 assessors extracted data about review and study characteristics and test performance . DATA SYNTHESIS 248 review s compared test accuracy ; of the 6915 studies , 2113 ( 31 % ) were comparative . Thirty-six review s ( with 52 meta-analyses ) had adequate studies to compare results of noncomparative and comparative studies by using a hierarchical summary receiver-operating characteristic meta-regression model for each test comparison . In 10 meta-analyses , noncomparative studies ranked tests in the opposite order of comparative studies . A total of 25 meta-analyses showed more than a 2-fold discrepancy in the relative diagnostic odds ratio between noncomparative and comparative studies . Differences in accuracy estimates between noncomparative and comparative studies were greater than expected by chance ( P < 0.001 ) . LIMITATION A paucity of comparative studies limited exploration of direction in bias . CONCLUSION Evidence derived from noncomparative studies often differs from that derived from comparative studies . Robustly design ed studies in which all patients receive all tests or are r and omly assigned to receive one or other of the tests should be more routinely undertaken and are preferred for evidence to guide test selection . PRIMARY FUNDING SOURCE National Institute for Health Research ( United Kingdom ) |
14,011 | 20,479,693 | CONCLUSION There was insufficient evidence to recommend a consensus view for optimal tumor parameters , dose fractionation , and technical delivery of treatment . | INTRODUCTION Hypofractionated stereotactic body radiotherapy ( SBRT ) is an emerging noninvasive technique for the treatment of oligometastatic cancer .
The use of small numbers of large doses , should in theory , achieve high rates of local control .
The aim of this literature review is to critically assess the use of SBRT for the treatment of pulmonary metastases as judged by its effect on local control , survival , and toxicity . | The dose-response for local tumor control after stereotactic radiotherapy of 92 pulmonary tumors ( 36 NSCLC and 56 metastases ) was evaluated . Short course irradiation of 1 - 8 fractions with different fraction doses was used . After a median follow-up of 14 months ( 2 - 85 months ) 11 local recurrences were observed with significant advantage for higher doses . When normalization to a biologically effective dose ( BED ) is used a dose of 94Gy at the isocenter and 50Gy at the PTV-margin are demonstrated to give 50 % probability of tumor control ( TCD50 ) . Multivariate analysis revealed the dose at the PTV-margin as the only significant factor for local control PURPOSE Surgical resection is st and ard therapy in stage I non-small-cell lung cancer ( NSCLC ) ; however , many patients are inoperable due to comorbid diseases . Building on a previously reported phase I trial , we carried out a prospect i ve phase II trial using stereotactic body radiation therapy ( SBRT ) in this population . PATIENTS AND METHODS Eligible patients included clinical ly staged T1 or T2 ( < or = 7 cm ) , N0 , M0 , biopsy-confirmed NSCLC . All patients had comorbid medical problems that precluded lobectomy . SBRT treatment dose was 60 to 66 Gy total in three fractions during 1 to 2 weeks . RESULTS All 70 patients enrolled completed therapy as planned and median follow-up was 17.5 months . The 3-month major response rate was 60 % . Kaplan-Meier local control at 2 years was 95 % . Altogether , 28 patients have died as a result of cancer ( n = 5 ) , treatment ( n = 6 ) , or comorbid illnesses ( n = 17 ) . Median overall survival was 32.6 months and 2-year overall survival was 54.7 % . Grade 3 to 5 toxicity occurred in a total of 14 patients . Among patients experiencing toxicity , the median time to observation was 10.5 months . Patients treated for tumors in the peripheral lung had 2-year freedom from severe toxicity of 83 % compared with only 54 % for patients with central tumors . CONCLUSION High rates of local control are achieved with this SBRT regimen in medically inoperable patients with stage I NSCLC . Both local recurrence and toxicity occur late after this treatment . This regimen should not be used for patients with tumors near the central airways due to excessive toxicity PURPOSE A Phase I dose escalation study of stereotactic body radiation therapy to assess toxicity and local control rates for patients with medically inoperable Stage I lung cancer . METHODS AND MATERIAL S All patients had non-small-cell lung carcinoma , Stage T1a or T1b N0 , M0 . Patients were immobilized in a stereotactic body frame and treated in escalating doses of radiotherapy beginning at 24 Gy total ( 3 x 8 Gy fractions ) using 7 - 10 beams . Cohorts were dose escalated by 6.0 Gy total with appropriate observation periods . RESULTS The maximum tolerated dose was not achieved in the T1 stratum ( maximum dose = 60 Gy ) , but within the T2 stratum , the maximum tolerated dose was realized at 72 Gy for tumors larger than 5 cm . Dose-limiting toxicity included predominantly bronchitis , pericardial effusion , hypoxia , and pneumonitis . Local failure occurred in 4/19 T1 and 6/28 T2 patients . Nine local failures occurred at doses < or = 16 Gy and only 1 at higher doses . Local failures occurred between 3 and 31 months from treatment . Within the T1 group , 5 patients had distant or regional recurrence as an isolated event , whereas 3 patients had both distant and regional recurrence . Within the T2 group , 2 patients had solitary regional recurrences , and the 4 patients who failed distantly also failed regionally . CONCLUSIONS Stereotactic body radiation therapy seems to be a safe , effective means of treating early-stage lung cancer in medically inoperable patients . Excellent local control was achieved at higher dose cohorts with apparent dose-limiting toxicities in patients with larger tumors PURPOSE Routine assessment was made of tumor metabolic activity as measured by 18F-fluorodeoxyglucose ( FDG ) positron emission tomography ( PET ) in Stage I non-small-cell lung cancer ( NSCLC ) . This report describes PET correlates prospect ively collected after stereotactic body radiotherapy ( SBRT ) for patients with medically inoperable NSCLC . METHODS AND MATERIAL S 14 consecutive patients with medically inoperable Stage I NSCLC were enrolled . All patients received SBRT to 60 - 66 Gy in three fractions . Patients underwent serial planned FDG-PET/computed tomography fusion imaging before SBRT and at 2 , 26 , and 52 weeks after SBRT . RESULTS With median follow-up of 30.2 months , no patients experienced local failure . One patient developed regional failure , 1 developed distant failure , and 1 developed a second primary . The median tumor maximum st and ardized uptake value ( SUV(max ) ) before SBRT was 8.70 . The median SUV(max ) values at 2 , 26 , and 52 weeks after SBRT were 6.04 , 2.80 , and 3.58 , respectively . Patients with low pre-SBRT SUV were more likely to experience initial 2-week rises in SUV , whereas patients with high pre-SBRT SUV commonly had SUV declines 2 weeks after treatment ( p = 0.036 ) . Six of 13 patients had primary tumor SUV(max ) > 3.5 at 12 months after SBRT but remained without evidence of local disease failure on further follow-up . CONCLUSIONS A substantial proportion of patients may have moderately elevated FDG-PET SUV(max ) at 12 months without evidence of local failure on further follow-up . Thus , slightly elevated PET SUV(max ) should not be considered a surrogate for local treatment failure . Our data do not support routine serial FDG-PET/computed tomography for follow-up of patients receiving SBRT for Stage I NSCLC PURPOSE In a previously reported r and omized Southeastern Cancer Study Group ( SECSG ) trial , three cycles of chemotherapy were found to be equivalent to four cycles in patients with favorable-prognosis germ-cell cancer . We have conducted a follow-up analysis of patients treated at Indiana University ( Indianapolis , IN ) to compare long-term survival between the two groups and to examine factors associated with survival . PATIENTS AND METHODS Sixty-nine patients with minimal-stage and 49 patients with moderate-stage disseminated germ-cell tumors were r and omized to either three or four courses of bleomycin , etoposide , and cisplatin ( BEP ) administered every 3 weeks . Median follow-up time is 10.1 years ( range , 7 months to 12.6 years ) . Ninety-two percent of patients have an actual follow-up time of > 5 years , and 97.5 % of patients have an actual follow-up time of > 3 years . RESULTS Survival analysis shows no significant difference between the two treatment groups in terms of overall ( P = .80 ) or disease-free ( P = .93 ) survival . Several clinical variables were examined by univariate analysis ; only serum human chorionic gonadotropin ( HCG ) had an impact on survival . There were two disease-related deaths in 104 patients with HCG < or = 1,000 mIU/mL and five disease-related deaths in 14 patients with HCG greater than 1,000 mIU/mL ( P < .001 ) . Ninety-eight percent ( 95 % CI , 95.2 to 100 ) of patients with favorable prognosis germ-cell tumor with an initial HCG of < or = 1,000 mIU/mL are alive without evidence of disease at 5 + years . CONCLUSION With long-term follow-up , there is no statistically significant difference in survival between three or four cycles of BEP chemotherapy in patients with favorable prognosis germ-cell carcinoma . Serum HCG elevation of greater than 1,000 mIU/mL is a significant predictor of poor outcome in patients with otherwise good-risk disease Background : The purpose of this study was to report initial results of a phase I study using single-fraction stereotactic radiotherapy ( RT ) in patients with inoperable lung tumors . Methods : Eligible patients included those with inoperable T1 - 2N0 non-small cell lung cancer ( NSCLC ) or solitary lung metastases . Treatments were delivered by means of the CyberKnife . All patients underwent computed tomography-guided metallic fiducial placement in the tumor for image-guided targeting . Nine to 20 patients were treated per dose cohort starting at 15 Gy/fraction followed by dose escalation of 5 to 10 Gy to a maximal dose of 30 Gy/fraction . A minimal 3-month period was required between each dose level to monitor toxicity . Results : Thirty-two patients ( 21 NSCLC and 11 metastatic tumors ) were enrolled . At 25 Gy , pulmonary toxicity was noted in patients with prior pulmonary RT and treatment volumes greater than 50 cc ; therefore , dose escalation to 30 Gy was applied only to unirradiated patients and treatment volume less than 50 cc . Ten patients received doses less than 20 Gy , 20 received 25 Gy , and two received 30 Gy . RT-related complications were noted for doses greater than 25 Gy and included four cases of grade 2 to 3 pneumonitis , one pleural effusion , and three possible treatment-related deaths . The 1-year freedom from local progression was 91 % for dose greater than 20 Gy and 54 % for dose less than 20 Gy in NSCLC ( p = 0.03 ) . NSCLC patients had significantly better freedom from relapse ( p = 0.003 ) and borderline higher survival than those with metastatic tumors ( p = 0.07 ) . Conclusions : Single-fraction stereotactic RT is feasible for selected patients with lung tumors . For those with prior thoracic RT , 25 Gy may be too toxic . Higher dose was associated with improved local control . Longer follow-up is necessary to determine the treatment efficacy and toxicity |
14,012 | 31,620,063 | In a relatively new area of research , the findings from these 4 articles are encouraging and provide initial support for the notion that skills training in a VE can improve real-world performance in sports . | In many setting s , sports training can be difficult to organize , logistically complicated and very costly .
Virtual environments ( VE ) have garnered interest as a tool to train real-world sports skills due to the realism and flexibility that they can deliver .
A key assumption of VE-based training is that the learned skills and experiences transfer to the real world , but do they ? | Objective : The current study examined whether training simulators for the acquisition of procedural skills should emphasize physical fidelity or cognitive fidelity of the task . Background : Simulation-based training for acquiring and practicing procedural skills is becoming widely established . Generally speaking , these simulators offer technological sophistication but disregard theory-based design , leaving unanswered the question of what task features should be represented in the simulators . The authors compared real-world training and two alternative virtual trainers , one emphasizing physical fidelity and the other cognitive fidelity of the task . Method : Participants were r and omly assigned to one of four training groups in a LEGO ® assembly task : virtual-physical fidelity , cognitive fidelity , real world , and control . A posttraining test to assess the development of procedural skills was conducted . Results : Both the virtual-physical fidelity and cognitive fidelity training methods produced better performance time than no training at all , as did the real-world training . The cognitive fidelity training was inferior in terms of test time compared to the real-world training , whereas the virtual-physical fidelity training was not . In contrast , only the real-world and the cognitive fidelity groups , and not the virtual-physical fidelity group , required significantly less time than the control group for error correction . Conclusion : The two training methods have complementary advantages . Application : Combining physical fidelity and cognitive training methods can enhance procedural skills acquisition when real-world training is not practicable Objective To demonstrate that virtual reality ( VR ) training transfers technical skills to the operating room ( OR ) environment . Summary Background Data The use of VR surgical simulation to train skills and reduce error risk in the OR has never been demonstrated in a prospect i ve , r and omized , blinded study . Methods Sixteen surgical residents ( PGY 1–4 ) had baseline psychomotor abilities assessed , then were r and omized to either VR training ( MIST VR simulator diathermy task ) until expert criterion levels established by experienced laparoscopists were achieved ( n = 8) , or control non-VR-trained ( n = 8) . All subjects performed laparoscopic cholecystectomy with an attending surgeon blinded to training status . Videotapes of gallbladder dissection were review ed independently by two investigators blinded to subject identity and training , and scored for eight predefined errors for each procedure minute ( interrater reliability of error assessment r > 0.80 ) . Results No differences in baseline assessment s were found between groups . Gallbladder dissection was 29 % faster for VR-trained residents . Non-VR-trained residents were nine times more likely to transiently fail to make progress ( P < .007 , Mann-Whitney test ) and five times more likely to injure the gallbladder or burn nontarget tissue ( chi-square = 4.27 , P < .04 ) . Mean errors were six times less likely to occur in the VR-trained group ( 1.19 vs. 7.38 errors per case;P < .008 , Mann-Whitney test ) . Conclusions The use of VR surgical simulation to reach specific target criteria significantly improved the OR performance of residents during laparoscopic cholecystectomy . This validation of transfer of training skills from VR to OR sets the stage for more sophisticated uses of VR in assessment , training , error reduction , and certification of surgeons We assessed the effectiveness of two generalized visual training programmes in enhancing visual and motor performance for racquet sports . Forty young participants were assigned equally to groups undertaking visual training using Revien and Gabor ’s Sports Vision programme ( Group 1 ) , visual training using Revien ’s Eyerobics ( Group 2 ) , a placebo condition involving reading ( Group 3 ) and a control condition involving physical practice only ( Group 4 ) . Measures of basic visual function and of sport-specific motor performance were obtained from all participants before and immediately after a 4-week training period . Significant pre- to post-training differences were evident on some of the measures ; however , these were not group-dependent . Contrary to the cl aims made by proponents of generalized visual training , we found no evidence that the visual training programmes led to improvements in either vision or motor performance above and beyond those result ing simply from test familiarity |
14,013 | 31,634,917 | The goals of fluid resuscitation are to restore end-organ | Acute upper gastrointestinal bleeding ( UGIB ) is common , but the annual incidence has been decreasing : from 78 to 61 cases in 100000 persons from 2001 to 2009 in one survey ( 1 ) .
Nonetheless , 30-day mortality remains high , at up to 11 % ( 2 ) .
The most recent guidelines for managing UGIB were published primarily between 2010 and 2015 , including those from our group ( in 2003 , with an up date in 2010 ) ( 3 , 4 ) , the American College of Gastroenterology ( in 2012 ) ( 5 ) , the American Society for Gastrointestinal Endoscopy ( in 2012 ) ( 6 ) , the National Institute for Health and Care Excellence ( NICE ) ( in 2012 ) ( 7 ) , and the European Society of Gastrointestinal Endoscopy ( in 2015 ) ( 8) .
More recently , guidelines from the Asia-Pacific Working Group were up date d in 2018 ( 9 ) .
The management of UGIB has advanced with new endoscopic techniques , and the pharmacologic l and scape has changed .
Anticoagulant or antiplatelet therapy , including combination therapy , is becoming more common , substantially increasing the risk for UGIB ( 10 ) .
Thus , the International Consensus Group agreed that an up date to the 2010 recommendations for the management of UGIB ( 4 ) was warranted . | BACKGROUND Upper-gastrointestinal haemorrhage is a frequent reason for hospital admission . Although most risk scoring systems for this disorder incorporate endoscopic findings , the Glasgow-Blatchford bleeding score ( GBS ) is based on simple clinical and laboratory variables ; a score of 0 identifies low-risk patients who might be suitable for outpatient management . We aim ed to evaluate the GBS then assess the effect of a protocol based on this score for non-admission of low-risk individuals . METHODS Our study was undertaken at four hospitals in the UK . We calculated GBS and admission ( pre-endoscopy ) and full ( post-endoscopy ) Rockall scores for consecutive patients presenting with upper-gastrointestinal haemorrhage . With receiver-operating characteristic ( ROC ) curves , we compared the ability of these scores to predict either need for clinical intervention or death . We then prospect ively assessed at two hospitals the introduction of GBS scoring to avoid admission of low-risk patients . FINDINGS Of 676 people presenting with upper-gastrointestinal haemorrhage , we identified 105 ( 16 % ) who scored 0 on the GBS . For prediction of need for intervention or death , GBS ( area under ROC curve 0.90 [ 95 % CI 0.88 - 0.93 ] ) was superior to full Rockall score ( 0.81 [ 0.77 - 0.84 ] ) , which in turn was better than the admission Rockall score ( 0.70 [ 0.65 - 0.75 ] ) . When introduced into clinical practice , 123 patients ( 22 % ) with upper-gastrointestinal haemorrhage were classified as low risk , of whom 84 ( 68 % ) were managed as out patients without adverse events . The proportion of individuals with this condition admitted to hospital also fell ( 96 % to 71 % , p<0.00001 ) . INTERPRETATION The GBS identifies many patients presenting to general hospitals with upper-gastrointestinal haemorrhage who can be managed safely as out patients . This score reduces admissions for this condition , allowing more appropriate use of in-patient re sources Background Hemorrhagic shock is responsible for one third of trauma related deaths . We hypothesized that intraoperative hypotensive resuscitation would improve survival for patients undergoing operative control of hemorrhage following penetrating trauma . Methods Between July 1 , 2007 , and March 28 , 2013 , penetrating trauma patients aged 14 years to 45 years with a systolic blood pressure of 90 mm Hg or lower requiring laparotomy or thoracotomy for control of hemorrhage were r and omized 1:1 based on a target minimum mean arterial pressure ( MAP ) of 50 mm Hg ( experimental arm , LMAP ) or 65 mm Hg ( control arm , HMAP ) . Patients were followed up 30 days postoperatively . The primary outcome of mortality ; secondary outcomes including stroke , myocardial infa rct ion , renal failure , coagulopathy , and infection ; and other clinical data were analyzed between study arms using univariate and Kaplan-Meier analyses . Results The trial enrolled 168 patients ( 86 LMAP , 82 HMAP patients ) before early termination , in part because of clinical equipoise and futility . Injuries result ed from gunshot wounds ( 76 % ) and stab wounds ( 24 % ) ; 90 % of the patients were male , and the median age was 31 years . Baseline vitals , laboratory results , and injury severity were similar between groups . Intraoperative MAP was 65.5 ± 11.6 mm Hg in the LMAP group and 69.1 ± 13.8 mm Hg in the HMAP group ( p = 0.07 ) . No significant survival advantage existed for the LMAP group at 30 days ( p = 0.48 ) or 24 hours ( p = 0.27 ) . Secondary outcomes were similar for the LMAP and HMAP groups : acute myocardial infa rct ion ( 1 % vs. 2 % ) , stroke ( 0 % vs. 3 % ) , any renal failure ( 15 % vs. 12 % ) , coagulopathy ( 28 % vs. 29 % ) , and infection ( 59 % vs. 58 % ) ( p > 0.05 for all ) . Acute renal injury occurred less often in the LMAP than in HMAP group ( 13 % vs. 30 % , p = 0.01 ) . Conclusion This study was unable to demonstrate that hypotensive resuscitation at a target MAP of 50 mm Hg could significantly improve 30-day mortality . Further study is necessary to fully realize the benefits of hypotensive resuscitation . LEVEL OF EVIDENCE Therapeutic study , level II BACKGROUND Rapid reversal of vitamin K antagonist (VKA)-induced anticoagulation is often necessary for patients needing urgent surgical or invasive procedures . The optimum means of VKA reversal has not been established in comparative clinical trials . We compared the efficacy and safety of four-factor prothrombin complex concentrate ( 4F-PCC ) with that of plasma in VKA-treated patients needing urgent surgical or invasive procedures . METHODS In a multicentre , open-label , phase 3b r and omised trial we enrolled patients aged 18 years or older needing rapid VKA reversal before an urgent surgical or invasive procedure . We r and omly assigned patients in a 1:1 ratio to receive vitamin K concomitant with a single dose of either 4F-PCC ( Beriplex/Kcentra/Confidex ; CSL Behring , Marburg , Germany ) or plasma , with dosing based on international normalised ratio ( INR ) and weight . The primary endpoint was effective haemostasis , and the co- primary endpoint was rapid INR reduction ( ≤1·3 at 0·5 h after infusion end ) . The analyses were intended to evaluate , in a hierarchical fashion , first non-inferiority ( lower limit 95 % CI greater than -10 % for group difference ) for both endpoints , then superiority ( lower limit 95 % CI > 0 % ) if non-inferiority was achieved . Adverse events and serious adverse events were reported to days 10 and 45 , respectively . This trial is registered at Clinical Trials.gov , number NCT00803101 . FINDINGS 181 patients were r and omised ( 4F-PCC n=90 ; plasma n=91 ) . The intention-to-treat efficacy population comprised 168 patients ( 4F-PCC , n=87 ; plasma , n=81 ) . Effective haemostasis was achieved in 78 ( 90 % ) patients in the 4F-PCC group compared with 61 ( 75 % ) patients in the plasma group , demonstrating both non-inferiority and superiority of 4F-PCC over plasma ( difference 14·3 % , 95 % CI 2·8 - 25·8 ) . Rapid INR reduction was achieved in 48 ( 55 % ) patients in the 4F-PCC group compared with eight ( 10 % ) patients in the plasma group , demonstrating both non-inferiority and superiority of 4F-PCC over plasma ( difference 45·3 % , 95 % CI 31·9 - 56·4 ) . The safety profile of 4F-PCC was generally similar to that of plasma ; 49 ( 56 % ) patients receiving 4F-PCC had adverse events compared with 53 ( 60 % ) patients receiving plasma . Adverse events of interest were thromboembolic adverse events ( six [ 7 % ] patients receiving 4F-PCC vs seven [ 8 % ] patients receiving plasma ) , fluid overload or similar cardiac events ( three [ 3 % ] patients vs 11 [ 13 % ] patients ) , and late bleeding events ( three [ 3 % ] patients vs four [ 5 % ] patients ) . INTERPRETATION 4F-PCC is non-inferior and superior to plasma for rapid INR reversal and effective haemostasis in patients needing VKA reversal for urgent surgical or invasive procedures . FUNDING CSL Behring BACKGROUND Concurrent therapy with a proton-pump inhibitor is a st and ard treatment for patients receiving aspirin who are at risk for ulcer . Current U.S. guidelines also recommend clopidrogel for patients who have major gastrointestinal intolerance of aspirin . We compared clopidogrel with aspirin plus esomeprazole for the prevention of recurrent bleeding from ulcers in high-risk patients . METHODS We studied patients who took aspirin to prevent vascular diseases and who presented with ulcer bleeding . After the ulcers had healed , we r and omly assigned patients who were negative for Helicobacter pylori to receive either 75 mg of clopidogrel daily plus esomeprazole placebo twice daily or 80 mg of aspirin daily plus 20 mg of esomeprazole twice daily for 12 months . The end point was recurrent ulcer bleeding . RESULTS We enrolled 320 patients ( 161 patients assigned to receive clopidogrel and 159 to receive aspirin plus esomeprazole ) . Recurrent ulcer bleeding occurred in 13 patients receiving clopidogrel and 1 receiving aspirin plus esomeprazole . The cumulative incidence of recurrent bleeding during the 12-month period was 8.6 percent ( 95 percent confidence interval , 4.1 to 13.1 percent ) among patients who received clopidogrel and 0.7 percent ( 95 percent confidence interval , 0 to 2.0 percent ) among those who received aspirin plus esomeprazole ( difference , 7.9 percentage points ; 95 percent confidence interval for the difference , 3.4 to 12.4 ; P=0.001 ) . CONCLUSIONS Among patients with a history of aspirin-induced ulcer bleeding whose ulcers had healed before they received the study treatment , aspirin plus esomeprazole was superior to clopidogrel in the prevention of recurrent ulcer bleeding . Our finding does not support the current recommendation that patients with major gastrointestinal intolerance of aspirin be given clopidogrel The number of published systematic review s of studies of healthcare interventions has increased rapidly and these are used extensively for clinical and policy decisions . Systematic review s are subject to a range of biases and increasingly include non-r and omised studies of interventions . It is important that users can distinguish high quality review s. Many instruments have been design ed to evaluate different aspects of review s , but there are few comprehensive critical appraisal instruments . AMSTAR was developed to evaluate systematic review s of r and omised trials . In this paper , we report on the updating of AMSTAR and its adaptation to enable more detailed assessment of systematic review s that include r and omised or non-r and omised studies of healthcare interventions , or both . With moves to base more decisions on real world observational evidence we believe that AMSTAR 2 will assist decision makers in the identification of high quality systematic review s , including those based on non-r and omised studies of healthcare interventions BACKGROUND Both balanced crystalloids and saline are used for intravenous fluid administration in critically ill adults , but it is not known which results in better clinical outcomes . METHODS In a pragmatic , cluster‐r and omized , multiple‐crossover trial conducted in five intensive care units at an academic center , we assigned 15,802 adults to receive saline ( 0.9 % sodium chloride ) or balanced crystalloids ( lactated Ringer 's solution or Plasma‐Lyte A ) according to the r and omization of the unit to which they were admitted . The primary outcome was a major adverse kidney event within 30 days — a composite of death from any cause , new renal‐replacement therapy , or persistent renal dysfunction ( defined as an elevation of the creatinine level to ≥200 % of baseline ) — all censored at hospital discharge or 30 days , whichever occurred first . RESULTS Among the 7942 patients in the balanced‐crystalloids group , 1139 ( 14.3 % ) had a major adverse kidney event , as compared with 1211 of 7860 patients ( 15.4 % ) in the saline group ( marginal odds ratio , 0.91 ; 95 % confidence interval [ CI ] , 0.84 to 0.99 ; conditional odds ratio , 0.90 ; 95 % CI , 0.82 to 0.99 ; P=0.04 ) . In‐hospital mortality at 30 days was 10.3 % in the balanced‐crystalloids group and 11.1 % in the saline group ( P=0.06 ) . The incidence of new renal‐replacement therapy was 2.5 % and 2.9 % , respectively ( P=0.08 ) , and the incidence of persistent renal dysfunction was 6.4 % and 6.6 % , respectively ( P=0.60 ) . CONCLUSIONS Among critically ill adults , the use of balanced crystalloids for intravenous fluid administration result ed in a lower rate of the composite outcome of death from any cause , new renal‐replacement therapy , or persistent renal dysfunction than the use of saline . ( Funded by the V and erbilt Institute for Clinical and Translational Research and others ; SMART‐MED and SMART‐SURG Clinical Trials.gov numbers , NCT02444988 and NCT02547779 . BACKGROUND & AIMS For 4 decades , stigmata of recent hemorrhage in patients with nonvariceal lesions have been used for risk stratification and endoscopic hemostasis . The arterial blood flow that underlies the stigmata rarely is monitored , but can be used to determine risk for rebleeding . We performed a r and omized controlled trial to determine whether Doppler endoscopic probe monitoring of blood flow improves risk stratification and outcomes in patients with severe nonvariceal upper gastrointestinal hemorrhage . METHODS In a single-blind study performed at 2 referral centers we assigned 148 patients with severe nonvariceal upper gastrointestinal bleeding ( 125 with ulcers , 19 with Dieulafoy 's lesions , and 4 with Mallory Weiss tears ) to groups that underwent st and ard , visually guided endoscopic hemostasis ( control , n = 76 ) , or endoscopic hemostasis assisted by Doppler monitoring of blood flow under the stigmata ( n = 72 ) . The primary outcome was the rate of rebleeding after 30 days ; secondary outcomes were complications , death , and need for transfusions , surgery , or angiography . RESULTS There was a significant difference in the rates of lesion rebleeding within 30 days of endoscopic hemostasis in the control group ( 26.3 % ) vs the Doppler group ( 11.1 % ) ( P = .0214 ) . The odds ratio for rebleeding with Doppler monitoring was 0.35 ( 95 % confidence interval , 0.143 - 0.8565 ) and the number needed to treat was 7 . CONCLUSIONS In a r and omized controlled trial of patients with severe upper gastrointestinal hemorrhage from ulcers or other lesions , Doppler probe guided endoscopic hemostasis significantly reduced 30-day rates of rebleeding compared with st and ard , visually guided hemostasis . Guidelines for nonvariceal gastrointestinal bleeding should incorporate these results . Clinical Trials.gov no : NCT00732212 ( CLIN-013 - 07F ) BACKGROUND & AIMS It is not clear whether H2-receptor antagonists ( H2RAs ) reduce the risk of gastrointestinal ( GI ) bleeding in aspirin users at high risk . We performed a double-blind r and omized trial to compare the effects of a proton pump inhibitor ( PPI ) vs a H2RA antagonist in preventing recurrent upper GI bleeding and ulcers in high-risk aspirin users . METHODS We studied 270 users of low-dose aspirin ( ≤325 mg/day ) with a history of endoscopically confirmed ulcer bleeding at 8 sites in Hong Kong and Japan . After healing of ulcers , subjects with negative results from tests for Helicobacter pylori resumed aspirin ( 80 mg ) daily and were assigned r and omly to groups given a once-daily PPI ( rabeprazole , 20 mg ; n = 138 ) or H2RA ( famotidine , 40 mg ; n = 132 ) for up to 12 months . Subjects were evaluated every 2 months ; endoscopy was repeated if they developed symptoms of upper GI bleeding or had a reduction in hemoglobin level greater than 2 g/dL and after 12 months of follow-up evaluation . The adequacy of upper GI protection was assessed by end points of recurrent upper GI bleeding and a composite of recurrent upper GI bleeding or recurrent endoscopic ulcers at month 12 . RESULTS During the 12-month study period , upper GI bleeding recurred in 1 patient receiving rabeprazole ( 0.7 % ; 95 % confidence interval [ CI ] , 0.1%-5.1 % ) and in 4 patients receiving famotidine ( 3.1 % ; 95 % CI , 1.2%-8.1 % ) ( P = .16 ) . The composite end point of recurrent bleeding or endoscopic ulcers at month 12 was reached by 9 patients receiving rabeprazole ( 7.9 % ; 95 % CI , 4.2%-14.7 % ) and 13 patients receiving famotidine ( 12.4 % ; 95 % CI , 7.4%-20.4 % ) ( P = .26 ) . CONCLUSIONS In a r and omized controlled trial of users of low-dose aspirin at risk for recurrent GI bleeding , a slightly lower proportion of patients receiving a PPI along with aspirin developed recurrent bleeding or ulcer than of patients receiving an H2RA with the aspirin , although this difference was not statistically significant . ClincialTrials.gov no : NCT01408186 BACKGROUND & AIMS R and omized trials suggest high-dose proton-pump inhibitors ( PPIs ) administered before gastroscopy in suspected upper gastrointestinal bleeding downstage bleeding ulcer stigmata . We assessed the cost-effectiveness of this approach . METHODS A decision model compared high-dose IVPPI initiated while awaiting endoscopy with IVPPI administration on the basis of endoscopic findings . IVPPIs were given to all patients undergoing endoscopic hemostasis for 72 hours thereafter . Once the IV regimen was completed or for patients with low-risk endoscopic lesions , an oral daily PPI was given for the remainder of the time horizon ( 30 days after endoscopy ) . The unit of effectiveness was the proportion of patients without rebleeding , representing the denominator of the cost-effectiveness ratio ( cost per no rebleeding ) . Probabilities and costs were derived from the literature and national data bases . RESULTS IVPPIs before endoscopy were both slightly more costly and effective than after gastroscopy in the U.S. and Canadian setting s , with cost-effectiveness ratios of US$ 5048 versus $ 4933 and CAN$6064 versus $ 6025 and incremental costs of US$ 45,673 and CAN$19,832 to prevent one additional rebleeding episode , respectively . Sensitivity analyses showed robust results in the US In Canada , intravenous proton-pump inhibitors ( IVPPIs ) before endoscopy became more effective and less costly ( dominant strategy ) when the uncomplicated stay for high-risk patients increased above 6 days or that of low-risk patients decreased below 3 days . CONCLUSIONS With conservative estimates and high- quality data , IVPPIs given before endoscopy are slightly more effective and costly than no administration . In Canada , this approach becomes dominant as the duration of hospitalization for high-risk ulcer patients increases or that of low-risk ulcer patients decreases AIM To compare the recurrent bleeding after endoscopic injection of different epinephrine volumes with hemoclips in patients with bleeding peptic ulcer . METHODS Between January 2005 and December 2009 , 150 patients with gastric or duodenal bleeding ulcer with major stigmata of hemorrhage and nonbleeding visible vessel in an ulcer bed ( Forrest IIa ) were included in the study . Patients were r and omized to receive a small-volume epinephrine group ( 15 to 25 mL injection group ; Group 1 , n = 50 ) , a large-volume epinephrine group ( 30 to 40 mL injection group ; Group 2 , n = 50 ) and a hemoclip group ( Group 3 , n = 50 ) . The rate of recurrent bleeding , as the primary outcome , was compared between the groups of patients included in the study . Secondary outcomes compared between the groups were primary hemostasis rate , permanent hemostasis , need for emergency surgery , 30 d mortality , bleeding-related deaths , length of hospital stay and transfusion requirements . RESULTS Initial hemostasis was obtained in all patients . The rate of early recurrent bleeding was 30 % ( 15/50 ) in the small-volume epinephrine group ( Group 1 ) and 16 % ( 8/50 ) in the large-volume epinephrine group ( Group 2 ) ( P = 0.09 ) . The rate of recurrent bleeding was 4 % ( 2/50 ) in the hemoclip group ( Group 3 ) ; the difference was statistically significant with regard to patients treated with either small-volume or large-volume epinephrine solution ( P = 0.0005 and P = 0.045 , respectively ) . Duration of hospital stay was significantly shorter among patients treated with hemoclips than among patients treated with epinephrine whereas there were no differences in transfusion requirement or even 30 d mortality between the groups . CONCLUSION Endoclip is superior to both small and large volume injection of epinephrine in the prevention of recurrent bleeding in patients with peptic ulcer BACKGROUND Urgent endoscopy in patients with acute upper-GI bleeding identifies many patients who may be safely treated without hospitalization . The aim of this multicenter trial was to determine whether urgent endoscopy effectively decreases health care re source utilization in a real-life setting where primary care providers determine the course of care . METHODS Ninety-three out patients with acute upper-GI bleeding were r and omized to either urgent endoscopy ( before hospitalization ) or elective endoscopy after admission . The results of urgent endoscopy and a recommendation regarding patient disposition were provided to the attending physician . Medical outcomes and re source utilization were measured . RESULTS The timing of endoscopy did not affect re source utilization or patient outcomes . Length of stay was similar ( urgent endoscopy , OR 3.98 days : 95 % CI[2.84 , 5.11 ] vs. elective endoscopy , OR 3.26 days : 95 % CI[2.32 , 4.21 ] , p=0.45 ) . The mean number of days in an intensive care unit was the same ( 1.2 days ) . The urgent endoscopy group had more high-risk endoscopic lesions ( 15 vs. 9 ; p=0.031 ) . Outpatient care was recommended for 19 patients ( 40 % ) . Only 4 patients were discharged . CONCLUSIONS Urgent endoscopy did not reduce hospitalization or re source utilization because the results of early endoscopy did not impact the decision by attending physicians regarding admission . For early ( triage ) endoscopy to impact re source utilization , the results of endoscopy must change subsequent patient care BACKGROUND Omeprazole , usually used in the antiplatelet therapy during percutaneous coronary intervention ( PCI ) in acute coronary syndrome ( ACS ) , has been reported to increase ischemic events in retrospective studies . However , other clinical trials gave paradoxical results . The aim of this study was to assess the effects of omeprazole on clopidogrel efficacy and clinical events . METHODS All patients ( n = 172 ) received aspirin ( loading dose 300 mg and maintenance dose 100 mg/d ) and clopidogrel ( loading dose 600 mg and maintenance dose 75 mg/d ) during the therapy . They were r and omized to receive omeprazole ( 20 mg/d ) or placebo for 30 days . Residual platelet activities in the adenosine 5'-diphosphate ( ADP ) pathway were detected on the fifth day after PCI with thrombelastography (TEG)-mapping . The clinical events were recorded after one month . RESULTS According to the five levels of platelet activities , the frequency distributions of the inhibition rates were significantly different ( P = 0.0062 ) . However , no significant change was seen in the distribution among the highest or the lowest inhibiting levels ( > 95 % and < 30 % inhibition rate ) . And there were no significant differences ( P > 0.05 ) in events incidence , while gastro-intestinal bleeding decreased in co-administration of omeprazole . CONCLUSIONS Omeprazole significantly blunts clopidogrel efficacy while not exacerbates ischemic events in ACS undergoing PCI . Omeprazole even can decrease gastro-intestinal bleeding in those patients BACKGROUND Gastrointestinal complications are an important problem of antithrombotic therapy . Proton-pump inhibitors ( PPIs ) are believed to decrease the risk of such complications , though no r and omized trial has proved this in patients receiving dual antiplatelet therapy . Recently , concerns have been raised about the potential for PPIs to blunt the efficacy of clopidogrel . METHODS We r and omly assigned patients with an indication for dual antiplatelet therapy to receive clopidogrel in combination with either omeprazole or placebo , in addition to aspirin . The primary gastrointestinal end point was a composite of overt or occult bleeding , symptomatic gastroduodenal ulcers or erosions , obstruction , or perforation . The primary cardiovascular end point was a composite of death from cardiovascular causes , nonfatal myocardial infa rct ion , revascularization , or stroke . The trial was terminated prematurely when the sponsor lost financing . RESULTS We planned to enroll about 5000 patients ; a total of 3873 were r and omly assigned and 3761 were included in analyses . In all , 51 patients had a gastrointestinal event ; the event rate was 1.1 % with omeprazole and 2.9 % with placebo at 180 days ( hazard ratio with omeprazole , 0.34 , 95 % confidence interval [ CI ] , 0.18 to 0.63 ; P<0.001 ) . The rate of overt upper gastrointestinal bleeding was also reduced with omeprazole as compared with placebo ( hazard ratio , 0.13 ; 95 % CI , 0.03 to 0.56 ; P = 0.001 ) . A total of 109 patients had a cardiovascular event , with event rates of 4.9 % with omeprazole and 5.7 % with placebo ( hazard ratio with omeprazole , 0.99 ; 95 % CI , 0.68 to 1.44 ; P = 0.96 ) ; high-risk subgroups did not show significant heterogeneity . The two groups did not differ significantly in the rate of serious adverse events , though the risk of diarrhea was increased with omeprazole . CONCLUSIONS Among patients receiving aspirin and clopidogrel , prophylactic use of a PPI reduced the rate of upper gastrointestinal bleeding . There was no apparent cardiovascular interaction between clopidogrel and omeprazole , but our results do not rule out a clinical ly meaningful difference in cardiovascular events due to use of a PPI . ( Funded by Cogentus Pharmaceuticals ; Clinical Trials.gov number , NCT00557921 . ) DESCRIPTION A multidisciplinary group of 34 experts from 15 countries developed this up date and expansion of the recommendations on the management of acute nonvariceal upper gastrointestinal bleeding ( UGIB ) from 2003 . METHODS The Appraisal of Guidelines for Research and Evaluation ( AGREE ) process and independent ethics protocol s were used . Sources of data included original and published systematic review s ; r and omized , controlled trials ; and abstract s up to October 2008 . Quality of evidence and strength of recommendations have been rated by using the Grading of Recommendations Assessment , Development , and Evaluation ( GRADE ) criteria . RECOMMENDATIONS Recommendations emphasize early risk stratification , by using vali date d prognostic scales , and early endoscopy ( within 24 hours ) . Endoscopic hemostasis remains indicated for high-risk lesions , whereas data support attempts to dislodge clots with hemostatic , pharmacologic , or combination treatment of the underlying stigmata . Clips or thermocoagulation , alone or with epinephrine injection , are effective methods ; epinephrine injection alone is not recommended . Second-look endoscopy may be useful in selected high-risk patients but is not routinely recommended . Preendoscopy proton-pump inhibitor ( PPI ) therapy may downstage the lesion ; intravenous high-dose PPI therapy after successful endoscopic hemostasis decreases both rebleeding and mortality in patients with high-risk stigmata . Although selected patients can be discharged promptly after endoscopy , high-risk patients should be hospitalized for at least 72 hours after endoscopic hemostasis . For patients with UGIB who require a nonsteroidal anti-inflammatory drug , a PPI with a cyclooxygenase-2 inhibitor is preferred to reduce rebleeding . Patients with UGIB who require secondary cardiovascular prophylaxis should start receiving acetylsalicylic acid ( ASA ) again as soon as cardiovascular risks outweigh gastrointestinal risks ( usually within 7 days ) ; ASA plus PPI therapy is preferred over clopidogrel alone to reduce rebleeding d c p B s i R This is one of a series of statements discussing the use of GI endoscopy in common clinical situations . The St and ards of Practice Committee of the American Society for Gastrointestinal Endoscopy ( ASGE ) prepared this text . In preparing this guideline , a search of the medical literature was performed by using PubMed . Additional references were obtained from the bibliographies of the identified articles and from recommendations of expert consultants . When few or no data exist from well- design ed prospect i ve trials , emphasis is given to results from large series and reports from recognized experts . Guidelines for appropriate use of endoscopy are based on a critical review of the available data and expert consensus at the time that the guidelines are drafted . Further controlled clinical studies may be needed to clarify aspects of this guideline . This guideline may be revised as necessary to account for changes in technology , new data , or other aspects of clinical practice . The recommendations are based on review ed studies and are grade d on the strength of the supporting evidence 1 ( Table 1 ) . he strength of individual recommendations is based on oth the aggregate evidence quality and an assessment of the nticipated benefits and harms . Weaker recommendations re indicated by phrases such as “ We suggest . . . , ” whereas tronger recommendations are typically stated as “ We recmmend . . . . ” This guideline is intended to be an educational device to provide information that may assist endoscopists in providing care to patients . This guideline is not a rule and should not be construed as establishing a legal st and ard of care or as encouraging , advocating , requiring , or discouraging any particular treatment . Clinical decisions in any particular case involve a complex analysis of the patient ’s condition and available courses of action . Therefore , clinical considerations may lead an endoscopist to take a course of action that varies from these guidelines The aim of the present study was to determine the effects of the short-term application of pantoprazole on the co-treatment of acute ST-segment elevation myocardial infa rct ion ( STEMI ) with aspirin and clopidogrel . A total of 207 acute patients showing primary symptoms of STEMI , who received successful emergent percutaneous coronary intervention treatment during hospitalization were r and omly divided into two groups . In the test group proton pump inhibitors ( PPIs ) , the patients were treated with a combination of aspirin and clopidogrel and pantoprazole , while those in the control group were treated only with aspirin and clopidogrel . Gastrointestinal bleeding events and major adverse cardiac events ( MACEs ) were observed in the two groups . Gastrointestinal bleeding events of the two groups mostly occurred within the first week of hospitalization , although the incidence in the PPIs group was significantly higher than that in the control group ( p<0.05 ) . However , no significant difference was observed for the incidence of MACEs between the two groups ( p>0.05 ) . In conclusion , the results of the present study have shown that the short-term application of pantoprazole combined with aspirin and clopidogrel does not increase the incidence of MACEs in patients with acute STEMI , reduces the risk of gastrointestinal bleeding , and is thus worth promoting clinical ly , particularly for high-risk groups Objective To compare the predictive accuracy and clinical utility of five risk scoring systems in the assessment of patients with upper gastrointestinal bleeding . Design International multicentre prospect i ve study . Setting Six large hospitals in Europe , North America , Asia , and Oceania . Participants 3012 consecutive patients presenting over 12 months with upper gastrointestinal bleeding . Main outcome measures Comparison of pre-endoscopy scores ( admission Rockall , AIMS 65 , and Glasgow Blatchford ) and post-endoscopy scores ( full Rockall and PNED ) for their ability to predict predefined clinical endpoints : a composite endpoint ( transfusion , endoscopic treatment , interventional radiology , surgery , or 30 day mortality ) , endoscopic treatment , 30 day mortality , rebleeding , and length of hospital stay . Optimum score thresholds to identify low risk and high risk patients were determined . Results The Glasgow Blatchford score was best ( area under the receiver operating characteristic curve ( AUROC ) 0.86 ) at predicting intervention or death compared with the full Rockall score ( 0.70 ) , PNED score ( 0.69 ) , admission Rockall score ( 0.66 , and AIMS 65 score ( 0.68 ) ( all P<0.001 ) . A Glasgow Blatchford score of ≤1 was the optimum threshold to predict survival without intervention ( sensitivity 98.6 % , specificity 34.6 % ) . The Glasgow Blatchford score was better at predicting endoscopic treatment ( AUROC 0.75 ) than the AIMS 65 ( 0.62 ) and admission Rockall scores ( 0.61 ) ( both P<0.001 ) . A Glasgow Blatchford score of ≥7 was the optimum threshold to predict endoscopic treatment ( sensitivity 80 % , specificity 57 % ) . The PNED ( AUROC 0.77 ) and AIMS 65 scores ( 0.77 ) were best at predicting mortality , with both superior to admission Rockall score ( 0.72 ) and Glasgow Blatchford score ( 0.64 ; P<0.001 ) . Score thresholds of ≥4 for PNED , ≥2 for AIMS 65 , ≥4 for admission Rockall , and ≥5 for full Rockall were optimal at predicting death , with sensitivities of 65.8 - 78.6 % and specificities of 65.0 - 65.3 % . No score was helpful at predicting rebleeding or length of stay . Conclusions The Glasgow Blatchford score has high accuracy at predicting need for hospital based intervention or death . Scores of ≤1 appear the optimum threshold for directing patients to outpatient management . AUROCs of scores for the other endpoints are less than 0.80 , therefore their clinical utility for these outcomes seems to be limited . Trial registration Current Controlled Trials IS RCT N16235737 PURPOSE The aim of this study is to evaluate the preventive effect of proton pump inhibitors on gastrointestinal ( GI ) bleeding in patients with acute coronary syndromes ( ACS ) who are at high risk for GI bleeding . MATERIAL S AND METHODS We enrolled 665 patients with ACS who had one or more of the following risk factors for GI bleeding : 75 years of age or older , history of peptic ulcer disease , history of GI bleeding , cardiogenic shock , and chronic renal dysfunction ( serum creatinine , > 2 mg/dL ) . Patients were r and omly assigned to receive 40 mg of pantoprazole or placebo twice daily for 7 days , in addition to st and ard treatment of ACS . The primary end point was the occurrence of GI bleeding during hospitalization . RESULTS During a median time of hospitalization of 12 days , 12 ( 3.6 % ) of 332 patients in the placebo group had an occurrence of GI bleeding , as compared with 4 ( 1.2 % ) of the 333 patients in the pantoprazole group ( P = .046 , Fisher exact test ) . The log-rank test showed a significant difference between the 2 groups in the time to the occurrence of GI bleeding ( P = .015 ) . Major GI bleeding occurred in 5 ( 1.5 % ) patients in the placebo group but only in 1 ( 0.3 % ) in the pantoprazole group ( P = .12 ) . Pneumonia developed in 22 ( 6.6 % ) patients in the placebo group and 24 ( 7.2 % ) in the pantoprazole group ( χ(2 ) = 0.077 , P = .88 ) . The 30-day mortality was 10.2 % ( 34/332 ) in the placebo group and 10.5 % ( 35/333 ) in the pantoprazole group . CONCLUSIONS In patients with ACS who are at high risk for GI hemorrhage , prophylactic treatment with pantoprazole could reduce the risk of GI bleeding with no significant effects on the incidence of hospital-acquired pneumonia and 30-day mortality BACKGROUND Performance of endoscopy within 24 h is recommended for patients with acute nonvariceal upper gastrointestinal bleeding ( ANVUGIB ) . It is unknown whether performing endoscopy early within this 24 h window is beneficial for clinical ly high-risk patients . METHODS A retrospective review was performed to identify patients presenting to two tertiary care centres with ANVUGIB and either systolic blood pressure lower than 100 mmHg or heart rate greater than 100 beats/min on presentation between 1999 and 2004 . Patients receiving endoscopy within 6 h ( rapid endoscopy [ RE ] ) were compared with patients undergoing endoscopy between 6 h and 24 h ( early endoscopy [ EE ] ) . The primary outcome measure was the development of any adverse bleeding outcome ( rebleeding , surgery for control of bleeding , in-hospital mortality or readmission within 30 days for ANVUGIB ) . RESULTS There were 169 patients who met the entry criteria ( 77 RE patients and 92 EE patients ) . There was no significant difference in the development of any adverse bleeding outcomes between RE and EE patients ( 25 % RE versus 23 % EE , difference between groups 2 % , 95 % CI --9 % to 13 % ) . Transfusion requirements and length of hospital stay also did not differ between the comparator groups . RE was not associated with fewer adverse outcomes , even after adjusting for confounders . CONCLUSION For clinical ly high-risk ANVUGIB patients , performing endoscopy within 6 h of presentation is no more effective than performing endoscopy between 6 h and 24 h after presentation . The role of RE in high-risk ANVUGIB patients requires further delineation in a prospect i ve fashion BACKGROUND Transfusion thresholds for acute upper gastrointestinal bleeding are controversial . So far , only three small , underpowered studies and one single-centre trial have been done . Findings from the single-centre trial showed reduced mortality with restrictive red blood cell ( RBC ) transfusion . We aim ed to assess whether a multicentre , cluster r and omised trial is a feasible method to substantiate or refute this finding . METHODS In this pragmatic , open-label , cluster r and omised feasibility trial , done in six university hospitals in the UK , we enrolled all patients aged 18 years or older with new presentations of acute upper gastrointestinal bleeding , irrespective of comorbidity , except for exsanguinating haemorrhage . We r and omly assigned hospitals ( 1:1 ) with a computer-generated r and omisation sequence ( r and om permuted block size of 6 , without stratification or matching ) to either a restrictive ( transfusion when haemoglobin concentration fell below 80 g/L ) or liberal ( transfusion when haemoglobin concentration fell below 100 g/L ) RBC transfusion policy . Neither patients nor investigators were masked to treatment allocation . Feasibility outcomes were recruitment rate , protocol adherence , haemoglobin concentration , RBC exposure , selection bias , and information to guide design and economic evaluation of the phase 3 trial . Main exploratory clinical outcomes were further bleeding and mortality at day 28 . We did analyses on all enrolled patients for whom an outcome was available . This trial is registered , IS RCT N85757829 and NCT02105532 . FINDINGS Between Sept 3 , 2012 , and March 1 , 2013 , we enrolled 936 patients across six hospitals ( 403 patients in three hospitals with a restrictive policy and 533 patients in three hospitals with a liberal policy ) . Recruitment rate was significantly higher for the liberal than for the restrictive policy ( 62 % vs 55 % ; p=0·04 ) . Despite some baseline imbalances , Rockall and Blatchford risk scores were identical between policies . Protocol adherence was 96 % ( SD 10 ) in the restrictive policy vs 83 % ( 25 ) in the liberal policy ( difference 14 % ; 95 % CI 7 - 21 ; p=0·005 ) . Mean last recorded haemoglobin concentration was 116 ( SD 24 ) g/L for patients on the restrictive policy and 118 ( 20 ) g/L for those on the liberal policy ( difference -2·0 [ 95 % CI -12·0 to 7·0 ] ; p=0·50 ) . Fewer patients received RBCs on the restrictive policy than on the liberal policy ( restrictive policy 133 [ 33 % ] vs liberal policy 247 [ 46 % ] ; difference -12 % [ 95 % CI -35 to 11 ] ; p=0·23 ) , with fewer RBC units transfused ( mean 1·2 [ SD 2·1 ] vs 1·9 [ 2·8 ] ; difference -0·7 [ -1·6 to 0·3 ] ; p=0·12 ) , although these differences were not significant . We noted no significant difference in clinical outcomes . INTERPRETATION A cluster r and omised design led to rapid recruitment , high protocol adherence , separation in degree of anaemia between groups , and non-significant reduction in RBC transfusion in the restrictive policy . A large cluster r and omised trial to assess the effectiveness of transfusion strategies for acute upper gastrointestinal bleeding is both feasible and essential before clinical practice guidelines change to recommend restrictive transfusion for all patients with acute upper gastrointestinal bleeding . FUNDING NHS Blood and Transplant Research and Development BACKGROUND The endoscopic hemoclip method is a safe and effective hemostatic method for managing bleeding peptic ulcers . We compared the hemostatic efficacy of the endoscopic hemoclip method with that of hypertonic saline-epinephrine ( HSE ) injection and a combined method in the management of bleeding peptic ulcers . METHODS From July 1994 to July 1997 , we conducted a r and omized clinical trial of endoscopic hemostasis involving 124 patients with actively bleeding or visible vessels at endoscopic inspection . RESULTS Patients were r and omly assigned to hemoclip ( 41 patients ) , HSE ( 41 patients ) , and combined treatment groups ( 42 patients ) . Initial hemostasis was achieved in 97.6 % , 95.1 % , and 97.6 % of cases , respectively . Recurrent bleeding developed in 2.4 % , 14.6 % , and 9.5 % of cases . Emergency operations were performed in 4.9 % , 14.6 % , and 2.3 % of cases . The hemostasis rate was 71.4 % , 50 % , and 66.7 % for spurting hemorrhage in each group . Permanent hemostasis was achieved in 95.1 % , 85.4 % , and 95.2 % of cases . Three patients had complications , all in the HSE group . CONCLUSIONS The hemoclip method is an effective hemostatic procedure and is safer than HSE injection . The combined method does not provide substantial advantage over use of the hemoclip method alone in the hemostatic management of bleeding peptic ulcers OBJECTIVES : The treatment of peptic ulcer bleeding ( PUB ) is complex , and mortality remains high . We present results from a nationwide initiative to monitor and improve the quality of care ( QOC ) in PUB . METHODS : All Danish hospitals treating PUB patients between 2004 and 2011 prospect ively registered demographic , clinical , and prognostic data . QOC was evaluated using eight process and outcome indicators , including time to initial endoscopy , hemostasis obtainment , proportion undergoing surgery , rebleeding risks , and 30-day mortality . RESULTS : A total of 13,498 PUB patients ( median age 74 years ) were included , of which one-quarter were in-hospital bleeders . Preadmission use of anticoagulants , multiple coexisting diseases , and the American Society of Anesthesiologists scores increased between 2004 and 2011 . Considerable improvements were observed for most QOC indicators over time . Endoscopic treatment was successful with primary hemostasis achieved in more patients ( 94 % in 2010–2011 vs. 89 % in 2004–2006 , relative risk ( RR ) 1.06 ( 95 % confidence intervals 1.04–1.08 ) ) , endoscopy delay for hemodynamically unstable patients decreased during this period ( 43 % vs. 34 % had endoscopy within 6 h , RR 1.33 ( 1.10–1.61 ) ) , and fewer patients underwent open surgery ( 4 % vs. 6 % , RR 0.72 ( 0.59–0.87 ) ) . After controlling for time changes in prognostic factors , rebleeding rates improved ( 13 % vs. 18 % , adjusted RR 0.77 ( 0.66–0.91 ) ) . Crude 30-day mortality was unchanged ( 11 % vs. 11 % ) , whereas adjusted mortality decreased nonsignificantly over time ( adjusted RR 0.89 ( 0.78–1.00 ) ) . CONCLUSIONS : QOC in PUB has improved substantially in Denmark , but the 30-day mortality remains high . Future initiatives to improve outcomes may include earlier endoscopy , having fully trained endoscopists on call , and increased focus on managing coexisting disease BACKGROUND Blood utilization has long been suspected to consume more health care re sources than previously reported . Incomplete accounting for blood costs has the potential to misdirect programmatic decision making by health care systems . Determining the cost of supplying patients with blood transfusions requires an in-depth examination of the complex array of activities surrounding the decision to transfuse . STUDY DESIGN AND METHODS To accurately determine the cost of blood in a surgical population from a health system perspective , an activity-based costing ( ABC ) model was constructed . Tasks and re source consumption ( material s , labor , third-party services , capital ) related to blood administration were identified prospect ively at two US and two European hospitals . Process frequency ( i.e. , usage ) data were captured retrospectively from each hospital and used to populate the ABC model . RESULTS All major process steps , staff , and consumables to provide red blood cell ( RBC ) transfusions to surgical patients , including usage frequencies , and direct and indirect overhead costs contributed to per-RBC-unit costs between $ 522 and $ 1183 ( mean , $ 761 + /- $ 294 ) . These exceed previously reported estimates and were 3.2- to 4.8-fold higher than blood product acquisition costs . Annual expenditures on blood and transfusion-related activities , limited to surgical patients , ranged from $ 1.62 to $ 6.03 million per hospital and were largely related to the transfusion rate . CONCLUSION Applicable to various hospital practice s , the ABC model confirms that blood costs have been underestimated and that they are geographically variable and identifies opportunities for cost containment . Studies to determine whether more stringent control of blood utilization improves health care utilization and quality , and further reduces costs , are warranted Background and study aims : The hemostatic powder TC-325 ( Hemospray ; Cook Medical , Winston-Salem , North Carolina , USA ) has shown promising results in the treatment of upper gastrointestinal bleeding ( UGIB ) in expert centers in pilot studies . The aim of this study was to evaluate the feasibility and efficacy of TC-325 in a large prospect i ve registry of use in routine practice . Patients and methods : The data of all patients treated with TC-325 were prospect ively collected through a national registry . Outcomes were the immediate feasibility and efficacy of TC-325 application , as well as the rates of rebleeding at Day 8 and Day 30 . Multivariate analysis was performed to determine predictive factors of rebleeding . Results : A total of 202 patients were enrolled and 64 endoscopists participated from 20 centers . TC-325 was used as salvage therapy in 108 patients ( 53.5 % ) . The etiology of bleeding was an ulcer in 75 patients ( 37.1 % ) , tumor in 61 ( 30.2 % ) , postendoscopic therapy in 35 ( 17.3 % ) , or other in 31 ( 15.3 % ) . Application of the hemostatic powder was found to be very easy or easy in 31.7 % and 55.4 % , respectively . The immediate efficacy rate was 96.5 % . Recurrence of UGIB was noted at Day 8 and Day 30 in 26.7 % and 33.5 % , respectively . Predictive factors of recurrence at Day 8 were melena at initial presentation and use of TC-325 as salvage therapy . Conclusion : These multicenter data confirmed the high rate of immediate hemostasis , excellent feasibility , and good safety profile of TC-325 , which could become the treatment of choice in bleeding tumors or postendoscopic bleeding but not in bleeding ulcers where r and omized studies are needed . TRIAL REGISTRATION Clinical Trials.gov ( NCT02595853 ) BACKGROUND & AIMS Current guidelines recommend testing for Helicobacter pylori infection among users of low-dose aspirin ( ASA ) who are at high risk for developing ulcers . However , it is not clear whether this strategy affects long-term risk of ulcer bleeding . We assessed the utility of testing ASA users with a high risk of ulcer bleeding for H pylori infection . METHODS In a prospect i ve study , we recruited 3 cohorts of ASA users ( ≤160 mg/day ) . The first group included H pylori-positive users of ASAs with bleeding ulcers in whom the infections were eradicated ( n = 249 ) . They resumed ASA after ulcer healing and H pylori eradication . The second group included H pylori-negative ( past and present ) users of ASA who developed bleeding ulcers ( n = 118 ) . They received enteric-coated ASA after ulcer healing . The average-risk cohort included new users of ASA without a history of ulcers ( n = 537 ) . None of the subjects received regular treatment with anti-ulcer drugs . The primary end point was ulcer bleeding with ASA use in 5048 patient-years of follow-up evaluation . RESULTS The incidence of ulcer bleeding ( per 100 patient-years ) in the H pylori-eradicated cohort ( 0.97 ; 95 % confidence interval [ CI ] , 0.53 - 1.80 ) did not differ significantly from that of the average-risk cohort ( 0.66 ; 95 % CI , 0.38 - 0.99 ) . The H pylori-negative cohort had a high incidence of recurrent bleeding ( 5.22 ; 95 % CI , 3.04 - 8.96 ) ( incidence rate ratio , 8.52 ; 95 % CI , 4.29 - 16.95 vs the average-risk cohort ) . CONCLUSIONS The long-term incidence of recurrent ulcer bleeding with ASA use is low after H pylori infection is eradicated . ASA users without current or past H pylori infections who develop ulcer bleeding have a high risk of recurrent bleeding . Tests for H pylori infection can be used to assign high-risk ASA users to groups that require different gastroprotective strategies BACKGROUND The role of gastric acid suppression in preventing the recurrence of ulcer complications after the eradication of Helicobacter pylori infection in patients taking long-term low-dose aspirin is uncertain . METHODS We enrolled 123 patients who had ulcer complications after using low-dose aspirin continuously for more than one month and who had H. pylori infection . After the ulcers had healed and the H. pylori infection was eradicated , the patients were r and omly assigned to treatment with 30 mg of lansoprazole daily or placebo , in addition to 100 mg of aspirin daily , for 12 months . The primary end point was the recurrence of ulcer complications . RESULTS During a median follow-up of 12 months , 9 of the 61 patients in the placebo group ( 14.8 percent ) , as compared with 1 of the 62 patients in the lansoprazole group ( 1.6 percent ) , had a recurrence of ulcer complications ( adjusted hazard ratio , 9.6 ; 95 percent confidence interval , 1.2 to 76.1 ) . Of these 10 patients , 4 had evidence of a recurrence of H. pylori infection and 2 had taken nonsteroidal antiinflammatory drugs before the onset of complications . Patients in the lansoprazole group were significantly less likely to have a recurrence of ulcer complications than patients in the placebo group ( P=0.008 ) . There was no significant difference in mortality between the two groups . CONCLUSIONS In patients who had ulcer complications related to the long-term use of low-dose aspirin , treatment with lansoprazole in addition to the eradication of H. pylori infection significantly reduced the rate of recurrence of ulcer complications BACKGROUND AND AIMS The role of clopidogrel in patients at risk for gastrointestinal complications is uncertain , although it has been recommended for patients who have gastrointestinal intolerance to aspirin . We tested the hypothesis that clopidogrel is as effective as esomeprazole and aspirin in preventing recurrences of ulcer complications . METHODS This was a prospect i ve , double-blind , r and omized , controlled study of 170 patients who developed ulcer bleeding after the use of low-dose aspirin between November 2002 and January 2005 . After healing of ulcers and eradication of Helicobacter pylori , if present , patients were assigned r and omly to treatment with esomeprazole 20 mg/day and aspirin 100 mg/day ( n = 86 ) or clopidogrel 75 mg/day ( n = 84 ) for 52 weeks . The primary end point was recurrent ulcer complications . RESULTS During a median follow-up period of 52 weeks , no patient in the esomeprazole group , as compared with 9 patients in the clopidogrel group , developed recurrent ulcer complications . The cumulative incidences of recurrent ulcer complications were 0 % in patients receiving esomeprazole and aspirin and 13.6 % in patients receiving clopidogrel ( absolute difference , 13.6 % ; 95 % confidence interval for the difference , 6.3 - 20.9 ; log-rank test , P = .0019 ) . CONCLUSIONS The combination of esomeprazole and aspirin is superior to clopidogrel in preventing ulcer complications in patients who have a past history of aspirin-related peptic ulcer bleeding The effect of citrated stored blood on coagulation was studied initially in a pilot study where 25 patients with acute severe gastrointestinal haemorrhage had their whole blood coagulation measured using the Biobridge Impedance Clotting Time ( ICT ) . This demonstrated that there is a hypercoagulable response to haemorrhage which was partially reversed by blood transfusion . Similar changes were noted in Kaolin Cephalin Clotting Times ( KCCT ) . A further 50 patients were then r and omized to receive , during the 24h after admission , either at least 2 units of blood or no blood transfusion unless the haemoglobin fell below 8 g/dl or they were shocked . In the transfused group nine patients re‐bled compared with only one in the non‐transfused group ( P < 0·01 , χ2 with Yates ' correction ) . Early blood transfusion appears to reverse the hypercoagulable response to haemorrhage thereby encouraging rebleeding and hence the need for an operation Preliminary studies on a new topical hemostatic agent , TC‐325 , have shown its safety and effectiveness in treating active upper gastrointestinal ( GI ) bleeding . However , to date there have been no r and omized trials comparing TC‐325 with the conventional combined technique ( CCT ) . Our pilot study aim ed to compare the efficacy and safety of TC‐325 with those of CCT in treating peptic ulcers with active bleeding or high‐risk stigmata BACKGROUND / AIM Bleeding from peptic ulcers can be effectively and safely treated with endoscopic hemoclips therapy . However , due to certain limiting factors of hemoclips , application of combination with another endoscopic method may give better results . The aim of this study was to examine the efficacy and safety of endoscopic hemoclips therapy and to evaluate potential benefits of this therapy combined with epinephrine in the treatment of bleeding peptic ulcers . METHODS This prospect i ve r and omized study included 70 patients with bleeding gastric or duodenal ulcer . In 34 of the patients endoscopic hemoclips therapy was applied ( group I ) , and in 36 of them a combined therapy of hemoclips and epinephrine ( group II ) . RESULTS Initial hemostasis was achieved in most patients treated with endoscopic hemoclips therapy ( 94.1 % ) as well as in the patients treated with combination therapy ( 97.2 % ) . After initial hemostasis achieved rebleeding occurred in 3 ( 9.3 % ) patients treated with hemoclips and in 2 ( 5.7 % ) patients treated with combination therapy , but this difference was not statistically significant ( p > 0.05 ) . The difference in the achieved final hemostasis between the group I ( 91.1 % ) and the group II ( 94.4 % ) was not statistically significant . Also , the differences between the two groups of patients in the need for blood transfusions , length of hospital stay , need for surgery and mortality were not statistically significant ( p > 0.05 ) . CONCLUSION Endoscopic hemoclips therapy is effective and safe in treatment of bleeding peptic ulcers . Combination therapy of hemoclips and epinephrine has no advantage over hemoclips monotherapy The benefit of early endoscopy in the management of peptic ulcer bleeding remains controversial . In this study we looked at the role of early endoscopy in bleeding peptic ulcer patients with clear , " coffee grounds , " or bloody nasogastric aspirate . A consecutive series of 325 patients with peptic ulcer bleeding were included ( 218 patients with clear aspirate , 77 patients with coffee-grounds aspirate , and 30 patients with bloody aspirate ) . They were r and omized to receive early endoscopy ( within 12 h of arrival at the emergency room ) or delayed endoscopy ( 12 h after arrival at the emergency room ) . Early endoscopy did not benefit patients with clear or coffee-grounds aspirate . However , combined with endoscopic therapy , it did significantly benefit patients with bloody aspirate in reducing the need for blood transfusion ( mean , 450 ml vs. 666 ml ; p < 0.001 ) and hospital stay ( mean , 4 vs. 14.5 days , p < 0.001 ) . Early endoscopy and endoscopic therapy are not needed in bleeding peptic ulcer patients with clear or coffee-grounds nasogastric aspirate . However , early endoscopy and endoscopic therapy benefit patients with bloody nasogastric aspirate BACKGROUND AND STUDY AIMS The role of urgent endoscopy in high-risk nonvariceal upper gastrointestinal bleeding ( NVUGIB ) is unclear . The aim of this study was to determine whether esophagogastroduodenoscopy ( EGD ) performed sooner than the currently recommended 24 h in high-risk patients presenting with NVUGIB is associated with lower all-cause in-hospital mortality . METHODS All adult patients undergoing EGD for the indications of coffee-grounds vomitus , hematemesis or melena at a university hospital over an 18-month period were enrolled . Patients with variceal and lower gastrointestinal bleeding were excluded . Data were prospect ively collected . RESULTS A total of 934 patients were included . The area under the receiver operating characteristic curve ( AUROC ) for the Glasgow-Blatchford score ( GBS ) was 0.813 for predicting all-cause in-hospital mortality , with a cut-off score of ≥ 12 result ing in 90 % specificity . In low-risk patients with GBS < 12 , presentation-to-endoscopy time in those who died and in those who survived was similar . In high-risk patients with GBS of ≥ 12 , presentation-to-endoscopy time was significantly longer in those who died than in those who survived . Multivariate analysis of the high-risk cohort showed presentation-to-endoscopy time to be the only factor associated with all-cause in-hospital mortality . For high-risk patients , the AUROC for presentation-to-endoscopy time in predicting all-cause in-hospital mortality was 0.803 , with a sensitivity of 100 % at the cut-off time of 13 h. All-cause in-hospital mortality in high-risk patients was significantly higher in those with presentation-to-endoscopy time of > 13 h compared with those undergoing endoscopy in < 13 h from presentation ( 44 % vs. 0 % ; P < 0.001 ) . CONCLUSIONS Endoscopy within 13 h of presentation was associated with lower mortality in high-risk but not low-risk NVUGIB BACKGROUND Many patients who have had upper gastrointestinal bleeding continue to take low-dose aspirin for cardiovascular prophylaxis or other non-steroidal antiinflammatory drugs ( NSAIDs ) for musculoskeletal pain . It is uncertain whether infection with Helicobacter pylori is a risk factor for bleeding in such patients . METHODS We studied patients with a history of upper gastrointestinal bleeding who were infected with H. pylori and who were taking low-dose aspirin or other NSAIDs . We evaluated whether eradication of the infection or omeprazole treatment was more effective in preventing recurrent bleeding . We recruited patients who presented with upper gastrointestinal bleeding that was confirmed by endoscopy . Their ulcers were healed by daily treatment with 20 mg of omeprazole for eight weeks or longer . Then , those who had been taking aspirin were given 80 mg of aspirin daily , and those who had been taking other NSAIDs were given 500 mg of naproxen twice daily for six months . The patients in each group were then r and omly assigned separately to receive 20 mg of omeprazole daily for six months or one week of eradication therapy , consisting of 120 mg of bismuth subcitrate , 500 mg of tetracycline , and 400 mg of metronidazole , all given four times daily , followed by placebo for six months . RESULTS We enrolled 400 patients ( 250 of whom were taking aspirin and 150 of whom were taking other NSAIDs ) . Among those taking aspirin , the probability of recurrent bleeding during the six-month period was 1.9 percent for patients who received eradication therapy and 0.9 percent for patients who received omeprazole ( absolute difference , 1.0 percent ; 95 percent confidence interval for the difference , -1.9 to 3.9 percent ) . Among users of other NSAIDs , the probability of recurrent bleeding was 18.8 percent for patients receiving eradication therapy and 4.4 percent for those treated with omeprazole ( absolute difference , 14.4 percent ; 95 percent confidence interval for the difference , 4.4 to 24.4 percent ; P=0.005 ) . CONCLUSIONS Among patients with H. pylori infection and a history of upper gastrointestinal bleeding who are taking low-dose aspirin , the eradication of H. pylori is equivalent to treatment with omeprazole in preventing recurrent bleeding . Omeprazole is superior to the eradication of H. pylori in preventing recurrent bleeding in patients who are taking other NSAIDs BACKGROUND Optimal resuscitation of hypotensive trauma patients has not been defined . This trial was performed to assess the feasibility and safety of controlled resuscitation ( CR ) versus st and ard resuscitation ( SR ) in hypotensive trauma patients . METHODS Patients were enrolled and r and omized in the out-of-hospital setting . Nineteen emergency medical services ( EMS ) systems in the Resuscitation Outcome Consortium participated . Eligible patients had an out-of-hospital systolic blood pressure ( SBP ) of 90 mm Hg or lower . CR patients received 250 mL of fluid if they had no radial pulse or an SBP lower than 70 mm Hg and additional 250-mL boluses to maintain a radial pulse or an SBP of 70 mm Hg or greater . The SR group patients received 2 L initially and additional fluid as needed to maintain an SBP of 110 mm Hg or greater . The crystalloid protocol was maintained until hemorrhage control or 2 hours after hospital arrival . RESULTS A total of 192 patients were r and omized ( 97 CR and 95 SR ) . The CR and SR groups were similar at baseline . The mean ( SD ) crystalloid volume administered during the study period was 1.0 L ( 1.5 ) in the CR group and 2.0 L ( 1.4 ) in the SR group , a difference of 1.0 L ( 95 % confidence interval [ CI ] , 0.6–1.4 ) . Intensive care unit – free days , ventilator-free days , renal injury , and renal failure did not differ between the groups . At 24 hours after admission , there were 5 deaths ( 5 % ) in the CR group and 14 ( 15 % ) in the SR group ( adjusted odds ratio , 0.39 ; 95 % CI , 0.12–1.26 ) . Among patients with blunt trauma , 24-hour mortality was 3 % ( CR ) and 18 % ( SR ) with an adjusted odds ratio of 0.17 ( 0.03–0.92 ) . There was no difference among patients with penetrating trauma ( 9 % vs. 9 % ; adjusted odds ratio , 1.93 ; 95 % CI , 0.19–19.17 ) . CONCLUSION CR is achievable in out-of-hospital and hospital setting s and may offer an early survival advantage in blunt trauma . A large-scale , Phase III trial to examine its effects on survival and other clinical outcomes is warranted . LEVEL OF EVIDENCE Therapeutic study , level BACKGROUND & AIMS Endoscopic hemostasis is effective in treatment of bleeding peptic ulcers . However , rebleeding is difficult to treat and associated with substantial morbidity and mortality . We performed a prospect i ve r and omized trial to determine whether over-the-scope clips ( OTSCs ) are more effective than st and ard treatment of severe recurrent upper gastrointestinal bleeding . METHODS We performed our study at 9 academic referral centers ( in Germany , Switzerl and , and Hong Kong ) from March 2013 through September 2016 . Adult patients with recurrent peptic ulcer bleeding following initially successful hemostasis ( 66 patients in the intent-to-treat analysis ) were r and omly assigned to groups ( 1:1 ) that underwent hemostasis with either OTSC or st and ard therapy . St and ard therapy was defined as hemostasis with through-the-scope clips ( TTSC , n = 31 ) or thermal therapy plus injection with diluted adrenaline ( n = 2 ) . The primary endpoint was further bleeding ( a composite endpoint of a persistent bleeding despite endoscopic therapy according to the protocol or recurrent bleeding within 7 days after successful hemostasis ) . Patients with further bleeding were allowed to cross over to OTSC therapy . Main secondary endpoints were mortality , necessity of surgical or angiographic salvage therapy , duration of stay in the hospital or intensive care , number of blood units transfused , and complications associated with endoscopic therapy . RESULTS Persistent bleeding after per- protocol hemostasis was observed in 14 patients ( 42.4 % ) in the st and ard therapy group and 2 patients ( 6.0 % ) in the OTSC group ( P = .001 ) . Recurrent bleeding within 7 days occurred in 5 patients ( 16.1 % ) in the st and ard therapy group vs 3 patients ( 9.1 % ) in the OTSC group ( P = .468 ) . Further bleeding occurred in 19 patients ( 57.6 % ) in the st and ard therapy group and in 5 patients ( 15.2 % ) in the OTSC group ( absolute difference 42.4 % ; 95 % confidence interval 21.6 - 63.2 ; P = .001 ) Within 30 days of follow-up , 1 patient in the st and ard therapy group ( 3.0 % ) and 1 patient in the OTSC group ( 3.0 % ) required surgical therapy ( P = .999 ) . Within 30 days of the procedure , 2 patients died in the st and ard therapy group ( 6.3 % ) and 4 patients died in the OTSC group ( 12.1 % ) ( P = .672 ) . There were no significant differences in the other secondary endpoints . CONCLUSIONS In prospect i ve r and omized trial , we found endoscopic treatment with OTSCs to be superior to st and ard therapy with TTSCs for patients with recurrent peptic ulcer bleeding . STING Study , Clinical trials.gov no : NCT1836900 BACKGROUND Many patients with upper gastrointestinal ( GI ) bleeding have a benign outcome and could receive less intensive and costly care if accurately identified . We sought to determine whether early endoscopy performed shortly after admission in the emergency department could significantly reduce the health care use and costs of caring for patients with nonvariceal upper GI bleeding without adversely affecting the clinical outcome . METHODS All eligible patients with upper GI bleeding and stable vital signs were r and omized after admission to undergo endoscopy in 1 to 2 days ( control ) or early endoscopy in the emergency department . Patients with low-risk findings on early endoscopy were discharged directly from the emergency department . Clinical outcomes and costs were prospect ively assessed for 30 days . RESULTS We r and omized 110 consecutive stable patients with nonvariceal upper GI bleeding during the 12-month study period . The baseline demographic features , endoscopic findings , and the clinical outcomes were no different between the two groups . However the findings of the early endoscopy allowed us to immediately discharge 26 of 56 ( 46 % ) patients r and omized to that group . No patient discharged from the emergency department suffered an adverse outcome . The hospital stay ( median of 1 day [ interquartile range of 0 to 3 days ] vs. 2 days [ interquartile range of 2 to 3 days ] , p = 0.0001 ) and the cost of care ( $ 2068 [ interquartile range of $ 928 to $ 3960 ] versus $ 3662 [ interquartile range of $ 2473 to $ 7280 ] , p = 0.00006 ) were significantly less for the early endoscopy group . CONCLUSIONS Early endoscopy performed shortly after admission in the emergency department safely triaged 46 % of patients with nonvariceal upper GI bleeding to outpatient care , which significantly reduced hospital stay and costs The efficacy of intravenous or intraosseous infusion of 250 ml of 7.5 % NaCl and 6 % dextran 60 ( H/H ) was compared with intravenous Ringer 's lactate ( RL ) for the initial treatment of patients with hemorrhagic shock due to upper gastrointestinal bleeding . 49 patients were r and omly assigned to receive either H/H ( n = 26 ) or RL ( n = 23 ) . In the first 16 patients with H/H and in all RL patients , solutions were infused by the intravenous route , while the intraosseous route through sternal puncture was chosen for the last 10 H/H subjects . H/H patients were analyzed together since no differences were noticed between the routes of infusion . The H/H group also received 2.3 + /- 0.7 liters of intravenous crystalloid solutions in the first hour and 4.4 + /- 0.1 liters in the 24-hour period , while RL received 3.3 + /- 0.7 and 7.3 + /- 2.4 liters , respectively . Blood pressure ( BP ) increased during the first 15 min in the H/H group ( from 61 + /- 17/30 + /- 12 to 85 + /- 30/48 + /- 14 mm Hg ) and thereafter , while remaining unchanged in the RL group ( from 75 + /- 18/40 + /- 12 to 75 + /- 17/40 + /- 14 mm Hg ; p less than 0.05 ) . The differences between groups were significant throughout 24 h. Urine output and improvement of the Glasgow Coma Score were also higher in H/H patients than in the control group ( p less than 0.05 ) . There were 5 deaths in RL group and 1 in the H/H group . Sternal of peripheral vein infusion of 250 ml of 7.5 % NaCl/6 % dextran 60 is an effective initial treatment of hemorrhagic shock BACKGROUND AND AIMS Although various methods are used in the treatment of peptic ulcer bleeding , there is not a st and ard recommended approach . The choice depends on multiple factors such as location of the ulcer , clinical experience of the endoscopist , and local facilities of the clinic . We aim ed to compare the efficacy of monopolar hemostatic forceps soft coagulation ( MHFSC ) and hemoclips ( HCs ) in the treatment of peptic ulcer-related upper GI bleeding . METHODS The study group included patients who had GI bleeding due to Forrest 1a , 1b , and 2a gastric or duodenal ulcers within 1 year . Patients with bleeding diathesis , history of gastrectomy , pregnancy , or younger than age 18 years were excluded . The remaining were r and omized to MHFSC and HC treatment groups and compared in terms of clinical and endoscopic features , initial hemostasis success rates , recurrent bleeding rates within the first 7 days , time to achieve hemostasis , length of hospitalization stay , and adverse events . RESULTS One hundred twelve patients were r and omized to MHFSC ( n = 56 ) and HC ( n = 56 ) groups . There was no statistically significant difference between the groups with respect to demographic features , medications , underlying chronic diseases , location , and Forrest classification of the ulcers . The initial hemostasis success rate was 98.2 % ( 55/56 ) in the MHFSC group and 80.4 % ( 45/56 ) in the HC group ( P = .004 ) . Recurrent bleeding was detected in 2 patients in the MHFSC group ( 3.6 % ) and 8 patients in the HC group ( 17.7 % ; P = .04 ) . The duration of endoscopic procedures ( 302 ± 87.8 vs 568 ± 140.4 seconds ) and the length of hospital stay ( 3.50 ± 1.03 vs 4.37 ± 1.86 days ) were significantly shorter in the MHFSC group . There were no adverse events in either group . CONCLUSIONS MHFSC is more effective in achieving initial hemostasis compared with HCs in the treatment of peptic ulcer bleeding and provides a shorter procedure time and a lower recurrent bleeding rate Background and aims Despite advances in pharmacological and endoscopic management of non-variceal upper gastrointestinal bleeding ( NVUGIB ) , mortality is still relevant . TC-325 ( Hemospray-Cook Medical ) is a mineral powder with adsorptive properties , design ed for endoscopic hemostasis . There are still no comparative trials study ing this new hemostatic modality . The objective of this research was to compare the use of TC-325 ( associated with epinephrine injection ) with the combined technique of endoscopic clipping and epinephrine injection for the treatment of patients with NVUGIB . Methods We conducted a pilot r and omized controlled trial with patients that presented NVUGIB with an actively bleeding lesion at the endoscopic evaluation . Patients were r and omized either to the Hemospray or Hemoclip group . The r and omization list was generated by a computer program and remained unknown throughout the entire trial . All patients underwent second-look endoscopy . Results Thirty-nine patients were enrolled . Peptic ulcer was the most frequent etiology . Primary hemostasis was achieved in all Hemospray cases and in 90 % of Hemoclip group ( p = 0.487 ) . Five patients in Hemospray group underwent an additional hemostatic procedure during second-look endoscopy , while no patient in the Hemoclip group needed it ( p = 0.04 ) . Rebleeding , emergency surgery and mortality rates were similar in both groups . No toxicity , allergy events , or gastrointestinal obstruction signs were observed in Hemospray group . Conclusions TC-325 presents similar hemostatic results when compared with conventional dual therapy for patients with NVUGIB . Hemospray ’s excellent primary hemostasis rate certifies it as a valuable tool in arduous situations of severe bleeding or difficult location site BACKGROUND & AIMS Antiplatelet and anticoagulants are associated with increased upper gastrointestinal bleeding . We evaluated whether proton pump inhibitor therapy could reduce this risk . METHODS We performed a 3x2 partial factorial double-blind trial of 17,598 participants with stable cardiovascular disease and peripheral artery disease . Participants were r and omly assigned to groups given pantoprazole 40 mg daily or placebo , as well as rivaroxaban 2.5 mg twice daily with aspirin 100 mg once daily , rivaroxaban 5 mg twice daily , or aspirin 100 mg alone . The primary outcome was time to first upper gastrointestinal event , defined as a composite of overt bleeding , upper gastrointestinal bleeding from a gastroduodenal lesion or of unknown origin , occult bleeding , symptomatic gastroduodenal ulcer or ≥5 erosions , upper gastrointestinal obstruction , or perforation . RESULTS There was no significant difference in upper gastrointestinal events between the pantoprazole group ( 102/8791 events ) and the placebo group ( 116/8807 events ) ( hazard ratio [ HR ] , 0.88 ; 95 % CI , 0.67 - 1.15 ) . Pantoprazole significantly reduced bleeding of gastroduodenal lesions ( HR , 0.52 ; 95 % CI , 0.28 - 0.94 ; P=.03 ) ; this reduction was greater when we used a post-hoc definition of bleeding gastroduodenal lesion ( HR , 0.45 ; 95 % CI , 0.27 - 0.74 ) although the number needed to treat still was high ( 982 ; 95 % CI , 609 - 2528 ) . CONCLUSIONS In a r and omized placebo-controlled trial , we found that routine use of proton pump inhibitors in patients receiving low-dose anticoagulation and /or aspirin for stable cardiovascular disease does not reduce upper gastrointestinal events but may reduce bleeding from gastroduodenal lesions . Clinical trials.gov no : NCT01776424 BACKGROUND & AIMS Proton pump inhibitors ( PPIs ) are effective at treating acid-related disorders . These drugs are well tolerated in the short term , but long-term treatment was associated with adverse events in observational studies . We aim ed to confirm these findings in an adequately powered r and omized trial . METHODS We performed a 3x2 partial factorial double-blind trial of 17,598 participants with stable cardiovascular disease and peripheral artery disease r and omly assigned to groups given pantoprazole ( 40 mg daily , n=8791 ) or placebo ( n=8807 ) . Participants were also r and omly assigned to groups that received rivaroxaban ( 2.5 mg twice daily ) with aspirin ( 100 mg once daily ) , rivaroxaban ( 5 mg twice daily ) , or aspirin ( 100 mg ) alone . We collected data on development of pneumonia , Clostridium difficile infection , other enteric infections , fractures , gastric atrophy , chronic kidney disease , diabetes , chronic obstructive lung disease , dementia , cardiovascular disease , cancer , hospitalizations , and all-cause mortality every 6 months . Patients were followed up for a median of 3.01 years , with 53,152 patient years of follow up . RESULTS There was no statistically significant difference between the pantoprazole and placebo groups in safety events except for enteric infections ( 1.4 % vs 1.0 % in the placebo group ; odds ratio , 1.33 ; 95 % CI , 1.01 - 1.75 ) . For all other safety outcomes , proportions were similar between groups except for C difficile infection , which was approximately twice as common in the pantoprazole vs the placebo group , although there were only 13 events , so this difference was not statistically significant . CONCLUSIONS In a large placebo-controlled r and omized trial , we found that pantoprazole is not associated with any adverse event when used for 3 years , with the possible exception of an increased risk of enteric infections . Clinical trials.gov identifier : NCT01776424 ( https:// clinical trials.gov/ct2/show/NCT01776424 ) IMPORTANCE Evidence supporting the choice of intravenous colloid vs crystalloid solutions for management of hypovolemic shock remains unclear . OBJECTIVE To test whether use of colloids compared with crystalloids for fluid resuscitation alters mortality in patients admitted to the intensive care unit ( ICU ) with hypovolemic shock . DESIGN , SETTING , AND PARTICIPANTS A multicenter , r and omized clinical trial stratified by case mix ( sepsis , trauma , or hypovolemic shock without sepsis or trauma ) . Therapy in the Colloids Versus Crystalloids for the Resuscitation of the Critically Ill ( CRISTAL ) trial was open label but outcome assessment was blinded to treatment assignment . Recruitment began in February 2003 and ended in August 2012 of 2857 sequential ICU patients treated at 57 ICUs in France , Belgium , North Africa , and Canada ; follow-up ended in November 2012 . INTERVENTIONS Colloids ( n = 1414 ; gelatins , dextrans , hydroxyethyl starches , or 4 % or 20 % of albumin ) or crystalloids ( n = 1443 ; isotonic or hypertonic saline or Ringer lactate solution ) for all fluid interventions other than fluid maintenance throughout the ICU stay . MAIN OUTCOMES AND MEASURES The primary outcome was death within 28 days . Secondary outcomes included 90-day mortality ; and days alive and not receiving renal replacement therapy , mechanical ventilation , or vasopressor therapy . RESULTS Within 28 days , there were 359 deaths ( 25.4 % ) in colloids group vs 390 deaths ( 27.0 % ) in crystalloids group ( relative risk [ RR ] , 0.96 [ 95 % CI , 0.88 to 1.04 ] ; P = .26 ) . Within 90 days , there were 434 deaths ( 30.7 % ) in colloids group vs 493 deaths ( 34.2 % ) in crystalloids group ( RR , 0.92 [ 95 % CI , 0.86 to 0.99 ] ; P = .03 ) . Renal replacement therapy was used in 156 ( 11.0 % ) in colloids group vs 181 ( 12.5 % ) in crystalloids group ( RR , 0.93 [ 95 % CI , 0.83 to 1.03 ] ; P = .19 ) . There were more days alive without mechanical ventilation in the colloids group vs the crystalloids group by 7 days ( mean : 2.1 vs 1.8 days , respectively ; mean difference , 0.30 [ 95 % CI , 0.09 to 0.48 ] days ; P = .01 ) and by 28 days ( mean : 14.6 vs 13.5 days ; mean difference , 1.10 [ 95 % CI , 0.14 to 2.06 ] days ; P = .01 ) and alive without vasopressor therapy by 7 days ( mean : 5.0 vs 4.7 days ; mean difference , 0.30 [ 95 % CI , -0.03 to 0.50 ] days ; P = .04 ) and by 28 days ( mean : 16.2 vs 15.2 days ; mean difference , 1.04 [ 95 % CI , -0.04 to 2.10 ] days ; P = .03 ) . CONCLUSIONS AND RELEVANCE Among ICU patients with hypovolemia , the use of colloids vs crystalloids did not result in a significant difference in 28-day mortality . Although 90-day mortality was lower among patients receiving colloids , this finding should be considered exploratory and requires further study before reaching conclusions about efficacy . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00318942 Importance More than 100 million units of blood are collected worldwide each year , yet the indication for red blood cell ( RBC ) transfusion and the optimal length of RBC storage prior to transfusion are uncertain . Objective To provide recommendations for the target hemoglobin level for RBC transfusion among hospitalized adult patients who are hemodynamically stable and the length of time RBCs should be stored prior to transfusion . Evidence Review Reference librarians conducted a literature search for r and omized clinical trials ( RCTs ) evaluating hemoglobin thresholds for RBC transfusion ( 1950-May 2016 ) and RBC storage duration ( 1948-May 2016 ) without language restrictions . The results were summarized using the Grading of Recommendations Assessment , Development and Evaluation method . For RBC transfusion thresholds , 31 RCTs included 12 587 participants and compared restrictive thresholds ( transfusion not indicated until the hemoglobin level is 7 - 8 g/dL ) with liberal thresholds ( transfusion not indicated until the hemoglobin level is 9 - 10 g/dL ) . The summary estimates across trials demonstrated that restrictive RBC transfusion thresholds were not associated with higher rates of adverse clinical outcomes , including 30-day mortality , myocardial infa rct ion , cerebrovascular accident , rebleeding , pneumonia , or thromboembolism . For RBC storage duration , 13 RCTs included 5515 participants r and omly allocated to receive fresher blood or st and ard-issue blood . These RCTs demonstrated that fresher blood did not improve clinical outcomes . Findings It is good practice to consider the hemoglobin level , the overall clinical context , patient preferences , and alternative therapies when making transfusion decisions regarding an individual patient . Recommendation 1 : a restrictive RBC transfusion threshold in which the transfusion is not indicated until the hemoglobin level is 7 g/dL is recommended for hospitalized adult patients who are hemodynamically stable , including critically ill patients , rather than when the hemoglobin level is 10 g/dL ( strong recommendation , moderate quality evidence ) . A restrictive RBC transfusion threshold of 8 g/dL is recommended for patients undergoing orthopedic surgery , cardiac surgery , and those with preexisting cardiovascular disease ( strong recommendation , moderate quality evidence ) . The restrictive transfusion threshold of 7 g/dL is likely comparable with 8 g/dL , but RCT evidence is not available for all patient categories . These recommendations do not apply to patients with acute coronary syndrome , severe thrombocytopenia ( patients treated for hematological or oncological reasons who are at risk of bleeding ) , and chronic transfusion-dependent anemia ( not recommended due to insufficient evidence ) . Recommendation 2 : patients , including neonates , should receive RBC units selected at any point within their licensed dating period ( st and ard issue ) rather than limiting patients to transfusion of only fresh ( storage length : < 10 days ) RBC units ( strong recommendation , moderate quality evidence ) . Conclusions and Relevance Research in RBC transfusion medicine has significantly advanced the science in recent years and provides high- quality evidence to inform guidelines . A restrictive transfusion threshold is safe in most clinical setting s and the current blood banking practice s of using st and ard-issue blood should be continued Background Idarucizumab , a monoclonal antibody fragment , was developed to reverse the anticoagulant effect of dabigatran . Methods We performed a multicenter , prospect i ve , open‐label study to determine whether 5 g of intravenous idarucizumab would be able to reverse the anticoagulant effect of dabigatran in patients who had uncontrolled bleeding ( group A ) or were about to undergo an urgent procedure ( group B ) . The primary end point was the maximum percentage reversal of the anticoagulant effect of dabigatran within 4 hours after the administration of idarucizumab , on the basis of the diluted thrombin time or ecarin clotting time . Secondary end points included the restoration of hemostasis and safety measures . Results A total of 503 patients were enrolled : 301 in group A , and 202 in group B. The median maximum percentage reversal of dabigatran was 100 % ( 95 % confidence interval , 100 to 100 ) , on the basis of either the diluted thrombin time or the ecarin clotting time . In group A , 137 patients ( 45.5 % ) presented with gastrointestinal bleeding and 98 ( 32.6 % ) presented with intracranial hemorrhage ; among the patients who could be assessed , the median time to the cessation of bleeding was 2.5 hours . In group B , the median time to the initiation of the intended procedure was 1.6 hours ; periprocedural hemostasis was assessed as normal in 93.4 % of the patients , mildly abnormal in 5.1 % , and moderately abnormal in 1.5 % . At 90 days , thrombotic events had occurred in 6.3 % of the patients in group A and in 7.4 % in group B , and the mortality rate was 18.8 % and 18.9 % , respectively . There were no serious adverse safety signals . Conclusions In emergency situations , idarucizumab rapidly , durably , and safely reversed the anticoagulant effect of dabigatran . ( Funded by Boehringer Ingelheim ; RE‐VERSE AD Clinical Trials.gov number , NCT02104947 . Background Patients with high Rockall scores have increased risk of ulcer rebleeding after 3-day esomeprazole infusions . Objective To investigate whether double oral esomeprazole given after a 3-day esomeprazole infusion decreases ulcer rebleeding for patients with high Rockall scores . Design We prospect ively enrolled 293 patients with peptic ulcer bleeding who had achieved endoscopic haemostasis . After a 3-day esomeprazole infusion , patients with Rockall scores ≥6 were r and omised into the oral double-dose group ( n=93 ) or the oral st and ard-dose group ( n=94 ) to receive 11 days of oral esomeprazole 40 mg twice daily or once daily , respectively . The patients with Rockall scores < 6 served as controls ( n=89 ) ; they received 11 days of oral esomeprazole 40 mg once daily . Thereafter , all patients received oral esomeprazole 40 mg once daily for two more weeks until the end of the 28-day study period . The primary end point was peptic ulcer rebleeding . Results Among patients with Rockall scores ≥6 , the oral double-dose group had a higher cumulative rebleeding-free proportion than the oral st and ard-dose group ( p=0.02 , log-rank test ) . The proportion of patients free from recurrent bleeding during the 4th–28th day in the oral double-dose group remained lower than that of the group with Rockall scores < 6 ( p=0.03 , log-rank test ) . Among patients with Rockall scores ≥6 , the rebleeding rate was lower in the oral double-dose group than in the oral st and ard-dose group ( 4th–28th day : 10.8 % vs 28.7 % , p=0.002 ) . Conclusions Double oral esomeprazole at 40 mg twice daily after esomeprazole infusion reduced recurrent peptic ulcer bleeding in high-risk patients with Rockall scores ≥6 . Trial registration number NCT01591083 Objective Patients with a history of Helicobacter pylori-negative idiopathic bleeding ulcers have a considerable risk of recurrent ulcer complications . We hypothesised that a proton pump inhibitor ( lansoprazole ) is superior to a histamine 2 receptor antagonist ( famotidine ) for the prevention of recurrent ulcer bleeding in such patients . Design In this industry-independent , double-blind , r and omised trial , we recruited patients with a history of idiopathic bleeding ulcers . After ulcer healing , we r and omly assigned ( 1:1 ) patients to receive oral lansoprazole 30 mg or famotidine 40 mg daily for 24 months . The primary endpoint was recurrent upper GI bleeding within 24 months , analysed in the intention-to-treat population as determined by an independent adjudication committee . Results Between 2010 and 2018 , we enrolled 228 patients ( 114 patients in each study group ) . Recurrent upper GI bleeding occurred in one patient receiving lansoprazole ( duodenal ulcer ) and three receiving famotidine ( two gastric ulcers and one duodenal ulcer ) . The cumulative incidence of recurrent upper GI bleeding in 24 months was 0.88 % ( 95 % CI 0.08 % to 4.37 % ) in the lansoprazole arm and 2.63 % ( 95 % CI 0.71 % to 6.91 % ) in the famotidine arm ( p=0.313 ; crude HR 0.33 , 95 % CI 0.03 to 3.16 , p=0.336 ) . None of the patients who rebled used aspirin , non-steroidal anti-inflammatory drugs or other antithrombotic drugs . Conclusion This 2-year , double-blind r and omised trial showed that among patients with a history of H. pylori-negative idiopathic ulcer bleeding , recurrent bleeding rates were comparable between users of lansoprazole and famotidine , although a small difference in efficacy can not be excluded . Trial registration number NCT01180179 ; Results Background — Patients experiencing major bleeding while taking vitamin K antagonists require rapid vitamin K antagonist reversal . We performed a prospect i ve clinical trial to compare nonactivated 4-factor prothrombin complex concentrate ( 4F-PCC ) with plasma for urgent vitamin K antagonist reversal . Methods and Results — In this phase IIIb , multicenter , open-label , noninferiority trial , nonsurgical patients were r and omized to 4F-PCC ( containing coagulation factors II , VII , IX , and X and proteins C and S ) or plasma . Primary analyses examined whether 4F-PCC was noninferior to plasma for the co primary end points of 24-hour hemostatic efficacy from start of infusion and international normalized ratio correction ( ⩽1.3 ) at 0.5 hour after end of infusion . The intention-to-treat efficacy population comprised 202 patients ( 4F-PCC , n=98 ; plasma , n=104 ) . Median ( range ) baseline international normalized ratio was 3.90 ( 1.8–20.0 ) for the 4F-PCC group and 3.60 ( 1.9–38.9 ) for the plasma group . Effective hemostasis was achieved in 72.4 % of patients receiving 4F-PCC versus 65.4 % receiving plasma , demonstrating noninferiority ( difference , 7.1 % [ 95 % confidence interval , –5.8 to 19.9 ] ) . Rapid international normalized ratio reduction was achieved in 62.2 % of patients receiving 4F-PCC versus 9.6 % receiving plasma , demonstrating 4F-PCC superiority ( difference , 52.6 % [ 95 % confidence interval , 39.4 to 65.9 ] ) . Assessed coagulation factors were higher in the 4F-PCC group than in the plasma group from 0.5 to 3 hours after infusion start ( P<0.02 ) . The safety profile ( adverse events , serious adverse events , thromboembolic events , and deaths ) was similar between groups ; 66 of 103 ( 4F-PCC group ) and 71 of 109 ( plasma group ) patients experienced ≥1 adverse event . Conclusions — 4F-PCC is an effective alternative to plasma for urgent reversal of vitamin K antagonist therapy in major bleeding events , as demonstrated by clinical assessment s of bleeding and laboratory measurements of international normalized ratio and factor levels . Clinical Trial Registration — URL : http://www . clinical trials.gov . Unique identifier : NCT00708435 |
14,014 | 28,770,974 | Due to the low- to very low- quality of the evidence for all treatment comparisons , outcomes , and follow-up periods investigated , it is uncertain if Back School is effective for chronic low back pain .
Although the quality of the evidence was mostly very low , the results showed no difference or a trivial effect in favour of Back School . | BACKGROUND Many people with low back pain ( LBP ) become frequent users of healthcare services in their attempt to find treatments that minimise the severity of their symptoms .
Back School consists of a therapeutic programme given to groups of people that includes both education and exercise .
However , the content of Back School has changed over time and appears to vary widely today .
This review is an up date of a Cochrane review of r and omised controlled trials ( RCTs ) evaluating the effectiveness of Back School .
We split the Cochrane review into two review s , one focusing on acute and subacute LBP , and one on chronic LBP . | OBJECTIVES To evaluate the effectiveness of a back school program in pain , functional status , quality of life , and in anxiety and depression in patients with non-specific low back pain . METHODS Sixty patients with low back pain were r and omized to an intervention and control group . The intervention group underwent a five-weekly back school program . The control group was seen in weekly medical visits , without educative approaches . Both groups took acetaminophen as analgesic medication . All subjects were evaluated by a blind physiotherapist after r and omization , 30 , 60 and 120 days . Roll and -Morris , SF-36 , STAI and Beck question naires , pain visual analogical scale and Schober 's test were applied . Non-steroidal anti-inflammatory drugs ( NSAID ) consumption was considered co-intervention . The statistical analyses were performed using Pearson 's Chi-Square analysis and Student 's t-test to compare the baseline characteristics of the groups and the analysis of variance ( ANOVA ) with repeated measures to assess changes inter/intra groups . RESULTS There were no significant differences in the baseline characteristics between the two groups . Fifty-five patients completed the study . The intervention group showed a significant improvement in the general health domain , assessed by SF-36 , and also in the reduction of acetaminophen and NSAID intake . There was no significant difference between the groups in pain , functional status , anxiety or depression . CONCLUSION The back school program was more effective than any educational intervention in general health status and in decreasing acetaminophen and NSAID intake . It was ineffective in the other quality of life domains , in pain , functional status , anxiety and depression OBJECTIVE To evaluate the effectiveness of the addition of back school to exercise and physical treatment modalities in relieving pain and improving the functional status of patients with chronic low back pain . DESIGN A r and omized controlled trial . PATIENTS A total of 146 patients with chronic low back pain were enrolled in the study . METHODS Subjects were divided into 2 groups : the back school group received exercise , physical treatment modalities and a back school programme ; and the control group received exercise and physical treatment modalities . Treatment efficacy was evaluated at the end of treatment and 3 months post-treatment , in terms of pain , measured with the Visual Analogue Scale , and functional status , measured with the Oswestry Low Back Pain Disability Question naire . RESULTS In both groups , Visual Analogue Scale and Oswestry Low Back Pain Disability Question naire were significantly reduced after therapy ( p < 0.01 ) , but the difference between the scores at the end of treatment and 3 months post-treatment was not significant . There was a significant improvement in Visual Analogue Scale and Oswestry Low Back Pain Disability Question naire in the back school group compared with the control group at the end of therapy and 3 months post-treatment ( p < 0.05 ) . CONCLUSION The addition of back school was more effective than exercise and physical treatment modalities alone in the treatment of patients with chronic low back pain In a prospect i ve trial , 222 adults with low-back pain of at least 2 weeks ' duration in a Health Maintenance Organization ( HMO ) were r and omly assigned to usual care ( UC ) , a 4-hour back school psychoeducational session ( LBS ) , or the same back school plus a 1-year “ compliance package ” program design ed to encourage appropriate self-management for back pain ( CP ) . Sixty-four percent of LBS and CP subjects attended their back school sessions . Follow-up measurement of pain level ( using the Visual Analogue Scale ) , functional status ( using the Sickness Impact Profile ) , and various other indicators of health status showed no measurable effect of either treatment condition ( LBS or CP ) compared with UC at 3 , 6 , 12 , and 18 months after entry into the study . Initial disability resolved by 3 months in most patients , and a minority of subjects ( 10–15 % ) showed residual or recurrent functional Impairment 1 year after entry . Health care utilization tended to be slightly higher after intervention In the CP group . With or without follow-up encouragement , back school instructions given in a single 4-hour session had no measurable impact on the comfort or functional status of the majority of patients with new onset back pain in this HMO Abstract Purpose : To determine the efficacy of the Feldenkrais method for relieving pain in patients with chronic low back pain ( CLBP ) and the improvement of interoceptive awareness . Method : This study was design ed as a single-blind r and omized controlled trial . Fifty-three patients with a diagnosis of CLBP for at least 3 months were r and omly allocated to the Feldenkrais ( mean age 61.21 ± 11.53 years ) or Back School group ( mean age 60.70 ± 11.72 years ) . Pain was assessed using the visual analog scale ( VAS ) and McGill Pain Question naire ( MPQ ) , disability was evaluated with the Waddel Disability Index , quality of life was measured with the Short Form-36 Health Survey ( SF-36 ) , and mind – body interactions were studied using the Multidimensional Assessment of Interoceptive Awareness Question naire ( MAIA ) . Data were collected at baseline , at the end of treatment , and at the 3-month follow-up . Results : The two groups were matched at baseline for all the computed parameters . At the end of treatment ( Tend ) , there were no significant differences between groups regarding chronic pain reduction ( p = 0.290 ) ; VAS and MAIA-N sub scores correlated at Tend ( R = 0.296 , p = 0.037 ) . By the Friedman analysis , both groups experienced significant changes in pain ( p < 0.001 ) and disability ( p < 0.001 ) along the investigated period . Conclusions : The Feldenkrais method has comparable efficacy as Back School in CLBP . Implication s for rehabilitation The Feldenkrais method is a mind – body therapy that is based on awareness through movement lessons , which are verbally guided explorations of movement that are conducted by a physiotherapist who is experienced and trained in this method . It aims to increase self-awareness , exp and a person ’s repertoire of movements , and to promote increased functioning in context s in which the entire body cooperates in the execution of movements . Interoceptive awareness , which improves with rehabilitation , has a complex function in the perception of chronic pain and should be investigated further in future research . The efficacy of the Feldenkrais method is comparable with that of BS for nonspecific chronic low back pain . The physician can recommend a body – mind rehabilitation approach , such as the Feldenkrais method , or an educational and rehabilitation program , such as BS , to the patient , based on his individual needs . The 2 rehabilitation approaches are equally as effective in improving interoceptive awareness Background Different interventions can reduce the burden of the chronic low back pain . One example is the use of a ' Back School Programme ' . This is a brief therapy that uses a health education method to empower participants through a procedure of assessment , education and skill development . This study aim ed to evaluate to what extent the programme could improve quality of life in those who suffer from the condition . Methods This was a r and omized controlled trial . One-hundred and two female patients with low back pain ( n = 102 ) were r and omly allocated into two groups , matched in terms of age , weight , education , socioeconomic status , occupation and some aspects of risk behavior . Group 1 ( back school group , n = 50 ) but not group 2 ( clinic group , n = 52 ) received the ' Back School Programme ' . Then quality of life using the Short Form Health Survey ( SF-36 ) was assessed at two time points : at baseline and at three months follow-up . The findings were compared both within and between two groups . Results The ' Back School Programme ' was effective in improving patients ' quality of life ; significant differences were found on all eight subscales of the SF-36 for group 1 . In the clinic group ( group 2 ) , improvement was observed on three scales ( bodily pain , vitality and mental health ) but these improvements were less than in group 1 . The mean improvement over all eight subscales of the SF-36 was significantly better for the ' Back School Programme ' group . Conclusion The ' Back School Programme ' is an effective intervention and might improve the quality of life over a period of 3 months in patients who experience chronic low back pain The purpose of this study was to assess the effects of two different treatment modalities on the rehabilitation process of chronic sacroiliac joint patients . The treatment modalities included spinal manipulative therapy given by a chiropractor and a program of back school therapy given by a physiotherapist . The rehabilitation process was assessed using clinical and biomechanical measures . It was found that back school therapy was a better treatment modality than the spinal manipulative therapy , according to the clinical measures of rehabilitation . Precisely the opposite result was found for the biomechanical measures The aim of this trial was to determine whether social interaction between patients with long-lasting nonspecific back pain reduces subjective or objective disability . The participants were selected from persons visiting an occupational health care unit because of back pain . After a clinical examination in a university clinic , subjects without a specific diagnosis and having no disabilities preventing active rehabilitation were selected for study . The subjects ( n = 108 ) were r and omized into treatment ( n = 54 ) and control groups ( n = 54 ) . Altogether 18 study groups , 9 treatment groups and 9 groups for controls , were formed . Before starting the back schools altogether 15 subjects dropped out . Both the treatment groups ( n = 47 ) and the controls ( n = 46 ) attended a back school consisting of 10 lessons and demonstrations supervised by a physiotherapist . The participants in treatment groups , but not the controls , had physical exercise and social intercourse with other members within the group . The clinical examination was repeated after 6 and 12 months . Both the treatment groups and the controls showed improvement in perceived functional capacity ( assessed with Oswestry disability question naire ) and in perceived life quality ( assessed with 15D score ) . At the 6-month follow-up life quality had improved statistically significantly more among the participants in treatment groups than among the controls , and at the 12-month follow-up the Oswestry index showed corresponding improvement . Among subjects suffering from nonspecific back pain , social support improves the results of active rehabilitation A clinical trial , aim ed at secondary prevention of low-back pain , was performed in 142 hospital employees reporting at least three annual episodes of this condition . Participants were r and omly assigned to one of three groups : a calisthenics program ( CAL ) for 3 months with biweekly sessions of flexion exercises , a back school program ( 5 sessions ) , and a control group . The effectiveness of the two intervention programs was evaluated over a 1-year period . Baseline preintervention data and evaluation at the end of 3 months of intervention and after an additional 6 months were collected . A monthly surveillance for the whole year showed a mean of 4.5 “ painful months ” in the CAL group versus 7.3 and 7.4 months in the back school and control groups , respectively ( P < 0.0001 ) . The superiority of the CAL group was achieved partly because of the significant increase in trunk forward flexion and to initial increment in abdominal muscle strength . The increased trunk flexion was associated with the rate of participation in the CAL sessions . Further research is needed to answer the question of “ intensity versus type of exercise ” by comparing different intervention programs , with similar intensity Stopping r and omized trials early because of an apparent benefit is a growing phenomenon . A recent systematic review found that the number of r and omized trials stopped early for benefit has more than doubled since 1990 ( 1 ) . To protect and promote the interests of trial participants , investigators may feel ethically obligated to stop a trial early because of the unexpected harm or apparent benefit of a study treatment . If a study treatment 's benefit far outweighs its adverse effects , is it not unethical to continue enrolling patients in a trial in which , as is typically the case , patients have a 50 % chance of receiving a placebo or an inferior treatment ? In this article , we argue that stopping a r and omized trial early for apparent benefit is often unethical and can be justified only under restricted circumstances . If the scientific community were to accept our arguments , then the approach that investigators , institutional review boards , and data monitoring committees take to the practice of stopping trials early for apparent benefit would substantially change . Ethical Considerations Emanuel and colleagues ( 2 ) describe a framework of 7 requirements for determining whether clinical research is ethical . We use this framework to identify and assess the ethical issues raised by stopping trials early because of apparent benefit ( Table ) . Table . Ethical Violations Result ing from Stopping a Trial Early for Apparent Benefit Scientific Validity The purpose of a trial of alternative interventions is to generate an estimate of treatment effect that closely approximates the true effect and is not misleading . This requires application of scientific procedures that yield valid and reliable data and thus minimize both systematic and r and om error . A systematic review of r and omized trials stopped early for apparent benefit ( 1 ) found that many of the trials yielded implausibly large treatment effects ; the median relative risk was 0.53 . Apparent large treatment effects occurred much more frequently when trials accrued only a small number of events . The odds of a treatment effect larger than the overall median relative risk of 0.53 was 28 times greater ( 95 % CI , 11 to 73 ) among trials in which fewer than the median of 66 events accrued than among trials in which more events accrued . These results , which are consistent with predictions from statistical theory ( 3 ) , suggest that stopping trials early for apparent benefit will systematic ally overestimate treatment effects . The scientific validity of trials that are stopped early is further compromised when trials yield inconclusive data about outcomes that did not influence trial truncation but are nonetheless important to patients , such as disease-free survival , symptom control , quality of life , and adverse effects of treatment . For example , a trial of vitamin E supplementation in premature newborns that was stopped early because of an apparent reduction in intracranial hemorrhage ( 4 ) failed to detect the increase in sepsis associated with vitamin E supplementation that subsequent trials identified ( 5 ) . Social or Scientific Value and Favorable RiskBenefit Ratio It is underst and able that investigators focus their ethical obligations on research participants . Such focus , however , risks neglecting obligations to society . The tendency of truncated trials to overestimate the effect of a treatment on the end point that result ed in trial truncation and to yield insufficient data about other important outcomes endangers the wider community to whom the results will be applied ( 6 ) . On review ing the results of a truncated trial , astute clinicians might appropriately conclude that the benefits of the intervention remain uncertain . However , less skeptical clinicians might assume that the results are true and inappropriately expose patients to the intervention and its unknown harms . Consider the results of a trial in which the investigators continued to enroll patients even though prespecified criteria for early stopping were met . Two interim analyses of a r and omized trial of 5 versus 4 courses of chemotherapy in patients with acute myeloid leukemia ( 7 ) found apparent large benefits to the 5-course regimen ( relative odds reduction of 53 % [ CI , 23 % to 71 % ; P= 0.003 ] in the first analysis and 45 % [ CI , 20 % to 62 % ; P= 0.0002 ] in the second analysis ) . Finding these results too good to be true , the data monitoring committee recommended continuing the trial , which ultimately showed a trend in favor of the 4-course regimen . Had the investigators terminated the trial in accordance with their stopping rule , subsequent patients with leukemia may have experienced the toxicity of an additional course of chemotherapy without benefit . Harm result ing from the misleading findings of truncated trials can be compounded if the findings influence the recommendations of clinical practice guideline panels . Investigators conducting a trial that involved patients undergoing vascular surgery ( 8) stopped the trial early when 2 of 53 patients r and omly assigned to receive the -blocker bisoprolol and 18 of 59 control patients had major cardiovascular events ( relative risk reduction , 90 % [ CI , 59 % to 98 % ] ) . These results contributed to recommendations by the American Heart Association and the American College of Cardiology favoring administration of -blockers to patients with cardiac risk factors who were undergoing noncardiac surgery ( 9 ) . However , these results contradict those of 2 much larger subsequently published trials , neither of which suggested that -blockers reduce cardiac risk in patients undergoing noncardiac surgery ( 10 , 11 ) . Further social detriment may occur when clinicians compromise the ability of others to conduct more definitive studies by placing undue confidence in the results of a truncated trial . Investigators ( including 2 contributors to this article ) who obtained funding for a trial of -blockers in noncardiac surgery with an enrollment target of 10000 patients ( 12 ) faced challenges in persuading clinicians that the question remained unanswered . Participant Consent and Respect for Participants Key prerequisites for informed consent include the participant 's decision-making capacity and voluntariness and whether he or she had received adequate information to decide that participation in the research was in alignment with his or her values and goals . However , informed consent is not a single event , but it is an ongoing collaboration between participants and investigators . When important changes occur during a trial , investigators should inform participants of the changes . One justification for stopping a trial early for benefit is to inform study participants of the preliminary results and offer them the superior treatment . According to this argument , uncertainty about the relative merits of alternative interventions ( equipoise ) has been lost and informed clinicians and patients will overwhelmingly choose the superior treatment ( 13 ) . However , as we have pointed out , the astute clinician or patient may remain skeptical about a treatment 's apparent benefits if the findings come from a truncated trial . Unfortunately , many clinicians and even more patients probably will not have the knowledge and underst and ing to appropriately interpret the results . Disclosing interim results to study participants may therefore prove misleading . Furthermore , if investigators were to continue a trial after informing patients of the interim results , patients would be unblinded and may cross over or leave the trial . These behaviors create problems in interpreting trial results by further weakening inferences about the efficacy and safety of the intervention and compromising the ethical requirement of scientific validity . Finally , stopping a trial early does not guarantee that current and potential trial participants will receive the apparently beneficial treatment ( assuming that one believes they should ) . Studies of dissemination of new treatments reveal that long delays , such as those between reports of r and omized trials and recommendations of experts in review articles and textbooks , are common ( 14 ) . Continuing a 2-group trial gives participants at least a 50 % chance of receiving the experimental treatment , whereas if the trial is stopped early , the probability that participants will receive the treatment due to rapid dissemination is likely to be considerably less than 50 % . Independent Review Trials may have stopping rules that allow early termination because of genuine ( although misguided ) ethical concerns . However , investigators , trial sponsors , journals , and patients may all have additional motives for stopping trials early for apparent benefit . For example , truncated trials that report a large treatment effect tend to be published in the most prestigious medical journals ( 1 ) , which enhances the careers of the investigators and increases the likelihood that they will receive grants . Funding agencies have an interest in stopping trials early to minimize research costs . Pharmaceutical and for-profit sources that financially support trials are interested not only in controlling costs but also in the publicity and market share that result from reporting a trial stopped early for apparent benefit . Medical journals are interested in these trials because of publicity and citations , which result in increased journal impact factor , prestige , and advertising revenue . And patients and their advocates are motivated to stop a trial early when the experimental intervention is promising in order to hasten delivery of the intervention to clinical practice . All of these motives may affect investigators ' decisions and encourage an inappropriately early stop to a trial . These considerations m and ate that institutional review boards and data monitoring committees underst and the principles outlined in this article and insist on appropriate st and ards for stopping a trial early for apparent benefit to maintain the ethical integrity of clinical trials . Study Design . R and omized controlled trial . Objectives . To compare high- and low-intensity back schools with usual care in occupational health care . Summary of Background Data . The content and intensity of back schools vary widely and the method ologic quality of r and omized controlled trials is generally weak . Until now , no back school has proven to be superior for workers sick-listed because of subacute nonspecific low back pain . Methods . Workers ( n = 299 ) sick-listed for a period of 3 to 6 weeks because of nonspecific low back pain were recruited by the occupational physician and r and omly assigned to a high-intensity back school , a low-intensity back school , or care as usual . Outcome measures were days until return to work , total days of sick-leave , pain , functional status , kinesiophobia , and perceived recovery and were assessed at baseline and at 3 and 6 months of follow-up . Principal analyses were performed according to the intention-to-treat principle . Results . We r and omly allocated 299 workers . Workers in the low-intensity back school returned to work faster compared with usual care and the high-intensity back school , with hazard ratios of 1.4 ( P = 0.06 ) and 1.3 ( P = 0.09 ) , respectively . The comparison between high-intensity back school and usual care result ed in a hazard ratio of 1.0 ( P = 0.83 ) . The median number of sick-leave days was 68 , 75 , and 85 in the low-intensity back school , usual care , and high-intensity back school , respectively . Beneficial effects on functional status and kinesiophobia were found at 3 months in favor of the low-intensity back school . No substantial differences on pain and perceived recovery were found between groups . Conclusions . The low-intensity back school was most effective in reducing work absence , functional disability , and kinesiophobia , and more workers in this group scored a higher perceived recovery during the 6-month follow-up Yang EJ , Park W-B , Shin H-I , Lim J-Y : The Effect of Back School Integrated with Core Strengthening in Patients with Chronic Low-Back Pain . Objective : To assess the effect of back school integrated with core-strengthening exercises on back-specific disability and pain-coping strategies and to examine how reactions to pain affect the outcomes of back school in patients with chronic low back pain . Design : A single-center prospect i ve trial was conducted with 142 participants with chronic low-back pain ( 38 men and 104 women ) who completed a back school program at the spine center of a university hospital . The subjects participated in a 4-wk program integrated with core-strengthening exercises . Back-specific disabilities were measured as a primary outcome before and after the program . Secondary outcomes were pain , Chronic Pain Coping Inventory , general health status assessed by the SF-36 , and quantitative functional evaluations of factors , such as trunk muscle strength , endurance , and the back performance scale . A subgroup of 28 subjects ( 12 men and 16 women ) of the total sample of 142 subjects was used to analyze the longitudinal association between coping strategies and the primary outcome in a long-term follow-up study . These participants were divided into three groups ( much improved , slightly improved , and unimproved ) based on changes in back-specific disability scores . Results : Participants improved significantly in terms of back-specific disability , pain , general health , and quantitative functional tests according to the short-term evaluation . They used more relaxation and exercise/stretching techniques as coping strategies . Of the groups participating in the longer-term follow-up ( T3 ) , the much-improved group showed significant improvement between T1 ( before back school ) and T2 ( after back school ) in scores for relaxation ( 1.6 ± 1.0 vs. 2.6 ± 1.1 ) , task persistence ( 2.9 ± 1.2 vs. 3.7 ± 1.2 ) , and exercise ( 3.3 ± 1.1 vs. 5.2 ± 1.9 ) , but the coping strategies of those in the slightly improved and unimproved groups did not change significantly at T2 . Conclusions : Our back school program may help patients with chronic low back pain reduce back-specific disability and pain and develop wellness-focused coping strategies such as exercise and stretching BACKGROUND AND OBJECTIVES The aim of this trial is to search effectiveness of specifically adapted exercise programs on its own and with low back school on pain , disability , trunk and quadriceps muscle strength , walking performance , spinal mobility , quality of life ( QOL ) , and depression in the patients with chronic low back pain ( CLBP ) . MATERIAL AND METHOD A total of 121 patients with definite CLBP were included in this study . The patients were r and omized into two groups . Group 1 ( n=60 ) was given exercises only and accepted as the control group . Group 2 ( n=61 ) received back school program and exercises . The exercise treatment was performed 3 days a week , for 3 months . The pain ( visual analog scale , VAS ) , disability ( Oswestry Disability Question naire , ODQ ) , walking performance ( 6 minute walking test , 6MWT ) , depression ( Beck Depression Inventory scores , BDI ) , and QOL ( Short Form 36 , SF-36 ) of all participants were evaluated . The trunk and knee muscle strength were measured with a h and held dynamometer . Patients were assessed at baseline ( BT ) , at the end of treatment ( AT ) , and at the six month follow-up ( F ) . RESULTS Statistically significant improvements were found between groups regarding all of the clinical parameters over time . Pain , disability , muscle strength , endurance , 6MWT , mobility , QOL , and depression of both groups also showed improvements AT . These improvements persisted at 6-months follow-ups ( P < 0.05 ) . There were statistically significant differences between the groups for pain , disability , muscle strength , endurance , 6MWT , QOL , and depression regarding the change scores between AT-BT test and F-BT test ( P < 0.05 ) . Group 2 improved more than group 1 except for mobility . CONCLUSION Exercise programs can be modified and used successfully in CLBP and this effect can be increased with addition of back school further . LEVEL OF EVIDENCE Diagnostic study Level-I-I ( prospect i ve study ) Ninety-two chronic low back pain patients were r and omly allocated to two groups to evaluate the effectiveness of a back school compared with an exercise-only regimen according to specified outcome variables . The data from 78 patients with 7 years mean duration of symptoms was analyzed . Three assessment s were made : before treatment and 6 and 16 weeks after treatment . Changes in patients ' levels of pain , functional disability , and other related variables were compared in the two groups . Almost all variables showed an improvement at 6 weeks . At 16 weeks , functional disability and pain levels showed a significant difference . Back school patients continued to make an improvement . This method of managing low back pain makes maximal use of limited re sources and appears to be effective , especially in the longer term BACKGROUND Low back pain is a worldwide health problem , affecting up to 80 % of adult population . Psychological factors are involved in its development and maintenance . Many clinical trials have evaluated the efficacy of different interventions for chronic non-specific low back pain . In this field , Back School program has been demonstrated effective for people with chronic non-specific low back . AIM To evaluate the relationship between the effects of the Back School treatment and psychological features measured by MMPI-II of patients with chronic non-specific low back pain . DESIGN A r and omised controlled trial with three and six-month follow-up . SETTING Ambulatory rehabilitative university centre . POPULATION Fifty patients with chronic non-specific low back pain out of 77 screened patients . METHODS Patients were r and omly placed in a 3:2 form and were allocated into two groups ( Treatment versus Control ) . The Treatment Group participated to an intensive multidisciplinary Back School program ( BSG , N.=29 ) , while the Control Group received medical assistance ( CG , N.=21 ) . Medication was the same in both groups . Then , patients were subgrouped in those with at least an elevation in one scale of MMPI-II , and those without it . The Short Form 36 Health Status Survey for the assessment of quality of life ( primary outcome measure ) , pain Visual Analogue Scale , Waddel Index and Oswestry Disability Index were collected at baseline , at the end of treatment , and at the three and six-month follow-up . RESULTS Only the two treated subgroups showed a significant improvements in terms of quality of life , disability and pain . Among treated subjects , only those with at least one scale elevation in MMPI-II showed also a significant improvement in terms of Short Form 36 mental composite score and relevant subscores . CONCLUSION These results suggest that Back School program has positive effects , even in terms of mental components of quality of life in patients with scale elevations of MMPI-II . Probably these findings are due to its educational and cognitive-behavioural characteristics . CLINICAL REHABILITATION IMPACT Because of its educational purpose s , the Back School treatment can have positive effects also on the mental status of patients with low back pain when it affects their psychological features OBJECTIVE To assess the efficacy of a back school program for patients with a first episode of acute work-related low back pain requiring compensation . DESIGN A r and omized single-blind controlled trial . SETTING A private physiatrics outpatient clinic . PATIENTS The mean duration of low back pain was 15 days . INTERVENTION Eligible patients were r and omized to a st and ard treatment program that included daily physiotherapy ( n = 86 ) or the same program with the addition of back school ( n = 82 ) . The back school program consisted of three 90-minute sessions given by a single trained instructor at 0 , 1 , and 8 weeks . MAIN OUTCOME MEASURES The primary outcomes were the time off work for the presenting episode of back pain and the number and duration of recurrences in the year following the study onset . Secondary outcomes included the level of pain , spinal mobility , active straight-leg raising , and functional disability assessed by the Oswestry and Rol and -Morris scales . RESULTS Those r and omized to the back school group gained significantly more knowledge , based on the multiple choice examination ( p = .0001 ) and performed the exercise program significantly better ( p = .0001 ) than the st and ard care group . There were no differences between the two treatment groups for either of the primary outcomes . The median time to return to work from r and omization was 33 days for both the back school and the st and ard care groups ( p = .48 ) . The number of compensated recurrences of low back pain over 1 year was similar ( back school = 14 , st and ard care = 10 , p = .16 ) , as was the median duration of these episodes ( back school = 25 days , st and ard care = 70 days , p = .21 ) . There were no significant differences favoring the back school group for any of the secondary outcomes at the posttreatment , 6-month , or 12-month assessment s. CONCLUSION A back school intervention in addition to st and ard care result ed in no reduction in the time to return to work or the number or duration of recurrences of low back pain requiring compensation over a period of one year The long-term outcome results of inpatient and outpatient treatment of low back pain ( LBP ) were studied in 476 subjects ( aged 35 - 54 , 63 % men ) r and omly assigned to three study groups : in patients ( n = 157 ) , out patients ( n = 159 ) , and controls ( n = 160 ) . The study included changes in the severity of low back pain , grade and disability , compliance with self-care , data on disability pensions , and days of sickness allowance during a 2.5-year follow-up period . These variables were used as outcome criteria . Pain and disability had decreased significantly in the two treated groups up to the 3-month follow-up . LBP was still a little slighter in the in patients at the 1.5-year and 22-month follow-ups , but there were no significant differences between the groups in disability caused by LBP . The refresher programme carried out 1.5 years after the first one did not bring about as clear short-term improvement in pain and disability as the first treatment . During the whole 2.5-year follow-up compliance with self-care was better in the two treated groups , especially in the in patients . Days of sickness allowance had increased somewhat more in the controls than in the in patients during the follow-up . No differences between the groups were found in the number of disability pensions granted Because back pain is a widespread and costly condition that tends to recur , treatment must focus on both the amelioration of acute symptoms and prevention over the long term . This paper reports a longitudinal evaluation of a program from a community hospital that emphasizes both these aspects . One hundred twenty patients routinely admitted to this program were r and omly assigned to treatment and control groups . These groups were assessed for differences in demonstrated physical strength , mobility , body mechanics , and self-care knowledge , and in levels of self-reported exercise , anxiety , and pain . There were significant immediate gains on physical measures of fitness and in observed body mechanics ; patients also reported significant gains in physical capabilities at home and in leisure activities . Self-care knowledge also improved . When assessed one year later , original gains in physical strength and mobility were being maintained , and self-reported physical capabilities also remained high . Although demonstrated knowledge of correct body mechanics declined over this period , it was still significantly greater than before the program . In light of these results , we believe that outpatient programs like the one reported here merit careful consideration in an era of concern about rising costs for primary health care Objectives A back school is a m and atory part of the multimodal rehabilitation program for patients with chronic low back pain in Germany . However , no st and ardized and evaluated back school program has been available for routine use . In this study , we report the evaluation of a new back school that was developed based on theories of health behavior , treatment evidence , practice guidelines , and quality criteria for patient education . Methods R and omized controlled trial of patients with low back pain ( n=360 ) in inpatient orthopedic rehabilitation clinic in Germany . Intervention patients received the new back school , whereas control patients a traditional back school ( usual care ) . Illness knowledge ( primary outcome ) and secondary behavioral and health outcomes were assessed at admission , discharge , and 6 and 12 months follow-up . Results Results showed a significant medium between-group treatment effect in patients ' knowledge about back pain at discharge ( & eegr;2=0.081 ) , after 6 ( & eegr;2=0.056 ) , and 12 months ( & eegr;2=0.026 ) . Furthermore , small-to-medium effects were observed among the secondary self-management behaviors , such as physical activity , back exercises , back posture habits , and coping with pain , after 6 and 12 months . Discussion The superior effectiveness of the back school based on a biopsychosocial approach was demonstrated with regard to illness knowledge and self-management behaviors up to 1 year . Thus , the program may be recommended for dissemination within medical rehabilitation OBJECTIVE < < Back School > > has been used as a way of preventing and treating back pain since 1969 , but reports in the literature on its effectiveness remain controversial . The purpose of this trial was to evaluate efficacy of a back school program for non- -specific chronic low-back pain . PATIENTS AND METHODS Seventy patients were r and omized into two groups : experimental group ( 34 patients ) and control group ( 36 patients ) . Experimental group patients participated in a theoretical and practical back school program , which was composed of 4 weekly classes of 60 minutes . Control group patients were allocated at a waiting list . Three evaluations took place ( baseline , after 4 and 16 weeks ) . The following variables were analyzed : pain intensity ( visual numeric analogue scale ) , functional disability ( Rol and -Morris Disability Question naire ) and spinal mobility ( Schöber index ) . Statistical analysis for intra-group and inter-group used significance level of p < 0.05 . RESULTS 57 patients were analyzed ( 29 in experimental group and 28 in control group ) . A statistically significant improvement was observed only in the experimental group , regarding pain intensity , functional disability and spine mobility . Such improvements have persisted after 16 weeks in pain intensity and functional disability variables . In the inter-group analysis we observed a statistically significant difference in the second and third evaluations concerning the functional disability variables and spinal mobility . CONCLUSION The Back School program proposed in this study seems to be effective for non-specific chronic low back pain Study Design . A r and omized controlled trial . Objective . To examine the effects of the back school program on quality of life in women with chronic low back pain . Summary of Background Data . There is a controversial debate whether back school program might improve quality of life in back pain patients . This study aim ed to address this issue . Methods . One hundred and two eligible women were r and omly allocated into 2 groups . The 2 groups including back school group who received the back school program plus medication ( n = 50 ) and clinic group who received just medication ( n = 52 ) were compared at 4 points in time . Data were collected at baseline and at 3 , 6 , and 12 months follow-up using the SF-36 question naire . Repeated measures analysis was performed to compare quality of life scores in 2 groups . Results . Quality of life scores were significantly different between 2 groups throughout the study ( P < 0.0001 ) indicating a better quality of life among intervention group . Conclusion . The back school program might improve the quality of life score in women with chronic low back pain Patients with chronic low back pain have a worse posture , probably related to poor control of the back muscles and altered perception of the trunk midline . The aim of this study was to evaluate the efficacy of a perceptive rehabilitation in terms of stability and pain relief in patients with chronic nonspecific low back pain . Thirty patients were enrolled and r and omized into two groups : 15 patients received rehabilitation , on the basis of a specific tool to perform perceptive exercises [ perceptive group ( PG ) ] , and 15 patients received a back school programme [ back school group ( BG ) ] . Both groups were assessed using stabilometry and the McGill Pain Question naire before and at the end of treatment . For the reference values of stabilometric parameters , 15 healthy individuals were enrolled . Significant reductions in sway length ( P=0.019 ) and laterolateral sway velocity ( P=0.038 ) were observed in the PG . The anteroposterior sway velocity was reduced in both the groups , but significantly only for BG ( P=0.048 ) . The percentage of sway length reduction was inversely and significantly correlated with the initial sway length value for PG ( R=−0.708 , P=0.003 ) , but not for BG ( R=−0.321 , P=0.243 ) . In the PG , the sagittal arrows and bi-acromial and bi-spinoiliac lines ’ angles were all significantly reduced . General pain relief was reported after treatment , without a significant difference ( P=0.436 ) . Our results suggest that a perceptive rehabilitation can improve the postural stability for the realignment of the trunk , controlling the back pain . The use of cognitive exercises may strengthen the usual rehabilitation of low back pain , avoiding the recurrence of symptoms . Patienten mit chronischen Kreuzschmerzen weisen eine schlechtere Körperhaltung auf , wahrscheinlich aufgrund der schlechten Kontrolle der Rückenmuskulatur und einer abweichenden Wahrnehmung der Mittellinie ihres Rumpfes . Ziel der vorliegenden Studie war die Evaluierung der Wirksamkeit einer perzeptiven Rehabilitation von Patienten mit chronischen unspezifischen Kreuzschmerzen , was Stabilität und Schmerzlinderung anbelangt . An der Studie nahmen insgesamt 30 Patienten teil , die r and omisiert in zwei Gruppen aufgeteilt wurden : 15 Patienten erhielten Rehabilitation auf der Grundlage eines spezifischen Tools zur Durchführung eines sensomotorisch-perzeptiven Trainings [ perzeptive Gruppe ( PG ) ] , die and eren 15 Patienten Rückenschulübungen [ Rückenschulgruppe ( RG ) ] . Beide Gruppen wurden vor und nach der Beh and lung mit Hilfe von Stabilometrie und dem McGill-Schmerz-Fragebogen evaluiert . Zu Referenzzwecken bei den stabilometrischen Parametern wurden 15 gesunde Prob and en in die Studie aufgenommen . In der PG wurden signifikante Reduktionen der Schwankungslänge ( P=0,019 ) und der laterolateralen Schwankungsgeschwindigkeit ( P=0,038 ) beobachtet . Die anteroposteriore Schwankungsgeschwindigkeit war in beiden Gruppen reduziert , wobei sie nur in der BG signifikant reduziert war ( P=0,048 ) . Der Prozentsatz der Schwankungslängenreduktion korrelierte umgekehrt und signifikant mit dem Wert der anfänglichen Schwankungslänge bei der PG ( R=−0,708 , P=0,003 ) , nicht aber bei der BG ( R=−0,321 , P=0,243 ) . In der PG waren die Sagittalebene und die Winkel der beidseitig akromialen und spinal-iliakalen Linien alle signifikant reduziert . Eine allgemeine Schmerzlinderung wurde nach der Beh and lung ohne signifikanten Unterschied ( P=0,436 ) berichtet . Unsere Ergebnisse legen den Schluss nahe , dass eine perzeptive Rehabilitation die Haltungsstabilität bei der Neuausrichtung des Rumpfes zu verbessern und somit Rückenschmerzen zu kontrollieren vermag . Die Anwendung kognitiver Übungen kann die übliche Rehabilitation bei Kreuzschmerzen unterstützen und somit ein erneutes Auftreten der Symptome vermeiden . Los pacientes con dolor lumbar crónico poseen una postura incorrecta , probablemente relacionada con la falta de control de los músculos lumbares y la percepción alterada de la línea media del tronco . El objetivo de este estudio fue evaluar la eficacia de la rehabilitación perceptiva en términos de estabilidad y alivio del dolor en pacientes con dolor lumbar crónico no específico . Treinta pacientes participaron en el estudio y fueron distribuidos en dos grupos de forma aleatoria : quince pacientes recibieron sesiones de rehabilitación utiliz and o una herramienta específica para la realización de ejercicios de percepción [ grupo perceptivo ] y los otros quince participaron en un programa de escuela de espalda [ grupo de escuela de espalda ] . Ambos grupos se evaluaron mediante estabilometría y el cuestionario del dolor McGill antes y después del tratamiento . Quince individuos sanos participaron en el estudio como valor de referencia de los parámetros estabilométricos . En el grupo perceptivo se observaron reducciones significativas en la longitud del balanceo ( P=0,019 ) y en la velocidad de balanceo latero-lateral ( P=0,038 ) . La velocidad de balanceo anteroposterior se vio reducida en ambos grupos , pero solo de forma significativa en el grupo de escuela de espalda ( P=0,048 ) . El porcentaje de la reducción de la longitud del balanceo mostró una correlación inversa y significativa con el valor inicial de la longitud del balanceo del grupo perceptivo ( R=−0,708 , P=0,003 ) pero no del grupo de escuela de espalda ( R=−0,321 , P=0,243 ) . En el grupo perceptivo , las flechas verticales y los ángulos de las líneas biacromiales y biespinailíacas se vieron reducidos de forma significativa . Tras el tratamiento se registró el alivio general del dolor sin ninguna diferencia significativa ( P=0,436 ) . Los result ados de este estudio sugieren que la rehabilitación perceptiva puede mejorar la estabilidad postural de la alineación del tronco mediante el control del dolor lumbar . El uso de ejercicios cognitivos puede reforzar la rehabilitación del dolor lumbar y evitar la recurrencia de los síntomas . Les patients atteints de lombalgie chronique adoptent une plus mauvaise posture , probablement liée à un mauvais contrôle des muscles du dos et la perception altérée de la ligne médiane du tronc . Cette étude avait pour objet d'évaluer l'efficacité d'une rééducation de la perception en termes de stabilité et de soulagement de la douleur chez les patients atteints de douleur chronique lombaire non spécifique . Trente patients ont été recrutés et r and omisés en deux groupes : 15 patients ont reçu une rééducation basée sur un outil spécifique destiné à effectuer des exercices de perception [ groupe de perception ( GP ) , et 15 patients ont reçu un programme d'exercice pour le dos ( GD ) . Les deux groupes ont été évalués par stabilométrie et par le question naire de McGill Pain avant et à la fin du traitement . Pour les valeurs de référence des paramètres stabilométriques , 15 individus en bonne santé ont été inclus . Des réductions significatives de longueur de balancement ( P = 0,019 ) et de la vitesse de balancement latérolatéral ( P = 0,038 ) ont été observées chez le GP . La vitesse de balancement antéro-postérieur a été réduite dans les deux groupes , mais uniquement de façon significative pour GE ( P = 0,048 ) . Le pourcentage de réduction de la longueur de balancement présentait une corrélation inverse significative avec la valeur de la longueur initiale pour GP ( R = −0,708 , P = 0,003 ) , mais pas pour GE ( R = 0,321 , P = 0,243 ) . Dans le GP , les flèches sagittales et biacromiales et les angles des lignes bi-spinoiliaques présentaient tous une réduction significative . Un soulagement général de la douleur a été signalé après le traitement , sans différence significative ( P = 0,436 ) . Nos résultats suggèrent que la rééducation de la perception peut améliorer la stabilité posturale pour le réalignement du tronc en contrôlant la douleur au dos . L'utilisation d'exercices cognitifs peut renforcer la rééducation habituelle de la douleur lombaire , en évitant la réapparition des symptômes Objective : To evaluate the efficacy of a perceptive rehabilitative approach , based on a new device , with regard to pain and disability in patients with chronic nonspecific low back pain . Design : Single blind , r and omized , controlled trial . Setting : An outpatient academic hospital . Patients : Seventy-five patients with chronic low back pain . Interventions : Patients were r and omized into three groups . Twenty-five subjects received 10 sessions in one month , based on specific perceptive exercises that were performed on a suitably developed device . Twenty-five patients entered a Back School programme . Twenty-five patients comprised a control group that received the same medical and pharmacological assistance as the other groups . Main outcome measures : Pain was assessed using the Visual Analogue Scale and McGill Pain Question naire . Disability was evaluated using the Oswestry Disability Index and Waddell Disability Index . All measurements were recorded before treatment , at the end of the study , and at 12 and 24 weeks . Results : General pain relief was recorded in all the groups , which was elicited more quickly in the perceptive treatment group ; significant differences in pain scores were observed at the end of treatment ( P < 0.001 for visual analogue scale and P = 0.001 for Question naire ) versus the other groups . Disability scores in the perceptive group did not differ significantly from those in the other group , whereas these scores significantly differed between Back School and control groups at the follow-ups ( P < 0.01 for both scales ) . Conclusion : Perceptive rehabilitation has immediate positive effects on pain . Back School reduces disabilities at follow-up Study Design . A stratified r and omized single-blinded clinical trial . Objective . To compare the efficacies of 2 active therapies for chronic low back pain ( CLBP ) . Summary of Background Data . Both a multidisciplinary biopsychosocial rehabilitation program and an intensive individual therapist-assisted back muscle strengthening exercise program used in Denmark have been reported to be effective for the treatment of CLBP . Methods . A total of 286 patients with CLBP were r and omized to either a group-based 12-week program comprising 73 hours of therapist exposure ( approximately 12 h/patient ) : 35 hours of hard physical exercise , 22 hours of light exercise/occupational therapy , and 16 hours of education ( group A ) or a 12-week program comprising 1 hour of personal training twice a week , i.e. , therapist exposure 24 h/patient ( group B ) . At baseline and at 3 , 6 , 12 , and 24 months , patients filled out question naires on pain ( visual analogue scale [VAS]-pain average , which was the primary outcome measure ) , Rol and -Morris disability question naire , global perceived outcome , and 36-Item Short-Form General Health Survey . Data were analyzed using the intention-to-treat principle . Results . Of the 286 patients , 14 patients did not start treatment . Of the remaining patients , 25 ( 9 % ) dropped out of therapy . The 2 groups were comparable regarding baseline characteristic . After treatment , significant improvements were observed with regard to pain , disability , and most of the quality of life dimensions . These effects were sustained over the 24-month follow-up period . There were some statistically significant differences between the 2 groups relating to secondary end points , Rol and -Morris disability question naire , and in the MOS 36-Item Short-Form Health Survey the “ physical functioning ” dimension and the “ physical component summary . ” Conclusion . Both groups showed long-term improvements in pain and disability scores , with only minor statistically significant differences between the 2 groups . The minor outcome difference in favor of the group-based multidisciplinary rehabilitation program is hardly of clinical interest for individual patients Background Back School and McKenzie methods are popular active treatment approaches that include both exercises and information for patients with chronic nonspecific low back pain . Objective The purpose of this study was to compare the effectiveness of Back School and McKenzie methods in patients with chronic nonspecific low back pain . Design The study was a prospect ively registered , 2-arm r and omized controlled trial with a blinded assessor . Setting The study was conducted in the outpatient physical therapy clinic in São Paulo , Brazil . Patients The study participants were 148 patients with chronic nonspecific low back pain . Interventions The 4-week treatment program ( one session/week ) was based on the Back School ( delivered to the group ) or McKenzie ( delivered individually ) principles . The participants also were instructed to perform a daily set of home exercises . Measurements Clinical outcomes were assessed at follow-up appointments at 1 , 3 , and 6 months after r and omization . Primary outcome measures were pain intensity ( measured by the 0–10 pain numerical rating scale ) and disability ( measured by the 24-item Rol and -Morris Disability Question naire ) 1 month after r and omization . Secondary outcome measures were pain intensity and disability at 3 and 6 months after r and omization , quality of life ( measured by the World Health Organization Quality of Life – BREF instrument ) at 1 , 3 , and 6 months after r and omization , and trunk flexion range of motion measured by an inclinometer at 1 month after r and omization . The data were collected by a blinded assessor . Results Participants allocated to the McKenzie group had greater improvements in disability at 1 month ( mean effect=2.37 points , 95 % confidence interval=0.76 to 3.99 ) but not for pain ( mean effect=0.66 points , 95 % confidence interval=−0.29 to 1.62 ) . No between-group differences were observed for all secondary outcome measures . Limitations It was not possible to monitor the home exercise program . Therapists and participants were not blinded . Conclusions The McKenzie method ( a more re source -intensive intervention ) was slightly more effective than the Back School method for disability , but not for pain intensity immediately after treatment in participants with chronic low back pain & NA ; The current investigation studied the effectiveness of a secondary prevention program for nurses with back pain who were deemed at risk for developing a chronic problem . A 2 × 3 repeated measures design was employed with 2 groups and 3 assessment periods . The treatment group received an intervention design ed to reduce current problems , but above all to prevent reinjury and minor pains from becoming chronic medical problems , and it included a physical and behavioral therapy package . The control group was placed on a waiting‐list . Results indicated that the treatment group had significantly greater improvements than the control group for pain intensity , anxiety , sleep quality and fatigue ratings , observed pain behavior , activities , mood , and helplessness . These differences were generally maintained at the 6 month follow‐up . In addition , the treatment group broke a trend for increasing amounts of pain‐related absenteeism , while the control group did not . Taken as a whole , the results suggest that a secondary prevention program aim ed at altering life style factors may represent an effective method for dealing with musculoskeletal pain problems STUDY DESIGN A three and six months follow-up in a r and omized controlled trial . BACKGROUND Back School has become a widespread exercise program for low back pain ( LBP ) , since its introduction in 1969 . Back School could improve quality of life ( QoL ) , but there are controversial data regarding its effectiveness . AIM To evaluate the effects of the Back School program on quality of life ( primary outcome ) , disability and pain perceptions ( secondary outcomes ) in patients with chronic and non-specific low back pain . SETTING Rehabilitative specialized centre . POPULATION Seventy four patients with chronic non-specific LBP . METHODS Patients were r and omly placed in a 3:2 form and were allocated into 2 groups ( treated-control ) . Treatment group participated in a intensive multidisciplinary Back School program including brief education and active back exercises ( BSG , N.=41 ) , while the control group received medical assistance ( CG , N.=29 ) . Medication was the same in both groups . The Short Form 36 Health Status Survey , Waddel Index , Oswestry Disability Index and Visual Analogue Scale were collected at baseline , at the end of treatment , and at the three and six month follow-up . RESULTS Quality of life significantly improved along time more in BSG , both in Physical and Mental Composite Score ( repeated measure Anova : interaction time per group : P<0.001 and P=0.002 , respectively ) . We also observed a significant improvement in disability scores along time ( P<0.001 ) in BSG with significant differences between groups at three and at six months for Waddell Index ( P=0.006 and P=0.009 respectively ) and for Oswestry Disability Index ( P=0.018 and 0.011 respectively ) . Moreover , pain perception score VAS showed a reduction in both groups , but it was significantly lower in BSG at end of treatment and both follow-ups ( P<0.001 ) . CONCLUSION Our Back School program can be considered an effective treatment in people with chronıc non-specıfıc LBP BACKGROUND Chronic non-specific low back pain is both a health and a socio-economic problem which is associated with disability as well as with emotional distress . The Mckenzie and Back School 's techniques have been shown to be effective in the treatment of this condition . OBJECTIVES to perform a preliminary analysis of the effects of these treatments in patients with chronic non specific low back pain for the following outcomes : pain , disability and trunk flexion range of motion and to test the feasibility of r and omized controlled trial testing these interventions on this population . METHODS the participants were assessed by a blinded assessor and r and omly assigned into one of the treatment groups . The data analysis was performed in only 18 patients and the study is still ongoing , so the results are restricted to these patients , as a single group . RESULTS the patients improved for the outcomes pain intensity ( mean difference of 2.4 points and 95 % CI 0.84 to 3.93 ) and disability ( 5.2 points and 95 % CI 2.55 to 7.78 ) , but no improvement in range of motion in flexion was observed ( 7.2 degrees 95 % CI -1.82 to 16.29 ) . CONCLUSION the Mckenzie and Back School 's approaches may be beneficial for the treatment of patients with chronic non specific low back pain for the outcomes pain intensity and disability . We also concluded that the study is feasible and we will continue performing the current study without any adjustments of the original research protocol . This study was prospect ively registered in the Australian New Zeal and Clinical Trials Registry ( ANZCTR ) number ACTRN12610000435088 Objective : To compare spinal manipulation , back school and individual physiotherapy in the treatment of chronic low back pain . Design : R and omized trial , 12-month follow-up . Setting : Outpatient rehabilitation department . Participants : 210 patients with chronic , non-specific low back pain , 140/210 women , age 59 ± 14 years . Interventions : Back school and individual physiotherapy scheduled 15 1-hour-sessions for 3 weeks . Back school included : group exercise , education/ ergonomics ; individual physiotherapy : exercise , passive mobilization and soft-tissue treatment . Spinal manipulation , given according to Manual Medicine , scheduled 4 to 6 20’-sessions once-a-week . Outcome : Rol and Morris Disability Question naire ( scoring 0 - 24 ) and Pain Rating Scale ( scoring 0 - 6 ) were assessed at baseline , discharge 3 , 6 , and 12 months . Results : 205 patients completed the study . At discharge , disability score decreased by 3.7 ± 4.1 for back school , 4.4 ± 3.7 for individual physiotherapy , 6.7 ± 3.9 for manipulation ; pain score reduction was 0.9 ± 1.1 , 1.1 ± 1.0 , 1.0 ± 1.1 , respectively . At 12 months , disability score reduction was 4.2 ± 4.8 for back school , 4.0 ± 5.1 for individual physiotherapy , 5.9 ± 4.6 for manipulation ; pain score reduction was 0.7 ± 1.2 , 0.4 ± 1.3 , and 1.5 ± 1.1 , respectively . Spinal manipulation was associated with higher functional improvement and long-term pain relief than back school or individual physiotherapy , but received more further treatment at follow-ups ( P<0.001 ) ; pain recurrences and drug intake were also reduced compared to back school ( P < 0.05 ) or individual physiotherapy ( P < 0.001 ) . Conclusions : Spinal manipulation provided better short and long-term functional improvement , and more pain relief in the follow-up than either back school or individual physiotherapy Outcome of inpatient and outpatient treatment of low back pain was studied in 459 patients ( aged 35 - 54 years , 63 % men ) ; 156 in patients , 150 out patients and 153 controls . Changes in low back pain and in disability caused by it , and adherence and accomplishment of back exercises were used as short-term outcome criteria . The overall results showed a significant decrease in pain and disability and better compliance in the two treated groups when compared to the controls . There was also a significant difference in treatment gains between the in patients and out patients ; i.e. the decrease in pain was greater and the frequency of back exercises higher in the in patients . The in patients also estimated their treatment benefits more positively than the out patients Study Design . A controlled clinical trial . Objectives . To examine the long‐term effect of an informative approach to low back pain . Summary of Background Data . In management and prevention of low back pain , back school based on an ergonomic approach have played an important role . The effect of such informative interventions is not clear . Methods . A 5‐year follow‐up study was done on patients included in a previous study . The outcome was measured by return to work or still on sick leave . The patients were allocated to an intervention group ( n = 245 ) and a control group ( n = 244 ) . Only the intervention group was called in for examination and intervention and answered a battery of tests for psychological and health factors . The intervention apart from the clinical examination consisted of education in a " mini back school . " The program was based on a new medical model for low back pain . Results . Forty‐seven ( 19 % ) of the patients in the intervention group , compared with 84 patients ( 34 % ) in the control group , were still on sick leave after 5 years ( P < 0.001 ) . There were fewer recurrences of sick leave ( P < 0.03 ) in the intervention group than in the control group . Based on Internal Health Locus of Control , number of children , and income , 75 % were correctly classified as nonreturners in the intervention group . Conclusions . This study indicates that subchronic low back pain may be managed successfully with an approach that includes clinical examination combined with information for patients about the nature of the problem , provided in a manner design ed to reduce fear and give them reason to resume light activity The purpose of the present study was to investigate the long-term effect of the Active Back School programme on minimizing recurrences of episodes of low back pain . Forty-three subjects were r and omly allocated to the Active Back School group and 38 to the control group . There were no significant differences between the groups with regard to baseline characteristics . The Active Back School programme comprised 20 lessons each divided into a 20-min theoretical and a 40-min exercise part during a 13-week period . Nine participants ( 11 % ) dropped out during the study period . Recurrence of new low back pain episodes was significantly less ( p = 0.04 ) , and the time from inclusion to the first new low back pain episode was significantly on the side of the Active Back School group ( p < 0.01 ) . The duration of sick leave was found to be significantly shorter ( p < 0.01 ) in the Active Back School group compared to the control group . The Active Back School reduced the recurrence and severity of new low back pain episodes at 36 months ' follow-up AIMS The purpose of the study was to measure the effectiveness of a spine training programme ( Back School ) in nurses who have been living with chronic low back pain . It was hypothesised that active therapy , ergonomics and education called Back School will significantly decrease the pain intensity levels and improve the body posture of the study participants . BACKGROUND A chronic low back pain is a significant work-related health problem among healthcare workers around the world . Proper body posture is essential for decreasing pain in healthcare workers who have history of chronic low back pain . By teaching proper body posture and with the creation of occupational setting s that are ' spine-friendly ' hospitals and other healthcare setting s can significantly lower the suffering of their nursing staff . DESIGN Single-blinded r and omised controlled trial was utilised with six- and 12-months follow-up . METHODS The study was carried out at the University of Pecs , Faculty of Health Sciences from 2007 to 2008 involving 124 nurses with low back pain . Participants were r and omly assigned to the study group ( who have received ergonomics training and education called Back School ) with an intervention conducted once a week for a six-week period . The control group received passive physiotherapy once a week for a six-week period . Further follow-up measurements were conducted at six and 12 months , respectively . The study variables and outcome measures were pain intensity and body posture ( angle of thoracic kyphosis and lumbar lordosis ) . The pain intensity was investigated with the Visual Analogue Scale . Body posture was recorded and analysed with the Zebris biomechanical motion analysis system . RESULTS The statistical analysis of repeated measures indicated a significant decrease in back pain intensity after the therapy in both groups , compared with measurements before the therapy ; however , the BS group showed significantly better results during the six-month and one-year follow-up period . The biomechanical analysis of postures after the therapy in the BS group showed significant improvements over the control group ; during the follow-up , the difference was still significant , yet slightly reduced . CONCLUSIONS This study has shown that a significant reduction in the pain intensity and improvement in body posture can be achieved by the usage of the active physical therapy methods ( Back School ) in nurses who are experiencing chronic lower back pain . RELEVANCE TO CLINICAL PRACTICE The Back School programme when compared with the passive physical therapies ( such as massage , ultrasound treatment , etc . ) shows significant improvement in reduction in pain and greatly improves the posture of healthcare workers . The adoption of the Back School programme for the treatment of the healthcare workers with chronic low back problems should be a treatment of choice and st and ard that should be adopted when design ing occupational healthcare policies and procedures Objective . This r and omized clinical trial was design ed to determine the effect of treating low back pain as a benign , self limiting condition by light normal activity . Methods . Patients on sickness leave from work for more than 8 weeks were r and omized into two groups : intervention ( n = 463 ) and control ( n = 512 ) . Those in the intervention group were examined , provided information , and given instruction . Outcome was measured by return or failure to return to work ( still on sickness leave ) . Results . Survival analysis showed a highly significant ( P = 0.000 ) reduction in sickness leave in the intervention group as compared with the control group . At 200 days 60 % were still on sickness leave in the control group vs. 30 % in the intervention group . A multivariate analysis with age , sex , and treatment as cofactors showed that sex had no effect on length of sickness leave and that treatment retained its effect when adjusting for differences in age composition . Conclusion . This study indicates that low back pain treated as a benign , self limiting condition recommended to light mobilization gives superior results as compared to treatment within a conventional medical system The use of an education program for patients with chronic low back pain ( Back School ) has been investigated . The effect evaluation is based on a pretest-post-test-control group design , including a follow-up after 8 weeks . The Maastricht Back School is based on the theory that pain is also maintained by emotional , cognitive and environmental factors . Information and training are given on these and physical factors . The purpose of the course is to teach patients to manage their own pain problem . The results suggest that the Back School program for patients with chronic low back pain can have a positive effect BACKGROUND AND AIM OF THE WORK Chronic low back pain ( CLBP ) is a major cause of disability , for which clinical practice guidelines suggest exercise programs , such as Back School program ( stretching and selective muscle reinforcement techniques ) and Hydrotherapy technique , as an effective treatment to reduce pain intensity and disability . METHODS We enrolled 56 elderly individuals , affected by non-specific CLBP , whose pain had worsened in the last three months , which were r and omly allocated to Back School ( group A ) or to Hydrotherapy program ( group B ) . Each group underwent two one-hour-treatment sessions per week , over a 12-week period . Each patient was evaluated using the Rol and Morris Disability Question naire ( RMDQ ) and the 36-Item Short Form Health Survey ( SF-36 ) V2.0 at the beginning ( T0 ) , at the end of treatment ( T1 ) and at the 3-month follow-up ( T2 ) . RESULTS At T1 and T2 we observed a highly significant statistical difference in the values measured in both groups : at T1 in group A RMDQ improvement of 3.26±1.02 ( p<0.001 ) and SF-36 of 13.30±1.44 ( p<0.001 ) ; in group B RMDQ improvement of 4.96±0.71 ( p<0.001 ) and SF-36 of 14.19±1.98 ( p<0.001 ) . We have also evaluated the difference in effectiveness of the two programs and no significant statistical differences were found between the two groups . CONCLUSIONS Back School program and Hydrotherapy could be valid treatment options in the rehabilitation of non-specific CLBP in elderly people . Both therapies proved to be effective and can be used in association with other rehabilitation programs . We believe that Back School program should be favored for its simplicity and the small number of re sources required Study Design . A r and omized , assessor-blinded clinical trial was conducted . Objective . To investigate the relative effectiveness of three manual treatments and back school for patients with subacute low back pain . Summary of Background Data . Literature comparing the relative effectiveness of specific therapies for low back pain is limited . Methods . Among the 5925 inquiries , 206 patients met the specific admission criteria , and 200 patients r and omly received one of four treatments for 3 weeks : back school , joint manipulation , myofascial therapy , and combined joint manipulation and myofascial therapy . These patients received assessment s at baseline , after 3 weeks of therapy , and 6 months after the completion of therapy . The primary outcomes were evaluated using visual analog pain scales and Rol and –Morris activity scales . Results . All four groups showed significant improvement in pain and activity scores after 3 weeks of care , but did not show further significant improvement at the 6-month follow-up assessment . No statistically significant between-group differences were found either at the 3-week or 6-month re assessment s. Conclusions . For subacute low back pain , combined joint manipulation and myofascial therapy was as effective as joint manipulation or myofascial therapy alone . Additionally , back school was as effective as three manual treatments STUDY DESIGN A r and omized , controlled , single-center trial with a stratified group design . OBJECTIVE To investigate the secondary prophylactic effect of the Active Back School program on minimizing recurrences of low back pain episodes . SUMMARY OF BACKGROUND DATA The results of back school interventions are controversial . Previous work often used short intervention periods and low doses of practical training . However , studies with the highest method ologic scores have shown the best results , especially when conducted in occupational setting s and coupled with a comprehensive rehabilitation program . METHODS By block r and omization , 19 men and 24 women were allocated to Active Back School , with 18 men and 20 women as control subjects . The Slumps test and number of low back pain episodes during the previous 36 months were used as stratification factors . There were no significant differences between the groups with regard to demographic factors and initially observed variables . Active Back School consisted of 20 lessons over a 13-week period . Each lesson was divided into a 20-minute theoretical part and a 40-minute exercise part . All participants were examined on enrollment , then 5 and 12 months after initiation of the program . Outcome measures were recurrence of low back pain episodes and number of days of sick leave . RESULTS The recurrence of new low back pain episodes was significantly lower ( P < 0.05 ) and the time from inclusion to the first new episode significantly longer ( P < 0.01 ) in the Active Back School group than in the control group . In the Active Back School group , seven participants took sick leave because of low back pain episodes during the first 12 months of follow-up compared with 11 among the control subjects . The number of sick leave days was significantly lower ( P < 0.05 ) in the Active Back School group than in the control group . CONCLUSION Active Back School reduced the recurrence and severity of new low back pain episodes according to results of follow-up examinations performed 5 and 12 months after enrollment Medical rehabilitation in Germany is still lacking in patient education programmes that meet certain quality requirements such as the use of manuals , patient-oriented didactics , and evaluations of effectiveness . For patients with chronic low back pain , no st and ardized and evaluated back school programme has so far been available for routine use . In this paper , we demonstrate the development of a quality -assured back school based on a health-education programme of the German statutory pension insurance scheme . Both topics and didactics incorporate treatment evidence , practice guidelines , quality criteria for patient education and theories of health and illness behaviour . First , formative evaluation was conducted to assess patient acceptance and practicability of the manual . Second , effects of the back school programme were assessed on a short-term ( at the end of rehabilitation ) , medium-term ( 6-month follow-up ) and long-term ( 12-month follow-up ) basis in a r and omized controlled study of patients with low back pain ( n=360 ) . Results show a significant medium treatment effect in patients ' knowledge about chronic back pain and its treatment at the end of rehabilitation ( p<0.001 ; eta (2)=0.080 ) . Furthermore , small to medium effects were also observed among some secondary outcomes , such as motivation to physical activity , pain beliefs and pain intensity . After the programme 's medium- and long-term effects have been demonstrated , it will be recommended for implementation in medical rehabilitation . The manual meets the requirements that allow for a successful transfer into clinical practice |
14,015 | 32,428,300 | Subgrouping did not suggest significant differences between replacement of saturated fat calories with polyunsaturated fat or carbohydrate , and data on replacement with monounsaturated fat and protein was very limited .
There was little or no effect on cancer mortality , cancer diagnoses , diabetes diagnosis , HDL cholesterol , serum triglycerides or blood pressure , and small reductions in weight , serum total cholesterol , LDL cholesterol and BMI .
There was no evidence of harmful effects of reducing saturated fat intakes .
The findings of this up date d review suggest that reducing saturated fat intake for at least two years causes a potentially important reduction in combined cardiovascular events .
Replacing the energy from saturated fat with polyunsaturated fat or carbohydrate appear to be useful strategies , while effects of replacement with monounsaturated fat are unclear .
The reduction in combined cardiovascular events result ing from reducing saturated fat did not alter by study duration , sex or baseline level of cardiovascular risk , but greater reduction in saturated fat caused greater reductions in cardiovascular events | BACKGROUND Reducing saturated fat reduces serum cholesterol , but effects on other intermediate outcomes may be less clear .
Additionally , it is unclear whether the energy from saturated fats eliminated from the diet are more helpfully replaced by polyunsaturated fats , monounsaturated fats , carbohydrate or protein .
OBJECTIVES To assess the effect of reducing saturated fat intake and replacing it with carbohydrate ( CHO ) , polyunsaturated ( PUFA ) , monounsaturated fat ( MUFA ) and /or protein on mortality and cardiovascular morbidity , using all available r and omised clinical trials . | The effect on serum high density lipoprotein subfractions of a low fat diet with a high ratio of polyunsaturated-to-saturated fatty acids was studied in 38 middle-aged volunteers ( 19 men and 19 women ) in North Karelia , Finl and . The mean serum HDL2 cholesterol decreased from 32 + /- 2 mg/dl ( mean + /- SE ) to 28 + /- 2 mg/dl ( p less than 0.001 ) during the experimental diet and returned to 33 + /- 2 mg/dl ( p less than 0.001 ) after a return to the original diet . No changes were observed in the concentration of HDL3 cholesterol . A highly significant decrease was observed in serum apoprotein A-I concentration , but not in apoprotein A-II concentration during the experimental diet . It is concluded that a low-fat , high-P/S ratio diet lowers LDL and HDL2 cholesterol in healthy volunteers , but does not influence the level of HDL3 subfraction The primary aim of this study was to test the association of early ( first 6 months ) adherence related to diet , self-monitoring , and attendance with changes in adiposity and cardiovascular risk factors . This study used data from the 24-month POUNDS LOST trial that tested the efficacy of four dietary macronutrient compositions for short- and long-term weight loss . A computer tracking system was used to record data on eight indicator variables related to adherence . Using canonical correlations at the 6 and 24 month measurement periods , early behavioral adherence was associated with changes in percent weight loss and waist circumference at 6 months ( R = 0.52 ) and 24 months ( R = 0.37 ) , but was not associated with cardiovascular disease risk factor levels . Early dietary adherence was associated with changes in insulin at 6 months ( R = 0.19 ) , but not at 24 months ( R = 0.08 , ns ) . Early dietary adherence was not associated with changes in adiposity Aims /hypothesisThe study aim ed to compare the effects of a 2 year intervention with a low-fat diet ( LFD ) or a low-carbohydrate diet ( LCD ) , based on four group meetings to achieve compliance . Methods This was a prospect i ve r and omised parallel trial involving 61 adults with type 2 diabetes consecutively recruited in primary care and r and omised by drawing ballots . Patients that did not speak Swedish could not be recruited . The primary outcomes in this non-blinded study were weight and HbA1c . Patients on the LFD aim ed for 55–60 energy per cent ( E% ) and those on LCD for 20 E% from carbohydrate . Results The mean BMI and HbA1c of the participants were 32.7 ± 5.4 kg/m2 and 57.0 ± 9.2 mmol/mol , respectively . No patients were lost to follow-up . Weight loss did not differ between groups and was maximal at 6 months : LFD −3.99 ± 4.1 kg ( n = 31 ) ; LCD −4.31 ± 3.6 kg ( n = 30 ) ; p < 0.001 within groups . At 24 months , patients on the LFD had lost −2.97 ± 4.9 kg and those on LCD −2.34 ± 5.1 kg compared with baseline ( p = 0.002 and p = 0.020 within groups , respectively ) . HbA1c fell in the LCD group only ( LCD at 6 months −4.8 ± 8.3 mmol/mol , p = 0.004 , at 12 months −2.2 ± 7.7 mmol/mol , p = 0.12 ; LFD at 6 months −0.9 ± 8.8 mmol/mol , p = 0.56 ) . At 6 months , HDL-cholesterol had increased with the LCD ( from 1.13 ± 0.33 mmol/l to 1.25 ± 0.47 mmol/l , p = 0.018 ) while LDL-cholesterol did not differ between groups . Insulin doses were reduced in the LCD group ( 0 months , LCD 42 ± 65 E , LFD 39 ± 51 E ; 6 months , LCD 30 ± 47 E , LFD 38 ± 48 E ; p = 0.046 for between-group change ) . Conclusions /interpretationWeight changes did not differ between the diet groups , while insulin doses were reduced significantly more with the LCD at 6 months , when compliance was good . Thus , aim ing for 20 % of energy intake from carbohydrates is safe with respect to cardiovascular risk compared with the traditional LFD and this approach could constitute a treatment alternative . Trial registration : Clinical Trials.gov NCT01005498 Funding : University Hospital of Linköping Research Funds , Linköping University , the County Council of Östergötl and , and the Diabetes Research Centre of Linköping The Minnesota Coronary Survey was a 4.5-year , open enrollment , single end-time , double-blind , r and omized clinical trial that was conducted In six Minnesota state mental hospitals and one nursing home . It Involved 4393 Institutionalized men and 4664 Institutionalized women . The trial compared the effects of a 39 % fat control diet ( 18 % saturated fat , 5 % polyunsaturated fat , 16 % monounsaturated fat , 446 mg dietary cholesterol per day ) with a 38 % fat treatment diet ( 9 % saturated fat , 15 % polyunsaturated fat , 14 % monounsaturated fat , 166 mg dietary cholesterol per day ) on serum cholesterol levels and the Incidence of myocardlal Infa rct ions , sudden deaths , and all-cause mortality . The mean duration of time on the diets was 384 days , with 1568 subjects consuming the diet for over 2 years . The mean serum cholesterol level In the pre-admission period was 207 mg/dl , falling to 175 mg/dl in the treatment group and 203 mg/dl In the control group . For the entire study population , no differences between the treatment and control groups were observed for cardiovascular events , cardiovascular deaths , or total mortality . A favorable trend for all these end-points occurred In some younger age groups The Trial of Antihypertensive Interventions and Management is a multicenter r and omized trial design ed to examine the diastolic blood pressure response of various combinations of pharmacological and dietary interventions in the treatment of mild hypertension ( diastolic blood pressure 90 - 100 mm Hg ) . Eight hundred and seventy-eight participants at 110 - 160 % of ideal weight were r and omly allocated to nine drug/diet treatment groups receiving either a placebo , chlorthalidone ( 25 mg ) , or atenolol ( 50 mg ) , combined with a usual , a weight loss , or a low sodium/high potassium diet The primary outcome was diastolic blood pressure change from baseline to 6 months . Seven hundred and eighty-seven participants had follow-up data . The mean baseline diastolic blood pressure was 93.8 mm Hg ; 55.9 % of the participants were male , and the weight loss diet group lost an average of 4.7 kg . Multiple comparisons were accounted for in the analysis . A significantly greater lowering of diastolic blood pressure ( 12.4 mm Hg ) was achieved in the atenolol group compared with either the low sodium/high potassium diet group ( 7.9 mm Hg , p=0.001 ) or weight loss group ( 8.8 mm Hg , p=0.006 ) . Adding weight loss to chlorthalidone significantly enhanced blood pressure lowering ( 15.1 mm Hg ) when compared with the diuretic alone ( 10.8 mm Hg , p=0.002 ) , but adding a low sodium/high potassium diet ( 12.2 mm Hg , p=0.029 ) did not In the short-term treatment of mild hypertension where diastolic blood pressure is the sole consideration , drugs outperform diet , and weight loss is beneficial , especially with diuretics The individual effects of dietary cholesterol and fat saturation on plasma lipoprotein concentrations were determined in an ethnically diverse population of normolipidemic young men ( 52 Caucasian , 32 non-Caucasian ) . The experimental diets contained approximately 200 or 600 mg/d of cholesterol , 36 - 38 % of calories as fat , and high or low proportions of saturated and polyunsaturated fat ( polyunsaturated/saturated fat ratio approximately 0.8 vs 0.3 ) . At the lower cholesterol intake , the high saturated fat diet had only a modest effect on LDL cholesterol in Caucasians ( + 6 mg/dl-1 ) and none in non-Caucasians . 600 mg cholesterol with high saturated fat led to a substantial mean increase in LDL cholesterol , which was significantly greater in Caucasian than in non-Caucasian subjects ( + 31 mg/dl vs 16 mg/dl , P < 0.005 ) . 600 mg cholesterol with increased polyunsaturated fat gave a mean LDL increase of 16 mg/dl , lower than found when the same high cholesterol intake was coupled with increased saturated fat . Variation in cholesterol rather than the proportions of saturated and polyunsaturated fat had the most influence on LDL-cholesterol levels . Among non-Caucasians it was the only significant factor Background Determinants of dietary changes obtained with a nutritional intervention promoting the Mediterranean diet have been rarely evaluated . Aim To identify predictors of higher success of an intervention aim ed to increase adherence to a Mediterranean diet ( MeDiet ) in individuals at high cardiovascular risk participating in a trial for primary prevention of cardiovascular disease : the PREDIMED ( PREvención con DIeta MEDiterránea ) trial . C and i date predictors included demographic and socioeconomic characteristics , cardiovascular risk factors , and baseline dietary habits . Methods A total of 1,048 asymptomatic subjects aged 55–80 years allocated to the active intervention groups ( subjects in the control group were excluded ) . Participants ’ characteristics were assessed at baseline among subjects . Dietary changes were evaluated after 12 months . Main outcome measures were : attained changes in five dietary goals : increases in ( 1 ) fruit consumption , ( 2 ) vegetable consumption , ( 3 ) monounsaturated fatty acid (MUFA)/saturated fatty acid ( SFA ) ratio , and decreases in ( 4 ) sweets and pastries consumption , ( 5 ) and meat consumption . Univariate and multivariate logistic regression analyses were used to examine associations between the c and i date predictors and likelihood of attaining optimum dietary change ( improved adherence to a MeDiet ) . Results Among men , positive changes toward better compliance with the MeDiet were more frequent among non-diabetics , and among those with worse dietary habits at baseline ( higher consumption of meat , higher SFA intake , lower consumption of fruit and vegetables ) . Among women , marital status ( married ) and worse baseline dietary habits ( high in meats , low in fruits and vegetables ) were the strongest predictors of success in improving adherence to the MeDiet . Conclusions Some participant characteristics ( marital status and baseline dietary habits ) could contribute to predicting the likelihood of achieving dietary goals in interventions aim ed to improve adherence to a MeDiet , and may be useful for promoting individualized long-term dietary changes and improving the effectiveness of dietary counseling BACKGROUND The Women 's Health Initiative Dietary Modification ( DM ) R and omized Controlled Trial evaluated the effects of a low-fat dietary pattern on chronic disease incidence , with breast cancer and colorectal cancer as primary outcomes . The trial protocol also listed ovarian cancer and endometrial cancer as outcomes that may be favorably affected by the intervention . METHODS A total of 48,835 postmenopausal women were r and omly assigned during 1993 - 1998 to a DM intervention ( n = 19,541 ) or comparison ( usual diet ; n = 29,294 ) group and followed up for an average of 8.1 years . The intervention goal was to reduce total fat intake to 20 % of energy and to increase consumption of vegetables , fruits , and grains . Cancer outcomes were verified by pathology report review . We used weighted log-rank tests to compare incidence of invasive cancers of the ovary and endometrium , total invasive cancer , and invasive cancers at other sites between the groups . All statistical tests were two-sided . RESULTS Ovarian cancer risk was lower in the intervention than in the comparison group ( P = .03 ) . Although the overall ovarian cancer hazard ratio ( HR ) was not statistically significantly less than 1.0 , the hazard ratio decreased with increasing intervention duration ( P(trend ) = .01 ) . For the first 4 years , the risk for ovarian cancer was similar in the intervention and control groups ( 0.52 cases per 1000 person-years in the intervention group versus 0.45 per 1000 person-years in the comparison group ; HR = 1.16 , 95 % confidence interval [ CI ] = 0.73 to 1.84 ) ; over the next 4.1 years , the risk was lower in the intervention group ( 0.38 cases per 1000 person-years in the intervention group versus 0.64 per 1000 person-years in the comparison group ; HR = 0.60 , 95 % CI = 0.38 to 0.96 ) . Risk of cancer of the endometrium did not differ between the groups ( P = .18 ) . The estimated risk of total invasive cancer was slightly lower in the intervention group than in the control group ( HR = 0.95 , 95 % CI = 0.89 to 1.01 ; P = .10 ) . CONCLUSIONS A low-fat dietary pattern may reduce the incidence of ovarian cancer among postmenopausal women OBJECTIVE To examine the influence of the PREMIER study lifestyle interventions on dietary intakes and adherence to the Dietary Approaches to Stop Hypertension ( DASH ) dietary pattern and the Dietary Reference Intakes ( DRI ) . DESIGN An 18-month multicenter , r and omized controlled trial comparing two multicomponent lifestyle intervention programs to an advice only control group . SUBJECTS/ SETTING A total of 810 participants were recruited from local communities and r and omized into the study . Individuals were eligible if they were aged 25 years or older , had body mass index between 18.5 and 45.0 , not taking antihypertensive medication , and had prehypertension or stage 1 hypertension ( systolic blood pressure 120 to 159 mm Hg and diastolic blood pressure 80 to 95 mm Hg ) . INTERVENTION The two active intervention programs were a behavioral lifestyle intervention that implements established recommendations , and an established intervention plus the DASH dietary pattern . Both interventions consisted of intensive group and individual counseling sessions . The control group received a brief advice session after r and omization and again after 6 months of data collection . Dietary intakes were collected by two r and om 24-hour recalls at baseline , 6 months , and 18 months . MAIN OUTCOME MEASURES The primary outcome of the PREMIER study was change in systolic blood pressure at 6 months . The main outcomes examined here include dietary variables collected by 24-hour recall at each time point . STATISTICAL ANALYSES Nutrient intakes were calculated and compared among the time points and the three intervention groups using mixed models with repeated measures at 6 and 18 months . Proportion of participants who met or achieved the original DASH nutrient intake levels and the DRIs were calculated and compared among the three intervention groups . P<0.01 was considered statistically significant . RESULTS Participants in both the established intervention and established intervention plus DASH dietary pattern groups substantially reduced energy , total fat , saturated fat , and sodium intake and these reductions persisted throughout the study . Established intervention plus DASH dietary pattern group participants increased intakes of fruits , vegetables , dairy , and many vitamins and minerals ; these increases were significantly greater than that of the control and established intervention groups . A majority of established intervention plus DASH dietary pattern group participants achieved at least two thirds of the DRI recommendations for most nutrients at 6 months , despite their reduction in total energy intake . Some but relatively small recidivism occurred at 18 months . CONCLUSIONS Both the established intervention and established intervention plus DASH dietary pattern group intervention were effective in helping participants follow established recommendations to control blood pressure . The advice-only control group also made some behavior changes , mainly decreasing energy and sodium intake . Only the established intervention plus DASH dietary pattern group significantly increased intakes of DASH-specific food groups , including fruits , vegetables , and dairy products , and nutrients , including protein , fiber , calcium , potassium , and magnesium . Most of the increases did not reach the levels consumed in the original DASH feeding studies . Whereas the established intervention plus DASH dietary pattern group intervention provides a useful platform to achieve the DASH dietary pattern and current DRI recommendations , intervention enhancements , including a greater emphasis on nutrient-dense foods , would likely improve this intervention Background A few observational studies have found an inverse association between adherence to a Mediterranean diet and the risk of depression . R and omized trials with an intervention based on this dietary pattern could provide the most definitive answer to the findings reported by observational studies . The aim of this study was to compare in a r and omized trial the effects of two Mediterranean diets versus a low-fat diet on depression risk after at least 3 years of intervention . Methods This was a multicenter , r and omized , primary prevention field trial of cardiovascular disease ( Prevención con Dieta Mediterránea ( PREDIMED Study ) ) based on community-dwelling men aged 55 to 80 years and women aged 60 to 80 years at high risk of cardiovascular disease ( 51 % of them had type 2 diabetes ; DM2 ) attending primary care centers affiliated with 11 Spanish teaching hospitals . Primary analyses were performed on an intention-to-treat basis . Cox regression models were used to assess the relationship between the nutritional intervention groups and the incidence of depression . Results We identified 224 new cases of depression during follow-up . There was an inverse association with depression for participants assigned to a Mediterranean diet supplemented with nuts ( multivariate hazard ratio ( HR ) 0.78 ; 95 % confidence interval ( CI ) 0.55 to 1.10 ) compared with participants assigned to the control group , although this was not significant . However , when the analysis was restricted to participants with DM2 , the magnitude of the effect of the intervention with the Mediterranean diet supplemented with nuts did reach statistical significance ( multivariate HR = 0.59 ; 95 % CI 0.36 to 0.98 ) . Conclusions The result suggest that a Mediterranean diet supplemented with nuts could exert a beneficial effect on the risk of depression in patients with DM2.Trial registration This trial has been registered in the Current Controlled Trials with the number IS RCT N Reduction of cumulative exposure to endogenous ovarian steroid hormones is a postulated method for reducing the risk of carcinoma of the breast and other malignancies . Although there are data from trials evaluating the effect of low‐fat and high‐fiber diets on sex hormone levels in premenopausal women , to the authors ' knowledge none of these trials has combined a relatively large number of participants , follow‐up of > 2–3 months , parallel controls receiving a usual diet , and careful timing of blood sampling within the menstrual cycle OBJECTIVE To test the effects of two Mediterranean diet ( MedDiet ) interventions versus a low-fat diet on incidence of diabetes . RESEARCH DESIGN AND METHODS This was a three-arm r and omized trial in 418 nondiabetic subjects aged 55–80 years recruited in one center ( PREDIMED-Reus , northeastern Spain ) of the Prevención con Dieta Mediterránea [ PREDIMED ] study , a large nutrition intervention trial for primary cardiovascular prevention in individuals at high cardiovascular risk . Participants were r and omly assigned to education on a low-fat diet ( control group ) or to one of two MedDiets , supplemented with either free virgin olive oil ( 1 liter/week ) or nuts ( 30 g/day ) . Diets were ad libitum , and no advice on physical activity was given . The main outcome was diabetes incidence diagnosed by the 2009 American Diabetes Association criteria . RESULTS After a median follow-up of 4.0 years , diabetes incidence was 10.1 % ( 95 % CI 5.1–15.1 ) , 11.0 % ( 5.9–16.1 ) , and 17.9 % ( 11.4–24.4 ) in the MedDiet with olive oil group , the MedDiet with nuts group , and the control group , respectively . Multivariable adjusted hazard ratios of diabetes were 0.49 ( 0.25–0.97 ) and 0.48 ( 0.24–0.96 ) in the MedDiet supplemented with olive oil and nuts groups , respectively , compared with the control group . When the two MedDiet groups were pooled and compared with the control group , diabetes incidence was reduced by 52 % ( 27–86 ) . In all study arms , increased adherence to the MedDiet was inversely associated with diabetes incidence . Diabetes risk reduction occurred in the absence of significant changes in body weight or physical activity . CONCLUSIONS MedDiets without calorie restriction seem to be effective in the prevention of diabetes in subjects at high cardiovascular risk CONTEXT Observational studies and polyp recurrence trials are not conclusive regarding the effects of a low-fat dietary pattern on risk of colorectal cancer , necessitating a primary prevention trial . OBJECTIVE To evaluate the effects of a low-fat eating pattern on risk of colorectal cancer in postmenopausal women . DESIGN , SETTING , AND PARTICIPANTS The Women 's Health Initiative Dietary Modification Trial , a r and omized controlled trial conducted in 48,835 postmenopausal women aged 50 to 79 years recruited between 1993 and 1998 from 40 clinical centers throughout the United States . INTERVENTIONS Participants were r and omly assigned to the dietary modification intervention ( n = 19,541 ; 40 % ) or the comparison group ( n = 29,294 ; 60 % ) . The intensive behavioral modification program aim ed to motivate and support reductions in dietary fat , to increase consumption of vegetables and fruits , and to increase grain servings by using group sessions , self-monitoring techniques , and other tailored and targeted strategies . Women in the comparison group continued their usual eating pattern . MAIN OUTCOME MEASURE Invasive colorectal cancer incidence . RESULTS A total of 480 incident cases of invasive colorectal cancer occurred during a mean follow-up of 8.1 ( SD , 1.7 ) years . Intervention group participants significantly reduced their percentage of energy from fat by 10.7 % more than did the comparison group at 1 year , and this difference between groups was mostly maintained ( 8.1 % at year 6 ) . Statistically significant increases in vegetable , fruit , and grain servings were also made . Despite these dietary changes , there was no evidence that the intervention reduced the risk of invasive colorectal cancer during the follow-up period . There were 201 women with invasive colorectal cancer ( 0.13 % per year ) in the intervention group and 279 ( 0.12 % per year ) in the comparison group ( hazard ratio , 1.08 ; 95 % confidence interval , 0.90 - 1.29 ) . Secondary analyses suggested potential interactions with baseline aspirin use and combined estrogen-progestin use status ( P = .01 for each ) . Colorectal examination rates , although not protocol defined , were comparable between the intervention and comparison groups . Similar results were seen in analyses adjusting for adherence to the intervention . CONCLUSION In this study , a low-fat dietary pattern intervention did not reduce the risk of colorectal cancer in postmenopausal women during 8.1 years of follow-up . CLINICAL TRIALS REGISTRATION Clinical Trials.gov Identifier : NCT00000611 Data from the Diet and Reinfa rct ion Trial were examined to check the prognostic effects of plasma fibrinogen , plasma viscosity , white blood cell count , haemoglobin and mean platelet volume in 92 deaths among 1755 men who had recently recovered from acute myocardial infa rct ion . All these variables were significantly associated with all-cause mortality over the following 18 months ( haemoglobin negatively , the others positively ) . Those who gave up smoking following their infa rct had a lower mortality than those who continued to smoke ( 4.1 % and 7.9 % respectively ) , and this effect appeared to be mediated by fibrinogen levels . Smoking habit accounted for only part of the prognostic effect of fibrinogen and white blood cell count . Haematological variables have an important prognostic significance after myocardial infa rct ion . Cessation of smoking after myocardial infa rct ion is worthwhile and has a favourable effect on plasma fibrinogen Objective : Vasomotor symptoms (VMS)(hot flashes , night sweats ) are associated with natural or surgically or chemotherapy-induced menopause , the latter occurring frequently in women treated for breast cancer . To manage VMS , some women seek alternatives to menopausal hormone therapy , such as supplements or modified food choices . The objective of the present analyses was to assess associations of VMS occurrence and change in severity of VMS over 12 months with dietary intakes of fiber , fat , and selected soy-containing foods , and use of phytoestrogen or vitamin E supplements in women with recent early stage breast cancer , adjusting for covariates . Design : Using multivariate logistic regression , data were analyzed from 2,198 women with early-stage breast cancer who enrolled 2 to 48 months after diagnosis in the Women 's Healthy Eating and Living r and omized , controlled trial of a high-vegetable , high-fiber , reduced-fat diet . Results : Being peri- or postmenopausal , using tamoxifen , having low social support or depressive symptoms , and using vitamin E or phytoestrogen supplements were significantly associated cross-sectionally with reporting moderate/severe VMS at enrollment . Increased symptom severity after 12 months was significantly associated with higher body mass index , tamoxifen use , and smoking . Decreased symptom severity at 12 months was significantly associated with high dietary fiber intake ; no decrease was observed in women who were peri- or postmenopausal , using tamoxifen , or had low fat intake or low social support . Conclusions High dietary fiber intakes , premenopausal , and high social support were related to decreased severity of VMS 1 year after study enrollment in women recently treated for breast cancer CONTEXT Obesity in the United States has increased dramatically during the past several decades . There is debate about optimum calorie balance for prevention of weight gain , and proponents of some low-carbohydrate diet regimens have suggested that the increasing obesity may be attributed , in part , to low-fat , high-carbohydrate diets . OBJECTIVES To report data on body weight in a long-term , low-fat diet trial for which the primary end points were breast and colorectal cancer and to examine the relationships between weight changes and changes in dietary components . DESIGN , SETTING , AND PARTICIPANTS R and omized intervention trial of 48,835 postmenopausal women in the United States who were of diverse background s and ethnicities and participated in the Women 's Health Initiative Dietary Modification Trial ; 40 % ( 19,541 ) were r and omized to the intervention and 60 % ( 29,294 ) to a control group . Study enrollment was between 1993 and 1998 , and this analysis includes a mean follow-up of 7.5 years ( through August 31 , 2004 ) . INTERVENTIONS The intervention included group and individual sessions to promote a decrease in fat intake and increases in vegetable , fruit , and grain consumption and did not include weight loss or caloric restriction goals . The control group received diet-related education material s. MAIN OUTCOME MEASURE Change in body weight from baseline to follow-up . RESULTS Women in the intervention group lost weight in the first year ( mean of 2.2 kg , P<.001 ) and maintained lower weight than control women during an average 7.5 years of follow-up ( difference , 1.9 kg , P<.001 at 1 year and 0.4 kg , P = .01 at 7.5 years ) . No tendency toward weight gain was observed in intervention group women overall or when stratified by age , ethnicity , or body mass index . Weight loss was greatest among women in either group who decreased their percentage of energy from fat . A similar but lesser trend was observed with increases in vegetable and fruit servings , and a nonsignificant trend toward weight loss occurred with increasing intake of fiber . CONCLUSION A low-fat eating pattern does not result in weight gain in postmenopausal women . Clinical Trial Registration Clinical Trials.gov , NCT00000611 To study the impact of diet and exercise and the combination thereof on cardiovascular risk factors , 157 healthy men aged 35 - 60 years ( mean + /- S.D. ; 46.2 + /- 5.0 ) with slightly to moderately raised cardiovascular risk factors , were r and omized to 4 groups , diet ( D , n = 40 ) , exercise ( E , n = 39 ) , diet plus exercise ( DE , n = 39 ) , and no active intervention ( controls ( C , n = 39 ) ) , and investigated at baseline and after 6 months . BMI was significantly reduced in Groups E and DE ( mean difference and 95 % confidence intervals ( CI ) , -0.3 ( -0.5 , -0.01 ) and -0.6 ( -0.9 , -0.3 ) kg/m2 , respectively ) . Waist circumference was reduced in all 3 intervention groups ( D , E , and DE ) , -1.3 ( -2.5 , -0.1 ) , -2.2 ( -3.2 , -1.3 ) and -3.0 ( -3.9 , -2.0 ) cm , but not in the control group . Blood pressure ( BP ) was reduced in all 3 intervention groups , systolic BP 4 - 7 mmHg and diastolic BP 2 - 6 mmHg . Serum cholesterol was reduced in Group DE , -0.45 ( -0.77 , -0.13 ) mmol/l . VLDL-cholesterol was reduced in Groups E and DE , -0.14 ( -0.26 , -0.03 ) and -0.09 ( -0.18 , -0.01 ) mmol/l , whereas LDL-cholesterol was reduced in Groups D and DE -0.30 ( -0.54 , -0.06 ) and -0.35 ( -0.64 , -0.05 ) mmol/l . In contrast , neither HDL-cholesterol nor serum triglycerides were influenced by the interventions . According to the coronary risk profile derived from the Framingham study , all 3 intervention groups ( D , E , and DE ) significantly reduced their estimated 10-year risk ( -13 , -12 , and -14 % , respectively ) . We conclude that even with rather moderate changes in diet and exercise , several important cardiovascular risk factors can be affected and that diet and exercise were about equally effective in reducing cardiovascular risk OBJECTIVE —The purpose of this study was to compare the effects of high – monounsaturated fatty acid ( MUFA ) and high-carbohydrate ( CHO ) diets on body weight and glycemic control in men and women with type 2 diabetes . RESEARCH DESIGN AND METHODS —Overweight/obese participants with type 2 diabetes ( n = 124 , age = 56.5 ± 0.8 years , BMI = 35.9 ± 0.3 kg/m2 , and A1C = 7.3 ± 0.1 % ) were r and omly assigned to 1 year of a high-MUFA or high-CHO diet . Anthropometric and metabolic parameters were assessed at baseline and after 4 , 8 , and 12 months of dieting . RESULTS —Baseline characteristics were similar between the treatment groups . The overall retention rate for 1 year was 77 % ( 69 % for the high-MUFA group and 84 % for the high-CHO group ; P = 0.06 ) . Based on food records , both groups had similar energy intake but a significant difference in MUFA intake . Both groups had similar weight loss over 1 year ( −4.0 ± 0.8 vs. −3.8 ± 0.6 kg ) and comparable improvement in body fat , waist circumference , diastolic blood pressure , HDL cholesterol , A1C , and fasting glucose and insulin . There were no differences in these parameters between the groups . A follow-up assessment of a subset of participants ( n = 36 ) was conducted 18 months after completion of the 52-week diet . These participants maintained their weight loss and A1C during the follow-up period . CONCLUSIONS —In individuals with type 2 diabetes , high-MUFA diets are an alternative to conventional lower-fat , high-CHO diets with comparable beneficial effects on body weight , body composition , cardiovascular risk factors , and glycemic control Effects of small amounts of sitosterol , sitostanol and sitostanol esters ( < 1 g/day of free sterols ) dissolved in rapeseed oil ( RSO ) were studied on serum lipids and cholesterol metabolism in patients with primary hypercholesterolemia and different apolipoprotein E phenotypes on an RSO diet . One of the four groups was an RSO-fed control . Serum total and LDL cholesterol reductions were small in different plant sterol-fed groups , tended to be highest in the sitostanol ester group ( -7 % ) , but were significantly reduced by about 5 % in the combined plant sterol groups . The reductions were -8 % in the subjects with epsilon 4 allele and insignificant in those with apo E3/3 phenotype . Cholesterol precursor sterols in serum , markers of cholesterol synthesis , were increased only in the subjects with epsilon 4 allele . Cholesterol absorption was reduced by 7 % , being 31 % in the subjects with epsilon 4 allele , and fecal elimination of cholesterol was increased , a finding also indicating increased cholesterol synthesis . The changes in cholesterol absorption were related to those in fecal plant sterols ( change in dietary intake ) and serum total and LDL cholesterol ( P = 0.04 , 0.01 and 0.05 , respectively ) . Thus , small amounts of dietary plant sterols ( < 1 g/day ) , especially sitostanol esters dissolved in dietary fats , decrease serum total and LDL cholesterol by a proportional decrease in cholesterol absorption which , in turn , is associated with a compensatory increase in cholesterol synthesis . The effects are most consistent in subjects with epsilon 4 allele , but for effective hypocholesterolemic treatment dietary amount of sitostanol ester should exceed 1 g/day Aims /hypothesisA diet low in saturated fatty acids and rich in wholegrains , vegetables and fruit is recommended in order to reduce the risk of obesity , cardiovascular disease and type 2 diabetes mellitus . However there is widespread interest in high-fat ( “ Atkins Diet ” ) and high-protein ( “ Zone Diet ” ) alternatives to the conventional high-carbohydrate , high-fibre approach . We report on a r and omised trial that compared these two alternative approaches with a conventional diet in overweight insulin-resistant women . Methods Ninety-six normoglycaemic , insulin-resistant women ( BMI > 27 kg/m2 ) were r and omised to one of three dietary interventions : a high-carbohydrate , high-fibre ( HC ) diet , the high-fat ( HF ) Atkins Diet , or the high-protein ( HP ) Zone Diet . The experimental approach was design ed to mimic what might be achieved in clinical practice : the recommendations involved advice concerning food choices and were not prescriptive in terms of total energy . There were supervised weight loss and weight maintenance phases ( 8 weeks each ) , but there was no contact between the research team and the participants during the final 8 weeks of the study . Outcome was assessed in terms of body composition and indicators of cardiovascular and diabetes risk . Results Body weight , waist circumference , triglycerides and insulin levels decreased with all three diets but , apart from insulin , the reductions were significantly greater in the HF and HP groups than in the HC group . These observations suggest that the popular diets reduced insulin resistance to a greater extent than the st and ard dietary advice did . When compared with the HC diet , the HF and HP diets were shown to produce significantly ( p<0.01 ) greater reductions in several parameters , including weight loss ( HF −2.8 kg , HF −2.7 kg ) , waist circumference ( HF −3.5 cm , HF −2.7 cm ) and triglycerides ( HF −0.30 mmol/l , HF −0.22 mmol/l ) . LDL cholesterol decreased in individuals on the HC and HP diets , but tended to fluctuate in those on the HF diet to the extent that overall levels were significantly lower in the HP group than in the HF group ( −0.28 mmol/l , 95 % CI 0.04–0.52 , p=0.02 ) . Of those on the HF diet , 25 % showed a > 10 % increase in LDL cholesterol , whereas this occurred in only 13 % of subjects on the HC diet and 3 % of those on the HP diet . Conclusions /interpretationIn routine practice a reduced-carbohydrate , higher protein diet may be the most appropriate overall approach to reducing the risk of cardiovascular disease and type 2 diabetes . To achieve similar benefits on a HC diet , it may be necessary to increase fibre-rich wholegrains , legumes , vegetables and fruits , and to reduce saturated fatty acids to a greater extent than appears to be achieved by implementing current guidelines . The HF approach appears successful for weight loss in the short term , but lipid levels should be monitored . The potential deleterious effects of the diet in the long term remain a concern BACKGROUND The Women 's Health Initiative Dietary Modification ( DM ) Trial was a r and omized controlled trial that compared the effects of a low-fat ( ≤20 % of total energy ) or a usual diet in relation to chronic disease risk in postmenopausal women . OBJECTIVE We characterized long-term body-composition changes associated with the DM trial and potential modifiers of these associations . DESIGN In the DM trial , 48,835 women aged 50 - 79 y were r and omly assigned to intervention ( 40 % ) or comparison ( 60 % ) groups . We studied a subset with whole-body dual-energy X-ray absorptiometry scans at baseline and during follow-up . Changes in fat mass ( FM ) , lean mass ( LM ) , and percentage body fat between the intervention ( n = 1580 ) and comparison ( n = 2731 ) groups at years 1 , 3 , and 6 were compared . By using generalized estimating equations , we calculated overall differences between groups and tested for interactions with age , diabetes , race-ethnicity ( white , black , and Hispanic ) , body mass index ( BMI ) , and hormone therapy ( HT ) . RESULTS The intervention women experienced significantly greater reductions in percentage body fat , FM , and LM at years 1 and 3 than did women in the comparison group ( all P < 0.05 ) . At year 6 , only the FM change was significantly different between groups . Overall , the intervention was associated with reductions in percentage body fat ( -0.8 % ; 95 % CI : -1.0 % , -0.6 % ) , FM ( -1.1 kg ; 95 % CI : -1.3 , -0.8 kg ) , and LM ( -0.17 kg ; 95 % CI : -0.28 , -0.06 kg ) during follow-up ( all P < 0.003 ) . Intervention associations varied by race-ethnicity , BMI , diabetes , and HT and remained significant after adjustment for physical activity . CONCLUSION This intervention was associated with modest long-term body-composition changes ; the findings were more robust in years 1 and 3 . This trial was registered at clinical trials.gov as NCT00000611 Background Health-related quality of life ( HRQOL ) is an important aspect of well-being that may improve with health behavior interventions . However , health behavior change is difficult with pressure to maintain status quo . Purpose This report examines the effects of two lifestyle interventions and an advice-only condition on HRQOL . Effects of meeting behavioral goals and weight loss also were examined . Methods Participants were 295 men and 467 women ( 34 % African American ) with pre-hypertension or stage 1 hypertension from the PREMIER trial . HRQOL was assessed by the Short Form-36 . Participants were assigned r and omly to ( 1 ) advice only ( ADVICE ) , ( 2 ) established guidelines for blood pressure control ( EST ) , or ( 3 ) established guidelines plus the Dietary Approaches to Stop Hypertension ( DASH ) dietary pattern ( EST + DASH ) . Results Assignment to EST result ed in improvement in three HRQOL subscales at 6 months and one at 18 months relative to ADVICE . EST + DASH improved in two subscales at 6 and 18 months compared with ADVICE . Across conditions , total fat , saturated fat , fruit , and vegetable intake change , along with ≥4-kg weight loss , result ed in HRQOL improvements at 6 and 18 months . No improvement was found for change in physical activity , and only a few HRQOL subscales were associated with change in sodium and low-fat dairy intake . Conclusions Intensive lifestyle interventions can result in improvements in HRQOL . Change in dietary intake and weight loss is also important Background : Data are limited on the efficacy of health-fo-cused interventions for young , low-acculturated Latino women . Because breast cancer is the most commonly diagnosed cancer and the most common cause of cancer mortality in this population , combined interventions that address both early detection and dietary patterns could help reduce both morbidity and mortality associated with breast cancer in this underserved population . Purpose : Mujeres Felices por ser Saludables was a r and omized intervention study design ed to assess the efficacy of an 8-month combined dietary and breast health intervention to reduce fat and increase fiber intake as well as to increase the frequency and proficiency of breast self-examination ( BSE ) and reduce anxiety related toBSE among Latinas Methods : Blocked r and omization in blocks of 6 was used to r and omize 256 20- to 40-year-old Latinas to the intervention ( n = 127 ) or control group ( n = 129 ) . The intervention group attended an 8-month multi-component education program design ed specifically for low-acculturated Latinas . The control group received mailed health education material on a schedule comparable to the intervention . A total of 195 women ( 76.2 % ) completed both the baseline and 8-month follow-up interviews . Results : The intervention and control groups were similar on baseline sociodemographic characteristics . At the 8-month follow up , the intervention group reported lower dietary fat ( p > .001 ) and higher fiber intake ( p = .06 ) ; a higher proportion reported practicingBSE at the recommended interval ( p > .001 ) and showed improvedBSE proficiency ( p > .001 ) compared to the control group . BSE-related anxiety was low for both groups at baseline , and no diffirrence in reduction was observed . Conclusions : This project provides a successful model for achirving dietary change and improving breast health behavior in young , low-acculturated Latinas BACKGROUND Circadian rhythm has been shown to be related to glucose metabolism and risk of diabetes , probably through effects on energy balance . Recent genome-wide association studies identified variants in circadian rhythm-related genes ( CRY2 and MTNR1B ) associated with glucose homeostasis . OBJECTIVE We tested whether CRY2 and MTNR1B genotypes affected changes in measures of energy expenditure in response to a weight-loss diet intervention in a 2-y r and omized clinical trial , the POUNDS ( Preventing Overweight Using Novel Dietary Strategies ) LOST Trial . DESIGN The variants CRY2 rs11605924 ( n = 721 ) and MTNR1B rs10830963 ( n = 722 ) were genotyped in overweight or obese adults who were r and omly assigned to 1 of 4 weight-loss diets that differed in their proportions of macronutrients . Respiratory quotient ( RQ ) and resting metabolic rate ( RMR ) were measured . RESULTS By 2 y of diet intervention , the A allele of CRY2 rs11605924 was significantly associated with a greater reduction in RQ ( P = 0.03 ) and a greater increase in RMR and RMR/kg ( both P = 0.04 ) . The G allele of MTNR1B rs10830963 was significantly associated with a greater increase in RQ ( P = 0.01 ) but was not related to changes in RMR and RMR/kg . In addition , we found significant gene-diet fat interactions for both CRY2 ( P-interaction = 0.02 ) and MTNR1B ( P-interaction < 0.001 ) in relation to 2-y changes in RQ . CONCLUSIONS Our data indicate that variants in the circadian-related genes CRY2 and MTNR1B may affect long-term changes in energy expenditure , and dietary fat intake may modify the genetic effects . This trial was registered at www . clinical trials.gov as NCT00072995 The aim of the present study was to investigate the effect of long-term diet and very long chain n-3 fatty acids ( VLC n-3 ) intervention on plasma coagulation factor VII ( FVII ) , choline-containing phospholipids ( PC ) and triglycerides ( TG ) , especially related to the R353Q polymorphism of the FVII gene . The present investigation included 219 subjects from the Diet and Omega-3 Intervention Trial on atherosclerosis ( DOIT ) , a 2x2 factorial design ed study in elderly men with long-st and ing hypercholesterolemia . The subjects were r and omly allocated to receive placebo capsules ( corn oil ) ( control ) , placebo capsules and dietary advice ( " Mediterranean type " diet ) , VLC n-3 capsules , or VLC n-3 capsules and dietary advice combined . The R353Q genotype and the levels of FVIIc , FVIIag , FVIIa , PC , and TG at baseline and after 6 months were determined . Diet intervention was followed by a significant reduction of 5.1 % in the levels of FVIIag and 2.4 mU/ml in FVIIa ( 95 % CI -7.4 , -2.9 , and -3.8 , -1.1 , respectively ) ( both p<0.001 ) compared to the no diet group , independent of genotype . No effects of diet intervention on FVIIc , PC or TG were observed . After VLC n-3 supplementation the TG levels were significantly reduced compared to placebo ( p=0.01 ) , whereas all FVII levels and PC remained unchanged . Dietary advice towards a " Mediterranean type " diet , but not VLC n-3 supplementation , was shown to reduce the levels of FVIIag and FVIIa after 6 months , independent of genotype . The results indicate the dietary advice to be more favourable in reducing this risk factor for CVD as compared to specific VLC n-3 supplementation The National Cancer Institute has initiated a r and omized trial to determine whether a low fat diet can reduce the incidence of breast cancer among women at increased risk for this disease . A feasibility trial involving 303 women has been conducted to examine recruitment strategies , study short-term compliance and , more generally , develop and refine trial procedures . The feasibility trial group also developed a detailed full-scale trial design plan , and r and omization of participants to such a trial is currently underway . The purpose of this report is to describe the major design features of this Women 's Health Trial , with particular emphasis on the statistical aspects of the design . The trial is planned to last 10 years and to include 32,000 participants . Of these 32,000 women , 12,800 will be assigned to a low fat diet intervention , and the other 19,200 will constitute a control group . The sample size of 32,000 arises from a range of estimates and assumptions pertaining to ( a ) the incidence of breast cancer at enrollment corresponding to selected eligibility criteria , ( b ) the relative risk of breast cancer as a function of a woman 's history of dietary fat intake , ( c ) compliance assumptions in terms of average percent fat in the intervention and control groups as a function of time from r and omization , and ( d ) rates of competing causes of death . These estimates and assumptions will be discussed , as will the robustness of the intended sample sizes to departures from such design assumptions Purpose The purpose of this study was to test effects of a culturally competent , dietary self-management intervention on physiological outcomes and dietary behaviors for African Americans with type 2 diabetes . Methods A longitudinal experimental study was conducted in rural South Carolina with a sample of 97 adult African Americans with type 2 diabetes who were r and omly assigned to either usual care or the intervention . The intervention consisted of 4 weekly classes in low-fat dietary strategies , 5 monthly peer-professional group discussion s , and weekly telephone follow-up . The culturally competent approach reflected the ethnic beliefs , values , customs , food preferences , language , learning methods , and health care practice s of southern African Americans . Results Body mass index and dietary fat behaviors were significantly lowered in the experimental group . At 6 months , weight decreased 1.8 kg ( 4 lb ) for the experimental group and increased 1.9 kg ( 4.2 lb ) for the control group , a net difference of 3.7 kg ( 8.2 lb ) . The experimental group reduced high-fat dietary habits to moderate while high-fat dietary habits of the control group remained essentially unchanged . A trend in reduction of A1C and lipids was observed . Conclusions Results suggest the effectiveness of a culturally competent dietary self-management intervention in improving health outcomes for southern African Americans , especially those at risk due to high-fat diets and body mass index ≥ 35 kg/mm2 . Given the burgeoning problem of obesity in South Carolina and the nation , the time has come to focus on aggressive weight management . Diabetes educators are in pivotal positions to assume leadership in achieving this goal for vulnerable , rural population The Trial of Antihypertensive Interventions and Management was a multicenter r and omized , placebo-controlled trial design ed to assess the effectiveness of various combinations of pharmacologic and dietary interventions in the treatment of mild hypertension ( diastolic blood pressure 90 - 100 mmHg ) . The primary outcome was blood pressure change between baseline and 6 months . The study consisted of a 3 X 3 factorial design wherein participants were r and omly allocated to nine drug-diet treatment groups . Drugs included placebo , diuretic , and beta-blocker . Diets were usual , weight loss , and low sodium/high potassium . The basic strategy was to address clinical questions of interest by comparing mean blood pressure changes of selected drug-diet combinations . This paper describes the study including experimental design , sample size considerations , statistical analysis , organizational structure , and baseline findings BACKGROUND Women 's long-term patterns of evidence -based preventive medication utilization following a coronary heart disease ( CHD ) diagnosis have not been sufficiently studied . METHODS Postmenopausal women 50 - 79 years were eligible for r and omization in the Women 's Health Initiative 's ( WHI ) hormone trials if they met inclusion and exclusion criteria and were > 80 % adherent during a placebo-lead-in period and in the dietary modification trial if they were willing to follow a 20 % fat diet . Those with adjudicated myocardial infa rct ion or coronary revascularization after the baseline visit were included in the analysis ( n=2627 ) . Baseline visits occurred between 1993 and 1998 , then annually until the trials ended in 2002 through 2005 ; medication inventories were obtained at baseline and years 1 , 3 , 6 and 9 . RESULTS Utilization at the first WHI visit following a CHD diagnosis increased over time for statins ( 49 % to 72 % ; p<0.0001 ) , beta-blockers ( 49 % to 62 % ; p=0.003 ) , and angiotensin-converting enzyme inhibitors/angiotensin-II receptor blockers ( ACEI/ARBs ) [ 26 to 43 % ; p<0.0001 ] . Aspirin use remained stable at 76 % ( p=0.09 ) . Once women reported using a statin , aspirin , or beta-blocker , 84 - 89 % reported use at 1 or more subsequent visits , with slightly lower rates for ACEI/ARBS ( 76 % ) . Statin , aspirin , beta-blocker , or ACEI/ARB use was reported at 2 or more consecutive visits by 57 % , 66 % , 48 % , and 28 % respectively . These drugs were initiated or resumed at a later visit by 24 % , 17 % , 15 % , and 17 % , respectively , and were never used during the period of follow-up by 19 % , 10 % , 33 % , and 49 % respectively . CONCLUSIONS Efforts to improve secondary prevention medication utilization should target both drug initiation and restarting drugs in patients who have discontinued them Following a heart-healthy diet to lower cholesterol levels is often assumed to be difficult , to be burdensome , and to have a negative impact on quality of life ( QOL ) . The purpose of this study was to evaluate the impact of medical nutrition therapy ( MNT ) versus usual care ( UC ) for hypercholesterolemia on patient satisfaction and QOL . Ninety ambulatory care patients ( 6 men and 30 women ) , age 28 to 66 , were r and omly assigned to receive either MNT from dietitians using a National Cholesterol Education Program-based protocol or UC from their physicians . Patients who received MNT reported no difference in QOL related to the taste or enjoyment of food compared with UC patients . However , the MNT group reported initial improvements in QOL related to the convenience and cost of following a low-fat diet when compared with the UC group . The MNT group also reported significant and lasting improvements in perceived QOL related to self-care compared with the UC group . MNT patients were more satisfied with the interaction at visits , knowledge and ability to manage their cholesterol , eating habits , appearance , time spent exercising , and life in general . Moreover , MNT patients did not report any negative impact related to following a low-fat diet in regard to feeling restricted by diet ; interference with lifestyle activities ; or difficulty planning , purchasing , or preparing meals or eating away from home . Contrary to popular belief , there is no apparent reduction but rather an improvement in some measures of QOL and patient satisfaction with MNT for hypercholesterolemia OBJECTIVE Evaluation of the effects of supplementation of n-3 and n-6 fatty acids on vascular tone and endothelial function in healthy men and women aged 40 to 65 years . METHODS In a double-blind , r and omised , placebo controlled study , 173 healthy volunteers took one of six oil supplements for 8 months . Supplements were placebo , oleic acid rich sunflower oil , evening primrose oil , soya bean oil , tuna fish oil , and tuna/evening primrose oil mix . Endothelium-dependent and independent vascular responses were measured in the forearm skin using laser Doppler imaging following iontophoretic applications of acetylcholine and sodium nitroprusside , respectively . RESULTS Acetylcholine , but not sodium nitroprusside responses were significantly improved after tuna oil supplementation ( P=0.02 ) . Additionally , there were significant positive correlations between acetylcholine responses and n-3 fatty acid levels in the plasma and erythrocyte membrane phospholipids after tuna oil supplementation . No significant changes in vascular response were seen after supplementation with any of the other oils . CONCLUSIONS Fish oil supplementation has a beneficial effect on endothelial function , even in normal healthy subjects . Modification of the diet by an increase of 6 % in eicosapentaenoic acid and 27 % in docosahexaenoic acid ( equivalent to eating oily fish 2 - 3 times/week ) might have significant beneficial effects on cardiovascular function and health Background : Weight loss reduces energy expenditure , but the contribution of different macronutrients to this change is unclear . Hypothesis : We tested the hypothesis that macronutrient composition of the diet might affect the partitioning of energy expenditure during weight loss . Design : A sub study of 99 participants from the Preventing Overweight Using Novel Dietary Strategies ( POUNDS LOST ) trial had total energy expenditure ( TEE ) measured by doubly labeled water , and resting energy expenditure ( REE ) measured by indirect calorimetry at baseline and repeated at 6 months in 89 participants . Participants were r and omly assigned to one of four diets with either 15 or 25 % protein and 20 or 40 % fat . Results : TEE and REE were positively correlated with each other and with fat-free mass and body fat , at baseline and 6 months . The average weight loss of 8.1±0.65 kg ( least-square mean±s.e . ) reduced TEE by 120±56 kcal per day and REE by 136±18 kcal per day . A greater weight loss at 6 months was associated with a greater decrease in TEE and REE . Participants eating the high-fat diet ( HF ) lost significantly more fat-free mass ( 1.52±0.55 kg ) than the low-fat ( LF ) diet group ( P<0.05 ) . Participants eating the LF diet had significantly higher measures of physical activity than the HF group . Conclusion : A greater weight loss was associated with a larger decrease in both TEE and REE . The LF diet was associated with significant changes in fat-free body mass and energy expenditure from physical activity compared with the HF diet The use of self-monitoring as a tool to facilitate behavioral modification is common in many lifestyle-based weight loss interventions . Electronic tracking programs , including computer-based systems and smart phone applications , have been developed to allow individuals to self-monitor their behavior digitally . These programs offer an advantage over traditional self-report modalities in that they can provide users with direct feedback about dietary and /or physical activity adherence levels and thereby assist them in real-time decision making . This article describes the use of an Internet-based computerized tracking system ( CTS ) that was developed specifically for the POUNDS LOST study , a 2-year r and omized controlled trial design ed to test the efficacy of four macronutrient diets for weight and fat reduction in healthy , overweight men and women ( body mass index range = 25.0–39.9 kg/m2 ) . The CTS served many functions in this study , including data collection , dietary and exercise assessment and feedback , messaging system , and report generation . Across all groups , participants with high usage of the CTS during the initial 8 weeks lost greater amounts of weight than participants with low usage ( 8.7 % versus 5.5 % of initial body weight , respectively ; p < .001 ) at week 32 . Rates of CTS utilization were highest during the first year of this 2-year intervention , and utilization of the CTS declined steadily over time . The unique features of the CTS combined with technological developments , such as smart phone applications , offer significant potential to improve the user 's self-monitoring experience and adherence to health promotion programs design ed specifically for individuals with obesity and type 2 diabetes Few well-controlled trials have evaluated the effects that macronutrient composition has on changes in food cravings during weight loss treatment . The present study , which was part of the Preventing Overweight Using Novel Dietary Strategies ( POUNDS LOST ) trial , investigated whether the fat and protein content of four different diets affected changes in specific food cravings in overweight and obese adults . A sample of 811 adults were recruited across two clinical sites , and each participant was r and omly assigned to one of four macronutrient prescriptions : 1 ) low fat ( 20 % of energy ) , average protein ( 15 % of energy ) ; 2 ) moderate fat ( 40 % ) , average protein ( 15 % ) ; 3 ) low fat ( 20 % ) , high protein ( 25 % ) ; 4 ) moderate fat ( 40 % ) , high protein ( 25 % ) . With few exceptions , the type of diet that participants were assigned did not differentially affect changes in specific food cravings . Participants assigned to the high-fat diets , however , had reduced cravings for carbohydrates at month 12 ( p<0.05 ) and fruits and vegetables at month 24 . Also , participants assigned to high-protein diets had increased cravings for sweets at month 6 and month 12 ( ps<0.05 ) . Participants in all four dietary conditions reported significant reductions in food cravings for specific types of foods ( i.e. , high fat foods , fast food fats , sweets , and carbohydrates/starches ; all ps<0.05 ) . Cravings for fruits and vegetables , however , were increased at month 24 ( p<0.05 ) . Calorically restricted diets ( regardless of their macronutrient composition ) yielded significant reductions in cravings for fats , sweets , and starches whereas cravings for fruits and vegetables were increased We compared observed and predicted changes in serum cholesterol in women with mammographic dysplasia who participated for 12 mo in a r and omized , controlled trial of a low-fat , high-carbohydrate diet , in which total fat intake was reduced from an average of 37 % of calories to 21 % and carbohydrate intake increased from 44 % to 52 % of calories . Changes observed in serum cholesterol were greater than those predicted ( by the formulas of Hegsted and Keys ) for subjects with initial serum cholesterol values in the upper tertile of the population , were not significantly different from those predicted for subjects with baseline values in the middle tertile , and were significantly less than those predicted for subjects with initial values in the lower tertile . These results show that the usefulness of serum cholesterol as a marker of change in dietary fat intake in women depends on the distribution of serum cholesterol values in the population studied We examined seven 1-d diet records kept during 1 y by 272 men and women instructed to follow a lipid-lowering diet while participating in a clinical trial of pravastatin , a new 3-hydroxy-3-methylglutaryl-coenzyme A ( HMG-CoA ) reductase inhibitor . The mean percentage of calories from total fat and saturated , unsaturated , and monounsaturated fatty acids was similar throughout the year even though the patients knew they were taking an effective lipid-lowering agent . However , the diets of greater than 40 % of women included less than two-thirds of the recommended dietary allowance ( RDA ) of folic acid , vitamins B-6 and D , and calcium and zinc ; in men , folic acid and zinc intakes were low . We conclude that patients comply with lipid-lowering diets even when they know that they are receiving an effective serum lipid-lowering agent . However , for both men and women special attention should be given to the intake of several nutrients Long-term ( 30 wk ) effects on serum lipoproteins and insulin sensitivity of two diets , one with a low polyunsaturated to saturated fat ratio ( P : S 0.3 ) and one with a P : S of 1.0 , were compared in 14 patients with noninsulin-dependent diabetes mellitus ( NIDDM ) in a crossover study . Total and LDL-cholesterol levels declined by 7.6 % ( p less than 0.01 ) and 9.8 % ( p less than 0.01 ) , respectively , during the high P : S diet . VLDL- , HDL2- , and HDL3-cholesterol ; triacylglycerol ; and apolipoprotein A1 , A2 , and B levels were not affected by the change in P : S. Despite a modest increase of insulin-mediated glucose disposal at physiologic insulinemia during the high P : S diet , no influence was seen on glycemic control , and on blood glucose , plasma insulin , and C peptide responses to mixed meals . In conclusion , a linoleic-enriched diet in patients with NIDD causes a less atherogenic lipoprotein profile but does not influence glycemic control and carbohydrate tolerance BACKGROUND Dietary energy density ( ED ) reductions are associated with energy intake ( EI ) reductions . Little is known about influences on body weight ( BW ) . OBJECTIVES We examined the effects of behavioral interventions on ED values and explored how 6-mo ED changes relate to BW . DESIGN Prehypertensive and hypertensive persons were r and omly assigned to 1 of 3 groups : the established group received an 18-session intervention implementing well-established hypertension recommendations ( eg , weight loss , sodium reduction , and physical activity ) , the established+Dietary Approaches to Stop Hypertension ( DASH ) group received an 18-session intervention also implementing the DASH diet , and the advice group received 1 session on these topics . Two 24-h dietary recalls were collected ( n=658 ) . RESULTS Each group had significant declines in EI , ED , and BW . The established and established+DASH groups had the greatest EI and BW reductions . The established+DASH group had the greatest ED reduction and the greatest increase in the weight of food consumed . When groups were combined and analyzed by ED change tertiles , participants in the highest tertile ( ie , largest ED reduction ) lost more weight ( 5.9 kg ) than did those in the middle ( 4.0 kg ) or lowest ( 2.4 kg ) tertile . Participants in the highest and middle tertiles increased the weight of food they consumed ( 300 and 80 g/d , respectively ) but decreased their EI ( 500 and 250 kcal/d ) . Conversely , those in the lowest tertile decreased the weight of food consumed ( 100 g/d ) , with little change in EI . The highest and middle tertiles had favorable changes in fruit , vegetable , vitamin , and mineral intakes . CONCLUSION Both large and modest ED reductions were associated with weight loss and improved diet quality Previous studies examining the hypocholesterolemic effects of high-soluble-fiber diets have not been design ed to control for dietary fat intake . Serum cholesterol reductions may therefore be accounted for by differences in consumption of fat . Moderately hypercholesterolemic , nonobese , Caucasian men and women , 30 - 50 y old were r and omly assigned to low-fat , low-fat plus high-fiber , or usual-diet groups and followed for 12 mo . At 12 mo the high-fiber group consumed significantly more soluble fiber than both the low-fat and usual-diet groups ( P = 0.0063 and P = 0.0001 ) ; the high-fiber group did not differ from the low-fat group in quantity of dietary fat consumed . The high-fiber group experienced a greater average reduction ( 13 % ) in serum cholesterol than did the low-fat ( 9 % ) and usual-diet ( 7 % ) groups . After adjustment for relevant covariates , the reduction in the high-fiber group was significantly greater than that in the low-fat group ( P = 0.0482 ) . Supplementation with soluble fiber reduces serum cholesterol beyond the reduction observed with low-fat diet alone BACKGROUND Dietary factors and very-long-chain n-3 polyunsaturated fatty acids ( n-3 PUFAs ) may influence the atherothrombotic process . Elevated concentrations of circulating cell adhesion molecules , thrombomodulin ( TM ) , von Willebr and factor ( vWF ) , and tissue-type plasminogen activator antigen ( tPAag ) are related to atherothrombotic cardiovascular disease . OBJECTIVE The r and omized Diet and Omega-3 Intervention Trial ( DOIT ) targeted a comparison of the effect of 3-y dietary counseling , n-3 PUFA supplementation ( 2.4 g/d ) , or both on circulating markers of endothelial activation . DESIGN The study included 563 elderly men with long-st and ing hyperlipidemia . The men were r and omly assigned by factorial design into 4 groups : control ( no dietary counseling and placebo capsules ) , dietary counseling ( and placebo capsules ) , n-3 PUFA supplementation ( no dietary counseling ) , and dietary counseling and n-3 PUFA supplementation . RESULTS Serum concentrations of fatty acids reflected good compliance . Dietary counseling was followed by significantly reduced concentrations of soluble intercellular adhesion molecule 1 ( sICAM-1 ; P < 0.001 ) , sTM ( P = 0.004 ) , and tPAag ( P < 0.001 ) than in subjects without dietary counseling . After n-3 PUFA supplementation , significantly reduced concentrations of sICAM-1 ( P < 0.001 ) and sTM ( P = 0.006 ) were observed when compared with subjects receiving placebo capsules . An increase in tPAag was not significantly different from that observed in subjects receiving placebo capsules . For sICAM-1 , a significant effect was observed for both interventions combined . CONCLUSIONS Each intervention ( dietary counseling or n-3 PUFA supplements ) reduced sTM and sICAM-1 concentrations , indicating decreased endothelial activation . The tPAag increase in the groups not receiving dietary counseling ( pooled ) , which indicates progression of atherosclerosis , was significantly counteracted by dietary counseling Effects of specific dietary alterations in patients with radiolucent gallstones treated with ursodeoxycholic acid ( UDCA , 750 mg at bedtime ) were investigated . Patients were allocated r and omly to one of four diets : st and ard ( 500 mg cholesterol/day ) , low-cholesterol ( 250 mg/day ) , added-bran ( 30 g/day ) , or substituted medium-chain triglycerides ( MCT ) oil ( 20 % of fat ) . Dietary intake and good compliance were verified by computerized analysis of dietary diaries . Bile-acid kinetics ( 26 patients ) or secretion of biliary lipids ( 23 other patients ) were determined at enrollment and at 6 and 9 mo , respectively , during treatment . Although MCT further decreased the UDCA-induced decrease in the synthesis of chenodeoxycholic acid , it did not lessen desaturation of bile . Otherwise , compared to the st and ard diet , no experimental diet significantly altered the UDCA-induced increase of the pools of total bile acids and UDCA or the UDCA-induced decrease in synthesis of bile acids and in biliary secretion or saturation of cholesterol . If these dietary manipulations facilitate dissolution of gallstones by UDCA , they do so by other mechanisms We examined weight changes over 1 and 2 y in 303 women enrolled in a low-fat dietary-intervention trial . Participants were r and omly assigned to an intervention group that received intensive instruction in maintaining a low-fat diet or to a control group . After 1 y intervention-group women had decreased fat intake by 45.3 g ( from 39.2 % to 21.6 % energy from fat ) and weight by 3.1 kg ( all P less than 0.0001 ) ; control-group women decreased fat intake by 8.8 g ( from 38.9 % to 37.3 % energy from fat ) and weight by 0.4 kg . In both univariate analyses and multivariate models , weight loss was more strongly associated with change in percent energy from fat than with change in total energy intake . These data , which are consistent with both epidemiologic and clinical studies , suggest that body adiposity is a function both of energy balance and the proportion of energy derived from fat Seventeen male Yeshiva students were r and omly allocated to a crossover study with two 12-wk dietary periods of monounsaturated fatty acids ( MUFAs ) vs a carbohydrate (CHO)-rich diet while concentrations of saturated ( SFAs ) and polyunsaturated ( PUFAs ) fatty acids were kept similar . Total plasma cholesterol ( TC ) decreased significantly by approximately 7.7 % and low-density-lipoprotein cholesterol ( LDL-C ) by 14.4 % on the MUFA diet , whereas on the CHO diet no significant change in cholesterol concentrations occurred , in contrast to that predicted by the equations of Keys and Hegsted . Concentrations of high-density-lipoprotein cholesterol ( HDL-C ) did not change significantly on either diet . On the MUFA diet there was a significantly lower proneness to peroxidation of plasma and LDL lipids and less extensive metabolism of conditioned LDL by peritoneal macrophages . We conclude that dietary MUFAs lower TC and LDL-C concentrations , independently of other dietary fatty acids and in addition may reduce the susceptibility of LDL to oxidative stress Excessive consumption of energy and fat increases the risk for obesity . Snacks containing sucrose polyesters ( SPE ) as a dietary fat replacer are on the market in the United States . SPE products have been shown to lower concentrations of serum carotenoids in short-term studies . Experimental studies on the longer-term effects on health of decreased carotenoid concentrations are lacking . A 1-y r and omized , double-blind , placebo-controlled parallel trial was performed . Subjects ( n = 380 ) with a habitual low or high fruit and vegetable intake were assigned to the treatments ( 0 , 7 , 10 or 17 g/d SPE ) . SPE was given in the form of spreads , chips or both . The groups were compared for serum carotenoids , vitamins and markers of oxidative damage , eye health , cardiovascular health and immune status . After 1 y , serum lipid-adjusted carotenoids showed the largest decrease in the SPE chips and spread group ( 17 g/d ) compared with the control group [ alpha-carotene 33 % ; beta-carotene 31 % , lycopene 24 % , beta-cryptoxanthin 18 % , lutein 18 % ( all P < 0.001 ) and zeaxanthin 13 % ( P < 0.05 ) ] . Consumption of SPE spread ( 10 g/d SPE ) decreased carotenoid concentrations by 11 - 29 % ( all P < 0.05 ) . SPE chips ( 7 g/d SPE ) decreased zeaxanthin ( 11 % ) , beta-carotene ( 12 % ) and alpha-carotene ( 21 % ; all P < 0.05 ) . Serum lipid adjusted alpha-tocopherol decreased significantly by 6 - 8 % ( all P < 0.001 ) in all SPE groups . No negative effects were observed on markers of oxidation , eye health , cardiovascular health or immune status . This study shows that decreases in serum carotenoid concentrations do not affect possible markers of disease risk Forty-two obese [ body mass index ( kg/m2 ) : 30 + /- 5 ; weight : 92.9 + /- 10.1 kg ] men aged 60 + /- 9 y were recruited to determine the effects of an American Heart Association ( AHA ) diet , with and without weight loss , on lipoprotein lipids . All subjects entered a 3-mo , weight-maintaining AHA diet followed by either a 9-mo weight-loss ( AHA + WL , n = 28 ) or a 9-mo AHA plus weight-maintenance ( AHA + WM , n = 14 ) intervention . Baseline diets were high in fat ( 35 + /- 6 % of energy ) and cholesterol ( 380 + /- 158 mg/d ) , and low in dietary fiber ( 18 + /- 5 g/d ) . The 3-mo AHA diet result ed in an 11 % decrease in plasma triacylglycerol ( 1.83 + /- 0.15 to 1.47 + /- 0.08 mmol/L , P < 0.05 ) , a 16 % decrease in plasma cholesterol ( 5.39 + /- 0.96 to 4.56 + /- 0.91 mmol/L , P = 0.0001 ) , a 17 % decrease in high-density-lipoprotein ( HDL ) cholesterol ( 1.09 + /- 0.23 to 0.91 + /- 0.18 mmol/L , P = 0.0001 ) , and a 14 % decrease in low-density-lipoprotein ( LDL ) cholesterol ( 3.47 + /- 0.83 to 2.98 + /- 0.78 mmol/L , P = 0.0001 ) The AHA + WL group lost 9.8 + /- 4.3 kg ( P < 0.001 , n = 28 ) and further reduced plasma triacylglycerol by 17 % ( P < 0.05 ) , total cholesterol by 4 % ( P < 0.05 ) , LDL cholesterol by 7 % ( P < 0.05 ) , and significantly increased HDL cholesterol by 15 % ( P < 0.05 ) when compared with their 3-mo AHA-intervention values . These changes were significant ( P < 0.05 ) when compared with the AHA + WM group , in whom lipoprotein lipids did not change . ( ABSTRACT TRUNCATED AT 250 WORDS Dietary adherence to four different fat-modified diets was examined in 160 subjects by determining the fatty acid composition of serum cholesterol esters ( CEs ) and erythrocyte ( ER ) and platelet ( PT ) membranes in addition to food records . Subjects were r and omly assigned to one of the following diet groups : 1 ) high-sat--35/14:104 ( % of energy from total/saturated : monounsaturated : polyunsaturated fatty acids in the actual diet ) 2 ) AHA ( American Heart Association ) type--32/10:8:8 3 ) monoene-enriched--34/11:11:5 , or 4 ) low-fat--30/12:8:3 for 6 mo . Decreases in the proportions of palmitic acid in CEs were found in the AHA-type and monoene-enriched-diet groups . An increased proportion of linoleic acid in CEs was found in the AHA-type group . The differences in the proportions of palmitic acid in CEs and linoleic and palmitoleic acids in PTs were significant in the AHA-type and monoene-enriched-diet groups compared with the high-sat group . An increase in alpha-linolenic acid in CEs was an indicator of the use of low erucic acid rapeseed oil , which was the main source of monoenes in the monoene-enriched-diet group Although a large body of evidence suggests that diet may play an important role in cancer prevention , r and omized controlled trials reported to date have not achieved sufficient increases in protective micronutrients and phytochemicals to adequately test the hypothesis that diet can reduce cancer risk . The Women 's Healthy Eating and Living ( WHEL ) Study , a r and omized controlled trial of the role diet modification may play in future breast cancer events , introduced an innovative theory-based telephone counseling intervention to teach participants to consume a high fiber , low fat diet emphasizing vegetables and fruits rich in carotenoids and other potentially protective phytochemicals . This report examines the baseline to 12-mo changes in dietary intakes of 2970 participants , assessed through 24-h recalls and vali date d with plasma carotenoid concentrations . At 12 mo , the intervention group reported a significantly increased daily vegetable intake ( + vegetable juice ) of 7.1 servings ( + 82 % ) and fruit intake of 3.9 servings ( + 18 % ) . Fiber intake increased from 3.04 to 4.16 g/(MJ . d ) , whereas energy from fat decreased significantly from 28.6 to 23.7 % . Plasma carotenoid concentrations increased significantly , i.e. , alpha-carotene ( + 223 % ) ; beta-carotene ( + 87 % ) ; lutein ( + 29 % ) ; and lycopene ( + 17 % ) . In the comparison group , dietary intake and plasma carotenoid concentrations were essentially identical to those of the intervention group at baseline and were unchanged at 12 mo . The WHEL Study showed that a telephone counseling intervention can achieve major increases in micronutrient- and phytochemical-rich vegetables , fruit and fiber intakes , enabling an investigation of the potential cancer preventive effects of these food components Research on the conceptualization of adherence to treatment has not addressed a key question : Is adherence best defined as being a uni-dimensional or multi-dimensional behavioral construct ? The primary aim of this study was to test which of these conceptual models best described adherence to a weight management program . This ancillary study was conducted as a part of the POUNDS LOST trial that tested the efficacy of four dietary macronutrient compositions for promoting weight loss . A sample of 811 overweight/obese adults was recruited across two clinical sites , and each participant was r and omly assigned to one of four macronutrient prescriptions : ( 1 ) Low fat ( 20 % of energy ) , average protein ( 15 % of energy ) ; ( 2 ) High fat ( 40 % ) , average protein ( 15 % ) ; ( 3 ) Low fat ( 20 % ) , high protein ( 25 % ) ; ( 4 ) High fat ( 40 % ) , high protein ( 25 % ) . Throughout the first 6 months of the study , a computer tracking system collected data on eight indicators of adherence . Computer tracking data from the initial 6 months of the intervention were analyzed using exploratory and confirmatory analyses . Two factors ( accounting for 66 % of the variance ) were identified and confirmed : ( 1 ) behavioral adherence and ( 2 ) dietary adherence . Behavioral adherence did not differ across the four interventions , but prescription of a high fat diet ( vs. a low fat diet ) was found to be associated with higher levels of dietary adherence . The findings of this study indicated that adherence to a weight management program was best conceptualized as being multi-dimensional , with two dimensions : behavioral and dietary adherence To evaluate which dietary fat may provide the best response in terms of plasma lipids and lipoproteins and also of platelet aggregability and superoxide formation by white blood cells , 12 type II patients were r and omly allocated to three different diets , which provided polyunsaturated fatty acids ( corn oil ) , monounsaturated fatty acids ( olive oil ) , and a supplementation of ethyl esters of n-3 fatty acids to a prudent diet . Olive oil and , more significantly , n-3 ethyl esters lowered total cholesterol best ( -2.2 % and -5.8 % , respectively ) ; the latter diet , as expected , also significantly lowered triglyceridemia ( -21.4 % ) . The corn-oil diet exerted a small , statistically significant reduction of high-density-lipoprotein cholesterol ( HDL ) ( -4.3 % ) , and it also lowered plasma total apo B concentrations ( -3.8 % ) . n-3 ethyl esters significantly raised both total ( + 3.1 % ) and particularly HDL2 cholesterol ( + 24 % ) . Platelet reactivity was insignificantly reduced by the three regimens , but all three significantly reduced thrombin-stimulated formation of thromboxane B2 . Finally , only the n-3 fatty acid supplementation significantly reduced O2- generation by adherent monocytes . Dietary unsaturated fatty acids are generally effective on the plasma lipid and lipoproteins in type II patients , but significant differences may be found between the three tested regimens BACKGROUND The effect of dietary fat and carbohydrate on glucose metabolism has been debated for decades . OBJECTIVE The objective was to compare the effect of 3 ad libitum diets , different in type and amount of fat and carbohydrate , on insulin resistance and glucose tolerance subsequent to weight loss . DESIGN Forty-six nondiabetic , obese [ mean ( + /-SEM ) body mass index ( in kg/m(2 ) ) : 31.2 + /- 0.3 ] men ( n = 20 ) and premenopausal women ( n = 26 ) aged 28.0 + /- 0.7 y were r and omly assigned to 1 of 3 diets after > or = 8 % weight loss : 1 ) MUFA diet ( n = 16 ) : moderate in fat ( 35 - 45 % of energy ) and high in monounsaturated fatty acids ( > 20 % of energy ) ; 2 ) LF diet ( n = 18 ) : low-fat diet ( 20 - 30 % of energy ) , and 3 ) control diet ( n = 12 ) : 35 % of energy as fat ( > 15 % of energy as saturated fatty acids ) . Protein accounted for 15 % of energy in all 3 diets . A 2-h oral-glucose-tolerance test ( OGTT ) was performed before and after the 6-mo dietary intervention . All foods were provided by a purpose -built supermarket . RESULTS After 6 mo , the MUFA diet reduced fasting glucose ( -3.0 % ) , insulin ( -9.4 % ) , and the homeostasis model assessment of insulin resistance score ( -12.1 % ) . Compared with the MUFA diet , the control diet increased these variables [ 1.4 % ( P = 0.014 ) , 21.2 % ( P = 0.030 ) , and 22.8 % ( P = 0.015 ) , respectively ] , as did the LF diet [ 1.4 % ( P = 0.090 ) , 13.1 % ( P = 0.078 ) , and 15.5 % ( P = 0.095 ) , respectively ] . No significant group differences were detected in glucose or insulin concentrations during the OGTT , in the Matsudas index , in body weight , or in body composition . CONCLUSION A diet high in monounsaturated fat has a more favorable effect on glucose homeostasis than does the typical Western diet in the short term and may also be more beneficial than the official recommended low-fat diet during a period of weight regain subsequent to weight loss BACKGROUND The effect of long-term increased intakes of alpha-linolenic acid ( ALA ; 18:3n-3 ) on cardiovascular risk factors is unknown . OBJECTIVES Our objectives were to assess the effect of increased ALA intakes on cardiovascular risk factors and the estimated risk of ischemic heart disease ( IHD ) at 2 y and the effect of nutritional education on dietary habits . DESIGN Subjects with multiple cardiovascular risk factors ( 124 men and 158 women ) were r and omly assigned in a double-blind fashion to consume a margarine rich in either ALA [ 46 % linoleic acid ( LA ; 18:2n-6 ) and 15 % ALA ; n = 114 ] or LA ( 58 % LA and 0.3 % ALA ; n = 168 ) . An intervention group ( n = 110 ; 50 % ALA ) obtained group nutritional education , and a control group ( n = 172 ; 34 % ALA ) received a posted leaflet containing the st and ard Dutch dietary guidelines . RESULTS Average ALA intakes were 6.3 and 1.0 g/d in the ALA and LA groups , respectively . After 2 y , the ALA group had a higher ratio of total to HDL cholesterol ( + 0.34 ; 95 % CI : 0.12 , 0.56 ) , lower HDL cholesterol ( -0.05 mmol/L ; -0.10 , 0 ) , higher serum triacylglycerol ( + 0.24 mmol/L ; 0.02 , 0.46 ) , and lower plasma fibrinogen ( -0.18 g/L ; -0.31 , -0.04 ; after 1 y ) than did the LA group ( adjusted for baseline values , sex , and lipid-lowering drugs ) . No significant difference existed in 10-y estimated IHD risk . After 2 y , the intervention group had lower saturated fat intakes and higher fish intakes than did the control group . CONCLUSIONS Increased ALA intakes decrease the estimated IHD risk to an extent similar to that found with increased LA intakes . Group nutritional education can effectively increase fish intake BACKGROUND The consumption of monounsaturated trans fatty acids ( TFAs ) increases the risk of cardiovascular disease ( CVD ) . Putative differences between the effects of TFAs from industrially produced and natural sources on CVD risk markers were not previously investigated in healthy subjects . OBJECTIVE We aim ed to compare the effects of TFAs from industrially produced and natural sources on HDL and LDL cholesterol , lipoprotein particle size and distribution , apolipoproteins , and other lipids in healthy subjects . DESIGN In a r and omized , double-blind , controlled , crossover design , 46 healthy subjects ( 22 men and 24 women ) consumed food items containing TFAs ( 11 - 12 g/d , representing approximately 5 % of daily energy ) from the 2 sources . RESULTS Forty subjects ( 19 men and 21 women ) completed the study . Compared with TFAs from industrially produced sources , TFAs from natural sources significantly ( P = 0.012 ) increased HDL cholesterol in women but not in men . Significant ( P = 0.001 ) increases in LDL-cholesterol concentrations were observed in women , but not in men , after the consumption of TFAs from natural sources . Apolipoprotein (apo)B and apoA1 concentrations confirmed the changes observed in LDL and HDL cholesterol . Analysis of lipoprotein subclass showed that only large HDL and LDL concentrations were modified by TFAs from natural sources but not by those from industrially produced sources . CONCLUSIONS This study shows that TFAs from industrially produced and from natural sources have different effects on CVD risk factors in women . The HDL cholesterol-lowering property of TFAs seems to be specific to industrial sources . However , it is difficult in the present study to draw a conclusion about the effect of TFAs from either source on absolute CVD risk in these normolipidemic subjects . The mechanism underlying the observed sex- and isomer-specific effects warrants further investigation BACKGROUND Dietary fat has been implicated as a risk factor for cardiovascular disease and obesity . OBJECTIVE We evaluated the effect on body weight , body fat , lipids , glucose , and insulin of replacing dietary fat with olestra in moderately obese men . DESIGN Forty-five healthy overweight men were r and omly assigned to 1 of 3 diets : control diet ( 33 % fat ) , fat-reduced diet ( 25 % fat ) , or fat-substituted diet ( one-third of dietary fat replaced by olestra to achieve a diet containing 25 % metabolizable fat ) . Body fat was measured by dual-energy X-ray absorptiometry and visceral and subcutaneous abdominal fat by computed tomography . RESULTS Thirty-six men completed the 9-mo study . Body weight and body fat in the fat-substituted group declined by a mean ( + /- SEM ) of 6.27 + /- 1.66 and 5.85 + /- 1.34 kg , respectively , over 9 mo compared with 3.8 + /- 1.34 and 3.45 + /- 1.0 kg in the control group and 1.79 + /- 0.81 and 1.68 + /- 0.75 kg in the fat-reduced diet group . At 9 mo , the mean difference in body fat between the fat-reduced and fat-substituted groups was -4.19 + /- 1.19 kg ( 95 % CI : -6.57 , -1.81 ) , that between the control and fat-substituted groups was -2.55 + /- 1.21 kg ( -0.13 , -4.97 ) , and that between the control and fat-reduced groups was 1.63 + /- 1.18 kg ( 3.96 , -0.70 ) . The men eating the fat-reduced diet asked for almost no extra foods , in contrast with the significantly higher requests ( P < 0.05 ) from both of the other 2 groups . CONCLUSION Replacement of dietary fat with olestra reduces body weight and total body fat when compared with a 25%-fat diet or a control diet containing 33 % fat BACKGROUND In a r and omized , controlled , 2 x 2 factorial trial on the effect of long-term changes in diet and exercise , a significant reduction in body weight and fat mass was observed . Alterations in leptin and plasminogen activator inhibitor-1 concentrations were previously reported from this study . OBJECTIVE We examined the separate and combined effects of a 1-y exercise and diet intervention on several adipokines ; adiponectin , interleukin-6 and -8 , tumor necrosis factor-alpha , monocyte chemoattractant protein-1 , hepatocyte growth factor , nerve growth factor , C-reactive protein , and resistin . DESIGN One hundred eighty-eight men with several risk factors for diabetes and cardiovascular disease were r and omly allocated to 4 groups : diet , exercise , combined diet and exercise , and control . RESULTS Plasma adiponectin concentrations remained unchanged , whereas body mass index and fat mass decreased after dietary changes and an increase in physical activity . In the control group , adiponectin concentrations were reduced . Analyzed according to the factorial design , only diet intervention had a significant ( P = 0.03 ) positive effect on plasma adiponectin relative to control , and this effect was largely explained by changes in fat mass . After adjustment for change in percentage body fat , there were significant positive effects on tumor necrosis factor-alpha in all 3 intervention groups ( P = 0.01 for the diet group , 0.03 for the exercise group , and 0.05 for the combined diet and exercise group ) . Minor changes were observed for the other adipokines . Neither baseline concentrations of nor changes in adiponectin and plasminogen activator inhibitor-1 were significantly correlated to the other adipokines , whereas concentrations of and changes in the other adipokines were significantly correlated . CONCLUSION Diet intervention had a significant positive effect on adiponectin concentrations , which is largely explained by a reduction in fat mass BACKGROUND Dietary fat has a lower thermogenic effect than does carbohydrate . A moderate-fat diet , high in monounsaturated fatty acids ( MUFA diet ) , may decrease energy expenditure ( EE ) and thereby induce weight gain . OBJECTIVE We aim ed to compare changes in 24-h EE and substrate oxidation after a 6-mo controlled dietary intervention with either a MUFA or a low-fat ( LF ) diet . DESIGN Twenty-seven overweight [ body mass index ( in kg/m(2 ) ) : 28.1 + /- 0.4 ] nondiabetic subjects aged 18 - 36 y followed an 8-wk low-calorie diet and a 2-wk weight-stabilizing diet and then were r and omly assigned to a MUFA ( n = 12 ) or LF ( n = 15 ) diet for 6 mo . Substrate oxidation and 24-h EE were measured by whole-body indirect calorimetry . The first measurement ( 0 mo ) was taken during the weight-stabilizing diet , and the second measurement was taken after the 6-mo intervention . RESULTS A tendency was seen toward a lower 24-h EE with the MUFA than with the LF diet ( P = 0.0675 ) , but this trend did not remain after adjustment for the initial loses of fat mass and fat-free mass ( P = 0.2963 ) . Meal-induced thermogenesis was significantly ( P < 0.05 ) lower with the MUFA than with the LF diet , but no time x treatment interaction was found . A significant ( P = 0.0456 ) treatment x time interaction was found for spontaneous physical activity . CONCLUSION Despite a slightly lower meal-induced thermogenesis , the MUFA diet had an effect on 24-h EE that was not significantly different from that of the LF diet after a 6-mo controlled dietary intervention BACKGROUND The possible advantage for weight loss of a diet that emphasizes protein , fat , or carbohydrates has not been established , and there are few studies that extend beyond 1 year . METHODS We r and omly assigned 811 overweight adults to one of four diets ; the targeted percentages of energy derived from fat , protein , and carbohydrates in the four diets were 20 , 15 , and 65 % ; 20 , 25 , and 55 % ; 40 , 15 , and 45 % ; and 40 , 25 , and 35 % . The diets consisted of similar foods and met guidelines for cardiovascular health . The participants were offered group and individual instructional sessions for 2 years . The primary outcome was the change in body weight after 2 years in two-by-two factorial comparisons of low fat versus high fat and average protein versus high protein and in the comparison of highest and lowest carbohydrate content . RESULTS At 6 months , participants assigned to each diet had lost an average of 6 kg , which represented 7 % of their initial weight ; they began to regain weight after 12 months . By 2 years , weight loss remained similar in those who were assigned to a diet with 15 % protein and those assigned to a diet with 25 % protein ( 3.0 and 3.6 kg , respectively ) ; in those assigned to a diet with 20 % fat and those assigned to a diet with 40 % fat ( 3.3 kg for both groups ) ; and in those assigned to a diet with 65 % carbohydrates and those assigned to a diet with 35 % carbohydrates ( 2.9 and 3.4 kg , respectively ) ( P>0.20 for all comparisons ) . Among the 80 % of participants who completed the trial , the average weight loss was 4 kg ; 14 to 15 % of the participants had a reduction of at least 10 % of their initial body weight . Satiety , hunger , satisfaction with the diet , and attendance at group sessions were similar for all diets ; attendance was strongly associated with weight loss ( 0.2 kg per session attended ) . The diets improved lipid-related risk factors and fasting insulin levels . CONCLUSIONS Reduced-calorie diets result in clinical ly meaningful weight loss regardless of which macronutrients they emphasize . ( Clinical Trials.gov number , NCT00072995 . BACKGROUND The Women 's Health Initiative Dietary Modification Trial tested the effects on chronic disease of a dietary pattern lower in fat and higher in vegetables , fruit , and grains . OBJECTIVE The objective was to evaluate the effects of dietary carbohydrate changes on lipids and lipoprotein composition . DESIGN Postmenopausal women were r and omly assigned to an intervention or a comparison group for a mean of 8.1 y. Lipoprotein analyses and subclasses were based on sub sample s of 2730 and 209 participants , respectively . RESULTS At year 6 , the total reported fat intake was 7.8 % lower and carbohydrate intake was 7.6 % higher in the intervention group than in the comparison group . Triglyceride change between groups differed by 2.3 , 3.8 , and -0.8 mg/dL at 1 , 3 , and 6 y , respectively , and HDL-cholesterol change differed by -1.6 , -0.7 , and -1.0 mg/dL at 1 , 3 , and 6 y , respectively . Changes did not differ by age , ethnicity , or obesity . In diabetic intervention women who were white , the triglyceride difference between the intervention and comparison groups was 33.8 mg/dL , whereas in black women with diabetes ( n = 50 in the intervention group ; n = 83 in the comparison group ) , the triglyceride difference was 6.4 mg/dL ( P for 3-factor interaction = 0.049 ) . No significant changes were observed in apolipoprotein or lipoprotein particles . Reductions in LDL cholesterol varied by quartile of reported lowering of saturated or trans fat . CONCLUSIONS The replacement of 7 - 8 % of fat intake with complex carbohydrates over 6 y was not associated with clinical ly adverse effects on triglycerides , HDL cholesterol , or lipoprotein subclasses . Diabetic white women with higher triglyceride concentrations may have greater increases in triglycerides Objectives : To compare effects on plasma total- , LDL- , and HDL-cholesterol concentrations of margarines enriched with different vegetable oil sterols or sitostanol-ester . Design : A r and omized double-blind placebo-controlled balanced incomplete Latin square design with five treatments and four periods of 3.5 weeks . Margarines enriched with sterols from soybean , sheanut or ricebran oil or with sitostanol-ester were compared to a non-enriched control margarine . Sterol intake was between 1.5–3.3 g/d . Two thirds of the soybean oil sterols were esterified to fatty acids . Setting : Unilever Research Laboratory , Vlaardingen , The Netherl and s . Subjects : One hundred healthy non-obese normocholesterolaemic and mildly hypercholesterolaemic volunteers aged 45±12.8 y , with plasma total cholesterol levels below 8 mmol/L at entry . Main outcome measures : Plasma lipid , carotenoid and sterol concentrations , blood clinical chemistry and haematology , fatty acid composition of plasma cholesterylesters and food intake . Results : Ninety-five volunteers completed the study . None of the margarines induced adverse changes in blood clinical chemistry , serum total bile acids or haematology . Plasma total- and LDL-cholesterol concentrations were significantly reduced by 8–13 % ( 0.37–0.44 mmol/L ) compared to control for margarines enriched in soybean oil sterol-esters or sitostanol-ester . No effect on HDL-cholesterol concentrations occurred . The LDL- to HDL-cholesterol ratio was reduced by 0.37 and 0.33 units for these margarines , respectively . Effects on blood lipids did not differ between normocholesterolaemic and mildly hypercholesterolaemic subjects . Plasma sitosterol and campesterol levels were significantly higher for the soybean oil sterol margarine and significantly lower for the sitostanol-ester margarine compared to control . Dietary intake was very similar across treatments . The fatty acid composition of plasma cholesterylesters confirmed the good compliance to the treatment . All sterol enriched margarines reduced lipid-st and ardized plasma α- plus β-carotene levels . Plasma lycopene levels were also reduced but this effect was not significant for all products . Conclusions : A margarine with sterol-esters from soybean oil , mainly esters from sitosterol , campesterol and stigmasterol , is as effective as a margarine with sitostanol-ester in lowering blood total- and LDL-cholesterol levels without affecting HDL-cholesterol concentrations . Incorporation in edible fat containing products of such substances may substantially reduce the risk of cardiovascular disease in the population .Sponsorship : Unilever Research Background — It is currently unknown whether dietary weight loss interventions can induce regression of carotid atherosclerosis . Methods and Results — In a 2-year Dietary Intervention R and omized Controlled Trial – Carotid ( DIRECT-Carotid ) study , participants were r and omized to low-fat , Mediterranean , or low-carbohydrate diets and were followed for changes in carotid artery intima-media thickness , measured with st and ard B-mode ultrasound , and carotid vessel wall volume ( VWV ) , measured with carotid 3D ultrasound . Of 140 complete images of participants ( aged 51 years ; body mass index , 30 kg/m2 ; 88 % men ) , higher baseline carotid VWV was associated with increased intima-media thickness , age , male sex , baseline weight , blood pressure , and insulin levels ( P<0.05 for all ) . After 2 years of dietary intervention , we observed a significant 5 % regression in mean carotid VWV ( −58.1 mm3 ; 95 % confidence interval , −81.0 to −35.1 mm3 ; P<0.001 ) , with no differences in the low-fat , Mediterranean , or low-carbohydrate groups ( −60.69 mm3 , −37.69 mm3 , −84.33 mm3 , respectively ; P=0.28 ) . Mean change in intima-media thickness was −1.1 % ( P=0.18 ) . A reduction in the ratio of apolipoprotein B100 to apolipoprotein A1 was observed in the low-carbohydrate compared with the low-fat group ( P=0.001 ) . Participants who exhibited carotid VWV regression ( mean decrease , −128.0 mm3 ; 95 % confidence interval , −148.1 to −107.9 mm3 ) compared with participants who exhibited progression ( mean increase , + 89.6 mm3 ; 95 % confidence interval , + 66.6 to + 112.6 mm3 ) had achieved greater weight loss ( −5.3 versus −3.2 kg ; P=0.03 ) , greater decreases in systolic blood pressure ( −6.8 versus −1.1 mm Hg ; P=0.009 ) and total homocysteine ( −0.06 versus + 1.44 & mgr;mol/L ; P=0.04 ) , and a higher increase of apolipoprotein A1 ( + 0.05 versus −0.00 g/L ; P=0.06 ) . In multivariate regression models , only the decrease in systolic blood pressure remained a significant independent modifiable predictor of subsequent greater regression in both carotid VWV ( β=0.23 ; P=0.01 ) and intima-media thickness ( β=0.28 ; P=0.008 ) levels . Conclusions — Two-year weight loss diets can induce a significant regression of measurable carotid VWV . The effect is similar in low-fat , Mediterranean , or low-carbohydrate strategies and appears to be mediated mainly by the weight loss – induced decline in blood pressure . Clinical Trial Registration — http://www . clinical trials.gov . Unique Identifier : NCT00160108 AIMS To compare the effects on health-related quality of life ( HRQoL ) of a 2-year intervention with a low-fat diet ( LFD ) or a low-carbohydrate diet ( LCD ) based on four group-meetings to achieve compliance . To describe different aspects of taking part in the intervention following the LFD or LCD . METHODS Prospect i ve , r and omized trial of 61 adults with Type 2 diabetes mellitus . The SF-36 question naire was used at baseline , 6 , 12 and 24 months . Patients on LFD aim ed for 55 - 60 energy percent ( E% ) and those on LCD for 20 E% from carbohydrates . The patients were interviewed about their experiences of the intervention . RESULTS Mean body-mass-index was 32.7 ± 5.4 kg/m(2 ) at baseline . Weight-loss did not differ between groups and was maximal at 6 months , LFD : -3.99 ± 4.1 kg , LCD : -4.31 ± 3.6 kg ( p<0.001 within groups ) . There was an increase in the physical component score of SF-36 from 44.1 ( 10.0 ) to 46.7 ( 10.5 ) at 12 months in the LCD group ( p < 0.009 ) while no change occurred in the LFD group ( p < 0.03 between groups ) . At 12 months the physical function , bodily pain and general health scores improved within the LCD group ( p values 0.042 - 0.009 ) while there was no change within the LFD group . CONCLUSIONS Weight-changes did not differ between the diet groups while improvements in HRQoL only occurred after one year during treatment with LCD . No changes of HRQoL occurred in the LFD group in spite of a similar reduction in body weight AIMS To evaluate the efficacy of interventions to promote a healthy diet and physical activity in people with impaired glucose tolerance ( IGT ) . METHODS A r and omised controlled trial in Newcastle upon Tyne , UK , 1995 - 98 . Participants included 67 adults ( 38 men ; 29 women ) aged 24 - 75 years with IGT . The intervention consisted of regular diet and physical activity counselling based on the stages of change model . Main outcome measures were changes between baseline and 6 months in nutrient intake ; physical activity ; anthropometric and physiological measurements including serum lipids ; glucose tolerance ; insulin sensitivity . RESULTS The difference in change in total fat consumption was significant between intervention and control groups ( difference -21.8 ( 95 % confidence interval ( CI ) -37.8 to -5.8 ) g/day , P=0.008 ) . A significantly larger proportion of intervention participants reported taking up vigorous activity than controls ( difference 30.1 , ( 95 % CI 4.3 - -52.7)% , P=0.021 ) . The change in body mass index was significantly different between groups ( difference -0.95 ( 95 % CI -1.5 to -0.4 ) kg/m(2 ) , P=0.001 ) . There was no significant difference in change in mean 2-h plasma glucose between groups ( difference -0.19 ( 95 % CI -1.1 to 0.71 ) mmol/l , NS ) or in serum cholesterol ( difference 0.02 ( 95 % CI -0.26 to 0.31 ) mmol/l , NS ) . The difference in change in fasting serum insulin between groups was significant ( difference -3.4 ( 95 % CI -5.8 to -1.1 ) mU/l , P=0.005 ) . CONCLUSIONS After 6 months of intensive lifestyle intervention in participants with IGT , there were changes in diet and physical activity , some cardiovascular risk factors and insulin sensitivity , but not glucose tolerance . Further follow-up is in progress to investigate whether these changes are sustained or augmented over 2 years STUDY OBJECTIVE : To investigate differences between smokers and non-smokers in health behaviour , cardiovascular risk factors , coronary heart disease ( CHD ) risks , health knowledge , health attitudes , and compliance with a CHD prevention programme . DESIGN : Differences between smokers and non-smokers were studied via medical examinations , question naires , physical exercise activity logs , and food record sheets . Data were analysed using univariate and multivariate analyses . The five and 10 year CHD risks were assessed using the Framingham CHD risk estimate . SETTING : The Karolinska Hospital , Stockholm , and Sollentuna Primary Health Centre , Sollentuna , Sweden . PARTICIPANTS : The analyses were based on 158 healthy smoking and non-smoking men aged 35 - 60 years with raised cardiovascular risk factors who enrolled in controlled , r and omised six month diet and exercise programmes . MAIN RESULTS : Discriminant analysis suggested that smokers , compared with non-smokers , were characterised by a higher alcohol energy percent , lower HDL cholesterol concentration , lower systolic blood pressure , and a higher plasminogen activator inhibitor-1 ( PAI-1 ) value . Knowledge of the risk factors for CHD was not a discriminating factor . Both smokers and non-smokers increased the exercise taken , improved their diet , and lowered their CHD risk . Before , as well as after the intervention , smokers had a higher CHD risk than non-smokers . CONCLUSIONS : The best CHD prevention action that could be taken by smokers would of course be to quit smoking . Those who can not stop should be encouraged to improve their diet and increase the amount of physical exercise they take in order to reduce the health hazards of their smoking behaviour Two groups of patients with non-insulin-dependent diabetes mellitus ( NIDDM ) , with dietary advice r and omized between a low-carbohydrate ( LC ) diet and a modified-fat ( MF ) diet , were followed to determine the effect of diet on phospholipid fatty acid composition of platelets and on development of retinopathy in the 7 years following diagnosis . There was a tendency for retinopathy to occur more frequently in those r and omized to the LC diet . This difference was not statistically significant , and fatty acid composition of platelets did not differ significantly in those with and without retinopathy . Linoleic acid values from platelet phospholipid fatty acids were significantly higher in NIDDM on an MF diet compared with an LC diet . There was no difference between the two dietary subgroups with respect to platelet arachidonic acid , but this was lower in the whole diabetic population when compared with non-diabetics . The arachidonic acid values correlated with neither glycosylated haemoglobin nor mean glycaemia . Significant correlation between the fatty acid values for platelets and plasma cholesterol esters was found only for 16:0 BACKGROUND The appearance of breast tissue on mammography varies according to its composition . Fat is radiolucent and appears dark on mammography , while stromal and epithelial tissue has greater optical density and appears light . Extensive areas of radiologically dense breast tissue seen on mammography are associated with an increased risk of breast cancer . PURPOSE The purpose of the present study was to determine whether the adoption of a low-fat , high-carbohydrate diet for 2 years would reduce breast density . METHODS Women with radiologic densities in more than 50 % of the breast area on mammography were recruited and r and omly allocated to an intervention group taught to reduce intake of dietary fat ( mean , 21 % of calories ) and increase complex carbohydrate ( mean , 61 % of calories ) or to a control group ( mean , 32 % of calories from fat and 50 % of calories from carbohydrates ) . Mammographic images from 817 subjects were taken at baseline and compared with those taken 2 years after r and om allocation by use of a quantitative image analysis system , without knowledge of the dietary group of the subjects or of the sequence in which pairs of images had been taken . The effects of the intervention on the mammographic features of breast area , area of dense tissues in the breast , and the percent of the breast occupied by dense tissue were examined using t tests . Multiple regression was used to examine these effects while accounting for age at trial entry , weight change , and menopausal status . RESULTS After 2 years , the total area of the breast was reduced by an average of 233.7 mm2 ( 2.4 % ) ( 95 % confidence interval [ CI ] = 106.9 - 360.6 ) in the intervention group compared with an average increase of 26.3 mm2 ( 0.3 % ) ( 95 % CI = -108.0 - 160.5 ) in the control group ( P = .01 ) . The area of density was reduced by 374.4 mm2 ( 6.1 % ) ( 95 % CI = 235.1 - 513.8 ) in the intervention group compared with an average of 127.7 mm2 ( 2.1 % ) ( 95 % CI = 8.6 - 246.7 ) in the control group ( P = .01 ) . Weight loss was associated with a reduction in breast area . The effect of the intervention on breast area was only marginally statistically significant after weight change , menopausal status , and age at trial entry were taken into account ( P = .06 ) . Greater weight loss and becoming postmenopausal were associated with statistically significant reductions in the area of density on the mammographic image at 2 years ( P = .04 and P<.001 , respectively ) . Age at entry into the trial was marginally significant in the same direction ( P = .06 ) . The effect of the intervention on area of density remained statistically significant after controlling for weight loss , age at entry , and menopausal status ( P = .03 ) . The change in the percentage of dense tissue in the mammographic image was not significantly different between the two groups ( P = .71 ) . CONCLUSIONS AND IMPLICATION S These results show that after 2 years , a low-fat , high-carbohydrate diet reduced the area of mammographic density , a radiographic feature of the breast that is a risk factor for breast cancer . Longer observation of a larger number of subjects will be required to determine whether these effects are associated with changes in risk of breast cancer The Women 's Health Initiative ( WHI ) is a large and complex clinical investigation of strategies for the prevention and control of some of the most common causes of morbidity and mortality among postmenopausal women , including cancer , cardiovascular disease , and osteoporotic fractures . The WHI was initiated in 1992 , with a planned completion date of 2007 . Postmenopausal women ranging in age from 50 to 79 are enrolled at one of 40 WHI clinical centers nationwide into either a clinical trial ( CT ) that will include about 64,500 women or an observational study ( OS ) that will include about 100,000 women . The CT is design ed to allow r and omized controlled evaluation of three distinct interventions : a low-fat eating pattern , hypothesized to prevent breast cancer and colorectal cancer and , secondarily , coronary heart disease ; hormone replacement therapy , hypothesized to reduce the risk of coronary heart disease and other cardiovascular diseases and , secondarily , to reduce the risk of hip and other fractures , with increased breast cancer risk as a possible adverse outcome ; and calcium and vitamin D supplementation , hypothesized to prevent hip fractures and , secondarily , other fractures and colorectal cancer . Overall benefit-versus-risk assessment is a central focus in each of the three CT components . Women are screened for participation in one or both of the components -- dietary modification ( DM ) or hormone replacement therapy (HRT)--of the CT , which will r and omize 48,000 and 27,500 women , respectively . Women who prove to be ineligible for , or who are unwilling to enroll in , these CT components are invited to enroll in the OS . At their 1-year anniversary of r and omization , CT women are invited to be further r and omized into the calcium and vitamin D ( CaD ) trial component , which is projected to include 45,000 women . The average follow-up for women in either CT or OS is approximately 9 years . Concerted efforts are made to enroll women of racial and ethnic minority groups , with a target of 20 % of overall enrollment in both the CT and OS . This article gives a brief description of the rationale for the interventions being studied in each of the CT components and for the inclusion of the OS component . Some detail is provided on specific study design choices , including eligibility criteria , recruitment strategy , and sample size , with attention to the partial factorial design of the CT . Some aspects of the CT monitoring approach are also outlined . The scientific and logistic complexity of the WHI implies particular leadership and management challenges . The WHI organization and committee structure employed to respond to these challenges is also briefly described Abstract In a clinical trial of a diet low in saturated fat and cholesterol , and high in unsaturated fat of vegetable origin , carried out on 846 middle-aged and elderly men living in an institution , the subjects were allocated r and omly to the experimental diet or to a control diet , and were followed double-blind . The combined incidence of myocardial infa rct ion , sudden death , and cerebral infa rct ion was significantly lower in the experimental group than in the control group . The incidence of fatal atherosclerotic events was also lower in the experimental group than in the control group , but total mortality-rates were similar for the two groups Abstract Background . Inflammation may play an important role in type 2 diabetes . It has been proposed that dietary strategies can modulate inflammatory activity . Methods . We investigated the effects of diet on inflammation in type 2 diabetes by comparing a traditional low-fat diet ( LFD ) with a low-carbohydrate diet ( LCD ) . Patients with type 2 diabetes were r and omized to follow either LFD aim ing for 55–60 energy per cent ( E% ) from carbohydrates ( n = 30 ) or LCD aim ing for 20 E% from carbohydrates ( n = 29 ) . Plasma was collected at baseline and after 6 months . C-reactive protein ( CRP ) , interleukin-1 receptor antagonist ( IL-1Ra ) , IL-6 , tumour necrosis factor receptor ( TNFR ) 1 and TNFR2 were determined . Results . Both LFD and LCD led to similar reductions in body weight , while beneficial effects on glycaemic control were observed in the LCD group only . After 6 months , the levels of IL-1Ra and IL-6 were significantly lower in the LCD group than in the LFD group , 978 ( 664–1385 ) versus 1216 ( 974–1822 ) pg/mL and 2.15 ( 1.65–4.27 ) versus 3.39 ( 2.25–4.79 ) pg/mL , both P < 0.05 . Conclusions . To conclude , advice to follow LCD or LFD had similar effects on weight reduction while effects on inflammation differed . Only LCD was found significantly to improve the sub clinical inflammatory state in type 2 diabetes . Trial registration : Clinical Trials.gov identifier : NCT01005498 THE National Diet-Heart Study which was supported by the National Heart Institute , has been completed , and the final report appears as a supplement to CIRCULATION . This was a large double-blind , 2-year study on the effects of diet on blood cholesterol levels in both free-living and closed population s. The relevance of such a study originated in our minds as a result of a study we conducted for 10 months with 55 volunteer couples using commercially prepared , fat-modified foods . These foods were low in saturated fat and relatively high in polyunsaturated oils . Individual diet instruction was not given . The average reduction in serum cholesterol was 14%.1 The general principles on which it was design ed have already been presented.2 Its great importance lies in the demonstration that adequate techniques have now been developed for large experimental studies using volunteers . This is the first study of its kind in which so complex and important a factor as diet was controlled double-blind in a freeliving population . Centers were established in Baltimore , Minneapolis-St . Paul , Oakl and , Chicago , and Boston , where studies of free-living In animals , carbohydrate and fat composition during dietary interventions influenced cardiac metabolism , structure , and function . Because reduced-carbohydrate and reduced-fat hypocaloric diets are commonly used in the treatment of obesity , we investigated whether these interventions differentially affect left ventricular mass , cardiac function , and blood pressure . We r and omized 170 overweight and obese subjects ( body mass index , 32.9±4.4 ; range , 26.5–45.4 kg/m2 ) to 6-month hypocaloric diets with either reduced carbohydrate intake or reduced fat intake . We obtained cardiac MRI and ambulatory blood pressure recordings over 24 hours before and after 6 months . Ninety subjects completing the intervention period had a full cardiac MRI data set . Subjects lost 7.3±4.0 kg ( 7.9±3.8 % ) with reduced-carbohydrate diet and 6.2±4.2 kg ( 6.7±4.4 % ) with reduced-fat diet ( P<0.001 within each group ; P = not significant between interventions ) . Caloric restriction led to similar significant decreases in left ventricular mass with low-carbohydrate diets ( 5.4±5.4 g ) or low-fat diets ( 5.2±4.8 g ; P<0.001 within each group ; P = not significant between interventions ) . Systolic and diastolic left ventricular function did not change with either diet . The 24-hour systolic blood pressure decreased similarly with both interventions . Body weight change ( & bgr;=0.33 ; P=0.02 ) and percentage of ingested n-3 polyunsaturated fatty acids ( & bgr;=−0.27 ; P=0.03 ) predicted changes in left ventricular mass . In conclusion , weight loss induced by reduced-fat diets or reduced-carbohydrate diets similarly improved left ventricular mass in overweight and obese subjects over a 6-month period . However , n-3 polyunsaturated fatty acid ingestion may have an independent beneficial effect on left ventricular mass Abstract : Breast cancer incidence and mortality rates are markedly lower in the south than in the north of Europe . This has been ascribed to differences in lifestyle and , notably , dietary habits across European countries . However , little information exists on the influence of different dietary regimens on estrogens and , hence , on breast cancer risk . Here we report results of our MeDiet Project , a r and omized , dietary intervention study aim ed to assess the effect of a Mediterranean diet on the profiles of endogenous estrogens in healthy postmenopausal women . Out of the 230 women who initially volunteered to participate in the study , 115 were found to be eligible and were enrolled . Women were then r and omly assigned into an intervention ( n = 58 ) and a control ( n = 57 ) group . Women in the intervention group adhered to a traditional , restricted Mediterranean diet for 6 mo , whereas women in the control group continued to follow their regular diet . Women in the intervention group changed their dietary regimen substantially , and this eventually led to a shift from a prevalent intake of animal fat and proteins to a prevalent intake of vegetable fat and proteins . Regarding urinary estrogens , no significant difference was observed between the intervention and control groups at baseline . After 6 mo , however , control women did not show any major change but women in the intervention group exhibited a significant decrease ( over 40 % ) of total estrogen levels ( P < 0.02 ) . The largest part of this modification was based on a marked decrease of specific estrogen metabolites , including hydroxy and keto-derivatives of estradiol or estrone . To our knowledge , this is the first report to show that a traditional Mediterranean diet significantly reduces endogenous estrogen . This may eventually lead to identify selected dietary components that more effectively decrease estrogens levels and , hence , provide a basis to develop dietary preventive measures for breast cancer Recent evidence suggests that the fat mass and obesity-associated gene ( FTO ) genotype may interact with dietary intakes in relation to adiposity . We tested the effect of FTO variant on weight loss in response to 2-year diet interventions . FTO rs1558902 was genotyped in 742 obese adults who were r and omly assigned to one of four diets differing in the proportions of fat , protein , and carbohydrate . Body composition and fat distribution were measured by dual-energy x-ray absorptiometry and computed tomography . We found significant modification effects for intervention varying in dietary protein on 2-year changes in fat-free mass , whole body total percentage of fat mass , total adipose tissue mass , visceral adipose tissue mass , and superficial adipose tissue mass ( for all interactions , P < 0.05 ) . Carriers of the risk allele had a greater reduction in weight , body composition , and fat distribution in response to a high-protein diet , whereas an opposite genetic effect was observed on changes in fat distribution in response to a low-protein diet . Likewise , significant interaction patterns also were observed at 6 months . Our data suggest that a high-protein diet may be beneficial for weight loss and improvement of body composition and fat distribution in individuals with the risk allele of the FTO variant rs1558902 BACKGROUND Actinic keratoses are premalignant lesions and are a sensitive and important manifestation of sun-induced skin damage . Studies in animals have shown that dietary fat influences the incidence of sun-induced skin cancer , but the effect of diet on the incidence of actinic keratosis in humans is not known . METHODS We r and omly assigned 76 patients with nonmelanoma skin cancer either to continue their usual diet ( control group ) or to eat a diet with 20 percent of total caloric intake as fat ( dietary-intervention group ) . For 24 months , the patients were examined for the presence of new actinic keratoses by physicians unaware of their assigned diets . RESULTS At base line , the mean ( + /- SD ) percentage of caloric intake as fat was 40 + /- 4 percent in the control group and 39 + /- 3 percent in the dietary-intervention group . After 4 months of dietary therapy the percentage of calories as fat had decreased to 21 percent in the dietary-intervention group , and it remained below this level throughout the 24-month study period . The percentage of calories as fat in the control group did not fall below 36 percent at any time . The cumulative number of new actinic keratoses per patient from months 4 through 24 was 10 + /- 13 in the control group and 3 + /- 7 in the dietary-intervention group ( P = 0.001 ) . CONCLUSIONS In patients with a history of nonmelanoma skin cancer , a low-fat diet reduces the incidence of actinic keratosis BACKGROUND Studies have shown that the psychosocial determinants attitude , self-efficacy , subjective norm , and health threat are important in predicting intention to change fat consumption . However , the role of habit in relation to these determinants is still largely unknown . OBJECTIVE We aim ed to assess whether and how habit influences intention in relation to attitude , self-efficacy , subjective norm , and health threat . DESIGN Cross-sectionally , we studied the self-reported psychosocial determinants and intention of 105 ( 52 intervention , 53 control ) patients who participated in a family practice -based tailored nutrition counseling intervention study for lowering cardiovascular risk . Fat intake 15 mo before the assessment of psychosocial determinants was used as a measure of habit . We used logistic regression analyses to develop a model predicting intention to change fat consumption . RESULTS Our regression model explained 43 % of the variance in intention . Patients who perceived higher subjective norm or more social support had a higher intention . Habit was a significant predictor of intention in interaction with self-efficacy and health threat . Attitude , health threat , age , and group membership ( ie , whether patients had been in the intervention group or the control group of the intervention study ) were also included in the regression model . CONCLUSIONS The results suggest that habit in addition to subjective norm and the other more frequently investigated psychosocial determinants are important in predicting intention to change fat consumption . To achieve sustainable health improvement through nutrition education programs , these programs should therefore start focusing more on subjective norm and habit CONTEXT The long-term effect of aggressively vs moderately fat-restricted diets has not been studied extensively in free-living subjects with different types of hyperlipidemia . OBJECTIVE To compare the cholesterol-lowering effects of 4 levels of dietary fat intake restriction after 1 year . DESIGN R and omized , parallel , comparison trial . SETTING Male employees of a large industry . PARTICIPANTS A total of 444 men had low-density lipoprotein cholesterol ( LDL-C ) levels above the 75th age-specific percentile . Subjects with triglyceride ( TG ) levels less than the 75th age-specific percentile were defined as hypercholesterolemic ( HC ) and those with TG levels at or above the 75th age-specific percentile were defined as combined hyperlipidemic ( CHL ) . INTERVENTIONS Hypercholesterolemic subjects were r and omized to diets 1 , 2 , 3 , and 4 taught to contain 30 % , 26 % , 22 % , and 18 % fat , and the CHL subjects were r and omized to diets 1 , 2 , and 3 . All 4 diets were taught to subjects and spouses or partners in 8 weekly 2-hour classes . MAIN OUTCOME MEASURES Plasma lipoprotein levels after 1 year . RESULTS Fat intake after 1 year declined from a mean of 34 % to 36 % of energy to 27 % , 26 % , 25 % , and 22 % in the 4 HC diet groups and 28 % , 26 % , and 25 % in the 3 CHL diet groups . Mean+/-SD percent LDL-C reductions were 5.3%+/-16.2 % , 13.4%+/-12.6 % , 8.4%+/-11.2 % , and 13.0%+/-15.7 % in the HC diet groups and 7.0%+/-16.2 % , 2.8%+/-15.8 % , and 4.6%+/-13.5 % in the CHL diet groups ( P<.01 in all but 1 instance ) . Apoprotein B levels decreased 8.6 % , 10.7 % , 4.3 % , and 5.3 % in the HC groups and 14.6 % , 11.4 % , and 9.9 % in the CHL groups ( P<.05-.01 in each instance ) . Triglyceride levels increased significantly in subjects following HC diets 3 and 4 , 21.7 % and 38.7 % ( P<.05 and .01 ) , but not in any CHL subjects . High-density lipoprotein cholesterol decreased 2.8 % and 3.2 % in subjects on HC diets 3 and 4 , respectively ( P<.05 in both cases ) . CONCLUSIONS After 1 year , moderate restriction of dietary fat intake attains meaningful and sustained LDL-C reductions in HC subjects and apoprotein B reductions in both HC and CHL subjects . More extreme restriction of fat intake offers little further advantage in HC or CHL subjects and potentially undesirable effects in HC subjects This r and omised controlled trial examined anthropometric changes and cardiovascular benefits of six months of weight management in 110 free living women , aged 18–68 y and BMI 25–50 kg/m2 , who received 1200 kcal/d diet treatments of either high ( 58 % energy , n=57 ) or low ( 35 % energy , n=53 ) carbohydrate ( CHO ) content . Body weight , plasma total , HDL and LDL cholesterol , triglyceride and blood pressure were measured . Examination at three months showed women on high CHO lost ( mean±s.e.m . ) 4.3±0.5 kg and those on low CHO lost 5.6±0.6 kg of body weight . Changes in risk factors did not significantly differ between the two diet treatments throughout the study . However those on high CHO diets significantly lowered their plasma total cholesterol by 0.33 mmol/l ( 95 % CI : 0.10 , 0.55 ) , LDL cholesterol by 0.23 mmol/l ( 0.02 , 0.43 ) and HDL cholesterol by 0.05 mmol/l ( 0.03 , 0.10 ) , while women on low CHO diets lowered only plasma triglyceride by 0.28 mmol/l ( 0.08 , 0.48 ) . Blood pressure did not change significantly on either diet . After six months , women on high CHO lost 5.6±0.8 kg and those on low CHO lost 6.8±0.8 kg . On the high CHO diet , total cholesterol remained significantly below the baseline value at 0.34 mmol/l ( 0.13 , 0.56 ) , triglyceride was significantly lowered by 0.27 mmol/l ( 0.10 , 0.45 ) , and HDL cholesterol returned to the baseline value . On the low CHO diet , triglyceride remained the only risk factor to be significantly improved . A subgroup of 46 postmenopausal women lost significantly ( P<0.05 ) more weight on the low CHO diet than high CHO diet . In conclusion , these results provided some support for preferring a high CHO diet to a lower CHO approach in weight management , from the point of view of risk reduction , but do not indicate a consistently more rapid weight loss with either diet OBJECTIVE Restriction of dietary fat and cholesterol are recommended for treating hyperlipidemia , but may alter vitamin or mineral intakes . We evaluated changes in nutrients of individuals taught the National Cholesterol Education Program ( NCEP ) Step II diet . METHODS Subjects participated in a r and omized controlled trial of the cholesterol-lowering effect of the NCEP Step II diet . Eligibility criteria included elevated fasting plasma LDL-cholesterol , no lipid-altering medications , and diet not already fat-modified . Subjects attended eight weekly dietitian-led classes . Four-day food records collected 6 months post-intervention were compared to baseline records . RESULTS Of 409 subjects with complete data , 123 met Step I and 166 met Step II diet criteria . Intakes of micronutrients associated with fruits and vegetables ( beta-carotene and vitamin A , vitamin C , folic acid , magnesium , and potassium ) increased on both diets . Patterns of decreased mean intake and /or fewer subjects consuming 2/3 Recommended Dietary Allowance were seen for calcium , vitamin E , and zinc . CONCLUSIONS NCEP Step I and II diets generally match or exceed unmodified diet for vitamin and mineral content . Premenopausal women do not appear to be at increased risk of low iron intake . Vitamin E intake decreases , although the significance is unknown in the context of lower fat intake and increased intake of other antioxidants . Diet counseling and material s should encourage sources of calcium for women , and zinc for both women and men Indicators of cardiovascular disease risk in premenopausal women before , during , and after a 2-year educational intervention measured prevalence of risk and program effectiveness . Women ( n = 277 ) were assigned to either treatment/education ( n = 174 ) or control ( n = 103 ) group . Many had at least one cardiovascular disease risk factor : high BMI ( n = 123 ) ; high-fat diet ( n = 160 ) ; and /or high body fat percent ( n = 136 ) . The treatment group was significant for change in calories from fat ( P < .01 ) . This study shows that premenopausal women have cardiovascular disease risks that should be addressed , and that nutrition education can successfully change dietary behavior Background Hypertension can be prevented by adopting healthy dietary patterns . Our aim was to assess the 4-year effect on blood pressure ( BP ) control of a r and omized feeding trial promoting the traditional Mediterranean dietary pattern . Methods The PREDIMED primary prevention trial is a r and omized , single-blinded , controlled trial conducted in Spanish primary healthcare centers . We recruited 7,447 men ( aged 55 to 80 years ) and women ( aged 60 to 80 years ) who had high risk for cardiovascular disease . Participants were assigned to a control group or to one of two Mediterranean diets . The control group received education on following a low-fat diet , while the groups on Mediterranean diets received nutritional education and also free foods ; either extra virgin olive oil , or nuts . Trained personnel measured participants ’ BP at baseline and once yearly during a 4-year follow-up . We used generalized estimating equations to assess the differences between groups during the follow-up . Results The percentage of participants with controlled BP increased in all three intervention groups ( P-value for within-group changes : P<0.001 ) . Participants allocated to either of the two Mediterranean diet groups had significantly lower diastolic BP than the participants in the control group ( −1.53 mmHg ( 95 % confidence interval ( CI ) −2.01 to −1.04 ) for the Mediterranean diet supplemented with extra virgin olive oil , and −0.65 mmHg ( 95 % CI -1.15 to −0.15 ) mmHg for the Mediterranean diet supplemented with nuts ) . No between-group differences in changes of systolic BP were seen . Conclusions Both the traditional Mediterranean diet and a low-fat diet exerted beneficial effects on BP and could be part of advice to patients for controlling BP . However , we found lower values of diastolic BP in the two groups promoting the Mediterranean diet with extra virgin olive oil or with nuts than in the control group . Trial registration Current Controlled Trials IS RCT We have examined the feasibility of carrying out a r and omized controlled trial of dietary fat reduction in women at increased risk for breast cancer . The r and omization was either to a control group who were taught the principles of balanced nutrition , but were not counselled to change their fat intake , or to an intervention group who were taught to reduce their dietary fat intake to 15 % of total calories from a baseline average of 35 % of calories . Potentially eligible subjects were women attending a breast diagnostic clinic who had the mammographic pattern of dysplasia . Subjects were recruited by letter from their referring surgeon followed by a telephone call . Subjects interested in participating in the study then entered by one of two phases . In Phase I , the study was explained , informed consent sought and willing subjects r and omized to the intervention or control group . Using this procedure 227 subjects were r and omized and 48 ( 21 % ) dropped out of the study in the 12 months following r and omization . ( A drop out was defined as a subject who persistently failed to keep appointments and provide nutrient data . ) Of these drop outs , 30 ( 63 % ) occurred at or soon after r and omization . A modified procedure of entry was then adopted in which subjects interested in the study were first taught the procedures involved , including keeping food records and clinic appointments , and were then asked to provide consent and r and omized . Two hundred and eighty subjects were enrolled using this modified procedure and 25 ( 9 % ) have dropped out in the 12 months following r and omization . ( ABSTRACT TRUNCATED AT 250 WORDS OBJECTIVE The aim of this r and omized trial was to compare the effects of a behavioral intervention focusing on either calorie restriction alone or calorie plus fat restriction on weight loss and changes in lipids and glycemic control in individuals with non-insulin-dependent diabetes mellitus ( NIDDM ) or a family history of diabetes . RESEARCH DESIGN AND METHODS We recruited 44 obese women with NIDDM and 46 obese women with a family history of NIDDM and r and omly assigned these subjects to calorie restriction ( CAL ) or to calorie plus fat restriction ( CAL + FAT ) . All subjects participated in a 16-week behavioral weight loss program , with training in diet , exercise , and behavior modification . Subjects assigned to the CAL condition were given a 1,000−1,500 kcal/day goal and self-monitored calories consumed . Subjects assigned to the CAL + FAT condition had the same calorie goal , but were also given a fat goal ( grams of fat/day ) , to produce a diet with < 20 % of calories from fat ; this group monitored both calories and fat grams . RESULTS Among NIDDM subjects , weight loss of the subjects in the CAL+FAT condition was significantly > subjects in the CAL condition ( 7.7 vs. 4.6 kg ) and the CAL+FAT condition group also maintained their weight loss better at the 1-year follow-up ( 5.2 vs. 1.0 kg ) . Significant decreases in glucose , high-density lipoprotein ( HDL ) cholesterol , and total cholesterol were seen after 16 weeks of treatment among NIDDM subjects ; these changes were similar in CAL and CAL+FAT groups , but a greater proportion of subjects in CAL condition required oral hypoglycemic medication . At the 1-year follow-up , all parameters had returned to baseline . No significant differences in weight loss or physiological changes were seen between CAL and CAL+FAT conditions in subjects with a family history of diabetes . CONCLUSIONS These results suggest that using the combination of calorie and fat restriction may help promote weight loss in obese NIDDM patients . No other long-term benefits of this regimen were observed The effects of two strictly controlled diets , one rich in complex carbohydrates , the other rich in olive oil , on serum lipids were studied in healthy men and women . Serum cholesterol levels fell on average by 0.44 mmol/l in the carbohydrate group and 0.46 mmol/l in the olive oil group . HDL cholesterol levels fell by 0.19 mmol/l in the carbohydrate group and rose by 0.03 mmol/l in the olive oil group . Serum triglycerides rose by 0.19 mmol/l in the carbohydrate group and fell by 0.06 mmol/l in the olive oil group . The changes in both HDL and triglycerides were larger in men than in women . These results clearly show that the olive-oil-rich diet , unlike the complex-carbohydrate-rich diet , caused a specific fall in non-HDL cholesterol while leaving serum triglyceride levels virtually unchanged INTRODUCTION The influence of dietary fat on breast tumour growth(1 ) and , more recently , on treatment outcomes , ( 2,3 ) suggests an important role for dietary advice in the future health of breast cancer patients . The Women 's Intervention Nutrition Study ( UK ) - Stage 1 assessed the feasibility of achieving and maintaining a ≥ 50 % reduction in reported fat intake in postmenopausal , early stage breast cancer patients in the UK . METHOD This study recruited patients in South-east Engl and between 2000 and 2005 . They were r and omly allocated into two groups . Group 1 ( n = 54 ) , received specific dietary counselling to halve their reported fat intake and maintain this low fat intake . Group 2 ( n = 53 ) received healthy eating advice only . Dietitian-led group sessions provided support for women in both groups over 2 years.(4 ) Vali date d four-day diaries were used to measure intake . Data analysis used Generalised Linear Model ( GLM ) for repeated measures and logistic regression . RESULTS A significantly greater proportion of women in Group 1 reported a fat intake reduction of ≥ 50 % at 3 months ( p < .001 ) and 24 months ( p < .001 ) than in Group 2 . The size of the effect of active dietary counselling was 37 % at 3 months ( 95%CI : 21 - 54 % ) and 35 % at 24 months ( 95%CI : 17 - 53 % ) . Mean fat intake was halved at 3 months and 24 months in Group 1 only . CONCLUSION Demonstrating such feasibility is a key step towards defining diet 's role in the secondary prevention of breast cancer Abstract Objective : To determine the relative efficacy in general practice of dietary advice given by a dietitian , a practice nurse , or a diet leaflet alone in reducing total and low density lipoprotein cholesterol concentration . Design : R and omised six month parallel trial . Setting : A general practice in Oxfordshire . Subjects : 2004 subjects aged 35 - 64 years were screened for hypercholesterolaemia ; 163 men and 146 women with a repeat total cholesterol concentration of 6.0 - 8.5 mmol/l entered the trial . Interventions : Individual advice provided by a dietitian using a diet history , a practice nurse using a structured food frequency question naire , or a detailed diet leaflet sent by post . All three groups were advised to limit the energy provided by fat to 30 % or less and to increase carbohydrate and dietary fibre . Main outcome measures : Concentrations of total cholesterol and low density and high density lipoprotein cholesterol after six months ; antioxidant concentration and body mass index . Results : No significant differences were found at the end of the trial between groups in mean concentrations of lipids , lipoproteins , and antioxidants or body mass index . After data were pooled from the three groups , the mean total cholesterol concentration fell by 1.9 % ( 0.13 mmol/l , 95 % confidence interval 0.06 to 0.22 , P<0.001 ) to 7.00 mmol/l , and low density lipoprotein cholesterol also fell . The total carotenoid concentration increased by 53 nmol/l ( 95 % confidence interval 3.0 to 103 , P=0.039 ) . Conclusions : Dietary advice is equally effective when given by a dietitian , a practice nurse , or a diet leaflet alone but results in only a small reduction in total and low density lipoprotein cholesterol . To obtain a better response more intensive intervention than is normally available in primary care is probably necessary . Key messages Key messages In this study dietary advice had only a modest effect on lipid and lipoprotein concentrations Personalised advice from a nurse or dietitian was no more effective than a detailed diet leaflet Antioxidant concentrations increased slightly , but this requires further study A mass approach to dietary change is needed to produce significant The Metroville Health Study aim ed to reduce consumption of total cooking fats by 33 % , salt by 25 % and replace ghee with vegetable oil in a lower middle class urban community in Pakistan . Households ( n=403 ) were r and omly assigned to Intervention and Control groups . A baseline screening collected data on CVD risk factors , knowledge and attitudes and household consumption of cooking fats and salt . Intervention households received information about CVD and regular visits by social workers who measured cooking fats and salt and counselled cooks on the goals of intervention . Two years later , 291 households were re-screened . Intervention households reduced consumption of fats and salt compared to differences were total fat , 48 % ( p<0.0001 ) ; ghee , 37 % ( p=0.005 ) ; vegetable oil , 33 % ( p=0.0001 ) ; and salt , 41 % ( p=0.011 ) . Household visits by trained social workers were effective in achieving reductions in consumption of cooking fat and salt in a lower class urban community . Asia Pac J Public Health 2003 ; 15(1 ) : 30 - 36 BACKGROUND Glucose-dependent insulinotropic polypeptide [ also known as gastric inhibitory polypeptide ( GIP ) ] and its receptor ( GIPR ) may link overnutrition to obesity , insulin resistance , and type 2 diabetes . A GIPR variant rs2287019 was recently associated with obesity and glucose metabolism . OBJECTIVE We aim ed to examine whether weight-loss diets that vary in fat content may modify the effect of this variant on changes in body weight , fasting glucose , and insulin resistance in the Preventing Overweight Using Novel Dietary Strategies ( POUNDS LOST ) trial . DESIGN We genotyped the GIPR rs2287019 in 737 overweight adults who were r and omly assigned to 1 of 4 weight-loss diets that varied in macronutrient contents for 2 y. We assessed the percentage changes in body weight , fasting glucose , and insulin resistance ( HOMA-IR ) across genotypes by the low-fat and high-fat diets . RESULTS At 6 mo of diet intervention , the T allele of rs2287019 was associated with greater weight loss ( β ± SE : -1.05 ± 0.56 % ; P = 0.06 ) and greater decreases in fasting glucose ( β ± SE : -2.33 ± 0.86 % ; P = 0.006 ) , fasting insulin ( β ± SE : -8.76 ± 4.13 % ; P = 0.03 ) , and HOMA-IR ( β ± SE : -10.52 ± 4.39 % ; P = 0.01 ) in participants who were assigned to low-fat diets , whereas there was no significant genotype effect on changes in these traits in the group assigned to the high-fat diet ( all P > 0.44 ; P-interaction = 0.08 , 0.04 , 0.10 , and 0.07 , respectively ) . After correction for multiple tests ( significant P = 0.008 ) , the genotype effect on changes in fasting glucose remained significant . Sensitivity analysis in white participants showed that the interactions were more evident on changes in insulin and HOMA-IR ( P-interaction < 0.008 ) . CONCLUSION The T allele of GIPR rs2287019 is associated with greater improvement of glucose homeostasis in individuals who choose a low-fat , high-carbohydrate , and high-fiber diet . The POUNDS LOST trial was registered at clinical trials.gov as NCT00072995 Weight loss reduces energy expenditure , but it is unclear whether dietary macronutrient composition affects this reduction . We hypothesized that energy expenditure might be modulated by macronutrient composition of the diet . The POUNDS LOST study , a prospect i ve , r and omized controlled trial in 811 overweight/obese people who were r and omized in a 2 × 2 design to diets containing 20en% or 40en% fat and 15en% or 25en% ( diets with 65 % , 55 % , 45 % and 35 % carbohydrate ) provided the data to test this hypothesis . Resting energy expenditure ( REE ) was measured at baseline , 6 and 24 months using a ventilated hood . REE declined at 6 months by 99.5±8.0 kcal/d in men and 55.2±10.6 kcal/d in women during the first 6 months . This decline was related to the weight loss , and there was no difference between the diets . REE had returned to baseline by 24 months , but body weight was still 60 % below baseline . Measured REE at 6 months was significantly lower than the predicted ( −18.2±6.7 kcal/d ) and was the result of significant reductions from baseline in the low fat diets ( 65 % or 55 % carbohydrate ) , but not in the high fat diet groups . By 24 months the difference had reversed with measured REE being slightly but significantly higher than predicted ( 21.8±10.1 kcal/d ) . In conclusion , we found that REE fell significantly after weight loss but was not related to diet composition . Adaptive thermogenesis was evident at 6 months , but not at 24 months BACKGROUND The " Mediterranean " diet and statin treatment have both independently been shown to improve survival and reduce the risk of cardiovascular events in patients with ischemic heart disease ( IHD ) , but no studies have evaluated the effect of this combination on endothelial function . We therefore sought to evaluate the effect of the combination dietary intervention and lipid-lowering treatment on brachial vasoreactivity . METHODS A total of 131 consecutive patients with documented IHD and a serum cholesterol level > or = 5 mmol/L ( 193 mg/dL ) were r and omized to receive Mediterranean dietary advice ( n = 68 ) or no specific dietary advice ( n = 63 ) . Endothelial function was assessed at baseline and after 12 months with noninvasive ultrasound scanning vessel-wall tracking of brachial artery flow-mediated vasodilatation ( FMD ) . All patients started statin treatment with Fluvastatin ( 40 mg once daily ) at baseline . RESULTS A total of 115 patients completed the study . At baseline , FMD was 4.30 % + /- 4.89 % in the control group versus 4.32 % + /- 6.15 % in the intervention group ( P = not significant ) . After 12 months of follow-up , FMD was significantly higher in the intervention group ( control group 5.72 % + /- 4.87 % vs intervention group 8.62 % + /- 6.60 % , P < .01 ) . This was accompanied by a larger intake of fatty fish and a significant decrease in triglyceride levels . In multivariate analysis , r and omization status was a significant predictor of FMD after adjustment for classic cardiovascular risk factors and vessel size ( P = .02 ; beta = -2.66 [ -4.91 ; -0.41 ] ) . CONCLUSION Dietary intervention with the Mediterranean diet and statin treatment improve FMD in the brachial artery in patients with IHD and hypercholesterolemia to a greater degree than statin treatment alone The fatty acid composition of serum cholesteryl esters is used as a qualitative biomarker of fatty acid intake , but quantitative data are scarce . Between 1987 and 1992 , the authors fed various fatty acids in four controlled trials to 232 healthy Dutch volunteers and measured the proportion of fatty acids in participants ' cholesteryl esters . Each 10 % of energy fed as linoleic acid ( 18:2 ) raised the proportion of linoleic acid in cholesteryl esters by 9.3 g per 100 g of fatty acids ( st and ard deviation ( SD ) 3.1 ) . For oleic acid ( cis-18:1 ) , this figure was 6.5 g/100 g ( SD 1.7 ) ; for trans fatty acids ( trans-18:1 ) , it was 1.1 ( SD 0.5 ) ; for stearic acid ( 18:0 ) , 1.0 ( SD 0.4 ) ; for palmitic acid ( 16:0 ) , 1.7 ( SD 0.5 ) ; for myristic acid ( 14:0 ) , 2.1 ( SD 0.7 ) ; and for a mixture of saturated fatty acids ( 12:0 , 14:0 , and 16:0 ) , it was 2.2 g/100 g ( SD 1.0 ) . The coefficient of variation of the responses was fairly constant , indicating that changes in intake for each of these fatty acids can be monitored with similar precision . These data can be used to estimate the degree of compliance in experimental studies involving exchanges of single dietary fatty acids . Most fatty acids in cholesteryl esters may also be used in observational studies to estimate differences in intake . However , because of multiple simultaneous differences in fatty acid intake between free-living individuals and between population s , such data can not provide information on absolute intake of fatty acids Abstract Objectives There are no human studies assessing the effect of nutritional interventions on plasma brain-derived neurotrophic factor ( BDNF ) concentrations . The aim of this study was to assess the role of a nutritional intervention based on a Mediterranean diet ( MeDiet ) on plasma BDNF levels . Methods PREvención con Dieta MEDiterránea ( PREDIMED ) is a r and omized clinical trial design ed to assess the effect of a Mediterranean diet ( MeDiet ) on the primary prevention of cardiovascular disease . For this analysis , 243 participants from the Navarra centre were r and omly selected . Participants were assigned to one of three dietary interventions : control ( low-fat ) diet , MeDiet supplemented with virgin olive oil ( MeDiet + VOO ) , or MeDiet supplemented with nuts ( MeDiet + Nuts ) . Plasma BDNF levels were measured after 3 years of intervention . Multivariate-adjusted means of BDNF for each intervention were compared using generalized linear models . Logistic regression models were fit to assess the association between the dietary intervention and the likelihood to have low plasma BDNF values ( < 13 µg/ml , 10th percentile ) . Analyses were repeated after stratifying the sample according to baseline prevalence of different diseases . Results Higher but non-significant plasma BDNF levels were observed for participants assigned to both MeDiets . Participants assigned to MeDiet + Nuts showed a significant lower risk ( odds ratios ( OR ) = 0.22 ; 95 % confidence intervals ( CI ) = 0.05–0.90 ) of low plasma BDNF values ( < 13 µg/ml ) as compared to the control group . Among participants with prevalent depression at baseline , significantly higher BDNF levels were found for those assigned to the MeDiet + Nuts . Discussion Adherence to a MeDiet was associated to an improvement in plasma BDNF concentrations in individuals with depression Context Weight loss and exercise decrease the development of diabetes in people with impaired glucose tolerance , but the effectiveness of these interventions in people with normal glucose tolerance is unknown . Contribution Using data from a large r and omized , controlled trial of cardiovascular disease prevention in men , the investigators show that participants with normal glucose tolerance at baseline developed diabetes at similar rates whether they received the diet and exercise intervention or usual care . However , the intervention was associated with lower risk of diabetes among nonsmokers . Implication s While diet and exercise may reduce the development of diabetes in nonsmokers with normal glucose metabolism at baseline , this benefit was not apparent among smokers . The Editors Epidemiologic studies have identified several potentially modifiable risk factors for type 2 diabetes mellitus , including obesity , a diet in which a high proportion of calories comes from fat , and low levels of physical activity ( 1 - 7 ) . Authorities have advocated that trials should test promising hypotheses about the primary prevention of type 2 diabetes ( 1 ) . R and omized intervention studies have demonstrated that , among those who already have impaired glucose tolerance , interventions that promote weight loss and increased exercise can reduce the risk for incident diabetes ( 8 - 10 ) . However , interventions should occur before at-risk individuals develop impaired glucose tolerance . A 2-year r and omized trial of diet , exercise , or both in individuals with a parental history of diabetes showed a statistically imprecise lower risk for developing diabetes in the intervention group ( 11 ) . To test such a hypothesis in groups who do not necessarily have a parental history of diabetes would be expensive . Strategies proposed for the primary prevention of type 2 diabetes include weight reduction , reduced dietary fat intake , and increased exercise ( 2 , 4 , 7 ) . These interventions are similar to those developed for preventing coronary heart disease ; therefore , examination of type 2 diabetes incidence rates in coronary heart disease prevention trials can provide preliminary evidence on the potential of such interventions to reduce type 2 diabetes risk . The Multiple Risk Factor Intervention Trial ( MRFIT ) enrolled 12866 middle-aged men at high risk for coronary heart disease and delivered either special intervention or usual care over 6 to 7 years . The research ers obtained fasting glucose values yearly , and participants self-reported their use of insulin or oral hypoglycemic agents . The glucose values and reports of diabetes medication use enable estimation of diabetes incidence during the trial . Previous reports from MRFIT have described risk factors for the development of diabetes in the usual care group ( 12 ) and the risk for death associated with incident diabetes in the combined special intervention and usual care groups ( 13 ) . In this paper , we compare the incidence of diabetes in the intervention and control groups of the MRFIT , report on an unexpected subgroup finding related to baseline cigarette smoking status , and explore reasons for the different results among smokers and nonsmokers . Methods Procedures Detailed descriptions of the MRFIT have been published ( 14 - 17 ) . Briefly , between 1973 and 1976 , the MRFIT investigators screened 361662 men for eligibility at 22 U.S. clinical centers . Of this group , 12866 men age 35 to 57 years were r and omly assigned : 6428 men to the special intervention group and 6438 men to the usual care group . Screening occurred at 3 visits . At the first screening visit , investigators assessed the risk for coronary heart disease by using measurements of serum cholesterol level , diastolic blood pressure , and self-reported cigarette smoking ( 14 ) . Men who were in the upper 15 % ( changed to 10 % after one third of the screening was completed ) of risk were invited to attend a second screening visit . Because of the eligibility criteria used in the MRFIT , the usual relationships among these risk factors were modified . For example , nonsmokers had to have higher blood pressure and lipid levels on average than smokers to be eligible for the trial . At the second screening visit , a blood sample was taken after an overnight fast . A central laboratory at the Institute of Medical Sciences in San Francisco , California , analyzed the blood sample s by using a protocol previously described ( 18 ) and measured serum glucose in the fasting sample and in a sample taken 1 hour after a 75-g oral glucose load . The MRFIT also measured height and weight ( after the patient had disrobed ) . Individuals with body weight 150 % or more of desirable weight were excluded from the trial ( defined as 0.9 of the average for men of the same height in the 19601962 National Health Examination Survey [ 19 ] ) . We used body mass index ( BMI ) as the measure of relative weight in our report . Men without evidence of cardiovascular or other life-threatening diseases were invited to attend a third screening visit . At this visit , eligible men who consented to the trial were r and omly assigned . All participants had annual examinations for at least 6 years . A fasting blood sample was taken at each annual examination , from which serum glucose concentration and plasma lipid levels were measured . In addition , at the sixth annual visit , a blood sample taken 1 hour after a 75-g oral glucose load was obtained . At each annual examination , participants were asked whether a physician had told them that they had diabetes at any time in the previous 12 months . Each participant was also asked whether he was using insulin or oral hypoglycemic agents . In the MRFIT , 24-hour dietary recalls were obtained at baseline and during follow-up ( 20 , 21 ) . We cited data from baseline and year 6 in our report . Intervention Details of the intervention program of the MRFIT have been reported ( 16 , 22 ) . Briefly , the special intervention group received nutritional counseling that was aim ed at reducing saturated fat and dietary cholesterol consumption and increasing polyunsaturated fat intake . Smokers participated in a behavioral intervention program aim ed at cessation . In men at or more than 115 % of desirable weight , reductions in caloric intake and increases in moderate physical activity were recommended . Elevated blood pressure was treated pharmacologically according to a stepped-care protocol that started with 50 mg of chlorthalidone or hydrochlorothiazide if weight reduction and moderate salt restriction did not achieve the desired blood pressure goals . Definition of Diabetes The definition of incident diabetes followed the American Diabetes Association ( ADA ) guidelines ( 23 ) . With this definition , a participant was considered to have developed diabetes if at any annual visit the fasting glucose level was 7 mmol/L or greater ( 126 mg/dL ) or the participant reported taking insulin or oral hypoglycemic agents . Use of a single fasting glucose determination to design ate diabetic participants is consistent with the ADA criteria for epidemiologic studies . Exclusions The MRFIT attempted at baseline to exclude men with identified diabetes from the trial . The trial excluded individuals who were using hypoglycemic drugs , as well as those who were not being treated but who exhibited clinical symptoms of hyperglycemia ( 15 ) . Despite these exclusion criteria , the trial included 42 men who reported ( without confirmation ) taking insulin , 414 men with a baseline fasting glucose level of 7 mmol/L or greater ( 126 mg/dL ) , and 52 men with a glucose level of 16.65 mmol/L or greater ( 300 mg/dL ) 1 hour after a 75-g oral glucose load . We excluded these 508 men and an additional 531 men ( 291 in the usual care group and 240 in the special intervention group ) with fewer than 2 fasting glucose values throughout the trial from our analyses , leaving 11827 men ( 5893 in the usual care group and 5934 in the special intervention group ) who , by our criteria , were at risk for developing diabetes over the next 6 years ( Figure ) . Figure . Description of study exclusions . Statistical Analysis We used time-to-event methods appropriate for interval-censored data to compare incidence of diabetes in the special intervention and usual care groups ( 24 ) . We estimated the cumulative percentage of patients developing diabetes , assuming that participants at risk who did not attend an annual visit did not meet our criteria for diabetes . We used proportional hazards regression models to study the influence of baseline predictors on hazard ratio estimates and to investigate treatment by subgroup interactions . We also used these models to study the influence of risk factor changes on the incidence of diabetes and on special interventionusual care hazard ratios . We checked the proportional hazards assumption by including a covariate corresponding to the interaction of failure time and special intervention or usual care . In these models , we up date d risk factor levels ( for example , BMI , use of antihypertensive drugs , and smoking status ) annually and considered them to be time-dependent covariates . With this approach , we considered the latest values of risk factors ( those immediately preceding diabetes ) and baseline levels as predictors . We also used longitudinal regression models for binary data ( 25 ) . With these models , participants could be classified as diabetic on several annual visits or at 1 annual visit and not the next . We used analysis of variance with covariates corresponding to baseline level of the factor being considered to compare risk factor levels at 6 years for special intervention and usual care men , both overall and according to baseline cigarette smoking status . With these models , we also investigated the interaction between treatment and smoking status . Both time-to-event analyses and analyses of variance are stratified by clinical center . We performed all analyses by using SAS , version 9.1 ( SAS Institute , Inc. , Cary , North Carolina ) . Role of the Funding Summary The purpose of the study was to determine the effect of a low-fat dietary intervention , with or without concomitant tamoxifen adjuvant therapy , on serum estrogen and sex hormone-binding globulin ( SHBG ) levels in postmenopausal patients with resected breast cancer . Ninety-three patients were r and omized to either reduce their fat intake to 15–20 % of total calories , or to a dietary control group . Serum estradiol , estrone , estrone sulfate , and SHBG concentrations were assayed at baseline , and at 6 , 12 , and 18 months thereafter . In 19 % of patients , the preintervention serum estradiol levels were below the sensitivity of the assay ( 5 pg/ml ) . Tamoxifen had no significant effect on serum estrogen levels , but produced an elevation in SHBG . Patients with reliably quantifiable preintervention estradiol concentrations ( ≥ 10 pg/ml ) showed a significant reduction in serum estradiol after 6 months on the low-fat diet ( average , 20 % ; p < 0.005 ) ; this was sustained over the 18 month study period . Serum SHBG levels were increased by tamoxifen therapy , but were reduced significantly ( p = 0.01 ) after 12 months on the low-fat diet in patients not receiving tamoxifen . No changes in serum estrone or estrone sulfate result ed from the dietary intervention . While the low-fat diet produced significant weight loss , patients treated with tamoxifen without dietary intervention showed a gain in body weight . These weight changes produced disruptions in the normal positive correlation between body weight and serum estrone sulfate , and the negative correlation with SHBG concentration Restriction of all dietary fat is a popular strategy for restricting saturated fat intake to lower LDL cholesterol . Some authorities advise the restriction of fat intake to the extreme of less than 10 % of daily energy on the assumption that more fat restriction is better . The two studies described herein address questions relating to whether increasing fat restriction produces proportionally increasing benefit on cardiovascular risk factors in hyperlipidemic subjects . The first study is the Dietary Alternatives Study ( DAS ) . The DAS was conducted in 531 male Boeing employees over a 2-year period . Subjects were defined as hypercholesterolemic ( HC ) or combined hyperlipidemic ( CHL ) based on age-specific 75th percentiles for plasma LDL-C and triglyceride levels . Hypothesis test analyses were performed at 1 year . HC subjects were r and omized to diets taught to attain fat intakes of 30 , 26 , 22 , and 18 % ( Diets levels 1 - 4 , respectively ) . CHL subjects ( slightly fewer in number ) were r and omized to Diets 1 - 3 . After 1 year , subjects ' total fat intakes were 27 , 26 , 25 , and 22 % of energy ( en% ) , result ing in saturated fat intakes of 8 , 7 , 7 , and 6 % , respectively . In HC subjects the greatest LDL-C decrease was with Diet 2 ( mean of 13.4 % ) and in CHL subjects with Diet 1 ( 7.0 % ) . Surprisingly , plasma triglyceride concentrations rose in HC subjects 20 % and 40 % above baseline on Diets 3 and 4 , respectively , with reciprocal reductions in HDL cholesterol of 2.5 % and 3 % , respectively . Furthermore , apo B reductions were attenuated below Diet 2 in HC subjects and Diet 1 in CHL subjects , and no further reductions were seen in plasma glucose and insulin concentrations , blood pressure , or body weight . Measurements of plasma total fatty acid composition showed a slight increase in plasma palmitate , whereas stearate decreased slightly , supporting the idea that de novo synthesis of palmitic acid was increased in the chronic high-carbohydrate feeding condition . The second study asked if the most effective diet in HC subjects , Diet 2 , has an equivalent effect in women and men . To answer this question , men and women Boeing employees were taught the closely similar National Cholesterol Education Program ( NCEP ) Step II diet . After 6 and 12 months , equivalent reductions in LDL cholesterol were observed in women compared with men . HDL cholesterol levels in men were unchanged from baseline at 6 and 12 months , but were reduced 8 % in HC women , with accompanying decreases of 18 % in HDL2-cholesterol and 5 % in apoprotein A-I ( all P < 0.01 ) . These data indicate that intakes of fat below about 25 en% and carbohydrate intake above approximately 60 en% yield no further LDL-C lowering in HC and CHL male subjects and can be counterproductive to triglyceride , HDL-C , and apo B levels . This lack of benefit appears to be explained by an enhanced endogenous synthesis of palmitic acid , which negates the benefit of further saturated fat restriction . The HDL-C decrease in HC women may have a similar cause and points to an underlying male-female difference . Alternative dietary approaches to limit saturated fat intake deserve intensive study One hundred and forty nine diabetic patients were ophthalmologically assessed seven years after r and omisation to a low carbohydrate or modified fat diet ( rich in linoleic acid ) . Glycaemic control , regardless of the type of diet , was a major determinant of the development of retinopathy . Poorly controlled patients ( haemoglobin A1c greater than 8 % ) with low levels of linoleic acid in cholesterol ester had a significantly greater frequency of retinopathy than well controlled patients or patients with similarly unsatisfactory control but higher levels of linoleic acid . The findings support an earlier suggestion that linoleic acid might protect against diabetic retinopathy The aim of the Finnish Diabetes Prevention Study is to assess the efficacy of an intensive diet-exercise programme in preventing or delaying type 2 diabetes in individuals with impaired glucose tolerance ( IGT ) and to evaluate the effect of the programme on the risk factors of atherosclerotic vascular diseases and the incidence of cardiovascular events . In this ongoing study , a total of 523 overweight subjects with IGT based on two oral glucose tolerance tests were r and omized to either an intervention group or a control group . The main measure in the intervention group is individual dietary advice aim ed at reducing weight and intake of saturated fat and increasing intake of dietary fibre . The intervention subjects are individually guided to increase their level of physical activity . The control group receives general information about the benefits of weight reduction , physical activity and healthy diet in the prevention of diabetes . A pilot study began in 1993 , and recruitment ended in 1998 . By the end of April 1999 there were 65 new cases of diabetes , 34 drop-outs and one death . The weight reduction was greater ( -4.6 kg ) at 1 year in the intervention group ( n = 152 ) than in the control group ( n = 143 , -0.9 kg , P < 0.0001 ) , and this difference was sustained in the second year of follow-up . At 1 year 43.4 % and at 2 years 41.8 % of the intervention subjects had achieved a weight reduction of at least 5 kg , while the corresponding figures for the control subjects were 14.0 and 12.0 % ( P < 0.001 between the groups ) . At 1 year the intervention group showed significantly greater reductions in 2 h glucose , fasting and 2 h insulin , systolic and diastolic blood pressure , and serum triglycerides . Most of the beneficial changes in cardiovascular risk factors were sustained for 2 years . These interim results of the ongoing Finnish Diabetes Prevention Study demonstrate the efficacy and feasibility of the lifestyle intervention programme OBJECTIVE To determine whether eating-pattern messages can effectively be used in a worksite cholesterol education program to change eating behaviors . SUBJECTS 91 r and omly selected participants with initial serum cholesterol levels of 5.2 mmol/L attended the program . INTERVENTION Eating-pattern messages were the focus of a successful 8-week worksite cholesterol education program conducted with city employees of Phoenix , Ariz. Participants completed self-administered question naires before and after the intervention that asked them to compare their current eating patterns with those addressed in the program . The majority ( n = 84 ) of the participants attended five or more of eight available sessions , led by registered dietitians , which focused on the skills needed to decrease dietary fat . STATISTICAL ANALYSES PERFORMED Parametric and nonparametric statistical tests were used to evaluate the direction and magnitude of changes in eating patterns . RESULTS Participants made statistically significant changes in 11 of 15 eating patterns linked to messages delivered during the intervention . Changes in eating behaviors were related to improvements in blood lipid profiles . Results from a multiple regression analysis indicated that intervention-related changes in total cholesterol were significantly associated with combined eating-pattern message scores , and total cholesterol decreased 0.33 mmol/L for each unit decrease in the combined eating-pattern message score . APPLICATIONS/ CONCLUSIONS These findings indicate that eating-pattern messages can be used successfully to evaluate changes in fat-related eating behaviors Fourteen women and five men participated in a 20-week controlled , cross-over trial of the interaction of simvastatin , an HMGCoA reductase inhibitor , with high and low fat diets . Simvastatin was found to be just as effective at lowering LDL cholesterol whether the subjects were on a 22 % fat diet or a 38 % fat diet ( 25 % and 29 % falls , respectively ) . Nevertheless , the lowest cholesterol levels were achieved by combining simvastatin with a low fat diet , the latter adding a further 5 % reduction in plasma cholesterol . Simvastatin plus a low or high fat diet increased HDL cholesterol by 10.0 % and 2.9 % respectively ( P = 0.003 overall ) and reduced triglyceride concentration by 15.9 % and 19 % respectively ( P less than 0.001 ) . Significant diet-drug interactions were seen in LDL and HDL3 cholesterol . Simvastatin blunted the effect of dietary fat change so that the difference in LDL cholesterol , which was 0.71 mmol/l between high and low fat in the absence of simvastatin , was only 0.22 mmol/l with simvastatin . On a high fat diet , simvastatin produced almost no rise in HDL3 cholesterol whereas on a low fat diet HDL3 cholesterol was increased by 8.8 % with simvastatin . The cholesterol content of VLDL and LDL were significantly reduced by simvastatin . The effects of diet and drug on apoproteins A-I and B resembles those on HDL and LDL cholesterol . The findings show interactions between simvastatin and dietary fat which have a bearing on the treatment of hypercholesterolemia BACKGROUND Current cancer prevention recommendations include reducing consumption of fat and increasing consumption of fruits and vegetables . METHODS Healthy women health maintenance organization members ( n = 616 ) ages 40 - 70 were r and omly assigned to either a nutrition intervention or a control intervention unrelated to diet . Intervention included two 45-min counseling sessions plus two brief follow-up telephone contacts . Counseling sessions included a 20-min , interactive , computer-based intervention using a touch-screen format . Intervention goals were reducing dietary fat and increasing fruit and vegetable consumption . Outcome measures included a food frequency question naire and the Fat and Fiber Behavior Question naire ( FFBQ ) . Total serum cholesterol was also measured at baseline and 12 months . RESULTS Twelve-month follow-up data showed improvements on all dietary outcome variables . Compared to the control , intervention participants reported significantly less fat consumption ( 3.75 points less for percentage of energy from fat ) , significantly greater consumption of fruit and vegetables combined ( 0.93 more servings per day ) , and a significant reduction in a behavioral measure of fat consumption ( 0.20 point change in the FFBQ ) . Group differences in total serum cholesterol , while in the desired direction , were not significant . CONCLUSIONS In appropriate circumstances , moderate-intensity dietary interventions can show significant effects for periods of at least 1 year A 2-year r and omized clinical trial was conducted to test whether free-living women aged 45 to 69 years can reduce the fat content of their diet from the typical US level of approximately 39 % to 20 % of energy from fat , using readily available foods , when given nutritional and behavioral counseling and social support . Three clinical units r and omized 303 selected volunteers into intervention ( low-fat eating plan ) or control ( customary diet ) groups . The two groups were comparable at baseline . The intervention group received nutrition instruction and behavioral counseling largely in permanent groups of 12 to 15 participants meeting weekly , then biweekly , and finally monthly . At 6 months , they had substantially reduced the mean proportion of total energy from fat from 39.1 % to 20.9 % , compared with the control group 's nonsignificant reduction from 39.0 % to 38.1 % . At 12 and 24 months , they sustained the reduction of energy from fat . Weight loss and plasma cholesterol level changes in the intervention group supported the self-recorded dietary intake changes . Attendance at intervention sessions averaged 75 % during the first 6 months and , subsequently , 60 % to 70 % . Four-day food records for the r and omized women were obtained at 6 and 12 months from approximately 95 % and at 24 months from 87 % . A clinical trial of a low-fat diet is feasible in women BACKGROUND Adherence to dietary recommendations for disease management is often hindered by the complexity of incorporating them into the daily diet . Nutrition and cardiovascular scientists and food technologists collaborated to develop a prepared meal plan that meets national dietary guidelines for cardiovascular risk reduction . OBJECTIVE To assess the clinical effects of this plan , which incorporates all National Academy of Sciences National Research Council recommended dietary allowances for vitamins , minerals , and macronutrients , compared with a patient-selected American Heart Association Step I and Step II diet plan . METHODS This multicenter , r and omized , parallel-intervention trial was conducted at 10 medical centers in the United States and Canada and involved 560 men and women with hypertension , dyslipidemia , or diabetes . Following calculation of prescriptions to meet individual nutritional requirements based on the Harris-Benedict equation , participants were r and omized to the Campbell 's Center for Nutrition and Wellness ( CCNW ) plan , which is composed of prepackaged breakfast , lunch , and dinner meals provided to participants , or a nutritionist-guided American Heart Association Step I and Step II diet , in which participants self-selected foods to meet their nutrition prescription for 10 weeks . MAIN OUTCOME MEASURES Blood pressure ( BP ) ; lipid , glucose , glycosylated hemoglobin ( HbA1c ) , and insulin levels ; body weight ; dietary intake ; and quality of life . RESULTS Patients ' BP , lipid levels , carbohydrate metabolism , weight , and quality of life ( P < or = .001 for all findings except low-density lipoprotein-high-density lipoprotein ratio , P = .25 ) all improved on both nutrition plans . Mean differences ( + /-SD ) between baseline and treatment clinical values for the CCNW and the self-selected diet groups ( between-group P values ) , respectively , were as follows : systolic BP , -6.4 + /- 9.2 mm Hg and -4.6 + /- 9.0 mm Hg ( P = .02 ) ; diastolic BP , -4.2 + /- 5.7 mm Hg and -3.0 + /- 5.1 mm Hg ( P = .006 ) ; cholesterol , -0.32 + /- 0.58 mmol/L and -0.27 + /- 0.56 mmol/L ( -12.4 + /- 22.5 mg/dL and -10.4 + /- 21.9 mg/dL ) ( P = .30 ) ; glucose , -0.65 + /- 1.88 mmol/L and -0.75 + /- 2.03 mmol/L ( -11.7 + /- 34.0 mg/dL and -13.5 + /- 36.6 mg/dL ) ( P = .10 ) ; and HbA1c , -0.4 % + /- 0.8 % and -0.3 % + /- 0.7 % ( P = .66 ) . Weight loss with the CCNW and self-selected plans , respectively , was as follows : men , -4.5 + /- 3.6 kg and -3.5 + /- 3.3 kg ; and women , -4.8 + /- 3.0 kg and -2.8 + /- 2.8 kg . Quality of life was significantly improved for daily and work activities ( P < .05 ) and nutritional health perceptions ( P < .05 ) with the CCNW plan relative to the self-selected group . Overall nutrient intake and compliance were both significantly ( P < .001 ) better with the CCNW plan . CONCLUSIONS Nutritionally balanced meals that meet the recommendations of national health organizations improved multiple risk factors for patients with cardiovascular disease . The CCNW plan result ed in greater clinical benefits , nutritional completeness , and compliance than the self-selected diet . The CCNW is a comprehensive nutrition plan , convenient for both prescription and practice , and appears viable for effecting favorable dietary changes in patients at high risk for cardiovascular disease Inflammation plays a central role in the development and progression of atherosclerosis , and inflammatory markers have been reported to predict cardiovascular events . Mediterranean-like diet and very long chain omega-3 polyunsaturated fatty acid ( n-3 PUFA ) supplementation have been reported to reduce the risk of cardiovascular mortality and morbidity , but the mechanisms are not fully clarified . The aims of the present study were to investigate the effect of such interventions on serum levels of inflammatory markers , and potential associations with changes in serum fatty acids and anthropometric measures . This was a r and omized 2 x 2 factorial- design ed trial comparing the effect of 3 years of dietary counseling , n-3 PUFA supplementation ( 2.4 g/d ) , or both on different measures of atherosclerosis in elderly high-risk men ( N = 563 ) . Levels of interleukin-18 ( IL-18 ) were decreased by diet ( -10.5 % vs baseline , P = .012 compared with no diet ) and by n-3 PUFA supplementation ( -9.9 % vs baseline , P = .008 compared with placebo ) . Other measured inflammatory markers were not affected . Changes in IL-18 were significantly correlated to changes in triglycerides ( r = 0.20 , P < .001 ) , eicosapentaenoic acid ( r = -0.14 , P = .030 ) , docosahexaenoic acid ( r = -0.14 , P = .034 ) , body mass index ( r = 0.16 , P < .001 ) , and waist circumference ( r = 0.12 , P = .007 ) . In conclusion , levels of IL-18 were significantly reduced by Mediterranean-like diet and n-3 PUFA supplementation . However , the changes correlated only weakly to changes in triglycerides , serum fatty acids , and anthropometric measures . The cardioprotective effects of both interventions might thus in part be explained by reduced levels of IL-18 , but probably beyond changes in serum fatty acids and body composition The Women On the Move through Activity and Nutrition ( WOMAN ) study is the first r and omized clinical trial of nonpharmacological intervention design ed to modify lipoproteins , weight loss and exercise among postmenopausal women using noninvasive measures of atherosclerosis as the primary endpoint . The trial was initially design ed to test whether intervention as compared to health education would be more effective in slowing progression of sub clinical atherosclerosis among women on hormone therapy ( HT ) , estrogen or estrogen+progestin . It was design ed and implemented prior to the results of the Women 's Health Initiative ( WHI ) . The trial was since modified to include women who had been on HT but went off after the results of the WHI were reported . Eligible women were between the ages of 52 - 62 , had waist circumference > or=80 cm , low density lipoprotein cholesterol between 100 - 160 mg% and controlled blood pressure . The intervention is low in total and saturated fat , trans fats , higher in fiber and promotes loss of 7 - 10 % of body weight and includes at least 150 min of physical activity per week . The study has recruited 508 women . The primary endpoints are change in extent of carotid intima-media wall thickness as measured by carotid ultrasound , pulse wave velocity as a measure of vascular stiffness and coronary artery calcium using electron beam computed tomography . Body composition is measured by dual-energy X-ray absorptiometry Few studies have evaluated the efficacy of cholesterol-lowering interventions in a community setting and have included a control or comparison group . As part of a preventive health demonstration project in rural Pennsylvania , Medicare beneficiaries underwent cholesterol screening to identify high-risk individuals with serum cholesterol levels > or = 240 mg/dL. These high-risk individuals were r and omized to a cholesterol-lowering intervention through either local hospitals or physicians ' offices or to a control group . Baseline and follow-up serum cholesterol levels collected two to three years later were compared according to service location ( hospital versus physician 's office ) , intervention attendance , degree of participation , baseline heart disease history , and cholesterol-lowering medication use at follow-up . Serum cholesterol levels decreased between 5.7 % and 6.6 % in the hospital-based and physician-based groups , as well as in a control group not offered the intervention . Participation rates did not differ between treatment groups , nor did participation affect serum cholesterol levels . Attendance level and heart disease history were not associated with a greater decrease in serum cholesterol levels . Individuals reporting cholesterol-lowering drug use at follow-up had significantly higher baseline serum cholesterol levels and a significantly greater decrease in total serum cholesterol ( P < .0001 ) than those not on medication . Both nonpharmacological ( diet ) and pharmacological ( drug ) interventions will reduce serum cholesterol levels and heart attack risk . The study results suggest that , at least for older individuals , the impact of nonpharmacological interventions on the community is minimal . We conclude that only very aggressive treatment will significantly loser serum cholesterol levels in older individuals at risk for heart attack Obesity and physical inactivity are associated with both elevated cardiovascular risk and blood pressure ( BP ) , but the interrelation of exercise , weight loss and BP is poorly understood . This study examines the independent effects of exercise and weight loss on both st and ard clinic and automated , ambulatory BP in 115 overweight , sedentary , normotensive men ( aged 30 to 59 years ) who were r and omly assigned to control status or to lose weight over 1 year by moderate caloric restriction ( dieting ) or by increased caloric expenditure ( exercise ) . Median daytime and evening BP were determined from measurements made every 20 minutes while the subjects were awake . After 1 year , the control group gained ( mean + /- st and ard deviation ) 0.5 + /- 3.8 kg while the diet group lost 6.9 + /- 4.4 kg and the exercise group lost 4.6 + /- 3.5 kg . Clinic BP decreased similarly in all 3 groups , but daytime and evening ambulatory BP decreased in both intervention groups and increased in the control group . Relative to the 1-year change in control subjects , net change in daytime ambulatory BP averaged -2 to -3 mm Hg in both dieters and exercisers , while net change in evening ambulatory BP averaged -3 to -4 mm Hg . These changes were all statistically significant ( p less than 0.05 ) when compared with control subjects except for daytime systolic BP in both intervention groups and evening diastolic BP in dieters . Weight loss achieved through caloric restriction or expenditure may cause important decreases in BP in normotensive men ; exercise appears to confer no unique benefit . If confirmed , these results have important public health implication s for the prevention of cardiovascular disease To assess the effect of dietary reduction of plasma cholesterol concentrations on coronary atherosclerosis , we set up a r and omised , controlled , end-point-blinded trial based on quantitative image analysis of coronary angiograms in patients with angina or past myocardial infa rct ion . Another intervention group received diet and cholestyramine , to determine the effect of a greater reduction in circulating cholesterol concentrations . 90 men with coronary heart disease ( CHD ) , who had a mean ( SD ) plasma cholesterol of 7.23 ( 0.77 ) mmol/l were r and omised to receive usual care ( U , controls ) , dietary intervention ( D ) , or diet plus cholestyramine ( DC ) , with angiography at baseline and at 39 ( SD 3.5 ) months . Mean plasma cholesterol during the trial period was 6.93 ( U ) , 6.17 ( D ) , and 5.56 ( DC ) mmol/l . The proportion of patients who showed overall progression of coronary narrowing was significantly reduced by both interventions ( U 46 % , D 15 % , DC 12 % ) , whereas the proportion who showed an increase in luminal diameter rose significantly ( U 4 % , D 38 % , DC 33 % ) . The mean absolute width of the coronary segments ( MAWS ) studied decreased by 0.201 mm in controls , increased by 0.003 mm in group D , and increased by 0.103 mm in group DC ( p less than 0.05 ) , with improvement also seen in the minimum width of segments , percentage diameter stenosis , and edge-irregularity index in intervention groups . The change in MAWS was independently and significantly correlated with LDL cholesterol concentration and LDL/HDL cholesterol ratio during the trial period . Both interventions significantly reduced the frequency of total cardiovascular events . Dietary change alone retarded overall progression and increased overall regression of coronary artery disease , and diet plus cholestyramine was additionally associated with a net increase in coronary lumen diameter . These findings support the use of a lipid-lowering diet , and if necessary of appropriate drug treatment , in men with CHD who have even mildly raised serum cholesterol concentrations To determine the value of weight reduction on blood pressure , we r and omly allocated 60 untreated , mildly hypertensive , obese individuals to a no-treatment control group or to a behaviourly-oriented weight loss ( ' diet ' ) programme administered by professional dietitians . Behavioural techniques included self-monitoring , shaping , reinforcement and modelling . Subjects were reassessed after six months by an observer who was unaware of their study group . Fifty-four subjects ( 90 % ) completed the study . Diet subjects lost 4.1 kg and controls only 0.8 kg ( P = 0.018 ) . However , neither systolic nor diastolic blood pressures differed . The chance that we missed a clinical ly important diastolic difference of 6 mmHg ( our pre- study target ) is less than 1 % . We conclude that our weight loss programme was successful in reducing weight but that weight loss is not useful in lowering blood pressure in mild , otherwise untreated hypertensives BACKGROUND Dietary intervention to reduce fat consumption and increase fiber consumption has been recommended by the National Cancer Institute , but there is little evidence concerning the effectiveness of self-help material s. The purpose of this study was to evaluate such self-help material s , introduced by a nurse in a primary care setting . METHODS A r and omized controlled trial involving 242 subjects was conducted in two primary care clinics in Chapel Hill , NC , in 1987 . Changes in fat and fiber consumption in the intervention and control groups during the 3-month interval between interviews were compared using analysis of covariance . RESULTS The estimated reduction in fat was 3.8 g larger for the intervention group than for the control group , but the confidence interval included zero . For those individuals who had some responsibility for meal preparation there was a larger difference ( -6.9 g ) in favor of the intervention group , although the difference using calorie-adjusted values was -3.8 g with a 95 % confidence interval ( -7.1 , -0.4 ) . The differences for fiber change were smaller . CONCLUSIONS We found significant small but consistent differential changes associated with a minimal self-help intervention , but we can not rule out the possibility of some response bias . Nonetheless , this study demonstrates that the use of self-help material s for dietary change is feasible , and may be effective Epidemiologic studies fairly consistently show in postmenopausal women that reproductive steroid hormones contribute to primary breast cancer risk , and this association is strongly supported by experimental studies using laboratory animals and model systems . Evidence linking sex hormone concentrations with risk for recurrence in women diagnosed with breast cancer is limited ; however , beneficial effects of antiestrogenic therapy on recurrence-free survival suggest that these hormones affect progression and risk for recurrence . This study examined whether baseline serum concentrations of estradiol , testosterone , and sex hormone binding globulin were associated with recurrence-free survival in a nested case-control cohort of women from a r and omized diet trial ( Women 's Healthy Eating and Living Study ) who were followed for > 7 years after diagnosis . In 153 case-control pairs of perimenopausal and postmenopausal women in this analysis , total estradiol [ hazard ratio ( HR ) , 1.41 per unit increase in log concentration ; 95 % confidence interval ( 95 % CI ) , 1.01 - 1.97 ] , bioavailable estradiol ( HR , 1.26 ; 95 % CI , 1.03 - 1.53 ) , and free estradiol ( HR , 1.31 ; 95 % CI , 1.03 - 1.65 ) concentrations were significantly associated with risk for recurrence . Recurred women had an average total estradiol concentration that was double that of nonrecurred women ( 22.7 versus 10.8 pg/mL ; P = 0.05 ) . Testosterone and sex hormone binding globulin concentrations did not differ between cases and controls and were not associated with risk for recurrence . Although genetic and metabolic factors likely modulate the relationship between circulating sex hormones and risk , results from this study provide evidence that higher serum estrogen concentration contributes to risk for recurrence in women diagnosed with early stage breast cancer . ( Cancer Epidemiol Biomarkers Prev 2008;17(3):614–20 Objective : High-carbohydrate (HC)–high-fibre diets are recommended for weight loss and for treating and preventing diseases such as diabetes and cardiovascular disease . We report a r and omised trial comparing high-fat ( HF ) and high-protein ( HP ) diets with the conventional approach . Research design and methods : A total of 93 overweight insulin-resistant women received advice following r and omisation to HF , HP or HC dietary regimes , to achieve weight loss followed by weight maintenance over 12 months . Weight , body composition and measures of carbohydrate and lipid metabolism were investigated . Results : Retention rates were 93 % for HP and 75 % for HC and HF . Features of the metabolic syndrome improved in all groups during the first 6 months , to a greater extent on HF and HP than an HC . During the second 6 months the HF group had increases in waist circumference ( mean difference 4.4 cm ( 95 % CI 3.0 , 5.8 ) ) , fat mass ( 2.3 kg ( 1.5 , 3.1 ) ) , triglycerides ( 0.28 mmol/l ( 0.09 , 0.46 ) ) and 2 h glucose ( 0.70 mmol/l ( 0.22 , 1.18 ) ) . Overall there was substantial sustained improvement in waist circumference , triglycerides and insulin in the HP group and sustained but more modest changes on HC . Dietary compliance at 12 months was poor in all groups . Conclusions : HP and HC approaches appear to be appropriate options for insulin-resistant individuals . When recommending HP diets appropriate composition of dietary fat must be ensured . HC diet recommendations must include advice regarding appropriate high-fibre , low glycaemic index foods The Women 's Intervention Nutrition Study is a r and omized clinical trial design ed to evaluate if a lifestyle intervention targeting fat intake reduction influences breast cancer recurrence in women with early stage , resected disease receiving conventional cancer management . This report details the concept , content , and implementation of the low-fat eating plan used in the dietary intervention group of this trial . Intervention group participants were given a daily fat gram goal . The intervention was delivered by central ly trained , registered dietitians who applied behavioral , cognitive , and motivational counseling techniques . The low-fat eating plan was implemented in an intensive phase with eight biweekly ( up to Month 4 ) , individual counseling sessions followed by a maintenance phase ( Month 5 up to and including Year 5 ) with registered dietitian visits every 3 months and optional monthly group sessions . Self-monitoring ( daily fat gram counting and recording ) , goal setting , and motivational interviewing strategies were key components . Dietary fat intake was equivalent at baseline and consistently lower in the intervention compared with the control group at all time points ( percent energy from fat at 60 months 23.2%+/-8.4 % vs 31.2%+/-8.9 % , respectively , P<0.0001 ) and was associated with mean 6.1 lb mean weight difference between groups ( P=0.005 ) at 5 years ( baseline and 5 years , respectively : control 160.0+/-35.0 and 161.7+/-32.8 lb ; intervention 160.2+/-35.1 and 155.6+/-32.1 lb ) . Together with previously reported efficacy results , this information suggests that a lifestyle intervention that reduces dietary fat intake and is associated with modest weight loss may favorably influence breast cancer recurrence . The Women 's Intervention Nutrition Study low-fat eating plan can serve as a model for implementing such a long-term dietary intervention in clinical practice OBJECTIVES We sought to describe the various cardiovascular complications that occurred in the Lyon Diet Heart Study ( a secondary prevention trial testing the protective effects of a Mediterranean type of diet ) , to analyze their relations with the associated drug treatments and to gain insights into the possible mechanisms underlying the beneficial effects of certain nutriments . BACKGROUND Dietary habits are implicated in coronary heart disease , and the traditional Mediterranean diet is thought to be cardioprotective . However , the exact mechanisms of this protection are unknown . METHODS A total of 605 patients ( 303 control subjects and 302 study patients ) were studied over a mean period of 27 months . Major primary end points ( cardiovascular death and nonfatal acute myocardial infa rct ion ) , secondary end points ( including unstable angina , stroke , heart failure and embolisms ) and minor end points ( stable angina , need for myocardial revascularization , postangioplasty restenosis and thrombophlebitis ) were analyzed separately and in combination . RESULTS When major primary and secondary end points were combined , there were 59 events in control subjects and 14 events in the study patients , showing a risk reduction of 76 % ( p < 0.0001 ) . When these end points were combined with the minor end points , there were 104 events in control subjects and 68 events in the study patients , giving a risk reduction of 37 % ( p < 0.005 ) . By observational analysis , only aspirin among the medications appeared to be significantly protective ( risk ratio after adjustment for prognosis factors 0.45 ; 95 % confidence interval 0.25 to 0.80 ) . CONCLUSIONS These data show a protective effect of the Mediterranean diet . However , the risk reduction varied depending on the type of end point considered . Our hypothesis is that different pathogenetic mechanisms were responsible for the development of the various complications . It is likely that certain nutriments characteristic of the Mediterranean diet ( omega-3 fatty acids , oleic acid antioxidant vitamins ) have specific cardioprotective effects Context Some experts attribute a low incidence of heart disease in Mediterranean countries to dietary habits . Contribution In this multicenter , 3-group trial , investigators r and omly assigned 772 adults at high risk for cardiovascular disease to a low-fat diet or to a Mediterranean diet supplemented with either virgin olive oil ( 1 L per week ) or nuts ( 30 g per day ) . After 3 months , the Mediterranean diet groups had lower mean plasma glucose level , systolic blood pressure , and total cholesterolhigh-density lipoprotein cholesterol ratio than the low-fat diet group . Caution s The Mediterranean diet groups received more nutritional education than the low-fat diet group . Implication s Mediterranean diets supplemented with olive oil or nuts may improve cardiovascular risk factors . The Editors Cardiovascular disease is the main cause of death in industrialized countries , but incidence rates have marked geographic differences . The low incidence of coronary heart disease ( CHD ) in Mediterranean countries has been partly ascribed to dietary habits ( 1 - 3 ) . Recent findings from large European cohort studies ( 4 - 6 ) suggest that a high degree of adherence to the Mediterranean diet is associated with a reduction in mortality . In small clinical studies , the Mediterranean diet or some of its components have reduced blood pressure ( 7 ) and have improved lipid profiles ( 8 , 9 ) and endothelial function ( 10 ) . Moreover , a recent cross-sectional study ( 11 ) and a 2-year feeding trial ( 12 ) have shown that adherence to the Mediterranean diet is associated with reduced markers of vascular inflammation . These beneficial effects on surrogate markers of cardiovascular risk add biological plausibility to the epidemiologic evidence that supports a protective effect of the Mediterranean diet . Olive oil , a rich source of monounsaturated fatty acids , is a main component of the Mediterranean diet . Virgin olive oil retains all the lipophilic components of the fruit , -tocopherol , and phenolic compounds with strong antioxidant and anti-inflammatory properties ( 13 , 14 ) . Tree nuts , which are also typical in the Mediterranean diet , have a favorable fatty acid profile and are a rich source of nutrients and other bioactive compounds that may beneficially influence the risk for CHD , such as fiber , phytosterols , folic acid , and antioxidants ( 15 ) . Frequent nut intake has been associated with decreased CHD rates in prospect i ve studies ( 15 ) . Walnuts differ from all other nuts through their high content of polyunsaturated fatty acids , particularly -linolenic acid , a plant n-3 fatty acid ( 16 ) , which may confer additional antiatherogenic properties ( 17 ) . Therefore , we design ed a large-scale feeding trial in high-risk participants to assess the effects of 2 Mediterranean diets , one supplemented with virgin olive oil and the other supplemented with mixed nuts , compared with a low-fat diet on cardiovascular outcomes . We report the results of a 3-month intervention on intermediate markers of cardiovascular risk in the first 772 participants who were recruited into the trial . Supplement . Original Version ( PDF ) Methods Study Design The Prevencin con Dieta Mediterrnea ( PREDIMED ) Study is a large , parallel-group , multicenter , r and omized , controlled , 4-year clinical trial that aims to assess the effects of the Mediterranean diet on the primary prevention of cardiovascular disease ( www.predimed.org ) . An estimated 9000 high-risk participants ( > 5000 participants are already recruited ) will be assigned to 3 interventions : Mediterranean diet with virgin olive oil , Mediterranean diet with mixed nuts , or low-fat diet . The main outcome is an aggregate of cardiovascular events ( cardiovascular death , nonfatal myocardial infa rct ion , or nonfatal stroke ) . The anticipated completion date of the trial is December 2010 . We design ed our present study to assess the 3-month effects of the dietary interventions on surrogate markers of cardiovascular risk in participants entering the study during the first 6 months of recruitment . The institutional review boards of the 10 participating centers approved the study protocol . Participants and Recruitment From October 2003 to March 2004 , we selected 930 potential participants in primary care centers affiliated with 10 teaching hospitals across Spain . Eligible participants were community-dwelling men , 55 to 80 years of age , and women , 60 to 80 years of age , who fulfilled at least 1 of 2 criteria : type 2 diabetes or 3 or more CHD risk factors ( current smoking , hypertension [ blood pressure > 140/90 mm Hg or treatment with antihypertensive drugs ] , low-density lipoprotein [ LDL ] cholesterol level 4.14 mmol/L [ 160 mg/dL ] [ or treatment with hypolipidemic drugs ] , high-density lipoprotein [ HDL ] cholesterol level 1.04 mmol/L [ 40 mg/dL ] , body mass index [ BMI ] 25 kg/m2 , or a family history of premature CHD ) . Exclusion criteria were history of cardiovascular disease , any severe chronic illness , drug or alcohol addiction , history of allergy or intolerance to olive oil or nuts , or low predicted likelihood of changing dietary habits according to the stages-of-change model ( 18 ) . The primary care physicians based participants ' eligibility on review of clinical records and a screening visit . They obtained a list of c and i date s from computer-based records of patients who attended each participating center and review ed their clinical records to exclude those who did not meet eligibility criteria . They then invited suitable c and i date s by telephone to attend a screening visit . The visit included an interview with administration of a 26-item question naire to inquire about medical conditions and risk factors related to eligibility . Of the eligible c and i date s who met entry requirements , 95 % agreed to participate and provided informed consent . R and omization and Intervention After the screening visit , each center r and omly assigned eligible participants to 1 of 3 diet groups by using a computer-generated r and om-number sequence . The coordinating center constructed the r and omization table , and participants were r and omly assigned into blocks of 50 participants balanced by center , sex , and age group ( < 70 years and 70 years ) . We concealed allocation into the intervention groups by using closed envelopes with correlative numbers by prespecified subgroups of sex and age . The baseline examination included the administration of a 14-item question naire , an extension of a previously vali date d question naire ( 19 ) , that assessed the degree of adherence to the traditional Mediterranean diet . We assigned values of 0 or 1 to each item ( Appendix Table 1 ) . We also administered a 137-item vali date d food frequency question naire ( 20 ) ; the vali date d Spanish version ( 21 ) of the Minnesota Leisure Time Physical Activity Question naire ; and a 47-item question naire about education , lifestyle , history of illnesses , and medication use . We performed anthropometric and blood pressure measurements and obtained sample s of fasting blood and spot urine . We repeated all examinations at 3 months . The same dietitian delivered the interventions to the 3 r and omized groups in each center . On the basis of the assessment of individual Mediterranean diet scores , the dietitian gave personalized dietary advice during a 30-minute session to each participant , with recommendations on the desired frequency of intake of specific foods . We advised participants who were allocated to the low-fat diet to reduce intake of all types of fat , and we gave them a leaflet with written recommendations according to the American Heart Association guidelines ( 22 ) . For total fat intake , these recommendations were opposite to those given to participants in the 2 Mediterranean diet groups , who received instructions intended to increase the 14-item Mediterranean diet score , including increased consumption of vegetable fats and oils . We did not suggest any energy restriction . While the participants who were allocated to the low-fat diet did not receive further intervention , those assigned the 2 Mediterranean diet groups had access to more intense intervention in 2 ways . First , they were given a free provision of typical Mediterranean fatty foods ( olive oil or nuts ) . Depending on group assignment , participants were given either free virgin olive oil ( 15 L [ 1 L/wk ] for 3 months ) or free sachets of walnuts , hazelnuts , and almonds ( 1350 g of walnuts [ 15 g/d ] , 675 g of hazelnuts [ 7.5 g/d ] , and 675 g of almonds [ 7.5 g/d ] for 3 months ) . To improve adherence and account for family needs , participants in the corresponding Mediterranean diet groups were given excess olive oil or additional 1000-g packets of nuts . We analyzed the nutrient composition of the olive oil and nuts used in the study by st and ard methods in a reference laboratory ( Appendix Table 2 ) ) . Second , 1 week after inclusion , the dietitian delivered a 1-hour group session with up to 20 participants , with separate sessions for each Mediterranean diet group . Each group session consisted of informative talks and provision of written material s with elaborate descriptions of typical Mediterranean foods and seasonal shopping lists , meal plans , and cooking recipes . Throughout the study , all participants had free and continuous access to their center dietitian for advice and consultation . Measurements Trained personnel measured weight and height by using calibrated scales and a wall-mounted stadiometer , respectively ; waist circumference midway between the lowest rib and the iliac crest by using an anthropometric tape ; and blood pressure in triplicate with a vali date d semiautomatic oscillometer ( Omron HEM-705CP , Hoofddorp , the Netherl and s ) . We calculated energy and nutrient intake from Spanish food composition tables ( 23 ) . At the 3-month visit and when consulted by participants , dietitians assessed any adverse effects from the interventions by administering a checklist of symptoms and gave advice on how to remedy them . The checklist included mouth symptoms ; bloating , fullness , or indigestion ; altered bowel Phase 1 of the Trials of Hypertension Prevention was conducted in 2182 adults , aged 35 - 54 y , with diastolic blood pressure of 80 - 89 mm Hg to test the feasibility and blood pressure-lowering effects of seven nonpharmacologic interventions ( weight loss , sodium reduction , stress management , and supplementation with calcium , magnesium , potassium , and fish oil ) . At 6 and 18 mo , weight loss and sodium reduction were well-tolerated and produced significant declines in systolic and diastolic blood pressures ( -2.9/-2.4 and -2.1/-1.2 mm Hg for weight loss and sodium reduction , respectively , at 18 mo ) . None of the other interventions lowered blood pressure significantly at either the 6- or 18-mo follow-up visits . These results suggest that both weight loss and sodium reduction provide an effective means to prevent hypertension . The long-term effects of both of these interventions are being tested in phase 2 of the trial The plasma lipid and lipoprotein responses to two modified isoenergetic diets including meat were studied in 15 free living men with hyperlipidaemia ( mean plasma cholesterol and triglyceride concentrations 8·1 and 3·4 mmol/l ) . A reference diet ( diet A , 42 % energy from fat , ratio of polyunsaturated to saturated fatty acids ( P : S ratio ) 0·2 ) was compared with a fat reduced diet ( diet B , 35 % energy from fat , P : S ratio 0·5 ) and with a further fat modified diet supplemented with fibre ( diet C , 27 % energy from fat , P : S ratio 1·0 ) . Daily intake of meat and meat products ( 180 g/day ) was the same in each dietary period ; that in diet A had a fat content typical of the average British diet , whereas that in diets B and C was based on very lean meat and meat products . During consumption of diet B the plasma cholesterol concentration fell by 8·6 % and low density lipoprotein cholesterol by 11 % . During consumption of diet C plasma cholesterol fell by 18·5 % and low density lipoprotein cholesterol by 23·8 % . Triglyceride and high density lipoprotein cholesterol concentrations and body weight did not change appreciably during the study . A modified diet including a moderate amount of lean meat and meat products is compatible with a reduced lipoprotein mediated risk of atherosclerotic heart disease The National Heart , Blood and Lung Institute-sponsored DELTA study is the first collaborative , multicenter diet study to utilize st and ardized protocol s to feed specific diets to study participants . In the first study , the investigators are focusing on the effects of reducing dietary saturated fat on plasma lipids , lipoproteins , and thrombogenic activity . Future studies will attempt to address important diet/public health questions dealing with high carbohydrate vs. high monounsaturated fat diets , and the cholesterol raising activity of specific saturated fatty acids . Moreover , DELTA will be an invaluable model for other multicenter diet studies The objective of this prospect i ve , r and omized controlled trial was to assess the effectiveness of the Food For Heart Program patient nutrition tool in hypercholesterolemic out patients . The setting for this study was an urban academic primary -care practice ; 175 hypercholesterolemic adults not taking cholesterol-lowering medications were enrolled as subjects . The study intervention involved four monthly dietary counseling visits , using the Food For Heart Program , conducted by the study research assistant . The main outcome measures were fasting serum lipids ( primary ) ; body weight ( secondary ) ; and change in Dietary Risk Assessment score ( intervention group only ) , analyzed using Student 's t test . Our results showed that total and low-density lipoprotein cholesterol decreased 0.40+/-0.65 mmol/L and 0.32+/-0.58 mmol/L , respectively , in the intervention group ( n=91 ) , compared with 0.06+/-0.57 mmol/L and 0.0088+/-0.56 mmol/L in the control group ( n=84 ) ( P < .001 ) . There was no significant change in high-density lipoprotein cholesterol . Intervention subjects lost a small but statistically significant amount of weight , 2.2+/-7.4 pounds ( P < .01 ) , and decreased their Dietary Risk Assessment score 5.9+/-6.5 points ( P < .001 ) . Based on these findings , we concluded that total and low-density lipoprotein cholesterol , weight , and dietary risk for coronary heart disease decreased significantly in hypercholesterolemic patients counseled using the Food For Heart Program Fat in the diet has been associated with increased breast cancer risk . In this study , blood sample s were obtained from 21 women at high risk for breast cancer who had been r and omly assigned to either a nonintervention diet or a low-fat diet . Oxidative damage was examined in the DNA from nucleated peripheral blood cells . The levels of oxidized thymine , specifically 5-hydroxymethyluracil , were threefold higher in the nonintervention diet group than in the low-fat diet group . Without regard to diet arm , there also was a significant linear relationship between daily total fat intake and 5-hydroxymethyluracil level . These results suggest that oxidative damage to DNA may be a marker of dietary fat intake . In addition , oxidative DNA damage may be a mechanistic link between fat in the diet and cancer risk , since such damage is associated with the process of tumor promotion BACKGROUND The blood pressure ( BP ) effects of changing the total fat intake and saturated-unsaturated fat ratio are still controversial , despite evidence that saturated fat-enriched diets are associated with higher BP levels . This double-blind , r and omized crossover study evaluated a possible difference between antihypertensive effects of monounsaturated ( MUFA ) ( extra-virgin olive oil ) and polyunsaturated fatty acids ( PUFA ) ( sunflower oil ) . METHODS Twenty-three hypertensive patients were assigned r and omly to MUFA or PUFA diet for 6 months and then crossed over to the other diet ; effects were evaluated on the basis of daily antihypertensives needed . RESULTS Diets high in MUFA and PUFA differed from the habitual diet for reduced total and saturated fats , whereas they differed from each other for MUFA ( 17.2 % vs 10.5 % ) and PUFA content ( 3.8 % vs 10.5 % ) . Resting BP was significantly lower ( P = .05 for systolic BP ; P = .01 for diastolic BP ) at the end of the MUFA diet compared with the PUFA diet . Blood pressure responses during sympathetic stimulation with the cold pressor test and isometric exercise were similar . Daily drug dosage was significantly reduced during the MUFA but not the PUFA diet ( -48 % vs - 4 % , P<.005 ) . All patients receiving the PUFA diet required antihypertensive treatment , whereas 8 of those receiving the MUFA diet needed no drug therapy . CONCLUSIONS A slight reduction in saturated fat intake , along with the use of extra-virgin olive oil , markedly lowers daily antihypertensive dosage requirement , possibly through enhanced nitric oxide levels stimulated by polyphenols BACKGROUND Despite the popularity of the low-carbohydrate , high-protein , high-fat ( Atkins ) diet , no r and omized , controlled trials have evaluated its efficacy . METHODS We conducted a one-year , multicenter , controlled trial involving 63 obese men and women who were r and omly assigned to either a low-carbohydrate , high-protein , high-fat diet or a low-calorie , high-carbohydrate , low-fat ( conventional ) diet . Professional contact was minimal to replicate the approach used by most dieters . RESULTS Subjects on the low-carbohydrate diet had lost more weight than subjects on the conventional diet at 3 months ( mean [ + /-SD ] , -6.8+/-5.0 vs. -2.7+/-3.7 percent of body weight ; P=0.001 ) and 6 months ( -7.0+/-6.5 vs. -3.2+/-5.6 percent of body weight , P=0.02 ) , but the difference at 12 months was not significant ( -4.4+/-6.7 vs. -2.5+/-6.3 percent of body weight , P=0.26 ) . After three months , no significant differences were found between the groups in total or low-density lipoprotein cholesterol concentrations . The increase in high-density lipoprotein cholesterol concentrations and the decrease in triglyceride concentrations were greater among subjects on the low-carbohydrate diet than among those on the conventional diet throughout most of the study . Both diets significantly decreased diastolic blood pressure and the insulin response to an oral glucose load . CONCLUSIONS The low-carbohydrate diet produced a greater weight loss ( absolute difference , approximately 4 percent ) than did the conventional diet for the first six months , but the differences were not significant at one year . The low-carbohydrate diet was associated with a greater improvement in some risk factors for coronary heart disease . Adherence was poor and attrition was high in both groups . Longer and larger studies are required to determine the long-term safety and efficacy of low-carbohydrate , high-protein , high-fat diets PURPOSE Cancer survivors are at increased risk for cardiovascular disease , diabetes , osteoporosis , and second primary tumors . Healthful lifestyle practice s may improve the health and well-being of survivors . The FRESH START trial tested the efficacy of sequentially tailored versus st and ardized mailed material s on improving cancer survivors ' diet and exercise behaviors . METHODS Five hundred forty-three individuals with newly diagnosed locoregional breast or prostate cancer were recruited from 39 states and two provinces within North America . Participants were r and omly assigned either to a 10-month program of tailored mailed print material s promoting fruit and vegetable ( F&V ) consumption , reducing total/saturated fat intake , and /or increasing exercise or to a 10-month program of nontailored mailed material s on diet and exercise available in the public domain . Telephone surveys conducted at baseline and 1 year assessed body mass index ( BMI ) , dietary consumption , physical activity , and other psychosocial/behavioral indices . Clinical assessment s were conducted on a 23 % sub sample ; information was used to vali date self-reports . RESULTS Five hundred nineteen participants completed the 1-year follow-up ( 4.4 % attrition ; sample characteristics : 57 + /- 10.8 years old , 83 % white , 56 % female , 64 % overweight/obese , and 0 % underweight ) . Although both arms significantly improved their lifestyle behaviors ( P < .05 ) , significantly greater gains occurred in the FRESH START intervention versus the control arm ( practice of two or more goal behaviors : + 34 % v + 18 % , P < .0001 ; exercise minutes per week : + 59.3 v + 39.2 minutes , P = .02 ; F&V per day : + 1.1 v + 0.6 servings , P = .01 ; total fat : -4.4 % v -2.1 % , P < .0001 ; saturated fat : -1.3 % v -0.3 % , P < .0001 ; and BMI : -0.3 v + 0.1 kg/m2 , respectively , P = .004 ) . CONCLUSION Mailed material interventions , especially those that are tailored , are effective in promoting healthful lifestyle changes among cancer survivors . Further study is needed to determine sustainability , cost to benefit , and generalizability to other cancer population OBJECTIVE To compare three sets of dietary guidelines for the treatment of non-insulin-dependent diabetes ( NIDDM ) in free-living individuals and to observe the effects on metabolic control over an 18-month period . RESEARCH DESIGN AND METHODS Seventy volunteer subjects with NIDDM were r and omly assigned to one of three diets , a weight-management diet , a high-carbohydrate/fiber diet , or a modified-lipid diet and followed for 18 months . Nutrient intakes , weight , blood lipids , and glycemic control were measured . RESULTS In all diet groups , glycated hemoglobin ( HbA1 ) fell significantly before diet intervention began , remaining lower throughout the study and at follow-up 9 months later . Low-density lipoprotein ( LDL ) cholesterol showed a sustained fall in all groups after diet intervention . Apart from transient changes in high-density lipoprotein ( HDL ) cholesterol and triglyceride ( TG ) in the diet groups with the higher carbohydrate intake , no lasting differences were found between the three diet groups . CONCLUSIONS In the long term , there were few differences in the outcome of the three dietary prescriptions . Even with intensive instruction , participants found it difficult to meet recommended nutrient intakes ; however , specific dietary advice did result in an improvement in LDL cholesterol . Adverse changes in HDL cholesterol and TG because of diet intervention were transient . The significant improvement in glycemic control during the recruitment phase may have been the result of particpants ' previous dietary knowledge and the increased attention that they received during the intervention Intervention on high risk persons for CHD has shown varying results depending on the effectiveness of the intervention . Most studies have concentrated on the high-risk person only . The present study focuses on the high-risk family as an entity . 1373 high-risk men , 30 - 55 years , were identified on the basis of high total cholesterol and /or low relative HDL ( HDL-cholesterol/tot . cholesterol ) in the Tromsø II screening in 1979/80 , and r and omly allocated to intervention or control group . The 673 men in the intervention group and their families , were offered advice to reduce their risk during two home visits and later by quarterly newsletters . Follow-up blood sample s drawn 1.5 years following the home-visit , show a small reduction in total cholesterol and an increase in the ratio of HDL cholesterol/total cholesterol . Both the intervention and control group were invited to the examination in connection with the Tromsø III screening in 1986/87 and are being followed for 10 years on cardiovascular morbidity and mortality The study deals with 412 men , aged 30 to 64 years , r and omized 1 to 2 years after a first myocardial infa rct ion . For the experimental group a diet low in saturated fats and cholesterol , and high in polyunsaturated fats was recommended . After 5 years , as reported previously , the incidence of fatal and nonfatal myocardial reinfa rct ion was found to be significantly reduced . “ Sudden death ” was uninfluenced . Major coronary heart disease ( CHD ) relapses , including fatal and nonfatal events ( MI ) , were significantly reduced ( P = 0.05).After 11 years , death from all causes had occurred in 101 of the original dieters and 108 controls . A significantly reduced myocardial infa rct ion mortality in the original diet group was found ( 32 versus 57 , P = 0.004 ) . The total number of coronary deaths ( fatal myocardial infa rct ion and sudden death ) was 79 in the diet group and 94 in the control group ( P = 0.097).The CHD mortality was correlated with age , serum cholesterol level , blood pressure , body weight , smoking habits , and a combination of these risk factors Objective : To investigate whether subjects consuming a fat-reduced , high-simple carbohydrate diet ( SCHO ) are at greater risk of micronutrient inadequacy than subjects consuming a fat-reduced , high-complex carbohydrate ( CCHO ) or a normal-fat diet ( control , CD ) . Design : A 6-month r and omised controlled dietary intervention trial with a parallel design . Methods : In total , 46 overweight ( BMI : 24.4–36.3 kg/m2 ) subjects ( 19 males , 27 females ) aged 21–54 y consumed one of three ad libitum diets : SCHO , CCHO , or CD . Nutrient intake was assessed by a 7-day weighed food record . Results : Self-reported energy intake did not differ between diet groups . The lowest intake of vitamin B12 was found in the SCHO group vs CCHO ( P=0.025 ) and vs. CD ( P=0.012 ) . In men , zinc intake was lower on the SCHO diet compared to the CD diet ( P=0.018 ) . The recommendations for zinc and vitamin B12 were , however , met by all the diet groups . No other diet differences were observed . Intake of several micronutrients were insufficient in all three diet groups , although in most cases comparable to average Danish intakes . Conclusion : Zinc intake in men and vitamin B12 intake in the combined gender groups were lower on a fat-reduced , simple carbohydrate-rich diet compared to a habitual , normal-fat diet , but not below recommended levels . Sponsorship : The EU-FAIR program ( PL 95 - 809 ) , the Sugar Bureau , the European Sugar Industries , the Danish Medical Research Council , and the Danish Research and Development Programme for Food Technology Purpose We studied effects of diet-induced postmenopausal weight loss on gene expression and activity of proteins involved in lipogenesis and lipolysis in adipose tissue . Methods Fifty-eight postmenopausal women with overweight ( BMI 32.5 ± 5.5 ) were r and omized to eat an ad libitum Paleolithic-type diet ( PD ) aim ing for a high intake of protein and unsaturated fatty acids or a prudent control diet ( CD ) for 24 months . Anthropometry , plasma adipokines , gene expression of proteins involved in fat metabolism in subcutaneous adipose tissue ( SAT ) and lipoprotein lipase ( LPL ) activity and mass in SAT were measured at baseline and after 6 months . LPL mass and activity were also measured after 24 months . Results The PD led to improved insulin sensitivity ( P < 0.01 ) and decreased circulating triglycerides ( P < 0.001 ) , lipogenesis-related factors , including LPL mRNA ( P < 0.05 ) , mass ( P < 0.01 ) , and activity ( P < 0.001 ) ; as well as gene expressions of CD36 ( P < 0.05 ) , fatty acid synthase , FAS ( P < 0.001 ) and diglyceride acyltransferase 2 , DGAT2 ( P < 0.001 ) . The LPL activity ( P < 0.05 ) and gene expression of DGAT2 ( P < 0.05 ) and FAS ( P < 0.05 ) were significantly lowered in the PD group versus the CD group at 6 months and the LPL activity ( P < 0.05 ) remained significantly lowered in the PD group compared to the CD group at 24 months . Conclusions Compared to the CD , the PD led to a more pronounced reduction of lipogenesis-promoting factors in SAT among postmenopausal women with overweight . This could have mediated the favorable metabolic effects of the PD on triglyceride levels and insulin sensitivity This paper reports research using data in the Nijmegen Family Practice Monitoring Project . One part of the research is follow-up , after 17 y , of a 1977 trial of dietary advice for patients with hypertension or a family history of premature cardiovascular disease . In the intervention group , 840 patients were given health education every 2 mo by trained practice nurses for 1 y. There were 497 patients with similar coronary risk factors in the control group , who received usual care . One year after the intervention a significant decrease was found ( and published ) in serum cholesterol concentrations and blood pressure in the intervention group . By the time of the 1995 reexaminations , however , there were no differences in coronary risk factors between the two groups . Blood pressures had come down , more so in the control group , and the percentage of smokers had decreased equally in both groups . There were no significant differences in intake of dietary fat or in type of fat . The lack of difference was still found when the groups were divided into those with serum cholesterol concentrations > and < 6.5 mmol/L. A second part of the research was to investigate in 1995 the relation between patients ' stage of change of fat intake and their dietary intake . It was found that those in stage 5 ( sustaining desired changes in behavior ) had the lowest saturated fat intake . Since 1977 both groups have been treated equally if hypertension was diagnosed . The two groups were not managed differently with regard to dietary advice after 1977 After polypectomy for adenomatous colorectal polyps , 201 persons were r and omized to receive counselling on a diet low in fat ( the lesser of 50 g/day or 20 % of energy ) and high in fibre ( 50 g/day ) ( LFHF ) , or to follow a normal western diet ( ND ) , high in fat and low in fibre . After 12 months of counselling , fat consumption was about 25 % of energy in the LFHF group and 33 % in the ND group ; fibre consumption was 35 g and 16 g respectively . After an average of two years of follow-up , an intention to treat analysis led to a ratio of cumulative incidence rates of 1.2 ( 95 % CL 0.6 - 2.2 ) for recurrence of neoplastic polyps , a finding which suggests no significant difference between dietary groups over the period of observation . An exploratory analysis conducted among 142 persons with substantial diet counselling indicated a reduced risk of neoplastic polyp recurrence in women ( RR = 0.5 ) , associated with reduced concentrations of faecal bile acids while on the LFHF diet , but indicated an increased risk of recurrence in men ( RR = 2.1 ) , associated with increased faecal bile acids . Although a larger study would be needed to rule out the role of chance , these findings of gender-specific associations between diet counselling and both faecal bile acid concentrations and recurrence of colorectal neoplasia are consistent with recently published evidence of differences between genders Aims /hypothesisThe aim of the study was to investigate ectopic fat deposition and insulin sensitivity , in a parallel single-blinded r and omised controlled trial , comparing Paleolithic diet alone with the combination of Paleolithic diet and exercise in individuals with type 2 diabetes . Methods Thirty-two individuals with type 2 diabetes with BMI 25–40 kg/m2 and 30–70 years of age followed a Paleolithic diet ad libitum for 12 weeks . In addition , study participants were r and omised by computer program to either supervised combined exercise training ( PD-EX group ) or st and ard care exercise recommendations ( PD group ) . Staff performing examinations and assessing outcomes were blinded to group assignment . Thirteen participants were analysed in each group : hepatic and peripheral insulin sensitivity were measured using the hyperinsulinaemic – euglycaemic clamp technique combined with [6,6 - 2H2]glucose infusion , and liver fat was assessed by proton magnetic resonance spectroscopy ; both analyses were secondary endpoints . Intramyocellular lipid ( IMCL ) content was measured by magnetic resonance spectroscopy as a secondary analysis . All examinations were performed at Umeå University Hospital , Umeå , Sweden . Results Both study groups showed a median body weight loss of 7 kg . Fat mass decreased by 5.7 kg in the PD group and by 6.5 kg in the PD-EX group . Maximum oxygen uptake increased in the PD-EX group only . Liver fat showed a consistent reduction ( 74 % decrease ) in the PD group , while the response in the PD-EX group was heterogeneous ( p < 0.05 for the difference between groups ) . IMCL content of the soleus muscle decreased by 40 % in the PD group and by 22 % in the PD-EX group ( p < 0.05 for the difference between groups ) . Both groups improved their peripheral and adipose tissue insulin sensitivity , but not their hepatic insulin sensitivity . Plasma fetuin-A decreased by 11 % in the PD group ( p < 0.05 ) and remained unchanged in the PD-EX group . Liver fat changes during the intervention were correlated with changes in fetuin-A ( rS = 0.63 , p < 0.01 ) . Participants did not report any important adverse events caused by the intervention . Conclusions /interpretationA Paleolithic diet reduced liver fat and IMCL content , while there was a tissue-specific heterogeneous response to added exercise training . Trial registration Clinical Trials.gov NCT01513798 Funding Swedish Diabetes Research Foundation , County Council of Västerbotten , Swedish Heart and Lung Foundation , King Gustav V and Queen Victoria ’s Objective XXXto assess the effect on cognition of a controlled intervention testing Mediterranean diets ( MedDiet ) . Design XXXr and omized trial after 6.5 years of nutritional intervention . Setting Eight primary care centers affiliated to the University of Navarra . Participants A r and om sub sample of 285 participants ( 95 r and omly allocated to each of 3 groups ) of the PREDIMED-NAVARRA trial . All of them were at high vascular risk ( 44.8 % men , 74.1± 5.7 years at cognitive evaluation ) . Interventions Nutritional intervention comparing two MedDiets ( supplemented with extra-virgin olive oil [ EVOO ] or mixed nuts ) versus a low-fat control diet . Participants received intensive education to increase adherence to the intended intervention . Participants allocated to the MedDiet groups received EVOO ( 1 l/week ) or 30 g/day of mixed nuts . Dietary habits were evaluated using a vali date d 137-item food frequency question naire ( FFQ ) . Additionally , adherence to MedDiet was appraised using a 14-item question naire both at baseline and yearly thereafter . Measurements XXXcognitive performance as a main outcome and cognitive status ( normal , mild cognitive impairment [ MCI ] or dementia ) as a secondary outcome were evaluated by two neurologists blinded to group assignment after 6.5 years of nutritional intervention . Results Better post-trial cognitive performance versus control in all cognitive domains and significantly better performance across fluency and memory tasks were observed for participants allocated to the MedDiet+EVOO group . After adjustment for sex , age , education , apolipoprotein E genotype , family history of cognitive impairment/dementia , smoking , physical activity , body mass index , hypertension , dyslipidaemia , diabetes , alcohol and total energy intake , this group also showed lower MCI ( OR=0.34 95 % CI : 0.12–0.97 ) compared with control group . Participants assigned to MedDiet+Nuts group did not differ from controls . Conclusion A long-term intervention with an EVOO-rich MedDiet result ed in a better cognitive function in comparison with a control diet . However , non-significant differences were found for most cognitive domains . Participants allocated to an EVOO-rich MedDiet had less MCI than controls Background — Although trials of lifestyle interventions generally focus on cardiovascular disease risk factors rather than hard clinical outcomes , 10-year coronary heart disease ( CHD ) risk can be estimated from the Framingham risk equations . Our objectives were to study the effect of 2 multicomponent lifestyle interventions on estimated CHD risk relative to advice alone and to evaluate whether differences can be observed in the effects of the lifestyle interventions among subgroups defined by baseline variables . Methods and Results — A total of 810 healthy adults with untreated prehypertension or stage I hypertension were r and omized to 1 of 3 intervention groups : An “ advice-only ” group , an “ established ” group that used established lifestyle recommendations for blood pressure control ( sodium reduction , weight loss , and increased physical activity ) , or an “ established-plus-DASH ” group that combined established lifestyle recommendations with the DASH ( Dietary Approaches to Stop Hypertension ) diet . The primary outcome was 10-year CHD risk , estimated from follow-up data collected at 6 months . A secondary outcome was 10-year CHD risk at 18 months . Of the 810 participants , 62 % were women and 34 % were black . Mean age was 50 years , mean systolic/diastolic blood pressure was 135/85 mm Hg , and median baseline Framingham risk was 1.9 % . The relative risk ratio comparing 6-month to baseline Framingham risk was 0.86 ( 95 % confidence interval 0.81 to 0.91 , P<0.001 ) in the established group and 0.88 ( 95 % confidence interval 0.83 to 0.94 , P<0.001 ) in the established-plus-DASH group relative to advice alone . Results were virtually identical in sensitivity analyses , in each major subgroup , and at 18 months . Conclusions — The observed reductions of 12 % to 14 % in estimated CHD risk are substantial and , if achieved , should have important public health benefits BACKGROUND Free radical-mediated oxidative damage to lipids is thought to be an important process in the pathogenesis of atherosclerosis . Although previous studies have demonstrated a beneficial impact of antioxidant vitamin supplements on lipid peroxidation , the effect of dietary patterns on lipid peroxidation is unknown . METHODS AND RESULTS During the 3-week run-in period of a r and omized trial , 123 healthy individuals were fed a control diet , low in fruits , vegetables , and dairy products , with 37 % of calories from fat . Participants were then r and omized to consume for 8 weeks : ( 1 ) the control diet , ( 2 ) a diet rich in fruits and vegetables but otherwise similar to the control diet , and ( 3 ) a combination diet rich in fruits , vegetables , and low-fat dairy products and reduced in fat . Serum oxygen radical-absorbing capacity , malondialdehyde ( an in vitro measure of lipid peroxidation ) , and breath ethane ( an in vivo measure of lipid peroxidation ) were measured at the end of run-in and intervention periods . Between run-in and intervention , mean ( 95 % CI ) change in oxygen radical-absorbing capacity ( U/mL ) was -35 ( -93 , 13 ) in the control diet , 26 ( -15 , 67 ) in the fruits and vegetables diet ( P=0.06 compared with control ) , and 19 ( -22 , 54 ) in the combination diet ( P=0.10 compared with control ) . Median ( interquartile range ) change in ethane was 0.84 ( 0.10 , 1.59 ) in the control diet , 0.02 ( -0.61 , 0.83 ) in the fruits and vegetables diet ( P=0.04 compared with control ) , and -1.00 ( -1.97 , 0.25 ) in the combination diet ( P=0.005 compared with control ) . Change in malondialdehyde did not differ between diets . CONCLUSIONS This study demonstrates that modification of diet can favorably affect serum antioxidant capacity and protect against lipid peroxidation Long-term supplementation with conjugated linoleic acid ( CLA ) reduces body fat mass ( BFM ) and increases or maintains lean body mass ( LBM ) . However , the regional effect of CLA was not studied . The study aim ed to evaluate the effect of CLA per region and safety in healthy , overweight and obese adults . A total of 118 subjects ( BMI : 28 - 32 kg/m2 ) were included in a double blind , placebo-controlled trial . Subjects were r and omised into two groups supplemented with either 3 x 4 g/d CLA or placebo for 6 months . CLA significantly decreased BFM at month 3 ( Delta=- 0 x 9 % , P=0 x 016 ) and at month 6 ( Delta=- 3 x 4 % , P=0 x 043 ) compared with placebo . The reduction in fat mass was located mostly in the legs ( Delta=- 0 x 8 kg , P<0 x 001 ) , and in women ( Delta=-1 x 3 kg , P=0 x 046 ) with BMI > 30 kg/m2 ( Delta=-1 x 9 kg , P=0 x 011 ) , compared with placebo . The waist-hip ratio decreased significantly ( P=0 x 043 ) compared with placebo . LBM increased ( Delta=+0 x 5 kg , P=0 x 049 ) within the CLA group . Bone mineral content was not affected ( P=0 x 70 ) . All changes were independent of diet and physical exercise . Safety parameters including blood lipids , inflammatory and diabetogenic markers remained within the normal range . Adverse events did not differ between the groups . It is concluded that supplementation with CLA in healthy , overweight and obese adults decreases BFM in specific regions and is well tolerated BACKGROUND It is known that obesity , sodium intake , and alcohol consumption factors influence blood pressure . In this clinical trial , Dietary Approaches to Stop Hypertension , we assessed the effects of dietary patterns on blood pressure . METHODS We enrolled 459 adults with systolic blood pressures of less than 160 mm Hg and diastolic blood pressures of 80 to 95 mm Hg . For three weeks , the subjects were fed a control diet that was low in fruits , vegetables , and dairy products , with a fat content typical of the average diet in the United States . They were then r and omly assigned to receive for eight weeks the control diet , a diet rich in fruits and vegetables , or a " combination " diet rich in fruits , vegetables , and low-fat dairy products and with reduced saturated and total fat . Sodium intake and body weight were maintained at constant levels . RESULTS At base line , the mean ( + /-SD ) systolic and diastolic blood pressures were 131.3+/-10.8 mm Hg and 84.7+/-4.7 mm Hg , respectively . The combination diet reduced systolic and diastolic blood pressure by 5.5 and 3.0 mm Hg more , respectively , than the control diet ( P<0.001 for each ) ; the fruits- and -vegetables diet reduced systolic blood pressure by 2.8 mm Hg more ( P<0.001 ) and diastolic blood pressure by 1.1 mm Hg more than the control diet ( P=0.07 ) . Among the 133 subjects with hypertension ( systolic pressure , > or = 140 mm Hg ; diastolic pressure , > or = 90 mm Hg ; or both ) , the combination diet reduced systolic and diastolic blood pressure by 11.4 and 5.5 mm Hg more , respectively , than the control diet ( P<0.001 for each ) ; among the 326 subjects without hypertension , the corresponding reductions were 3.5 mm Hg ( P<0.001 ) and 2.1 mm Hg ( P=0.003 ) . CONCLUSIONS A diet rich in fruits , vegetables , and low-fat dairy foods and with reduced saturated and total fat can substantially lower blood pressure . This diet offers an additional nutritional approach to preventing and treating hypertension Abstract Objective : To assess the effectiveness of three different methods of promoting secondary prevention of coronary heart disease in primary care . Design : Pragmatic , unblinded , cluster r and omised controlled trial . Setting : Warwickshire . Subjects : 21 general practice s received intervention ; outcome measured in 1906 patients aged 55 - 75 years with established coronary heart disease . Interventions : Audit of notes with summary feedback to primary health care team ( audit group ) ; assistance with setting up a disease register and systematic recall of patients to general practitioner ( GP recall group ) ; assistance with setting up a disease register and systematic recall of patients to a nurse led clinic ( nurse recall group ) . Main outcome measures : At 18 months ' follow up : adequate assessment ( defined ) of 3 risk factors ( blood pressure , cholesterol , and smoking status ) ; prescribing of hypotensive agents , lipid lowering drugs , and antiplatelet drugs ; blood pressure , serum cholesterol level , and plasma cotinine levels . Results : Adequate assessment of all 3 risk factors was much more common in the nurse and GP recall groups ( 85 % , 76 % ) than the audit group ( 52 % ) . The advantage in the nurse recall compared with the audit group was 33 % ( 95 % confidence interval 19 % to 46 % ) ; in the GP recall group compared with the audit group 23 % ( 10 % to 36 % ) , and in the nurse recall group compared with the GP recall group 9 % ( −3 % to 22 % ) . However , these differences in assessment were not reflected in clinical outcomes . Mean blood pressure ( 148/80 , 147/81 , 148/81 mm Hg ) , total cholesterol ( 5.4 , 5.5 , 5.5 mmol/l ) , and cotinine levels ( % probable smokers 17 % , 16 % , 19 % ) varied little between the nurse recall , GP recall , and audit groups respectively , as did prescribing of hypotensive and lipid lowering agents . Prescribing of antiplatelet drugs was higher in the nurse recall group ( 85 % ) than the GP recall or audit groups ( 80 % , 74 % ) . After adjustment for baseline levels , the advantage in the nurse recall group compared with the audit group was 10 % ( 3 % to 17 % ) , in the nurse recall group compared with the GP recall group 8 % ( 1 % to 15 % ) and in the GP recall group compared with the audit group 2 % ( −6 % to 10 % ) . Conclusions : Setting up a register and recall system improved patient assessment at 18 months ' follow up but was not consistently better than audit alone in improving treatment or risk factor levels . Underst and ing the reasons for this is the key next step in improving the quality of care of patients with coronary heart disease . What is already known on this topic Effective preventive care of patients with any chronic disease requires planned and quality assured follow up on the basis of an up to date register Strategies for changing clinical practice in primary care have been of limited effectiveness What this study adds Setting up a coronary heart disease register for a practice substantially increases follow up and adequate assessment of patients at risk Improved assessment and follow up does not necessarily improve clinical outcome Follow up by nurses is as effective as , and may be more effective than , follow up by doctors Patients are being followed up and adequately assessed without the recommended preventive drugs being Seventy-five patients in London and Belfast with multiple sclerosis were given daily supplements of a vegetable oil mixture containing either linoleate or oleate for two years in a double-blind control trial . Relapses tended to be less frequent and were significantly less severe and of shorter duration in the linoleate-supplemented group than in those receiving the oleate mixture , but clear evidence that treatment affected the overall rate of clinical deterioration was not obtained Background Non-alcoholic fatty liver disease , the most prevalent liver disease in developed countries , remains difficult to manage with no proven safe and effective pharmacotherapy available . While weight reduction is the most commonly practice d treatment strategy , this is difficult to both achieve and /or maintain in the majority . Furthermore evidence -based dietary recommendations to guide the nutritional management of these patients are lacking . Using a r and omised controlled trial design , this study compares the effectiveness of the Mediterranean diet to a st and ard low fat diet in terms of differences in insulin sensitivity , hepatic steatosis and metabolic outcomes in participants with non-alcoholic fatty liver disease . Methods Ninety four eligible patients who have non-alcoholic fatty liver disease and who are insulin resistant , will be r and omised into either a Mediterranean or low fat diet group for a 3 month intervention period . Insulin sensitivity will be measured on peripheral blood using Homeostatic Model Assessment and liver fat content quantified using Magnetic Resonance Spectroscopy . Both arms will consist of three face to face and three telephone call follow up consultations delivered by an Accredited Practicing Dietitian . The intervention arm focuses on recommendations from the traditional Mediterranean diet which have been tailored for use in the Australian population The st and ard arm uses the Australian Guide to Healthy Eating and the Australian National Heart Foundation dietary guidelines . Study recruitment will take place at four major metropolitan hospitals in Melbourne , Australia . Data collection will occur at all face to face review s including baseline , 6 , and 12 weeks . A follow up assessment to measure sustainability will take place at 6 and 12 months . The primary end point is improved insulin sensitivity scores at the 12 week time point . Discussion This trial aims to demonstrate in a large cohort of participants with NALFD that a Mediterranean diet independent of weight loss can result in significant benefits in liver fat and insulin sensitivity and that these changes are sustained at 12 months . These metabolic changes would potentially lead to reductions in the risk of chronic liver disease , heart disease , type 2 diabetes and liver cancer . Trial registration Australia and New Zeal and Clinical Trials Register ACTRN : ACTRN12615001010583 Overweight and obesity are associated with increased high sensitivity C-reactive protein ( hsCRP ) levels . The purpose of this study was to determine if weight loss diets differing in fat , protein , or carbohydrate composition differentially reduce hsCRP . POUNDS ( Preventing Overweight Using Novel Dietary Strategies ) LOST was a two-year trial of overweight and obese adults r and omly allocated to one of four weight loss diets with targeted percentages of energy derived from fat , protein , and carbohydrates ( 20,15,65%;20,25,55%;40,15,45%;40,25,35 % , respectively ) . hsCRP was measured at baseline , 6 , and 24 months among 710 participants , and adiposity as measured by dual X-ray absorptiometry ( N=340 ) or abdominal computed tomography ( N=126 ) was correlated with hsCRP change . At 6 months , hsCRP was reduced in all trial participants by −24.7 % ( IQR + 7%,−50 % ) , weight by −6.7 % ( IQR −3%,−11 % ) , and waist circumference by −6.0 % ( IQR −3%,−10 % ) ( all P<.002 ) , with no significant differences according to dietary composition . The percent change in hsCRP at 6 and 24 months correlated modestly with change in weight , waist circumference , fasting insulin , fasting glucose , HOMA , and most lipid levels . Reductions in hsCRP persisted despite an approximate 50 % regain of weight by 24 months . The percent change in hsCRP at 24 months significantly correlated with changes in total body fat ( r=0.42 ) , total abdominal adiposity ( r=0.52 ) , subcutaneous abdominal adiposity ( r=0.52 ) , visceral adiposity ( r=0.47 ) , and hepatic tissue density ( r=−0.34 ) ( all P<0.0006 ) . In conclusion , weight loss decreased hsCRP by similar magnitude , irrespective of dietary composition . Clinicians concerned about inflammation and cardiovascular risk should recommend weight loss diets most likely to succeed for their patients OBJECTIVE Few multiple lifestyle behavior change programs have been design ed to reduce the risk of coronary heart disease in postmenopausal women with type 2 diabetes . This study tested the effectiveness of the Mediterranean Lifestyle Program ( MLP ) , a comprehensive lifestyle self-management program ( Mediterranean low-saturated fat diet , stress management training , exercise , group support , and smoking cessation ) , in reducing cardiovascular risk factors in postmenopausal women with type 2 diabetes . RESEARCH DESIGN AND METHODS Postmenopausal women with type 2 diabetes ( n = 279 ) were r and omized to either usual care ( control ) or treatment ( MLP ) conditions . MLP participants took part in an initial 3-day retreat , followed by 6 months of weekly meetings , to learn and practice program components . Biological end points were changes in HbA(1c ) , lipid profiles , BMI , blood pressure , plasma fatty acids , and flexibility . Impact on quality of life was assessed . RESULTS Multivariate ANCOVAs revealed significantly greater improvements in the MLP condition compared with the usual care group on HbA(1c ) , BMI , plasma fatty acids , and quality of life at the 6-month follow-up . Patterns favoring intervention were seen in lipids , blood pressure , and flexibility but did not reach statistical significance . CONCLUSIONS These results demonstrate that postmenopausal women with type 2 diabetes can make comprehensive lifestyle changes that may lead to clinical ly significant improvements in glycemic control , some coronary heart disease risk factors , and quality of life BACKGROUND TCF7L2 gene variants have been associated with increased risk of type 2 diabetes and higher adiposity . Observational studies and short-term trials have suggested that macronutrients may modify these effects . However , to our knowledge , this has yet to be verified in long-term interventions . OBJECTIVE In a long-term intervention setting , we investigated the effects of TCF7L2 polymorphisms rs7903146 and rs12255372 and dietary total fat on changes in body composition and subsequent glycemic control . DESIGN Data were analyzed for 591 participants in the Preventing Overweight Using Novel Dietary Strategies ( Pounds Lost ) trial , which is a 2-y weight-loss r and omized clinical trial of diets that differed in macronutrient proportions . Adjusted means for changes in body composition at 6 and 24 mo were obtained for gene main effects and interactions with a low-fat diet ( 20 % from energy ) compared with a high-fat diet ( 40 % from energy ) . Interactions with protein and carbohydrate intakes were also tested . Predicted changes in glycemic control from changes in adiposity were determined by genotype and diet type . RESULTS Significant interactions were observed for rs12255372 TT ( risk genotype ) and fat intake for changes in BMI , total fat mass , and trunk fat mass ( all P/q < 0.05 ) at 6 mo , with nonsignificant larger decreases for TT carriers on a low-fat diet . No significant associations were observed at 24 mo or for other macronutrients . Changes in body composition for TT carriers predicted reductions in plasma glucose and insulin only on the low-fat diet . CONCLUSIONS Individuals with the TCF7L2 rs12255372 risk genotype may reduce body adiposity by consuming a diet lower in total fat . These reductions may induce better glycemic control for such individuals predisposed to type 2 diabetes . The Pounds Lost trial was registered at clinical trials.gov as NCT00072995 OBJECTIVE To compare the effects of a eucaloric diet higher in carbohydrate/lower in fat versus lower in carbohydrate/higher in monounsaturated fat on postmeal triglyceride ( TG ) concentrations and other cardiovascular disease risk factors in nonobese subjects with type 1 diabetes and in good glycemic control . RESEARCH DESIGN AND METHODS In a parallel group design study , 30 subjects were r and omly assigned and completed one of the two eucaloric diets . Assessment s included : BMI , blood pressure , A1C , plasma lipids , and markers of oxidation , thrombosis , and inflammation . At 6 months , subjects were hospitalized for 24 h to measure plasma TG excursions . RESULTS There were no significant differences between groups other than decreased plasminogen activator inhibitor 1 ( PAI-1 ) levels and weight gain in the lower-carbohydrate/higher – monounsaturated fat group . During the 24-h testing , the lower-carbohydrate/higher – monounsaturated fat group had a lower plasma TG profile . CONCLUSIONS A diet lower in carbohydrate/higher in monounsaturated fat could offer an appropriate choice for nonobese type 1 diabetic individuals with good metabolic and weight control OBJECTIVE To determine whether reducing dietary fat would reduce body weight and improve long-term glycemia in people with glucose intolerance . RESEARCH DESIGN AND METHODS A 5-year Follow-up of a 1-year r and omized controlled trial of a reduced-fat ad libitum diet versus a usual diet . Participants with glucose intolerance ( 2-h blood glucose 7.0 - 11.0 mmol/l ) were recruited from a Workforce Diabetes Survey . The group that was r and omized to a reduced-fat diet participated in monthly small-group education sessions on reduced-fat eating for 1 year . Body weight and glucose tolerance were measured in 136 participants at baseline 6 months , and 1 year ( end of intervention ) , with follow-up at 2 years ( n = l04 ) , 3 years ( n = 99 ) , and 5 years ( n = 103 ) . RESULTS Compared with the control group , weight decreased in the reduced-fat-diet group ( P < 0.0001 ) ; the greatest difference was noted at 1 year ( -3.3 kg ) , diminished at subsequent follow-up ( -3.2 kg at 2 years and -1.6 kg at 3 years ) , and was no longer present by 5 years ( 1.1 kg ) . Glucose tolerance also improved in patients on the reduced-fat diet ; a lower proportion had type 2 diabetes or impaired glucose tolerance at 1 year ( 47 vs. 67 % , P < 0.05 ) , but in subsequent years , there were no differences between groups . However , the more compliant 50 % of the intervention group maintained lower fasting and 2-h glucose at 5 years ( P = 0.041 and P = 0.026 respectively ) compared with control subjects . CONCLUSIONS The natural history for people at high risk of developing type 2 diabetes is weight gain and deterioration in glucose tolerance . This process may be ameliorated through adherence to a reduced fat BACKGROUND Low-fat vegetarian and vegan diets are associated with weight loss , increased insulin sensitivity , and improved cardiovascular health . OBJECTIVE We compared the effects of a low-fat vegan diet and conventional diabetes diet recommendations on glycemia , weight , and plasma lipids . DESIGN Free-living individuals with type 2 diabetes were r and omly assigned to a low-fat vegan diet ( n = 49 ) or a diet following 2003 American Diabetes Association guidelines ( conventional , n = 50 ) for 74 wk . Glycated hemoglobin ( Hb A(1c ) ) and plasma lipids were assessed at weeks 0 , 11 , 22 , 35 , 48 , 61 , and 74 . Weight was measured at weeks 0 , 22 , and 74 . RESULTS Weight loss was significant within each diet group but not significantly different between groups ( -4.4 kg in the vegan group and -3.0 kg in the conventional diet group , P = 0.25 ) and related significantly to Hb A(1c ) changes ( r = 0.50 , P = 0.001 ) . Hb A(1c ) changes from baseline to 74 wk or last available values were -0.34 and -0.14 for vegan and conventional diets , respectively ( P = 0.43 ) . Hb A(1c ) changes from baseline to last available value or last value before any medication adjustment were -0.40 and 0.01 for vegan and conventional diets , respectively ( P = 0.03 ) . In analyses before alterations in lipid-lowering medications , total cholesterol decreased by 20.4 and 6.8 mg/dL in the vegan and conventional diet groups , respectively ( P = 0.01 ) ; LDL cholesterol decreased by 13.5 and 3.4 mg/dL in the vegan and conventional groups , respectively ( P = 0.03 ) . CONCLUSIONS Both diets were associated with sustained reductions in weight and plasma lipid concentrations . In an analysis controlling for medication changes , a low-fat vegan diet appeared to improve glycemia and plasma lipids more than did conventional diabetes diet recommendations . Whether the observed differences provide clinical benefit for the macro- or microvascular complications of diabetes remains to be established . This trial was registered at clinical trials.gov as NCT00276939 As a result of the Seven Countries Study , the Mediterranean diet has been popularized as a healthy diet . Nevertheless , it has not replaced the prudent diet commonly prescribed to coronary patients . Recently , we completed a secondary , r and omized , prospect i ve prevention trial in 605 patients recovering from myocardial infa rct ion in which we compared an adaptation of the Cretan Mediterranean diet with the usual prescribed diet . After a mean follow-up period of 27 mo , recurrent myocardial infa rct ion , all cardiovascular events , and cardiac and total death were significantly decreased by > 70 % in the group consuming the Mediterranean diet . These protective effects were not related to serum concentrations of total , low-density-lipoprotein ( LDL ) , or high-density-lipoprotein ( HDL ) cholesterol . In contrast , protective effects were related to changes observed in plasma fatty acids : an increase in n-3 fatty acids and oleic acid and a decrease in linoleic acid that result ed from higher intakes of linolenic and oleic acids , but lower intakes of saturated fatty acids and linoleic acid . In addition , higher plasma concentrations of antioxidant vitamins C and E were observed . We conclude that a Cretan Mediterranean diet adapted to a Western population protected against coronary heart disease much more efficiently than did the prudent diet . Thus , it appears that the favorable life expectancy of the Cretans could be largely due to their diet Milk chocolate does not adversely affect plasma lipids and lipoproteins despite its relatively high content of saturated fatty acids ( SFAs ) . Evidence from well-controlled feeding studies indicates that this unique response is due to the high proportion of stearic acid in milk chocolate . In experimental diets containing very high amounts ( eg , 280 g/d , or 10 oz/d ) and more typical amounts ( 46.2 g , or 1.65 oz ) of milk chocolate , plasma total- and low-density-lipoprotein-cholesterol concentrations are not elevated . Furthermore , isoenergetic substitution of one milk chocolate bar per day for a high-carbohydrate snack in a National Cholesterol Education Program/American Heart Association Step 1 Diet does not adversely affect the cholesterol-lowering response . These findings indicate that stearic acid is not hypercholesterolemic as are the other long-chain SFAs . Thus , as illustrated by the different results generated from the predictive equations that group all long-chain SFAs vs those that consider stearic acid separately , grouping stearic acid with other SFAs appears to misrepresent the actual blood cholesterol response We studied separately the effects of weight loss by calorie restriction ( dieting ) and by calorie expenditure ( primarily , running ) on lipoprotein subfraction concentrations in sedentary , moderately overweight men assigned at r and om into three groups as follows : exercise without calorie restriction ( n = 46 ) , calorie restriction without exercise ( n = 42 ) , and control ( n = 42 ) . Plasma lipoprotein mass concentrations were measured by analytic ultracentrifugation for flotation rates ( F0(1.20 ) , S0f ) within high density lipoprotein ( HDL ) ( F0(1.20 ) 0 - 9 ) , low density lipoprotein ( LDL ) ( S0f 0 - 12 ) , intermediate density lipoprotein ( IDL ) ( S0f 12 - 20 ) , and very low density lipoprotein ( VLDL ) ( S0f 20 - 400 ) particle distributions . Particle diameter and flotation rate of the most abundant LDL species were determined by nondenaturing polyacrylamide gradient gel electrophoresis and analytic ultracentrifugation , respectively . During the 1-year trial , the exercisers ran ( mean + /- SD ) 15.6 + /- 9.1 km/wk , and the dieters ate 340 + /- 71 fewer kilocalories per day than at baseline . Total body weight was reduced significantly more in dieters ( -7.2 + /- 4.1 kg ) and exercisers ( -4.0 + /- 3.9 kg ) than controls ( 0.6 + /- 3.7 kg ) . As compared with mean changes in controls , the exercisers and dieters significantly increased HDL2 mass ( 48.6 % and 47.1 % , respectively ) , decreased VLDL mass ( -23.9 % and -25.5 % ) , and increased LDL peak particle diameter ( 2.4 and 3.2 A ) . When adjusted to an equivalent change in body mass index by analysis of covariance , 1 ) exercise-induced and diet-induced weight loss produced comparable mean changes in the mass of small LDL and VLDL , and in LDL peak particle diameter ; 2 ) the exercisers versus control group difference in HDL2 was attributed to the exercisers ' reduced body mass index ; and 3 ) HDL2 increased significantly less in dieters than in exercisers . In dieters , low calorie intake might mitigate the effects of weight loss on HDL2 BACKGROUND Breast cancer is the most commonly diagnosed cancer and the most common cause of cancer mortality among Latino women . Several behavioral factors such as early detection and dietary practice s could help decrease morbidity and mortality associated with breast cancer in this population . Unfortunately , there are few data regarding the efficacy of health-related interventions for young Latino women . METHODS Mujeres Felices por ser Saludables is a r and omized intervention project design ed to assess breast cancer risk reduction behavior among Latino women ages 20 - 40 years . The primary objectives of the project were to determine whether an 8-month integrated dietary/breast health intervention could lead to a greater reduction in dietary fat , increase in dietary fiber , increase in the frequency and proficiency of breast self examination ( BSE ) , and reduction in anxiety related to BSE compared to controls . Herein we describe the overall design of the project and present baseline characteristics of the 256 r and omized women . RESULTS Our results suggest that the average daily intake of dietary fat ( percentage of total energy ) was slightly below 30 % ( percentage of total energy ) among the women r and omized . While over half of these women reported that they practice BSE , and few reported anxiety related to BSE , less than 27 % of women were proficient in the recommended BSE technique . CONCLUSIONS There are few data on the dietary and breast health behaviors of young low-acculturated Latino women . This study documents the feasibility of recruiting , r and omizing , and obtaining both baseline dietary and breast health data on this unique and underserved population OBJECTIVE : To compare the effects of a st and ard American diet , a traditional low-fat diet , and a low-fat diet containing the fat substitute olestra on risk factors for heart disease and diabetes . DESIGN : A 9-month , double-blind , r and omized , parallel-arm , feeding study comparing three diets : ( 1 ) control ( 33 % fat ) , ( 2 ) fat-reduced ( FR ; 25 % fat ) , and ( 3 ) fat-substituted ( FS ) where olestra replaced 1/3 of dietary fat ( 33 % lipid and 25 % digestible fat ) . Subjects were allowed to adjust their total energy intake as desired , allowing weight to fluctuate . SUBJECTS : A total of 37 healthy , obese men ( age 36.7±1.3 y ; body mass index 30.8±0.4 kg/m2 ) . MEASUREMENTS : Body weight and composition by dual-energy X-ray absorptiometry , blood pressure , serum lipids , lipoproteins , hemostatic factors , glucose , insulin , and leptin at baseline and every 3 months . RESULTS : The FS group lost 6.27 kg of body weight by 9 months vs 4.0 kg in the control and 1.79 kg in the FR groups . There was a significant diet main effect on cholesterol ( P=0.002 ) , low-density lipoprotein cholesterol ( P=0.003 ) , and triglycerides ( P=0.01 ) , all of which decreased in the FS group but not the other groups by 9 months . Apolipoprotein B ( ApoB ) increased in the FR and control groups but was unchanged in the FS group ( diet main effect P=0.04 ) . High-density lipoprotein ( HDL ) cholesterol increased in all groups over 9 months ( time main effect P=0.0001 ) . Time main effects were also observed for cholesterol , ApoA1 , ApoB , Factor VII , diastolic blood pressure , and glucose . After adjustment for % fat loss at 9 months , the effects of diet on change in risk factors remained significant only for triglycerides . DISCUSSION : Consumption of a low-fat diet containing olestra for 9 months produced significant improvement in cardiovascular risk factors , an effect largely explained by weight loss . Long-term low-fat diet consumption with or without olestra does not decrease HDL cholesterol The objective of the present study was to determine the effects of a long-term moderate-fat diet ( 30 % energy from fat ) v. a low-fat one ( 20 % energy from fat ) on metabolic risks . The study was a r and omised , prospect i ve 14-month trial on overweight and obese patients ( eighty-nine overweight and obese men and women ) . The intervention was a moderate-fat diet ( 30 % energy ) or a low-fat diet ( 20 % energy ) . The main outcome measurements were change in body weight , waist circumference , LDL-cholesterol , HDL-cholesterol , total cholesterol , TAG , and systolic and diastolic blood pressure . Forty-five subjects on the moderate-fat diet and forty-four subjects on the low-fat one were studied . Characteristics of all r and omised participants were similar in both groups . After 7 months , the moderate- and low-fat diets had similar effects on cardiovascular risks . The moderate-fat diet was more successful after 14 months in reducing weight ( -5.0 ( SD 2.5 ) kg in the moderate-fat group v. -1.2 ( SD 1.1 ) kg in the low-fat one ; P < 0.0001 ) , waist circumference ( -5.5 ( SD 2.4 ) cm in the moderate-fat group v. - 2.3 ( SD 1.3 ) cm in the low-fat one ; P < 0.0001 ) , and other cardiovascular risk factors as well ( LDL , TAG , total cholesterol and systolic blood pressure ) . In conclusion , a moderate-fat energy-restricted diet in the long term might have more beneficial effects on weight maintenance and cardiovascular risk factors compared with a low-fat diet . Better dietary adherence with the moderate-fat diet may be the reason for its successful effects Ecological correlations derived from national mortality data and case – control studies have suggested a positive relation between dietary fat and risk of breast cancer . However , in the many large prospect i ve studies that have been conducted more recently , little or no association has been found between total fat intake and breast cancer incidence . The recently released results from the Women ’s Health Initiative Fat Reduction Trial found no significant effect of a low-fat diet on risk of breast cancer or total cancer incidence . However , method ologic limitations of this trial , particularly low compliance with the dietary intervention , make these data difficult to interpret , and in the end this massive trial contributes little to our underst and ing of the role of fat intake in the risk of breast cancer . A substantial body of available evidence now suggests that the percentage of energy derived from fat intake during midlife does not appear to be an important risk factor for breast cancer and is not the primary reason for the large international differences in disease incidence . Diet has a major impact on breast cancer risk , mainly mediated through childhood growth rates and weight gain in later life . Minimizing weight gain during midlife or weight loss after menopause reduces the risk of postmenopausal breast cancer . Massive r and omized trials of behavior change to prevent cancer will usually not be a good investment , as clear answers are unlikely . The best information on prevention by diet and lifestyle will generally come from long-term prospect i ve studies combined with controlled trials of intermediate endpoints OBJECTIVE To compare two interventions for reducing dietary fat intake in first degree relatives of recent heart attack victims . DESIGN A r and omised controlled trial comparing a low cost mail-out advice program ; referral to a general practitioner ( GP ) ; and no intervention ( control group ) . PARTICIPANTS Adult children or siblings , aged less than 70 years , of survivors of definite or suspected heart attack who had been admitted to hospitals in the Lower Hunter Region of New South Wales . MAIN OUTCOME MEASURES Dietary fat intake ( evaluated with a vali date d short question naire ) and measurement of blood cholesterol levels at six months . RESULTS Of the 342 relatives who participated ( 36 % of those invited ) , 109 , 120 and 113 , respectively , were r and omly assigned to receive a mail-out intervention , advice from their GP or to be part of a control group . The six-month follow-up question naire was completed by only 59 % of those in the mail-out intervention group compared with 71 % of the GP group and 77 % of the control group . Younger participants , cigarette smokers and children ( compared with siblings ) were less likely to return a follow-up question naire . The mail-out group showed a statistically significant 20 % reduction in self-reported dietary fat intake , but this was not seen in either the GP group or the controls . The low response rate meant the study had insufficient power to detect hypothesised changes in blood cholesterol . CONCLUSION Because of the poor response rate and possible biases from a differential response to follow-up , we conclude that this low intensity intervention for relatives of people with recent heart attack produces only a modest improvement in reported dietary fat intake . Alternative strategies may be more effective in reducing the risk of heart disease Despite evidence that dietary fat intake may influence breast cancer risk , there is little information about the effects of dietary fat on the human breast . We have studied the effects of dietary fat on the breast by examining the influence of dietary fat reduction on mammographic dysplasia ( nodular or sheetlike areas of radiological density ) . Subjects with mammographic dysplasia were r and omly allocated to a control group , in which they received advice about maintaining a balanced diet ( 36 % of calories as fat ) , or an intervention group , in which they were taught to reduce dietary fat to a target of 15 % of calories . A total of 295 patients consented to r and omization , and after 1 year , 20 % of the intervention group and 5 % of the control group had dropped out ( failed to keep appointments and provide nutrient data ) . The remaining patients closely adhered to the dietary goals of the study as assessed by food records , chemical analysis of duplicate meals , and serum cholesterol measurements . Comparison of mammograms before and after 1 year of dietary fat reduction shows no significant influence on the extent or density of mammographic dysplasia . Surgical biopsies performed in subjects after entry in the study showed five cancers in the control group and two cancers in the intervention group ; this total of seven cancers is four times the number expected . These data show that clinical trials of the effects of dietary fat reduction on breast cancer risk are feasible and that long-term compliance with a low-fat diet can be achieved , and they confirm that the patients selected because they had mammographic dysplasia had increased risk of breast cancer OBJECTIVE To evaluate the effectiveness of a training program for physician-delivered nutrition counseling , alone and in combination with an office-support program , on dietary fat intake , weight , and blood low-density lipoprotein cholesterol levels in patients with hyperlipidemia . PARTICIPANTS AND METHODS Forty-five primary care internists at the Fallon Community Health Plan , a central Massachusetts health maintenance organization , were r and omized by site into 3 groups : ( 1 ) usual care ; ( 2 ) physician nutrition counseling training ; and ( 3 ) physician nutrition counseling training plus an office-support program . Eleven hundred sixty-two of their patients with blood total cholesterol levels in the highest 25th percentile , having previously scheduled physician visits , were recruited . Physicians in groups 2 and 3 attended a 3-hour training program on the use of brief patient-centered interactive counseling and the use of an office-support program that included in-office prompts , algorithms , and simple dietary assessment tools . Primary outcome measures included change at 1-year of follow-up in percentage of energy intake from saturated fat ; weight ; and blood low-density lipoprotein cholesterol levels . RESULTS Improvement was seen in all 3 primary outcome measures , but was limited to patients in group 3 . Compared with group 1 , patients in group 3 had average reductions of 1.1 percentage points in percent of energy from saturated fat ( a 10.3 % decrease ) ( P = .01 ) ; a reduction in weight of 2.3 kg ( P<.001 ) ; and a decrease of 0.10 mmol/L ( 3.8 mg/dL ) in low-density lipoprotein cholesterol level ( P = .10 ) . Average time for the initial counseling intervention in group 3 was 8.2 minutes , 5.5 minutes more than in the control group . CONCLUSION Brief supported physician nutrition counseling can produce beneficial changes in diet , weight , and blood lipids The effect of an ordinary lipid-lowering diet on serum insulin response to oral glucose load was investigated in a r and omized , primary preventive trial of the Oslo Study of coronary heart disease in healthy high risk middle aged men . After 3 years intervention the treated group showed a significantly lower insulin response curve , a lower serum total cholesterol , a higher cholesterol ratio ( defined as the ratio between high density lipoprotein cholesterol and low density + very low density lipoprotein cholesterol ) , lower fasting triglycerides and lower relative body weight than the control group . Increased levels of serum insulin and elevated insulin response to oral glucose load has been shown in earlier studies to be associated with increased susceptibility for atherosclerotic diseases . Therefore , it might be of importance , that lipid-lowering diet induce a lowering of serum insulin response in healthy , coronary prone men . As a contrast to the two high risk groups , the very low response curve of serum insulin and glucose in a group of coronary low risk men is also presented , and it is suggested that serum insulin levels should be added to the coronary prone syndrome of hyperlipidemia , obesity and physical inactivity We studied separately the effects of weight-loss by dieting or by running on apolipoprotein ( apo ) A-I , apo A-II , and high-density lipoprotein ( HDL ) subfractions in sedentary , moderately overweight men assigned at r and om into three groups : exercise without calorie restriction , calorie restriction without exercise , and control . The absorbance of protein-stained polyacrylamide gradient gels was used as an index of mass concentrations for five HDL subclasses that have been identified by their particle sizes : HDL3c ( 7.2 to 7.8 nm ) , HDL3b ( 7.8 to 8.2 nm ) , HDL3a ( 8.2 to 8.8 nm ) , HDL2a ( 8.8 to 9.7 nm ) , and HDL2b ( 9.7 to 12.9 nm ) . During the 1-year trial , the exercisers ran ( mean + /- SD ) 15.6 + /- 9.1 km/wk , and the dieters reported eating 340 + /- 71 fewer calories per day than at baseline . Total body weight and fat weight were both reduced significantly more in dieters ( -7.2 + /- 4.1 and -6.2 + /- 4.1 kg , respectively ) and in exercisers ( -4.0 + /- 3.9 and -4.6 + /- 3.5 kg ) than in controls ( 0.6 + /- 3.7 and -0.7 + /- 2.7 kg ) . As compared with mean changes in controls , exercisers and dieters each decreased HDL3b and increased HDL2b . Exercisers also significantly increased plasma apo A-I concentrations . Analysis of covariance was used to statistically adjust the mean lipoprotein changes for the effects of weight-loss . The adjustment eliminated the significant reductions in HDL3b and the significant increases in HDL2b in exercisers and dieters , and it eliminated the significant increase in apo A-I in exercisers . When adjusted , the dieters ' mean changes in HDL2b had significantly decreased relative to those of both exercisers and controls . ( ABSTRACT TRUNCATED AT 250 WORDS BACKGROUND This article describes the design and baseline findings of The Next Step Trial , a health promotion intervention targeting automobile industry employees at increased colorectal cancer risk . The intervention encouraged colorectal cancer screening participation and adoption of low-fat , high-fiber diets . METHODS Twenty-eight worksites ( n = 5,042 ) were r and omized to control ( a company-sponsored screening program ) or intervention ( an enhanced screening program including a personalized educational booklet and motivational telephone call and diet-change program including nutrition classes , self-help material s , and computer-generated personalized feedback ) . Outcomes included screening compliance and fat and fiber intake . RESULTS Pretrial data indicated targeted employees were predominantly older , well educated , married , Caucasian men . Sixty-one percent ( SE = 2 ) participated in the screening program in the preceding 2 years , and 24 % ( SE = 1 ) reported a history of colorectal polyps or cancer . Fifty-eight percent of the cohort responded to the baseline question naire ; respondents were older and more educated ; more were married , retired , and Caucasian than nonrespondents . Mean dietary intakes were 36.9 % energy from fat ( SE = 0.21 ) , 8.8 g fiber/1000 kcal ( SE = 0.07 ) , and 3.4 servings of fruits and vegetables per day ( SE = 0.04 ) . CONCLUSIONS Baseline data show moderate screening participation and dietary intakes that did not meet guidelines ; hence intervention efforts were warranted . Data from this trial will support a rigorous test of whether this high-risk employee population is responsive to targeted health promotion , early cancer detection , and prevention interventions The Women ’s Health Initiative ( WHI ) Clinical Trial ( CT ) includes three overlapping components , each a r and omized controlled comparison among women who were postmenopausal and 50 to 79 years of age at r and omization . The dietary modification ( DM ) component r and omly assigned 48,836 ( target 48,000 ) eligible women to either a sustained low-fat eating pattern ( 40 % ) or self-selected dietary behavior ( 60 % ) , with breast cancer and colorectal cancer as design ated primary outcomes and coronary heart disease as a secondary outcome . The nutrition goals for women assigned to the DM intervention group have been to reduce total dietary fat to 20 % , and saturated fat to less than 7 % of daily calories and , secondarily , to increase daily servings of vegetables and fruits to at least five and of grain products to at least six and to maintain these changes throughout trial follow-up . The r and omization of 40 % , rather than 50 % , of participating women to the DM intervention group was intended to reduce trial costs , while testing trial hypotheses with specified power . The postmenopausal hormone therapy ( PHT ) component comprises two r and omized , double-blind trials among 27,347 ( target 27,500 ) women , with coronary heart Hypercholesterolemic women ( n = 19 ) sequentially maintained on a long-term saturated ( SAT ) or a polyunsaturated ( PUFA ) fatty acid-rich diet , respectively , were studied in the fasting state and after a meal rich in SAT or PUFA . When apo B-containing lipoprotein was excluded from plasma the in vitro HDL-14C-cholesterol esterification rate was identical for the saturated ( SAT ) and polyunsaturated ( PUFA ) fatty acid diets , and did not increase during the postpr and ial period . Rates of transfer of 14C-cholesteryl ester to apo B-containing lipoproteins from HDL were also similar for both diets in the fasting state and increased to the same extent in the postpr and ial period in parallel with the rise in plasma triglycerides . When transfer data were related to the plasma concentration of apo B , the gain of cholesteryl ester by the triglyceride-containing particles ( VLDL + LDL ) also increased in the postpr and ial period to a similar extent for both diets . Cholesteryl ester transfer protein ( CETP ) concentration measured by radioimmunoassay was similar during both experimental diets , although greater in the postpr and ial period for the PUFA diet . The rate limiting factor for CETP-mediated transfer of HDL-derived cholesteryl ester ( CE ) was the plasma triglyceride concentration , that is , the content of triglycerides per lipoprotein particle and the quantity of TG-containing particles ( VLDL + LDL ) . In contrast , the fatty acid composition of these particles had less effect on CETP-mediated CE transfer Dietary intervention is recognized as a key component in prevention and management of type 2 diabetes ( T2DM ) and the debate persists : which dietary strategy is most effective . In the Dietary Intervention R and omized Controlled Trial ( DIRECT ) 322 moderately obese participants were r and omized for 2 years to one of three diet groups : low-fat , Mediterranean and low-carbohydrate . Differential effects were observed in the sub-group of patients with T2DM at 24 months : participants r and omized to the Mediterranean diet , which had the highest intake of dietary fibers and unsaturated to saturated fat ratio , achieved greater significant improvements in fasting plasma glucose and insulin levels . Patients who were r and omized to the low-carbohydrate diet , which had the minimal intake of carbohydrates , achieved a significant reduction of hemoglobin A1C . Although improvements were observed in all groups , the low-fat diet was likely to be less beneficial in terms of glycemic control and lipid metabolism . Interpretation of results from different studies on dietary strategies may be complex since there is often no consistency in diet compositions , calorie restriction , intensity of intervention , dietary assessment or extent of adherence in the trial . Nevertheless , it seems that low fat restricted calorie diets are effective for weight loss and are associated with some metabolic benefits ; however , some recent trials have shown that low carbohydrate diets are as efficient in inducing weight loss and in some metabolic measures such as serum triglycerides and HDL-cholesterol may be even superior to low fat diets . When addressing the issue of diet quality rather than quantity applying the glycemic index may have some added benefits . Furthermore special features of the Mediterranean diet have apparent additional favorable effects for patients with T2DM Type 2 diabetes is associated with impaired episodic memory functions and increased risk of different dementing disorders . Diet and exercise may potentially reverse these impairments . In this study , sedentary individuals with type 2 diabetes treated by lifestyle ± metformin were r and omized to a Paleolithic diet ( PD , n = 12 ) with and without high intensity exercise ( PDEX , n = 12 ) for 12 weeks . Episodic memory function , associated functional brain responses and hippocampal gray matter volume was measured by magnetic resonance imaging . A matched , but not r and omized , non-interventional group was included as a reference ( n = 6 ) . The PD included a high intake of unsaturated fatty acids and protein , and excluded the intake of dairy products , grains , refined sugar and salt . The exercise intervention consisted of 180 min of supervised aerobic and resistance exercise per week . Both interventions induced a significant weight loss , improved insulin sensitivity and increased peak oxygen uptake without any significant group differences . Furthermore , both interventions were associated with increased functional brain responses within the right anterior hippocampus , right inferior occipital gyrus and increased volume of the right posterior hippocampus . There were no changes in memory performance . We conclude that life-style modification may improve neuronal plasticity in brain areas linked to cognitive function in type 2 diabetes . Putative long-term effects on cognitive functions including decreased risk of dementing disorders await further studies . Clinical trials registration number : Clinical trials . gov NCT01513798 OBJECTIVES To study the effects of advice on diet , exercise and their combination on oral glucose tolerance ( OGTT ) , insulin secretion , insulin-like growth factor-1 ( IGF-1 ) and its binding protein , IGFBP-1 . DESIGN A 6-month , r and omized , controlled intervention study . SETTING Primary health care centres in Sollentuna , Stockholm and the Department of Medicine , Karolinska Hospital , Stockholm , Sweden . SUBJECTS One hundred and fifty-seven normoglycaemic healthy men , mean age 46 years , range 35 - 60 years , with slightly to moderately raised cardiovascular risk factors . INTERVENTIONS Advice on diet ( D , n = 40 ) , exercise ( E , n = 39 ) a combination of both ( DE , n = 39 ) and a control group ( C , n = 39 ) . MAIN OUTCOME MEASURES An OGTT , insulin secretion , IGF-1 and its binding protein , IGFBP-1 . RESULTS The number of pathological OGTTs in the intervention groups decreased from 42/118 to 33/118 whilst the number in the control group did not change . Fasting insulin levels decreased in groups E and DE from 8.8 - 7.4 mU L-1 ( P < 0.01 ) and from 8.3 - 6.7 mU L-1 ( P < 0.01 ) , respectively . Accordingly , the insulin area under the curve decreased from 5278 to 4828 ( P < 0.05 ) in group E , and from 5482 to 4809 ( P < 0.01 ) in group DE . IGF-1 only increased in group D. The most prominent changes were noted for IGFBP-1 , which increased in all three intervention groups and to the highest degree in group DE ( from 33.7 - 42.6 micrograms L-1 , P < 0.001 ) . CONCLUSIONS A combination of increased exercise and improved diet , as well as increased exercise alone , favourably affect glucose and insulin homeostasis in middle-aged men with moderately elevated cardiovascular risk factors . The most marked changes were noted for IGFBP-1 , possibly suggesting a decreased insulin secretion and an enhanced insulin sensitivity We evaluated dietary counselling by dietitians in hypercholesterolaemic hypertensives over 6 months . A total of 141 patients were r and omly assigned to intensive advice or usual care . Body weight fell significantly in the intervention group , but did not in the controls . There was a modest but significant fall in total cholesterol from 7.1 to 6.8 and 7.1 to 6.9 mmol/l in the diet and the control groups , respectively ( 4 and 3 % ) . A similar pattern emerged from the triglyceride measurements . Low-density lipoprotein fell in both groups , but only achieved significance ( P less than 0.05 ) in the intervention group . High-density lipoprotein did not change . There was a more marked change in cholesterol when serum levels during the study were compared with the previous annual review . These falls occurred after selection for the study but before r and om allocation to groups . They are unlikely to reflect regression to the mean as the lipids were stable for 2 or more years before the study , but may reflect spontaneous changes in diet after the patients were labelled hypercholesterolaemic . Dietary advice can lower total cholesterol but the magnitude of this decrease is small . Additional approaches are likely to be required to reduce plasma cholesterol to a normal range OBJECTIVE To assess the cost of adopting a plant-based diet . METHODS Breast cancer survivors r and omized to dietary intervention ( n=1109 ) or comparison ( n=1145 ) group ; baseline and 12-month data on diet and grocery costs . RESULTS At baseline , both groups reported similar food costs and dietary intake . At 12 months , only the intervention group changed their diet ( vegetable-fruit : 6.3 to 8.9 serv/d . ; fiber : 21.6 to 29.8 g/d ; fat : 28.2 to 22.3 % of E ) . The intervention change was associated with a significant increase of $ 1.22/ person/week ( multivariate model , P=0.027 ) . CONCLUSIONS A major change to a plant-based diet was associated with a minimal increase in grocery costs 1 . Diets containing 45 % joules as fat , 45 % joules as carbohydrate and 10 % joules as calcium caseinate were given for 5 days to ten men and seven women . The fats used were sunflower seed oil or cream , and the carbohydrates were either glucose and fructose , glucose and raw starch or fructose and raw starch . 2 . Sunflower seed oil in the diet result ed , after 5 days , in a significant fall in the concentration of triglyceride , cholesterol and phospholipid in the serum taken from subjects fasted for 12 h irrespective of the carbohydrate mixture of the diet . 3 . Although there were changes in serum lipid concentrations in relation to the different mixtures of carbohydrate they were much less than those seen after ingesting sunflower seed oil . 4 . Men and women differed in their response to carbohydrates , but this distinction was not seen in response to dietary fats OBJECTIVES To test the feasibility and effectiveness of a diet intervention ( consisting of interactive mailings , computer-generated phone calls , and classes ) in hypercholesterolemic low-income public clinic patients . METHODS Clinic patients with serum cholesterol > 200 mg/dl , referred by their primary care physician were r and omized to a 6-month special intervention ( SI ) or usual care ( UC ) . The intervention included mailings , computer phone calls , and four 1-hour classes . Serum total cholesterol ( TC ) was measured before and after intervention , and participation was monitored . RESULTS One hundred sixty-five of the 212 patients referred ( 77.8 % ) agreed to participate . A medical records review revealed 123 ( 74.5 % ) met eligibility criteria . Eligible subjects had a mean age of 56.7 years , 80.0 % were African American , 74.8 % were female , 33.6 % were married , and 89.4 % had a high school or lower education . Subjects were r and omized with 80.5 % ( 99 ) completing follow-up cholesterol measures . SI subjects were encouraged to use all three components , with 84.6 % ( 55 of 65 ) actively participating in at least one component . Seventy-two percent ( 47 of 65 ) returned at least one mailing , 49.1 % ( 28 of 57 ) of those with touch-tone phones accessed the computer system , and 43.1 % ( 28 of 65 ) attended classes . The TC in SI decreased from 273.2 mg/dl to 265.0 mg/dl ( P = 0.05 ) and in UC 272.4 mg/dl to 267.6 mg/dl ( P = 0.32 ) . The net reduction in SI compared with UC was 3.4 mg/dl ( P = 0.58 ) . CONCLUSIONS ( 1 ) Low-income public clinic patients will participate in diet interventions , ( 2 ) computer-generated interactive phone calls are feasible in this population , and ( 3 ) clinical ly meaningful decreases in serum cholesterol are difficult to achieve with interventions of practical intensity BACKGROUND Many rural residents do not have access to high- quality nutrition counseling for high blood cholesterol . The objective of this study was to assess the effectiveness of an intervention program design ed to facilitate dietary counseling for hypercholesterolemia by rural public health nurses . METHODS Eight health departments ( 216 participants ) were r and omized to give the special intervention ( SI ) and nine ( 252 participants ) to give the minimal intervention ( MI ) . The SI consisted of three individual diet counseling sessions given by a public health nurse , using a structured dietary intervention ( Food for Heart Program ) , referral to a nutritionist if lipid goals were not achieved at 3-month follow-up , and a reinforcement phone call and newsletters . Diet was assessed by the Dietary Risk Assessment ( DRA ) , a vali date d food frequency question naire , at baseline , 3- , and 12-month follow-up ; blood lipids and weight were assessed at baseline , 3- , 6- , and 12-month follow-up . RESULTS Participants were largely female ( 71 % ) , older ( mean age 55 ) , and white ( 80 % ) . At 3-month follow-up , the average reduction ( indicating dietary improvement ) in total Dietary Risk Assessment score was 3.7 units greater in the SI group ( 95 % confidence interval [ CI ] 1.9 to 5.5 , P = 0.0006 ) , while both groups experienced a similar reduction in blood cholesterol , 14.1 mg/dL ( 0.37 mmol/L ) for SI and 14.5 mg/dL ( 0.38 mmol/L ) for minimal intervention group ( difference -0.4 mg/dL [ -0.010 mmol/L ] , 95 % CI -12.5 to 11.7 [ -0.32 to 0.30 ] , P = 0.9 ) . At 12-month follow-up , the reduction in total Dietary Risk Assessment score was 2.1 units greater in the SI group ( 95 % CI 0.8 to 3.5 , P = 0.005 ) , while the reduction in blood cholesterol was similar in both groups , 18.4 mg/dL ( 0.48 mmol/L ) for SI and 15.6 mg/dL ( 0.40 mmol/L ) for minimal intervention group ( difference 2.8 mg/dL [ 0.07 mmol/L ] , 95 % CI -7.5 to 13.1 [ -0.19 to 0.34 ] , P = 0.6 ) . During follow-up , weight loss was greater in the SI group ; the difference between groups was statistically significant at 3 ( 1.9 lb [ 0.86 kg ] , 95 % CI 0.3 to 3.4 [ 0.14 to 1.55 ] , P = 0.022 ) and 6 months ( 2.1 lb [ 0.95 kg ] , 95 % CI 0.1 to 4.1 [ 0.04 to 1.86 ] , P = 0.04 ) . At 12 months , the difference was not significant ( 1.6 lb [ 0.73 kg ] , 95 % CI -0.05 to 3.7 [ -0.02 to 1.68 ] , P = 0.13 ) . CONCLUSIONS Improvement in self-reported dietary intake was significantly greater in the SI group , while reduction in blood cholesterol was similar in both groups A dietary intervention trial has shown a significant reduction in occurrence of actinic keratosis and nonmelanoma skin cancer in skin cancer patients who adopt diets in which the percentage of calories from fat is markedly lowered . The purpose of this study was to examine the dietary parameters of a low-fat diet found to be effective in reducing occurrence of skin cancer . Skin cancer patients were taught fat reduction strategies to complement their individual food preferences and life-styles . Diet composition was calculated using st and ard dietary assessment and nutrient analysis techniques . The dietary intervention was effective in reducing the percentage of calories from fat to 21 % by Month 4 and maintaining that level for the remainder of the two-year study . Practical dietary advice with respect to reduction of percentage of calories from fat , along with an increase in the intake of grains , fruits , and vegetables , could make an important contribution to the management and prevention of skin cancer Background and Objectives : A major limitation of dietary trials is that double blind design is not feasible . These trials are therefore prone to biases . The Lyon diet heart study is a single-blind secondary prevention trial to test the hypothesis that a Mediterranean-type of diet may prevent recurrences after a first myocardial infa rct ion . A surprising 73 % reduction of the risk of new major cardiac events was observed in the experimental group . For this reason , it is important to describe the methods used in the trial . We now report our techniques to r and omize the patients , to change their diet and to control for possible bias , in particular any investigator or attending physician bias . Design : In this dietary trial , a specific design was used to recruit and r and omize the patients without informing them and their physicians that they were participating in a comparative trial . The attending physician bias was evaluated by study ing drug usage and the investigator bias by constructing a question naire from which specific scores were used to evaluate ( 1 ) how the patients appreciated their participation in the study and ( 2 ) whether this participation result ed in significant changes in their way of living . Subjects : 605 survivors of a first myocardial infa rct ion were r and omized into either a control or a Mediterranean group . Results : The two r and omized groups were similar for all the variables of prognosis . Drug usage was not significantly different between groups , suggesting that there was no major attending physician bias . Analyses of the appreciation scores and of the change score did not detect any significant investigator bias . Conclusions : Although the study can not be completely shielded from minor biases , the data presented here provide evidence that the dietary modifications per se were protective , not other ( including psychosocial ) changes result ing from the participation to the trial A r and omized controlled trial has been set up to examine the effect of diet on the secondary prevention of myocardial infa rct ion , involving 2033 men . The trial has a factorial design , subjects being r and omized independently to receive advice or no advice regarding three dietary factors : 1 . a reduction in total fat and an increase in polyunsaturated fat intake ; 2 . an increase in fatty fish intake ; 3 . an increase in cereal fibre intake . Nearly half the men under 70 years of age who survived myocardial infa rct ion during the recruitment period entered the trial , the commonest reason for exclusion being that the subject was already eating ( or intended to eat ) a diet which included one or more of the regimens being investigated . Detailed dietary question naires were completed by each subject after 6 months in the trial . The results suggest that compliance with the advice is reasonably good . The differences between the diets of the groups given and not given advice on fish and fibre were substantial ; the difference attributable to advice on fat has been somewhat less than anticipated , partly because of failure to comply with advice and partly because of spontaneous changes in the diets of control subjects Dietary patterns that involve a decrease in fat and an increase in fruit and vegetable ( FV ) intake have been suggested to decrease cancer risks . In this study , intervention methods to selectively modify dietary fat and /or FV intakes were developed . Compliance to the diets and the effects on body weight are shown , because both of these dietary changes can impact on and be confounded by changes in energy intake . A total of 122 women with a family history of breast cancer were r and omized onto one of four diets for 12 mo . Counseling methods were devised to increase amount and variety of FV consumed with or without a decrease in fat intake using modified exchange list diets . Women on the low-fat and combination low-fat/high-FV diet arms decreased their fat intakes to ~16 % of energy . Women on the high-FV and the combination low-fat/high-FV diet arms increased FV intakes to ~11 servings/day . Despite counseling efforts to maintain baseline energy intakes , mean body weight increased significantly by 6 pounds in women in the high-FV diet arm and decreased significantly by 5 pounds in women in the low-fat diet arm . Percent body fat also was increased in the high-FV diet arm and decreased in the low-fat diet arm . Body weight and percent body fat in the combination diet arm did not change significantly . Control of energy intake , therefore , appears to have been achieved only when the addition of FV to the diet was balanced by a decrease in fat intake and both dietary components were enumerated daily . Maintenance of energy intake , therefore , did not appear to be attained intrinsically when individuals were counseled to make changes in the composition of their diets BACKGROUND AND AIM Plant foods may lower the risk of cardiovascular disease . METHODS AND RESULTS We assessed changes in the intima media thickness ( IMT ) of the carotid artery and diet in elderly men . Men ( n=563 ) aged 70+/-5 years were r and omly assigned to 1 of 4 groups ( dietary intervention , omega-3 supplementation , both or neither ) using a 2 x 2 factorial design . B-mode ultrasound of the carotid arteries and calculation of dietary intake were performed at baseline and after 3 years . We previously showed that omega-3 supplementation did not influence the IMT , thus the dietary intervention ( n=233 ) and no dietary intervention ( n=231 ) groups were pooled . The dietary intervention group had less progression in the carotid IMT compared with the controls ( 0.044+/-0.091 mm versus 0.062+/-0.105 mm ; P=0.047 ) . This group increased their daily vitamin C intake ( P=0.005 ) and intake of fruit , berries and vegetables ( P < or=0.001 ) . Increased intake of vitamin C and of fruit and berries was inversely associated with IMT progression ( r=-0.181 ; P=0.006 and r=-0.125 ; P=0.056 , respectively ) . Multivariate linear regression analysis showed that increased intakes of vitamin C and of fruit and berries were associated with less IMT progression in the intervention group and in the total study population , after adjustment for consumption of dietary cholesterol , cheese , saturated fat and group assignment . CONCLUSION Vitamin C containing foods may protect against the progression of carotid atherosclerosis in elderly men BACKGROUND The intake of olive oil has been related to the prevention of osteoporosis in experimental and in in vitro models . Very few prospect i ve studies have evaluated the effects of olive oil intake on circulating osteocalcin ( OC ) in humans . OBJECTIVE The objective of the study was to examine the longitudinal effects of a low-fat control diet ( n=34 ) , a Mediterranean diet enriched with nuts ( MedDiet+nuts , n=51 ) , or a Mediterranean diet enriched with virgin olive oil ( MedDiet+VOO , n=42 ) on circulating forms of OC and bone formation markers in elderly men at high cardiovascular risk . DESIGN Longitudinal associations between baseline and follow-up ( 2 yr ) measurements of total OC , undercarboxylated osteocalcin , C-telopeptide of type I collagen , and procollagen I N-terminal propeptide ( P1NP ) concentrations were examined in 127 elderly men r and omized to three healthy dietary interventions . RESULTS Baseline characteristics ( age , body mass index , waist circumference , lipid profile , fasting insulin levels , and bone formation and resorption markers ) were similar in all intervention groups . The total osteocalcin concentration increased robustly in the MedDiet+VOO group ( P=0.007 ) in parallel to increased P1NP levels ( P=0.01 ) and homeostasis model assessment -β-cell function ( P=0.01 ) but not in subjects on the MedDiet+nuts ( P=0.32 ) or after the control diet ( P=0.74 ) . Interestingly , the consumption of olives was associated positively with both baseline total osteocalcin ( r=0.23 , P=0.02 ) and the 2-yr osteocalcin concentrations ( r=0.21 , P=0.04 ) in the total cohort . CONCLUSIONS Consumption of a Mediterranean diet enriched with virgin olive oil for 2 years is associated with increased serum osteocalcin and P1NP concentrations , suggesting protective effects on bone The Women 's Health Trial Vanguard Study was conducted to examine the feasibility of a nationwide , r and omized multicenter intervention trial to test the hypothesis that a low-fat diet followed for a period of 10 years will reduce breast cancer risk . Women ages 45 - 69 years at increased risk of breast cancer were r and omized into intervention ( low-fat diet , n = 184 ) and control ( usual diet , n = 119 ) groups . On the basis of 4-day food records , baseline fat intakes were comparable in the two groups , averaging 1,718 kcal with 39 % of energy as fat . Intervention women reported substantially lower fat intake at 6 ( 20.9 % kcal ) , 12 ( 21.6 % ) , and 24 months ( 22.6 % kcal ) . In contrast , control women reported only slight reductions in fat intake ( 37.3 % kcal at 12 months and 36.8 % kcal at 24 months ) . Evidence that these women were indeed complying with the low-fat dietary intervention comes from ( a ) the reasonable nature of reported nutrient changes within food groups in the intervention women and ( b ) agreement between observed and expected differences in plasma total cholesterol between the control and the intervention groups . At 12 months , the observed control - intervention plasma cholesterol difference was 13.1 + /- 4.6 mg/dl while the expected difference based on the Keys equation was 15.1 + /- 1.1 mg/dl ; at 24 months , the observed difference was 15.5 + /- 4.3 mg/dl and the expected difference was 12.0 + /- 1.2 mg/dl . These analyses indicate that the intervention women made substantial dietary changes and have successfully maintained these changes over a 2-year period . This study thus demonstrates the feasibility of a r and omized trial with an intensive low-fat dietary intervention OBJECTIVE To examine whether the effects of physical and emotional status on adherance to a low-fat ( 20 % energy ) dietary pattern are mediated by participation in an intervention program ( attending sessions and self-monitoring ) . DESIGN The Baron and Kenny mediator model , a series of 4 regression analyses , was used to evaluate whether : a ) physical and emotional status predicted program participation , b ) program participation predicted dietary adherence , c ) physical and emotional status factors predicted dietary adherence , and , ultimately d ) the effects of physical and emotional status on dietary adherence were mediated by program participation . SUBJECTS/ SETTING Data from 13,277 postmenopausal women r and omly assigned to the low-fat intervention arm of the Women 's Health Initiative Dietary Modification Trial . INTERVENTION The nutrition goals for women r and omly assigned to the low-fat intervention were to reduce total fat intake to 20 % or less of energy from fat and to consume 5 or more fruit/vegetable servings daily and 6 or more grain servings daily . MAIN OUTCOME MEASURES Year 1 program participation ( degree of attending group sessions and su bmi tting fat scores ) and adherence to the low-fat dietary pattern ( percent energy from fat ) as predicted by baseline physical and emotional status ( eight SF-36 Health Survey subscales ) . RESULTS Participating in the dietary intervention program reduced ( mediated ) the negative effect of poorer mental health on dietary adherence by 15 % . Additional findings included that a 10 % increase in physical functioning increased session attendance by 0.4 % ( P<.001 ) and a 10 % increase in mental health predicted a decrease in percent energy from fat of 0.3 % ( P<.001 ) . Program participation had a marked effect on dietary adherence : a 10 % increase in session attendance predicted a 1.2 % decrease in percent energy from fat ( P<.001 ) . APPLICATIONS/ CONCLUSIONS Underst and ing and using instruments to assess the physical and emotional status of a target population will help dietetic professionals promote healthful dietary change and maintenance We analyzed serum total cholesterol , triglycerides , and lipoprotein profile changes occurring in the participants ( N = 121 ) through 210 weeks of the study . On average , baseline lipid levels were within normal limits . The most consistent changes occurred in the high‐density lipoprotein cholesterol ( HDL‐C ) , serum total cholesterol/HDL‐C ratios , and triglyceride levels . HDL‐C increased significantly ( p < 0.01 ) , compared with baseline , by 10 % at week 34 , 15 % at week 54 , 19 % at week 104 , and 27 % at week 139 . At week 210 , 20 weeks after treatment had ended , HDL‐C was 15 % higher than baseline . At weeks 34 , 54 , 104 , and 139 , the serum total cholesterol/HDL‐C ratio was significantly decreased , compared with baseline , by 9 % , 19 % , 17 % , and 25 % , respectively . At week 210 , serum total cholesterol/HDL‐C ratio was 8 % less than week 0 . Compared with baseline , triglyceride levels decreased significantly by 21 % , 31 % , 29 % , and 29 % at weeks 34 , 54 , 104 , and 139 , respectively . At week 210 , triglyceride levels were 16 % below baseline . Total cholesterol levels and low‐density lipoprotein cholesterol ( LDL‐C ) showed less dramatic changes . Patterns of lipid and lipoprotein changes were qualitatively similar between men and women . However , greater decreases in serum total cholesterol , LDL‐C , and triglyceride levels were observed in participants with high ( n = 10 ) compared with low ( n = 10 ) baseline lipid levels . Cholesterol changes were not affected by anorexiant medications . However , triglyceride levels at week 34 were significantly ( p < 0.025 ) less in the participants treated with anorexiants . Overall , participants in the long‐term weight control study had beneficial changes in their lipid profiles , thus decreasing their risk of coronary heart disease We report the effect of weight changes of the type of antihypertensive medication prescribed in a trial of the relative efficacy of drug and dietary measures in mild hypertension . The Trial of Antihypertensive Interventions and Management studied 878 mildly hypertensive individuals r and omly assigned , in a 3 x 3 design , to no diet change , weight loss , or a low sodium-high potassium diet and to placebo , 25 mg chlorthalidone , or 50 mg atenolol . The type of drug prescribed affected weight change with all diets . The drug effect on weight change , present in all groups at 6 months , was most pronounced in those r and omly assigned to the weight loss diet , where the placebo group lost 4.4 kg , the atenolol group lost 3.0 kg , and the chlorthalidone group lost 6.9 kg . The group differences were attenuated but persisted at 24 months . We suggest that the antihypertensive drug prescribed affects the success of a conjoint weight loss program and speculate that the difference between the drugs may be due to their intrinsic effects on the sympathetic nervous system and related metabolic changes Introduction : The aim of this study was to analyze the effects of the rs9939609 ( T/A ) gene variant in fat mass and obesity-associated gene ( FTO ) on body weight changes after 3 years and its modification by a r and omized nutritional intervention with a Mediterranean-style diet in a population of subjects at high cardiovascular risk . Design : A sub study of PREDIMED , which is a r and omized trial aim ed at assessing the effect of the Mediterranean diet ( MD ) for primary cardiovascular disease prevention . There were three nutritional intervention groups : two of them with a Mediterranean-style diet and the third was a control group advised to follow a conventional low-fat diet . Subjects : A total of 776 high cardiovascular risk subjects aged 55–80 years . Measurements : Anthropometric measurements were recorded at baseline and at 3 years . The participants were genotyped by RT-PCR , followed by allelic discrimination . Results : Homozygous subjects had the highest baseline body weight . The dominant model showed that subjects carrying the A allele had the lowest body weight gain ( B=−0.685 ; P=0.022 ) after 3 years of nutritional intervention compared with nonmutated subjects ( TT genotype ) regardless of the nutritional intervention . Moreover , this effect was statistically significant in carriers of the A allele only among those allocated to the MD groups ( B=−0.830 ; P=0.018 ) , but it was not significant among those allocated to the control group ( P for interaction=0.649 ) . Conclusion : This study confirmed the association between body weight and the FTO rs9939609 polymorphism . Interestingly , our results showed that , although at baseline the A allele was associated with higher body weight , after 3 years of nutritional intervention with a Mediterranean-style-diet , A-allele carriers had lower body weight gain than wild type subjects . No interaction between nutritional intervention and the polymorphism was found OBJECTIVE : We describe the design and baseline data of the Prevention Education Program ( PEP ) , a home-based and family oriented intervention program , aim ed to assess and improve cardiovascular risk factors in school children and their families during an intervention period of 10 y. DESIGN AND METHODS : At study entry all participants were r and omized either to an intervention group ( screening and intervention program ) or to a control group ( risk screening , general advice ) . Cardiovascular risk factors ( hypertension , elevated lipids , smoking , obesity ) as well as dietary behaviour are evaluated yearly using structured interview , physical examination , laboratory analysis , and seven-day dietary protocol . RESULTS : During the years 1993–1998 , 3547 adults ( age 36.2±7 y ) and 3495 children ( age 6.5±2 y ) were recruited . Adults show a high prevalence of risk factors : hypertension 21 % ; active smoking 39 % , elevated LDL-cholesterol 19 % ; and obesity 42 % . Children exhibit these risk factors in comparable frequency : hypertension 20 % ; passive smoking 44 % ; elevated LDL-cholesterol 17 % ; and obesity 19 % . The analysis of the dietary protocol s ( 1926 adults , 1569 children ) shows that both generations adhere to a diet exceeding the recommended fat intake ( adults 38 % of total energy , children 38 % ) , while carbohydrate intake ( adults 43 % of total energy intake , children 50 % ) is reduced compared to NCEP-(step I)- guidelines . CONCLUSION : The finding , that children show a prevalence of risk factors which is comparable to that found in adults , supports the need for an early beginning of intervention . Since both generations adhere to an unhealthy diet which contributes to cardiovascular risk , dietary intervention may be a promising method in primary prevention of cardiovascular risk Context Can changes in diet prevent diabetes in older adults ? Contribution This subgroup analysis of a multicenter trial involved older adults with high risk for heart disease who were r and omly assigned to a Mediterranean diet supplemented with either extra-virgin olive oil or mixed nuts or to a low-fat control diet . Neither energy restriction nor increased physical activity was advised . After 4 years of follow-up , fewer persons in the Mediterranean diet groups developed diabetes than in the control group . Implication Changes in dietary patterns that do not necessarily lead to weight loss or include energy restrictions could help prevent diabetes in some older adults . The Editors Type 2 diabetes mellitus represents a major health problem because worldwide prevalence has more than doubled in the past 3 decades , with nearly 347 million persons with diabetes in 2010 ( 1 ) , and is a potent risk factor for cardiovascular disease ( CVD ) , blindness , renal failure , and lower limb amputation ( 2 ) . Compelling evidence shows that diabetes can be prevented with lifestyle changes . Intensive lifestyle modification promoting weight loss through energy-restricted diets together with increased physical activity can decrease incident diabetes to as low as 50 % ( 3 ) . Indeed , lifestyle modification has performed better than pharmacologic approaches ( such as metformin or rosiglitazone ) in diabetes prevention ( 46 ) . Of interest , the benefit of lifestyle changes in decreasing diabetes risk seems to extend beyond the termination of active intervention ( 68 ) . However , there is little information on whether changes in the overall dietary pattern , without energy restriction , increased physical activity , and ensuing weight loss , may also be effective to prevent diabetes . Prospect i ve epidemiologic studies strongly suggest that dietary patterns characterized by high consumption of fruit , vegetables , whole grains , and fish and reduced consumption of red and processed meat , sugar-sweetened beverages , and starchy foods delay diabetes onset ( 9 ) . In the last 6 years , the traditional Mediterranean diet has emerged as a healthy dietary pattern that is also associated with a decreased risk for diabetes ( 1012 ) . The Mediterranean diet is moderately rich in fat ( 35 % to 40 % of energy ) , especially from vegetable sources ( rich in olive oil and nuts ) , and relatively low in dairy products . Moderate consumption of alcohol , mostly wine , and frequent use of sauces with tomato , onions , garlic , and spices for meal preparation are also typical . Preliminary data from the PREDIMED ( Prevencin con Dieta Mediterrnea ) study ( 1317 ) showed that traditional Mediterranean diets enriched with high-fat foods of vegetable origin decreased the incidence of diabetes ( 18 ) . However , that report studied participants only from 1 of the 11 PREDIMED recruiting centers . In this analysis , we provide the final results on diabetes incidence in the whole multicenter trial after a median follow-up of 4.1 years . Methods Design Overview The PREDIMED study is a parallel-group , r and omized , primary cardiovascular prevention trial done in Spain in persons at high risk but without CVD at baseline . The protocol , design , objectives , and methods have been reported in detail elsewhere ( 13 , 14 ) . Briefly , participants were r and omly assigned in a 1:1:1 ratio to 1 of 3 nutrition interventions : Mediterranean diet supplemented with extra-virgin olive oil ( EVOO ) , Mediterranean diet supplemented with mixed nuts , or a control diet consisting of advice to reduce intake of all types of fat . A complete list of PREDIMED study investigators is available in Supplement 1 . The local institutional review boards approved the protocol at each study location , and all participants provided written informed consent . Supplement . Original Version ( PDF ) Supplement 1 . List of Prevencin con Dieta Mediterrnea Study Investigators Setting and Participants Eligible participants were community-dwelling men ( aged 55 to 80 years ) and women ( aged 60 to 80 years ) without CVD at baseline who had either type 2 diabetes or at least 3 or more cardiovascular risk factors , namely current smoking , hypertension , hypercholesterolemia , low high-density lipoprotein cholesterol levels , overweight or obesity , and family history of premature CVD . Exclusion criteria have previously been reported ( 13 ) . R and omization and Intervention From October 2003 to June 2009 , 7447 suitable c and i date s were enrolled in the trial . The study nurse from each recruiting center r and omly assigned each participant to the corresponding intervention group following computer-generated r and om numbers for allocation contained in sealed envelopes , which were central ly prepared for each center by the coordinating unit . Four strata of r and omization were built by sex and age ( cutoff , 70 years ) but not by baseline diabetes status . The primary care physicians did not participate in the r and omization process . The study nurses were independent of the nursing staff of the primary care health centers . Therefore , they were not involved in the usual clinical care of participants , and their exclusive role was to collect data for the trial . Given the nature of the interventions ( nutritional advice and provision of foods ) , only investigators assessing outcomes were blinded with respect to intervention assignment . This was done by providing them with coded data sets and medical records blinded with respect to the personal identity of the participant and without any information on treatment allocation . Because our main objective was to determine the effect of the 3 interventions on diabetes incidence , this report includes data only on participants who did not have diabetes at baseline and for whom we could ascertain the incidence of diabetes during follow-up ( n= 3541 ) ( Figure 1 ) . Figure 1 . Study flow diagram . EVOO = extra-virgin olive oil ; MedDiet = Mediterranean diet . A behavioral intervention promoting the Mediterranean diet was implemented in the corresponding groups of the trial , as described ( 13 ) . Dietitians gave personalized advice to participants about the amount and use of EVOO for cooking and dressing ; weekly intake of nuts ; increased consumption of vegetables , fruits , legumes , and fish ; recommended intake of white meat instead of red or processed meat ; avoidance of butter , fast food , sweets , pastries , or sugar-sweetened beverages ; and the dressing of dishes with sofrito sauce ( using tomato , garlic , onion , and spices simmered in olive oil ) . Reduction of alcoholic beverages other than wine was advised to all participants . Wine with meals was recommended with moderation only to habitual drinkers . At baseline and quarterly thereafter , dietitians conducted individual and group dietary training sessions to provide information on typical Mediterranean foods , seasonal shopping lists , meal plans , and recipes for each group . In each session , a 14-item question naire was used to assess adherence to the Mediterranean diet ( 13 , 14 ) so that personalized advice could be provided to up grade participants adherence . The same question naire was assessed yearly in the control group . Participants assigned to the 2 Mediterranean diet groups received allotments of either EVOO ( 50 mL/d ) or mixed nuts ( 30 g/d : 15 g of walnuts , 7.5 g of almonds , and 7.5 g of hazelnuts ) at no cost . Participants assigned to the control diet received recommendations to reduce intake of all types of fat ( from both animal and vegetable sources ) and received nonfood gifts ( kitchenware , tableware , aprons , or shopping bags ) . Through October 2006 , participants in the control group received only a leaflet describing the low-fat diet . Thereafter , participants assigned to the control diet also received personalized advice and were invited to group sessions with the same frequency and intensity as those in the Mediterranean diet groups . A separate 9-item dietary question naire ( 14 ) was used to assess adherence to the low-fat diet . Neither energy restriction nor increased physical activity was advised for any intervention group . At baseline examination and yearly during follow-up , we administered a 137-item vali date d semiquantitative food-frequency question naire ( 19 ) ; the vali date d Spanish version of the Minnesota Leisure-time Physical Activity Question naire ( 20 ) ; and a 47-item question naire about education , lifestyle , medical history , and medication use . At baseline , trained personnel performed electrocardiography and anthropometric and blood pressure measurements . Blood pressure was measured in triplicate by using a vali date d semiautomatic oscillometer with a 5-minute interval between measurements and the participant in a sitting position ( Omron HEM-705CP , Omron , Hoofddorp , the Netherl and s ) . Fasting blood and spot urine were sample d at baseline and follow-up years 1 , 3 , 5 , and 7 . After an overnight fast , tubes for EDTA plasma , citrate plasma , and serum and urine sample s were collected and aliquots were coded and stored at 80C in the central laboratory until analysis . Serum glucose , cholesterol , and triglyceride levels were measured using st and ard enzymatic methods . High-density lipoprotein cholesterol was measured after precipitation with phosphotungstic acid and magnesium chloride . Biomarkers of adherence to the supplemental foods , including urine hydroxytyrosol levels and plasma -linolenic acid proportions , which are reliable biomarkers of EVOO and walnut intake , respectively , were measured in r and om sub sample s of participants during the first 5 years of follow-up ( by gas chromatographymass spectrometry and by gas chromatography , respectively ) . Laboratory technicians were blinded to intervention group . Outcomes and Follow-up Diabetes was a prespecified secondary outcome of the PREDIMED trial . IT was considered to be present at baseline by clinical diagnosis or use of antidiabetic medication . New-onset diabetes during follow-up was diagnosed using the American Diabetes Association criteria , namely fasting plasma glucose levels of 7.0 mmol/L or Associations between plasma lipoprotein subfractions and changes in coronary artery diseases ( CAD ) were examined in 74 men who completed the St. Thomas ' Atherosclerosis Regression Study ( STARS ) . Plasma lipoproteins were isolated by stepwise , preparative ultracentrifugation at repeated intervals during the 38-month trial . Paired coronary angiograms were quantitatively analyzed by a computerized method . In univariate linear regression analysis , changes in mean absolute width ( delta MAWS ) and minimum absolute with ( delta MinAWS ) of coronary segments were significantly correlated with in-trial concentrations of cholesterol in intermediate-density lipoprotein ( [ IDL ] d = 1.006 to 1.019 kg/L ) , low-density lipoprotein ( [ LDL2 ] d = 1.019 to 1.040 kg/L ; LDL3 , d = 1.040 to 1.063 kg/L ) , and high-density lipoprotein ( [ HDL3 ] d = 1.125 to 1.210 kg/L ) subfractions ; no significant associations were found with other lipoproteins . IDL , LDL3 , and HDL3 cholesterol were then selected for multiple linear regression analysis because these variables were not co-correlated and because they attained a significance of P less than or equal to .1 in univariate regression . In this analysis , only LDL3 cholesterol level was a significant negative predictor ( P < .05 ) of both delta MAWS and delta MinAWS ; a positive association between delta MinAWS and HDL3 cholesterol level just failed to reach conventional statistical significance ( P = .066 ) . Correlations between changes in coronary luminal dimensions and LDL3 cholesterol level were independent of age , smoking , weight , and blood pressure . Most patients showing regression of coronary atherosclerosis had an LDL3 cholesterol level of less than 1.8 mmol/L. The findings suggest that LDL3 is the plasma lipoprotein subfraction that exerts the single most powerful effect on the course of CAD in middle-aged men with hypercholesterolemia OBJECTIVES Apolipoprotein (Apo)B , ApoA-I , and their ratio could predict coronary heart disease ( CHD ) risk more accurately than conventional lipid measurements . Our aim was to assess the effect of a traditional Mediterranean diet ( TMD ) on apolipoproteins . METHODS High-cardiovascular risk subjects ( n=551 , 308 women and 243 men ) , aged 55 - 80 years , were recruited into a large , multicenter , r and omized , controlled , parallel-group , clinical trial ( The PREDIMED Study ) aim ed at testing the efficacy of TMD on primary cardiovascular disease prevention . Participants assigned to a low-fat diet ( control ) ( n=177 ) , or TMDs ( TMD+virgin olive oil ( VOO ) , n=181 or TMD+nuts , n=193 ) received nutritional education and either free VOO ( ad libitum ) or nuts ( dose : 30 g/day ) . A 3-month evaluation was performed . RESULTS Both TMDs promoted beneficial changes on classical cardiovascular risk factors . ApoA-I increased , and ApoB and ApoB/ApoA-I ratio decreased after TMD+VOO , the changes promoting a lower cardiometabolic risk . Changes in TMD+VOO versus low-fat diet were -2.9 mg/dL ( 95 % CI , -5.6 to -0.08 ) , 3.3mg/dL ( 95 % CI , 0.84 to 5.8 ) , and -0.03 mg/dL ( -0.05 to -0.01 ) for ApoB , ApoA-I , and ApoB/ApoA-I ratio , respectively . CONCLUSIONS Individuals at high-cardiovascular risk who improved their diet toward a TMD pattern rich in virgin olive oil , reduced their Apo B and ApoB/ApoA-I ratio and improved ApoA-I concentrations The Trial of Antihypertensives Interventions and Management ( T AIM ) was a multicenter double-blind placebo-controlled clinical trial of drug and diet combinations for the treatment of mild hypertension among 878 participants , ages 21 to 65 , 110 % to 160 % ideal weight , and with baseline diastolic blood pressure 90 to 100 mm Hg . The drugs used were placebo , chlorthalidone ( 25 mg/daily ) or atenolol ( 50 mg/daily ) . The diets studied were usual , weight loss , sodium reduction/potassium increase . Trial end points were 6-month diastolic blood pressure change , cardiovascular risk change , and quality of life change . Either drug combined with weight loss produced the greatest blood pressure reduction of 15 mm Hg , compared to 8 mm Hg on placebo/usual diet . Adding sodium restriction to either drug did not enhance blood pressure lowering effect . Drugs outperformed diet in terms of antihypertensive effect . However , those on placebo and assigned to weight reduction who lost more than 4.5 kg and those on sodium restriction who reduced sodium to less than 70 mEq daily lowered blood pressure to a similar extent as those on either of the two drugs alone . Cardiovascular risk at 6 months relative to baseline ranged from 0.85 in weight loss/atenolol subgroup to 1.04 in the usual diet/chlorthalidone subgroup . Blacks were more responsive to chlorthalidone plus weight loss and whites to atenolol plus weight loss . Quality of life , as measured by scales of distress and well-being , was favorably affected by weight reduction . Although there were few side effects of the drugs and most patients improved on most parameters , sexual complaints were worsened among those on chlorthalidone and usual diet compared to placebo . ( ABSTRACT TRUNCATED AT 250 WORDS Summary We conducted a 2-year prospect i ve r and omised study to investigate the effects of a linoleic-acid-enriched diet on albuminuria and lipid levels in Type 1 ( insulin-dependent ) diabetic patients with elevated urinary albumin excretion ( overnight urinary albumin excretion rate between 10 and 200 μg/min ) . Thirty-eight patients were r and omly assigned to increase dietary polyunsaturated : saturated fatty acids ratio to 1.0 by replacement of saturated fat with linoleic-acid-rich products ( n=18 , two dropouts , analysis was performed in n=16 ) or to continue their usual diet ( n=20 ) . The total fat and protein content of the diet was unaltered . Clinical characteristics , albuminuria , blood pressure , glomerular filtration rate , metabolic control and dietary composition were similar in the two groups at baseline . In the high linoleic acid diet group , linoleic intake rose from 7±4 to 11±2 energy % and polyunsaturated : saturated fatty acids ratio rose from 0.60±0.28 to 0.96±0.16 ( p<0.001 compared to usual diet group ) . The median increase albuminuria was 58 % ( 95 % confidence interval , 13 to 109 ) during the first year ( p<0.02 ) and 55 % ( 95 % confidence interval , 11 to 127 ) ( p<0.01 ) during the second year . Glomerular filtration rate remained unaltered and filtration fraction tended to rise ( p<0.05 compared to usual diet group ) . In the usual diet group , albuminuria did not significantly increase by 16 % ( 95 % confidence interval , -17 to 38 ) and glomerular filtration rate declined during the second year . Blood pressure tended to rise similarly in both groups . Multiple regression analysis showed an independent effect of the high linoleic acid diet on the progression of albuminuria as well as the lack of decrease in glomerular filtration rate . Low density lipoprotein cholesterol and apolipoprotein B levels decreased in the high linoleic acid diet group ( p<0.05 ) . High density lipoprotein cholesterol declined in both groups ( p<0.05 ) . It is concluded that a linoleic-acid-enriched diet reduces atherogenic lipoproteins but does not have a beneficial effect on and might even promote renal functional abnormalities in Type 1 diabetic patients with elevated urinary albumin excretion BACKGROUND AND AIM The Oslo Diet and Antismoking Study was a 5-year r and omised controlled trial initiated in 1972 - 1973 and ended in 1977 - 1978 , which showed that dietary change and smoking cessation reduced the incidence of coronary heart disease among high risk middle-aged men . In an extended follow-up we studied the incidence of myocardial infa rct ion ( MI ) 16 years after the end of the trial in the intervention and control groups . METHODS The primary endpoint was the first occurrence of non-fatal and fatal MI including sudden death up to December 31 1993 . Cases of fatal MI were identified by linkage to Statistics Norway using each subject 's individual personal number . Cases of non-fatal MI were extracted from the hospital records . Cox proportional hazards regression models estimated relationships between changes in total cholesterol and triglyceride concentrations and smoking status and the primary endpoints up to 16 years following the end of the trial . RESULTS At 5 and 10 years following the end of the trial the incidence of MI among the 604 men in the intervention ( I ) and 628 in the control ( C ) group differed significantly ( 5-year event rate ( I/C ) = 0.059/0.090 ; P=0.038 and 10-year event rate ( I/C ) = 0.111/0.155 ; P=0.023 ) , but the difference faded slowly and subsequently ( P=0.069 at 16 years ) . The reduction in MI in the intervention group was primarily explained by the differences in total cholesterol and triglyceride concentrations between the groups . CONCLUSION This extended follow-up of the Oslo Diet and Antismoking Study found a prolonged benefit of the intervention lasting for at least a decade after the close of the trial . This finding is in accordance with statin and other studies showing that the effect of cholesterol lowering may be prolonged after the end of the intervention Health-related quality of life was assessed in a diet and exercise intervention study among 157 healthy men aged 35–60 years ( mean ± s.d . ; 46.2 ± 5.0 ) with moderately raised cardiovascular risk factors . The men were r and omized to four groups , diet ( D , n=40 ) , exercise ( E , n=39 ) , diet plus exercise ( DE , n=39 ) , and no active intervention ( controls ( C ) n=39 ) . Quality of life was measured with two self-administered question naires ; Subjective Symptoms Assessment Profile and Minor Symptom Evaluation Profile , at baseline and after 1.5 , 3 and 6 months . Cardiovascular risk factors were investigated at baseline and after 6 months . As a result of changes in dietary habits and physical exercise in the three intervention groups , several important cardiovascular risk factors were significantly reduced . The quality of life/well-being did not differ between the four groups and did not change significantly in any of the groups during the study . There was , however , a tendency towards fewer gastrointestinal symptoms in group D and fewer cardiac symptoms in group DE . We conclude that advice on lifestyle changes in the form of diet and exercise reduce risk factors in middle-aged men without negative effects on their quality of life BACKGROUND This study evaluated a tailored , multiple-component self-help intervention design ed to promote lower fat and higher fruit and vegetable consumption . METHODS Participants were 1,459 adults selected at r and om , stratified by sex and age ( 18 - 34 , 35 - 54 , 55 - 69 ) , from enrollees of a large health maintenance organization . After completing a baseline telephone survey , participants were r and omized to receive the intervention ( consisting of a computer-generated personalized letter , a motivational phone call , a self-help manual , a package of supplementary material s , computer-generated behavioral feedback based on a self-administered food frequency question naire , and newsletters ) or to receive no material s. Evaluation was based on 1,205 ( 86.5 % ) participants who completed both a 3- and a 12-month follow up survey . RESULTS The intervention effect + /- SE for fat , based on a diet habits question naire , was -0.10 + /- 0.02 ( P < 0.001 ) , corresponding to a reduction of approximately 0.8 percentage points of percentage energy from fat . For fruits and vegetables , the intervention effect was 0.47 + /- 0.10 servings/day ( P < 0.001 ) . Intervention effects were similar across age and sex groups . CONCLUSIONS Tailored , self-help interventions can effectively promote dietary change among both men and women and among younger as well as older adults OBJECTIVE To assess the reported baseline dietary intake of Hispanic and non-Hispanic white breast cancer survivors in the Women 's Healthy Eating and Living study , a r and omized plant-based dietary intervention clinical trial . DESIGN Dietary data from 4 days repeated 24-hour recalls within 3 weeks included daily total intake of energy , protein , carbohydrates , cholesterol , total fat , monounsaturated fat , saturated fat , polyunsaturated fat , fruit/vegetable servings , carotenoids , alcohol , caffeine , and percentage of energy from protein , carbohydrates , alcohol , and fats . SUBJECTS One hundred sixty-five Hispanic breast cancer survivors age-matched to 165 non-Hispanic white breast cancer survivors diagnosed with Stage I , II , or IIIA primary operable breast cancer . STATISTICAL ANALYSES Two- sample t tests and Wilcoxon rank sum tests to compare dietary intake , and logistic and ordinal logistic regression analyses to examine the association between ethnicity , alcohol , and lycopene consumption , while controlling for place of birth , education , body mass index , and time since diagnosis . RESULTS Hispanics were more likely to be foreign-born ( P<0.001 ) , less educated ( P<0.0001 ) and to consume higher amounts of lycopene ( P=0.029 ) , while non-Hispanic whites were more likely to consume alcohol ( P=0.001 ) . However , no differences were observed in the average amounts of alcohol consumed or total percents of energy from alcohol . Both groups consumed more than five servings of fruits and vegetables daily . Being Hispanic remained a significant predictor of lower alcohol use ( P=0.004 ) and higher lycopene consumption ( P=0.005 ) after controlling for place of birth , education , body mass index , and time since diagnosis . CONCLUSIONS There are more similarities than differences in the dietary intake of Hispanic and non-Hispanic white breast cancer survivors in the Women 's Healthy Eating and Living study . Further analysis is needed to determine if higher lycopene consumption shown among the Hispanic participants will translate to greater protection against breast cancer recurrence or increased survival This report presents the final evaluation of Language for Health , part of a federally funded initiative to develop heart disease prevention interventions for low-literate population s. Language for Health specifically intervened with recent immigrants enrolled in English-as-a-second- language classes , incorporating nutritional behavior change material s into English- language curricula . Latino participants ( n = 732 ) were exposed to either nutrition education or stress management classes ( attention-placebo group ) design ed specifically for low-English-literate adults . Participants completed physiological measures assessing blood pressure , total and high-density lipoprotein ( HDL ) cholesterol , waist and hip circumference , and weight . Self-report surveys were administered to collect students ’ nutrition-related knowledge , attitudes , self-reported fat avoidance behaviors , and demographic information . Data were collected at baseline , 3-month posttest , and 6-month follow-up . Results indicated long-term effects of the intervention on nutrition knowledge and fat avoidance , yet only short-term effects on total cholesterol : HDL ratio and systolic blood pressure BACKGROUND Accumulation of myocardial triglycerides ( MTG ) is associated with impaired left ventricular ( LV ) remodelling and function in obese and diabetic subjects . The role of MTG accumulation in development of heart failure in this group of patients is unknown . Short-term studies suggest that diets that lead to weight loss could mobilize MTG , with a favourable effect on cardiac remodelling . In a 24-month , r and omized , investigator-blinded study , we assessed the effect of two different diets and subsequent weight loss on cardiac function and MTG in postmenopausal women . METHODS Sixty-eight healthy postmenopausal women with body mass index [ BMI ] ≥27kg/m(2 ) were r and omized to an ad libitum Palaeolithic diet ( PD ) or a Nordic Nutrition Recommendation ( NNR ) diet for 24months . Morphology , cardiac function , and MTG levels were measured using magnetic resonance ( MR ) scanning , including proton spectroscopy at baseline and 6 and 24months . RESULTS Despite mean weight losses of 4.9 ( 1.0 ) kg ( NNR ) and 7.8 ( 1.1 ) kg ( PD ) , the MTG content did not change over time ( p=0.98 in the NNR and p=0.11 in the PD group at 24months ) . Reduced left ventricular mass was observed in both diet groups over 24months . Blood pressure was reduced at 6months , but returned to baseline levels at 24months . End diastolic volume , stroke volume , and cardiac output decreased over time . No differences between diet groups were observed . CONCLUSIONS Diet intervention and moderate weight loss over 24months improved LV remodelling but did not alter MTG levels in overweight/obese postmenopausal women Background : Cohort studies suggest that higher circulating carotenoid concentrations through food sources may reduce breast cancer events . Other intervention studies have not achieved the level of change in circulating carotenoids required to properly test this hypothesis . Methods : In a r and omized trial of 2,922 breast cancer survivors , we examined blood and self-reported diet at baseline and 1 year . Intensive telephone counseling encouraged a plant-based diet in the intervention group . Diet was measured via 24-hour recalls , and a panel of plasma carotenoid concentrations was assessed at both time points . Results : The study intervention was associated with a 51 % increase in total carotenoid concentration , from 2.272 ± 1.294 to 3.440 ± 2.320 μmol/L , achieved mainly by marked increases in targeted carotenoids : α-carotene , β-carotene , and lutein . For each of these targeted carotenoids , the proportion of the intervention sample remaining below the cutpoint for the lowest baseline quartile decreased by one third to one half . After 1 year of study , half of the intervention group was in the highest baseline quartile . No change in distribution was observed in comparison group . Intervention participants achieved this change by both dietary pattern and vegetable juice consumption . Participants who chose to change dietary pattern without consuming significant quantities of vegetable juice achieved 75 % of the level of change observed in other intervention participants . Conclusions : Innovative telephone counseling intervention and dietary targets in the Women 's Healthy Eating and Living study were associated with the level of change in circulating carotenoid concentration necessary to test the diet and breast cancer hypothesis suggested by cohort studies . ( Cancer Epidemiol Biomarkers Prev 2006;15(10):1886–92 UNLABELLED Obesity-related hepatic steatosis is a major risk factor for metabolic and cardiovascular disease . Fat reduced hypocaloric diets are able to relieve the liver from ectopically stored lipids . We hypothesized that the widely used low carbohydrate hypocaloric diets are similarly effective in this regard . A total of 170 overweight and obese , otherwise healthy subjects were r and omized to either reduced carbohydrate ( n = 84 ) or reduced fat ( n = 86 ) , total energy restricted diet ( -30 % of energy intake before diet ) for 6 months . Body composition was estimated by bioimpedance analyses and abdominal fat distribution by magnetic resonance tomography . Subjects were also su bmi tted to fat spectroscopy of liver and oral glucose tolerance testing . In all , 102 subjects completed the diet intervention with measurements of intrahepatic lipid content . Both hypocaloric diets decreased body weight , total body fat , visceral fat , and intrahepatic lipid content . Subjects with high baseline intrahepatic lipids ( > 5.56 % ) lost ≈7-fold more intrahepatic lipids compared with those with low baseline values ( < 5.56 % ) irrespective of diet composition . In contrast , changes in visceral fat mass and insulin sensitivity were similar between subgroups , with low and high baseline intrahepatic lipids . CONCLUSION A prolonged hypocaloric diet low in carbohydrates and high in fat has the same beneficial effects on intrahepatic lipid accumulation as the traditional low-fat hypocaloric diet . The decrease in intrahepatic lipids appears to be independent of visceral fat loss and is not tightly coupled with changes in whole body insulin sensitivity during 6 months of an energy restricted diet A controlled intervention trial , with the purpose of testing the hypothesis that the incidence of coronary heart disease ( CHD ) could be decreased by the use of a serum-cholesterol-lowering ( SCL ) diet , was carried out in two mental hospitals near Helsinki in 1959 - 71 . The subjects were hospitalized middle-aged women . One of the hospitals received the SCL diet , ie a diet low in saturated fats and cholesterol and relatively high in poly-unsaturated fats , while the other served as the control with a normal hospital diet . Six years later the diets were reversed , and the trial was continued another six years . The use of the SCL diet was associated with markedly lowered serum cholesterol values . The incidence of CHD , as measured by the appearance of certain electrocardiographic patterns and by the occurrence of coronary deaths , was in both hospitals during the SCL-diet periods lower than during the normal-diet periods . The differences , however , failed to reach statistical significance . An examination of a number of potential confounding variables indicated that the changes in them were small and failed to account for the reduction in the incidence of CHD . Although the results of this trial do not permit firm conclusions , they support the idea that also among female population s the SCL diet exerts a preventive effect on CHD Population s vary in consistency of diets . The precision of estimates ( E ) of nutrient intake depends both on the ratio ( R ) of intraindividual to interindividual variances , as well as on the number of days of dietary intake recorded ( k ) . We present baseline data from 872 participants in the Trial of Antihypertensive Interventions and Management ( T AIM ) , a r and omized clinical trial of diet and drug treatment for mild hypertension . There is wide variation in R among different demographic groups and for different nutrients . This has implication s for the ability to estimate the correlations between the nutrient and a physiologic variable such as blood pressure , as well as for power calculations to compare group means on nutrient intake . For example , to achieve the same degree of precision ( E = 0.80 ) in estimating the correlation between sodium intake and blood pressure for whites in New York , 7 days of food records would be required , compared to 2 days for whites in Alabama . Tables are presented indicating within- and between-person variances for different groups and different nutrients . Methods of calculating E , determining k , and calculating sample s size are provided . Investigators design ing nutritional epidemiologic studies should take into account ratios of intraindividual to interindividual variances of different population subgroups and different nutrients in order to determine the number of daily food records that must be obtained and the sample size for group comparisons Recommendations for control of high blood pressure ( BP ) emphasize lifestyle modification , including weight loss , reduced sodium intake , increased physical activity , and limited alcohol consumption . The Dietary Approaches to Stop Hypertension ( DASH ) dietary pattern also lowers BP . The PREMIER r and omized trial tested multicomponent lifestyle interventions on BP in demographic and clinical subgroups . Participants with above-optimal BP through stage 1 hypertension were r and omized to an Advice Only group or one of two behavioural interventions that implement established recommendations ( Est ) or established recommendations plus DASH diet ( Est plus DASH ) . The primary outcome was change in systolic BP at 6 months . The study population was 810 individuals with an average age of 50 years , 62 % women , 34 % African American ( AA ) , 95 % overweight/obese , and 38 % hypertensive . Participants in all the three groups made lifestyle changes . Mean net reductions in systolic ( S ) BP in the Est intervention were 1.2 mmHg in AA women , 6.0 in AA men , 4.5 in non-AA women , and 4.2 in non-AA men . The mean effects of the Est Plus DASH intervention were 2.1 , 4.6 , 4.2 , and 5.7 mmHg in the four race – sex subgroups , respectively . BP changes were consistently greater in hypertensives than in nonhypertensives , although interaction tests were nonsignificant . The Est intervention caused statistically significant BP reductions in individuals over and under age 50 . The Est Plus DASH intervention lowered BP in both age groups , and significantly more so in older individuals . In conclusion , diverse groups of people can adopt multiple lifestyle changes that can lead to improved BP control and reduced CVD risk To evaluate the feasibility of using a reduction in dietary fat intake as a component of treatment regimens for patients with resected breast cancer , a multi-disciplinary cooperative group protocol was developed . Females 50 to 75 years of age with stage II breast cancer who completed primary local therapy were eligible for r and omization to a Control Dietary Group in which dietary fat intake was to remain unchanged from baseline level ( at approximately 38 % of calories derived from fat ) and an Intensive Intervention Dietary Group design ed to reduce dietary fat intake . Both Dietary Groups were given tamoxifen 20 mg/day . To facilitate early experience with dietary regimen delivery , patients entered during an initial pilot phase could receive any chemotherapy and /or hormonal treatment . A prer and omization nutrition ‘ run-in ’ of clinical ly eligible patients assessed adherence to nutrition data collection procedures and screened patients for nutrition eligibility criteria . Of 59 patients beginning ‘ run-in ’ , 49 were r and omized and , at present , 32 have completed at least three months follow-up . The change in dietary fat intake ( as assessed by Four Day Food Records ) seen in both arms is outlined below Objective Previous observational studies reported beneficial effects of the Mediterranean diet ( MedDiet ) on cognitive function , but results were inconsistent . We assessed the effect on cognition of a nutritional intervention using MedDiets in comparison with a low-fat control diet . Methods We assessed 522 participants at high vascular risk ( 44.6 % men , age 74.6 ± 5.7 years at cognitive evaluation ) enrolled in a multicentre , r and omised , primary prevention trial ( PREDIMED ) , after a nutritional intervention comparing two MedDiets ( supplemented with either extra-virgin olive oil ( EVOO ) or mixed nuts ) versus a low-fat control diet . Global cognitive performance was examined by Mini-Mental State Examination ( MMSE ) and Clock Drawing Test ( CDT ) after 6.5 years of nutritional intervention . Research ers who assessed the outcome were blinded to group assignment . We used general linear models to control for potential confounding . Results After adjustment for sex , age , education , Apolipoprotein E genotype , family history of cognitive impairment/dementia , smoking , physical activity , body mass index , hypertension , dyslipidaemia , diabetes , alcohol and total energy intake , participants allocated to the MedDiet+EVOO showed higher mean MMSE and CDT scores with significant differences versus control ( adjusted differences : + 0.62 95 % CI + 0.18 to + 1.05 , p=0.005 for MMSE , and + 0.51 95 % CI + 0.20 to + 0.82 , p=0.001 for CDT ) . The adjusted means of MMSE and CDT scores were also higher for participants allocated to the MedDiet+Nuts versus control ( adjusted differences : + 0.57 ( 95 % CI + 0.11 to + 1.03 ) , p=0.015 for MMSE and + 0.33 ( 95 % CI + 0.003 to + 0.67 ) , p=0.048 for CDT ) . These results did not differ after controlling for incident depression . Conclusions An intervention with MedDiets enhanced with either EVOO or nuts appears to improve cognition compared with a low-fat diet . IS RCT The Women 's Health Trial ( WHT ) , a large , multi-unit r and omized controlled trial , would have cost a total of $ 130 million to test the hypothesis that a 50 % reduction in the percentage of calories from dietary fat would yield a detectable reduction in breast cancer incidence . However , the WHT was discontinued because evidence to support the hypothesized rela tionship between dietary fat and breast cancer was judged insufficient to justify the trial . The analysis presented here was undertaken in order to contribute an economic perspective on this issue . Principles of decision analysis and cost-effectiveness analysis are employed to obtain a preliminary estimate of the expected cost per year of life saved of the WHT , as a function of the prior probability that the hypothesis is true ( PRIOR ) . Under specified base- case assumptions , the estimated expected costs per year of life saved range from $ 11,900 when PRIOR is assumed to be 0.9 to $ 25,615 when PRIOR is assumed to be 0.1 . Sensitivity analyses suggest that the results are most sensitive to assumptions about the strength of the relationship between dietary fat and breast cancer risk , and that cost-effectiveness is improved when it is assumed that dietary change can be achieved by an inexpensive in tervention . The expected cost-effectiveness of the WHT is well within the range of estimates of cost-effectiveness of other disease prevention interventions BACKGROUND It is unclear whether participation in home-delivered meal programs similar to the Older Americans Act home-delivered meals program influence weight status among older adults with hypertension and /or hyperlipidemia . OBJECTIVE To examine the influence of a home-delivered Dietary Approaches to Stop Hypertension ( DASH ) meal intervention on body mass index ( BMI ) , energy consumed , and percent of energy needs consumed . DESIGN A 1-year r and omized control trial of home-delivered DASH meals and medical nutrition therapy conducted from 2003 through 2005 . Participants who received DASH meals were compared with those who did not receive meals . Data were collected in participants ' homes at baseline , 6 months , and 12 months . PARTICIPANTS / SETTING The study sample was composed of 298 adults aged > 60 years with hypertension and /or hyperlipidemia residing in a county in the southeastern part of North Carolina . INTERVENTION Participants in the meals intervention group received seven frozen meals per week for 1 year . The meals were design ed to meet one third of participants ' energy and nutrient needs and to comply with the DASH diet . MAIN OUTCOME MEASURES Change in BMI , energy consumed , and percent of energy needs consumed . STATISTICAL ANALYSES PERFORMED Difference-in-differences models were used to estimate the effects of the meal intervention on BMI , energy consumed , and percent of daily energy needs consumed . Analyses were conducted among the full sample and by subgroup ( ie , race , income , and baseline obesity status ) . RESULTS In the full sample , receipt of meals did not have a significant effect on BMI , energy consumed , or percent of daily energy needs consumed . Among those living at or above the 165 % poverty threshold , receipt of home-delivered meals was significantly associated with a decrease in energy consumed and , therefore , percent of daily energy needs consumed . CONCLUSIONS Participation in a home-delivered DASH meal program did not lead to weight gain or weight loss in a group of mostly overweight or obese older adults with hypertension and /or hyperlidemia OBJECTIVE To identify predictors of dietary change to and maintenance of a low-fat eating pattern ( < 20 % energy from fat , > or = 5 servings fruits/vegetables daily , and > or = 6 servings grains daily ) among a cohort of postmenopausal women . C and i date predictors included intrapersonal , interpersonal , intervention program characteristics , and clinical center . DESIGN Longitudinal study within the Women 's Health Initiative Dietary Modification Trial . Dietary change was evaluated after 1 year of participation in the Women 's Health Initiative Dietary Modification Trial , and dietary maintenance after 3 years . SUBJECTS Postmenopausal women aged 50 to 79 years at baseline who were r and omized to the intervention arm of the Women 's Health Initiative Dietary Modification Trial ( n=19,541 ) . STATISTICAL ANALYSIS Univariate and multivariate linear regression analysis was performed and associations evaluated between c and i date predictors and each of the three dietary goals : percent energy from fat , fruit/vegetable servings , and grain servings . RESULTS Year 1 ( change ) predictors of percent energy from fat ( P<0.005 ) included being younger ( beta=2.12 ; 70 to 79 years vs 50 to 59 years ) , more educated ( beta=-.69 ; college vs high school ) , more optimistic ( beta=-.07 ) , attending more sessions ( beta=-.69 ) , and su bmi tting more self-monitoring records ( beta=-.74 ) . At year 3 ( maintenance ) , the predictors of percent energy from fat ( P<0.005 ) included attending more sessions ( beta=-.65 ) and su bmi tting more self-monitoring scores ( beta=-.71 ) . The analytic model predicted 22 % of the variance in fat intake at year 1 and 27 % at year 3 ( P<0.01 ) . CONCLUSIONS The strongest predictors of dietary change and maintenance were attending intervention sessions and self-monitoring dietary intake . Novel was the finding that optimism predicted dietary change Objective To assess whether lifestyle counselling is effective in non-pharmacological treatment of hypertension in primary health care . Design Open r and omized controlled trial . Setting Ten municipal primary health care centres in eastern Finl and . Patients Seven hundred and fifteen subjects aged 25–74 years with systolic blood pressure 140–179 mmHg and /or diastolic blood pressure 90–109 mmHg or antihypertensive drug treatment . Interventions Systematic health counselling given by local public health nurses for 2 years . Main outcome measures Blood pressure , lipids and lifestyle data were collected annually . Results Among participants with no antihypertensive drug treatment , the net reductions after 1 year both in systolic blood pressure [ −2.6 mmHg ; 95 % confidence interval ( CI ) , −4.7 to −0.5 mmHg ] and in diastolic blood pressure ( −2.7 mmHg ; 95 % CI , −4.0 to −1.4 mmHg ) were significant in favour of the intervention group . This difference in blood pressure change was maintained during the second year . In participants with antihypertensive drug treatment , no significant difference in blood pressure reduction was seen between the groups during the study . Conclusions A relatively modest , but systematic counselling in primary health care can , at least among untreated hypertensive subjects , produce reductions in blood pressure levels that are modest for the individual , but very important from the public health point of view PURPOSE To determine whether a low-fat diet high in vegetables , fruit , and fiber differentially affects prognosis in breast cancer survivors with hot flashes ( HF ) or without HF after treatment . PATIENTS AND METHODS A secondary analysis was conducted on 2,967 breast cancer survivors , age 18 to 70 years , who were r and omly assigned between 1995 and 2000 in a multicenter , controlled trial of a dietary intervention to prevent additional breast cancer events and observed through June 1 , 2006 . We compared the dietary intervention group with a group who received five-a-day dietary guidelines . RESULTS Independent of HF status , a substantial between-group difference among those who did and did not receive dietary guidelines was achieved and maintained at 4 years in intake of vegetable/fruit servings per day ( 54 % higher ; 10 v 6.5 servings/d , respectively ) , fiber ( 31 % higher ; 25.5 v 19.4 g/d , respectively ) , and percent energy from fat ( 14 % lower ; 26.9 % v 31.3 % , respectively ) . Adjusting for tumor characteristics and antiestrogen treatment , HF-negative women assigned to the intervention had 31 % fewer events than HF-negative women assigned to the comparison group ( hazard ratio [ HR ] = 0.69 ; 95 % CI , 0.51 to 0.93 ; P = .02 ) . The intervention did not affect prognosis in the women with baseline HFs . Furthermore , compared with HF-negative women assigned to the comparison group , HF-positive women had significantly fewer events in both the intervention ( HR = 0.77 ; 95 % CI , 0.59 to 1.00 ; P = .05 ) and comparison groups ( HR = 0.65 ; 95 % CI , 0.49 to 0.85 ; P = .002 ) . CONCLUSION A diet with higher vegetable , fruit , and fiber and lower fat intakes than the five-a-day diet may reduce risk of additional events in HF-negative breast cancer survivors . This suggestive finding needs confirmation in a trial in which it is the primary hypothesis OBJECTIVES The aim was to study the effect of a 5-year diet intervention on 24-year mortality in middle aged men with combined hyperlipidaemia . SETTING We studied 104 initially healthy men ( in 1972 ) aged 40 - 49 years with baseline values of total serum cholesterol > 6.45 mmol L-1 and fasting triglycerides > 2.55 mmol L-1 , within the r and omized diet and smoking cessation trial of the Oslo study ( n = 1232 ) . METHODS The participants were r and omized to a 5-year diet intervention or a control group . The diet consisted of a traditional lipid-lowering diet with emphasis on reduction of saturated fat , total caloric intake and body weight . The groups were initially well balanced with regard to traditional risk factors for mortality . RESULTS Thirty-three subjects died during the 24-year observation period [ 17 of cardiovascular disease ( CVD ) and 12 of cancer ] . In the diet intervention group , mortality was 51 % lower ( RR = 0.49 , 95 % CI 0.22 - 0.91 , P = 0.022 ) as compared with the control group . This difference remained significant in a Cox regression analysis after adjusting for age and smoking status ( RR = 0.47 , 95 % CI 0.23 - 0.96 , P = 0.038 ) . CONCLUSION This study indicates that the investigated 5-year diet intervention significantly reduces late mortality in healthy middle-aged men with combined hyperlipidaemia BACKGROUND Trials comparing the effectiveness and safety of weight-loss diets are frequently limited by short follow-up times and high dropout rates . METHODS In this 2-year trial , we r and omly assigned 322 moderately obese subjects ( mean age , 52 years ; mean body-mass index [ the weight in kilograms divided by the square of the height in meters ] , 31 ; male sex , 86 % ) to one of three diets : low-fat , restricted-calorie ; Mediterranean , restricted-calorie ; or low-carbohydrate , non-restricted-calorie . RESULTS The rate of adherence to a study diet was 95.4 % at 1 year and 84.6 % at 2 years . The Mediterranean-diet group consumed the largest amounts of dietary fiber and had the highest ratio of monounsaturated to saturated fat ( P<0.05 for all comparisons among treatment groups ) . The low-carbohydrate group consumed the smallest amount of carbohydrates and the largest amounts of fat , protein , and cholesterol and had the highest percentage of participants with detectable urinary ketones ( P<0.05 for all comparisons among treatment groups ) . The mean weight loss was 2.9 kg for the low-fat group , 4.4 kg for the Mediterranean-diet group , and 4.7 kg for the low-carbohydrate group ( P<0.001 for the interaction between diet group and time ) ; among the 272 participants who completed the intervention , the mean weight losses were 3.3 kg , 4.6 kg , and 5.5 kg , respectively . The relative reduction in the ratio of total cholesterol to high-density lipoprotein cholesterol was 20 % in the low-carbohydrate group and 12 % in the low-fat group ( P=0.01 ) . Among the 36 subjects with diabetes , changes in fasting plasma glucose and insulin levels were more favorable among those assigned to the Mediterranean diet than among those assigned to the low-fat diet ( P<0.001 for the interaction among diabetes and Mediterranean diet and time with respect to fasting glucose levels ) . CONCLUSIONS Mediterranean and low-carbohydrate diets may be effective alternatives to low-fat diets . The more favorable effects on lipids ( with the low-carbohydrate diet ) and on glycemic control ( with the Mediterranean diet ) suggest that personal preferences and metabolic considerations might inform individualized tailoring of dietary interventions . ( Clinical Trials.gov number , NCT00160108 . OBJECTIVE To compare the effects of weight loss vs aerobic exercise training on coronary artery disease risk factors in healthy sedentary , obese , middle-aged and older men . DESIGN R and omized controlled trial . SUBJECTS A total of 170 obese ( body mass index , 30 + /- 1 kg/m2 [ mean + /- SEM ] ) , middle-aged and older ( 61 + /- 1 years ) men . INTERVENTIONS A 9-month diet-induced weight loss interventions , 9-month aerobic exercise training program , and a weight-maintenance control group . MAIN OUTCOME MEASURES Change in body composition , maximal aerobic capacity ( V02 max ) , blood pressure , lipoprotein concentrations , and glucose tolerance . RESULTS Forty-four of 73 men r and omized to weight loss completed the intervention and had a 10 % mean reduction in weight ( - 9.5 + /- 0.7 kg ; P < .001 ) , with no 22 change in VO2 max . Forty-nine of 71 men r and omized to aerobic exercise completed the intervention , increased their VO2 max by a mean of 17 % ( P < .001 ) , and did not change their weight , whereas the 18 men who completed in the control group had no significant changes in body composition or VO2 max . Weight loss decreased fasting glucose concentrations by 2 % , insulin by 18 % , and glucose and insulin areas during the oral glucose tolerance test ( OGTT ) by 8 % and 26 % , respectively ( P < .01 ) . By contrast , aerobic exercise did not improve fasting glucose or insulin concentrations or glucose responses during the OGTT but decreased insulin areas by 17 % ( P < .001 ) . In analysis of variance , the decrement in fasting glucose and insulin levels and glucose areas with intervention differed between weight loss and aerobic exercise when compared with the control group ( P < .05 ) . Similarly , weight loss but not aerobic exercise increased high-density lipoprotein cholesterol levels ( + 13 % ) and decreased blood pressure compared with the control group . In multiple regression analyses , the improvement in lipoprotein and glucose metabolism was related primarily to the reduction in obesity . CONCLUSIONS These results suggest that weight loss is the preferred treatment to improve coronary artery disease risk factors in overweight , middle-aged and older men We studied the effects of exercise ( primarily running ) , calorie restriction ( dieting ) , and a low-fat , high-carbohydrate diet on changes in lipoprotein subfractions in moderately overweight men in a r and omized controlled clinical trial . After 1 year , complete data were obtained for 39 men assigned to lose weight through dieting without exercise , 37 men assigned to lose weight through dieting with exercise ( primarily running ) , and 40 nondieting sedentary controls . We instructed both diet groups to consume no more than 30 % total fat , 10 % saturated fat , and 300 mg/d of cholesterol , and at least 55 % carbohydrates , and the controls were instructed to maintain their usual food choices . Analytic ultracentrifugation was used to measure changes in plasma lipoprotein mass concentrations . In addition , the absorbance of protein-stained polyacrylamide gradient gels was used as an index of concentrations for five high-density lipoprotein ( HDL ) subclasses that have been identified by their particle sizes , ie , HDL3c ( 7.2 to 7.8 nm ) , HDL3b ( 7.8 to 8.2 nm ) , HDL3a ( 8.2 to 8.8 nm ) , HDL2a ( 8.8 to 9.7 nm ) , and HDL2b ( 9.7 to 12 nm ) . Relative to controls , weight decreased significantly in men who dieted with exercise ( net difference + /- SE , -3.3 + /- 0.4 kg/m2 ) and in men who dieted without exercise ( -2.0 + /- 0.4 kg/m2 ) . Dieting with exercise significantly decreased very-low-density lipoprotein (VLDL)-mass concentrations and significantly increased plasma HDL2-mass , HDL3a , HDL2a , and HDL2b relative to both control and dieting without exercise . There were no significant changes in lipoprotein mass and HDL protein for dieters who did not run . ( ABSTRACT TRUNCATED AT 250 WORDS CONTEXT : Long-term success in weight loss with dietary treatment has been elusive . OBJECTIVE : To evaluate a diet moderate in fat based on the Mediterranean diet compared to a st and ard low-fat diet for weight loss when both were controlled for energy . DESIGN : A r and omized , prospect i ve 18 month trial in a free-living population . PATIENTS : A total of 101 overweight men and women ( 26.5–46 kg/m2).INTERVENTION : ( 1 ) Moderate-fat diet ( 35 % of energy ) ; ( 2 ) low-fat diet ( 20 % of energy).MAIN OUTCOME MEASUREMENTS : Change in body weight . RESULTS : After 18 months , 31/50 subjects in the moderate-fat group , and 30/51 in the low fat group were available for measurements . In the moderate-fat group , there were mean decreases in body weight of 4.1 kg , body mass index of 1.6 kg/m2 , and waist circumference of 6.9 cm , compared to increases in the low-fat group of 2.9 kg , 1.4 kg/m2 and 2.6 cm , respectively ; P≤0.001 between the groups . The difference in weight change between the groups was 7.0 kg . ( 95 % CI 5.3 , 8.7 ) . Only 20 % ( 10/51 ) of those in the low-fat group were actively participating in the weight loss program after 18 months compared to 54 % ( 27/50 ) in the moderate-fat group , ( P<0.002 ) . The moderate-fat diet group was continued for an additional year . The mean weight loss after 30 months compared to baseline was 3.5 kg ( n=19 , P=0.03 ) . CONCLUSIONS : A moderate-fat , Mediterranean-style diet , controlled in energy , offers an alternative to a low-fat diet with superior long-term participation and adherence , with consequent improvements in weight loss To study the impact of dietary intervention on the plasma total and high density lipoprotein cholesterol ( HDL cholesterol ) levels in hypercholesterolemic men , the authors selected 80 male participants in a monitoring risk factor project carried out in Amsterdam , The Netherl and s. These men had plasma total cholesterol levels of between 6.5 and 10.0 mmol/liter ( between 251 and 387 mg/dl ) and were r and omly assigned to either the intervention ( n = 39 ) or the control ( n = 41 ) group . At the start of the intervention period , after 5 weeks , and after 26 weeks , both the intervention and the control groups were examined . This examination consisted of a measurement of height , weight , plasma total and HDL cholesterol , and a dietary interview . The intervention program consisted of a personalized dietary advice to the respondent , based on the report of the Netherl and s Nutrition Council . The study took place between September 1987 and November 1988 . Because of this intervention program , the plasma total and HDL cholesterol levels decreased . The difference in change in plasma total cholesterol between the intervention and control groups was 0.47 mmol/liter ( 18 mg/dl ) after 5 weeks and 0.30 mmol/liter ( 12 mg/dl ) after 26 weeks . For HDL cholesterol , a significant difference in change after 5 weeks disappeared after 26 weeks . The public health implication s of the decrease in plasma total cholesterol are discussed OBJECTIVE The purpose of this study was to develop , implement , and evaluate the efficacy of an intensive intervention program ( IIP ) based on motivational interviewing to motivate participants within the dietary study of the Women 's Health Initiative ( WHI ) to meet the study 's nutritional goals . SUBJECTS/ DESIGN WHI dietary intervention participants ( n=175 ) from 3 clinical centers were r and omly assigned to either intervention or control status . Participants assigned to IIP intervention received 3 individual motivational interviewing contacts from a dietitian , plus the usual WHI Dietary Intervention . Participants r and omly assigned to IIP control received the usual WHI dietary modification ( DM ) Intervention . Percent of energy from fat was estimated at study baseline and at follow-up ( 1 year later ) using the WHI Food Frequency Question naire . RESULTS The change in percent energy from fat between IIP baseline and IIP 1-year follow-up was -1.2 % for IIP intervention participants and + 1.4 % for IIP control participants , giving an overall difference of 2.6 % ( P<.001 ) . Participants having the highest IIP baseline fat intake ( > 30 % energy ) showed the largest overall change in percent energy from fat between IIP baseline and IIP follow-up . CONCLUSIONS The results of this study indicate that a protocol based on motivational interviewing and delivered through contacts with trained dietitians is an efficacious way to further lower dietary fat intake among participants exposed to ongoing intervention . These data will be useful in future intervention situations when there is a need to increase motivation to change OBJECTIVE To assess the effect of lifestyle intervention over 2 years on changes in weight , coronary heart disease ( CHD ) risk factors , and incidence of diabetes in overweight individuals with a parental history of diabetes . RESEARCH DESIGN AND METHODS Participants ( n = 154 ) , who were 30–100 % over ideal body weight , had one or both parents with diabetes , and were currently nondiabetic , were r and omly assigned to 2-year treatments focused on diet ( decreasing calories and fat intake ) , exercise ( goal of 1,500 kcal/week of moderate activity ) , or the combination of diet plus exercise or to a no-treatment control group . Subjects were reassessed at 6 months , 1 year , and 2 years . RESULTS At 6 months , the groups differed significantly on measures of eating , exercise , and fitness ; weight losses in the diet and diet-plus-exercise groups were significantly > in the exercise and control conditions . Weight losses were associated with positive changes in CHD risk factors . After 6 months , there was gradual deterioration of behavioral and physiological changes , so that at 2 years , almost no between-group differences were maintained . Differences between groups in risk of developing diabetes were of borderline significance ( P = 0.08 ) . Strongest predictors were impaired glucose tolerance at baseline , which was positively related to risk of developing diabetes , and weight loss from baseline to 2 years , which was negatively related ; in all treatment groups , a modest weight loss of 4.5 kg reduced the risk of type 2 diabetes by ∼ 30 % compared with no weight loss . CONCLUSIONS Although initially successful , the interventions studied here were not effective in producing long-term changes in behavior , weight , or physiological parameters . However , weight loss from 0 to 2 years reduced the risk of developing type 2 diabetes . Since modest weight loss significantly reduced risk of type 2 diabetes , further research is needed to determine how best to increase the percentage of subjects achieving at least a modest weight loss The PREMIER trial assessed the aggregate effect on blood pressure ( BP ) of nationally recommended lifestyle modifications in free-living adults with high-normal ( stage 1 ) hypertension . Participants ( N=810 ) were r and omized to the advice-only group ; the established group ( consisting of weight loss , increased physical activity , and reduced sodium and alcohol intake ) ; or the established plus Dietary Approaches to Stop Hypertension ( DASH ) diet group ( consisting of the established interventions in addition to the DASH dietary pattern ) . The primary outcome was change in systolic BP at 6 months . Net of advice only , mean systolic BP declined by 3.7 mm Hg for members of the established group ( p<0.001 ) and 4.3 mm Hg for the established plus DASH group ( p<0.001 ) . The prevalence of hypertension decreased from a baseline of 38 % to 17 % in the established group ( p=0.01 ) and to 12 % in the established plus DASH group ( p<0.001 ) compared with a decrease to 26 % in the advice-only group . The PREMIER trial demonstrated that persons with above-optimal BP and stage 1 hypertension can make multiple lifestyle changes leading to better control of BP Summary Type 2 ( insulin independent ) diabetic women were r and omly allocated to receive advice for low fat diets or low carbohydrate diets . By 24 h weighed dietary intakes before and after a mean interval of six months , patients in the low fat group had reduced their fat intake from 41 % to 31 % of total energy , while carbohydrate percentage of total energy intake increased from 38 % to 46 % . Percentage energy intake from fat and carbohydrate in the control group remained unchanged . Body weight fell in both groups , especially for patients in the low fat group who were obese ( weight/height2 ⩾ 28 kg/m2 ) . Mean plasma glucose , HbA1 , and triglycerides were unchanged . Mean plasma total cholesterol fell significantly in the low fat group compared with the controls ( p < 0.001 ) , but there was no significant difference in the small reduction of high density lipoprotein cholesterol observed in both groups . Thus , adherence to low fat diets occurred without deterioration of diabetes and with benefit for weight and total cholesterol OBJECTIVE To determine the effectiveness of an intensive dietary intervention on diet and body mass in women with breast cancer . DESIGN R and omized clinical trial . SUBJECTS 172 women aged 20 to 65 years with stage I or II breast cancer . INTERVENTION A 15-session , mainly group-based and dietitian-led nutrition education program ( NEP ) was compared to a mindfulness-based stress reduction clinic program ( SRC ) ; or usual supportive care ( UC ) . MAIN OUTCOME MEASURES Dietary fat , complex carbohydrates , fiber , and body mass were measured . STATISTICAL ANALYSIS In addition to descriptive statistics , analysis of variance was conducted to test for differences according to intervention group . RESULTS Of the 157 women with complete dietary data at baseline , 149 had complete data immediately postintervention ( at 4 months ) and 146 had complete data at 1 year . Women r and omized to NEP ( n = 50 ) experienced a large reduction in fat consumption ( 5.8 % of energy as fat ) at 4 months and much of this reduction was preserved at 1 year ( 4.1 % of energy ) ( both P < .0002 ) vs no change in either SRC ( n = 51 ) or UC ( n = 56 ) . A 1.3-kg reduction in body mass was evident at 4 months in the NEP group ( P = .003 ) vs no change in the SRC and UC groups . Women who had higher-than-average expectations of a beneficial effect of the intervention experienced larger changes . APPLICATIONS Dietitians ' use of group nutrition interventions appear to be warranted . Increasing their effectiveness and maintaining high levels of adherence may require additional support , including the involvement of significant others , periodic individual meetings , or group booster sessions BACKGROUND Low-carbohydrate , ketogenic diets ( LCKD ) are effective for weight loss , but concerns remain regarding cardiovascular risk . The purpose of this study was to determine the effect of an LCKD program on serum lipoprotein subclasses . METHODS This was a r and omized , two-arm clinical trial in an outpatient research clinic involving overweight , hyperlipidemic community volunteers motivated to lose weight . Subjects were r and omized to either an LCKD ( n = 59 ) and nutritional supplementation ( including fish , borage and flaxseed oil ) , or a low-fat , reduced-calorie diet ( LFD , n = 60 ) . The main outcomes were fasting serum lipoprotein subclasses determined by nuclear magnetic resonance analysis . RESULTS The mean age of subjects was 44.9 years , the mean BMI was 34.4 kg/m(2 ) , and 76 % were women . Comparing baseline to 6 months , the LCKD group had significant changes in large VLDL ( -78 % ) , medium VLDL ( -60 % ) , small VLDL ( -57 % ) , LDL particle size ( + 2 % ) , large LDL ( + 54 % ) , medium LDL ( -42 % ) , small LDL ( -78 % ) , HDL particle size ( + 5 % ) , large HDL ( + 21 % ) , and LDL particle concentration ( -11 % ) . Compared with the LFD group , the LCKD group had greater reductions in medium VLDL ( p = 0.01 ) , small VLDL ( p = 0.01 ) and medium LDL ( p = 0.02 ) , and greater increases in VLDL particle size ( p = 0.01 ) , large LDL ( p = 0.004 ) , and HDL particle size ( p = 0.05 ) . CONCLUSIONS The LCKD with nutritional supplementation led to beneficial changes in serum lipid subclasses during weight loss . While the LCKD did not lower total LDL cholesterol , it did result in a shift from small , dense LDL to large , buoyant LDL , which could lower cardiovascular disease risk OBJECTIVE : To examine the relationship between waist circumference and cardiovascular risk factors during weight loss , and to consider possible waist reduction targets for weight management . DESIGN : Single str and six month weight loss study on food based diets in 110 women aged 18–68 y , and body mass index≥25 kg/m2 set at an outpatient clinic . MAIN OUTCOME MEASURES : Waist circumference , weight , body mass index ( BMI ) , total plasma cholesterol , low ( LDL ) and high density lipoprotein ( HDL ) cholesterol , triglyceride , and blood pressure . RESULTS : Anthropometric and metabolic measurements improved with mean weight loss of 4.9 ( s.e.m.±0.4 ) kg at three months and 6.2 ( s.e.m.±0.4 ) kg at six months . Weight loss closely related to waist reduction ( % Weight loss=0.85 × Waist reduction ( cm ) – 2.09 ; r=0.79 ) . The proportion of subjects with waist circumference below Action Level 1 ( < 80 cm ) or above Action Level 2 ( ≥88 cm ) were 9 and 60 % at baseline , 29 and 38 % at three months and 36 and 33 % at six months . Waist reduction ( adjusted for age , smoking , alcohol consumption , diet treatment and baseline dependent and independent variables ) correlated significantly with falls in total cholesterol ( r=0.31 ; P<0.01 ) , LDL cholesterol ( r=0.35 ; P<0.01 ) and diastolic blood pressure ( r=0.32 ; P<0.01 ) , but not significantly with HDL cholesterol , triglyceride or systolic blood pressure . BMI showed similar correlations , whereas waist to hip ratio changes were not associated with changes in any cardiovascular risk factors . Amongst those whose waist fell by ≥5 cm , 45 at three months and 43 at six months , there were ≥10 % improvements in at least one risk factor for 71 and 84 % respectively . Amongst those whose waist fell by 5–10 cm , 40 women at three months and 30 at six months , at least one risk factor improved by ≥10 % in 70 % and in 83 % respectively . CONCLUSIONS : Waist reduction of 5–10 cm in Caucasian women , across a range of baseline BMI 25–50 kg/m2 or waist circumference 72–133 cm , may be used as guideline to encourage overweight women to achieve a realistic target with a high probability of health benefits OBJECTIVE To compare the effectiveness of different approaches to participant enrollment in a behavior modification trial . DESIGN Concurrent , prospect i ve evaluation performed in context of recruitment for a r and omized , controlled trial . SETTING Four study centers located in Baltimore , Maryl and , Memphis , Tennessee New Brunswick , New Jersey , and Winston-Salem , North Carolina . PARTICIPANTS Men and women aged 60 to 80 years who were being treated with a prescription medication for control of hypertension . MAIN OUTCOME MEASURES Visit counts and percent yields were assessed at each stage of the screening and r and omization process . Logistic regression was used to contrast the r and omization yields for different recruitment strategies and to explore the impact of sociodemographic characteristics and geographic location on recruitment yields . RESULTS The overall r and omization yields from a prescreen contact and a first screening visit to enrollment in the trial were 11 % and 31 % , respectively . R and omization yields varied significantly by participant age , education , and marital status . CONCLUSIONS Our results demonstrate the feasibility of recruitment for trials of nonpharmacologic interventions in older people and suggest that mass mailing and mass media advertising campaigns provide an effective means of enrolling in such studies participants with a broad range of personal characteristics The National Cholesterol Education Program has underscored the need for health professionals to work together to promote dietary changes and reduce blood cholesterol levels across the population . This article reports the results of an evaluation of several low-intensity intervention programs design ed for the general public that could be offered on a larger scale , either through traditional outlets for short courses or on an outpatient basis after physician referral . The interventions were design ed as classes , required approximately 8 hr of contact time with the participants , cost approximately $ 20 per participant , and were taught by nutritionists and dietitians recruited from the community and trained for this program . Results indicated that similar net reductions in total cholesterol of about 4 % were achieved at 1-yr follow-up either from a course which focused on changing eating patterns or from one which focused on weight loss and weight-loss management . These results support the hypothesis that cholesterol reduction is possible with inexpensive and simple methods in healthy , low-risk population We have investigated the relationship of diet to plasma lipid and lipoprotein levels in 6494 hypercholesterolemic ( Type MA ) men who were instructed in an isocaloric , 400 mg cholesterol , 0.8 polyunsaturated-to-saturated fat ratio diet in the course of recruitment for the Lipid Research Clinics Coronary Primary Prevention Trial . Single 24-hour dietary recalls , plasma total and high density lipoprotein cholesterol , and total triglyceride determinations were obtained approximately 1 month before and after dietary instruction . Cross-sectional correlation analysis disclosed no significant association between diet and plasma cholesterol at entry . However , when diet-associated changes were similarly analyzed , weight loss , decreased intakes of saturated fat and cholesterol , and increased intake of polyunsaturated fat were all significantly and independently predictive of falls in plasma cholesterol , mainly in its low density lipoprotein fraction . The multiple correlation coefficient for the result ant four-variable regression model was 0.29 . Diet-associated changes in plasma very low density lipoprotein cholesterol were less marked but in the same direction . These dietary changes were also weakly associated with a lowering of plasma high density lipoprotein cholesterol , while weight loss had an opposite effect of similar strength . When one takes into account the variability of dietary recall data , the observed diet-associated changes in plasma cholesterol were compatible with the findings of metabolic ward studies The relation between nutrient intake and progression of coronary artery disease was examined in 50 men receiving a lipid-lowering diet or usual care in the St. Thomas ' Atherosclerosis Regression Study . Nutrient intake was assessed by diet history . Changes in coronary angiograms were measured by quantitative image analysis . In univariate linear regression analysis progression of disease over 39 months , as measured by decrease in minimum absolute width of coronary segments , was directly related to dietary energy ( p < 0.001 ) and to the absolute intakes of total fat ( p < 0.001 ) , saturated fat ( p < 0.001 ) , monounsaturated fat ( p = 0.016 ) and cholesterol ( p = 0.06 ) . No significant associations were seen with polyunsaturated fat , carbohydrate , protein , fiber , alcohol or with the ratio of intakes of polyunsaturated fatty acids to saturated fatty acids . In multiple linear regression analysis the associations of change in minimum absolute width of coronary segments with total or saturated fat persisted when adjusted for plasma low-density lipoprotein cholesterol concentration , age , weight , blood pressure , smoking or treatment group assignment . The findings suggest that in middle-aged men , progression of CAD is strongly influenced by intake of saturated fatty acids , an effect mediated in part by mechanisms other than the influence of this nutrient on plasma cholesterol and low-density lipoprotein cholesterol To assess whether baseline plasma high-density lipoprotein ( HDL ) cholesterol levels affected the HDL response to weight loss , we examined lipoprotein changes in overweight men aged 30 to 59 years who were r and omized to lose weight by exercise training ( primarily running , n = 46 ) or by caloric restriction ( ie , dieting , n = 42 ) or to remain sedentary , nondieting controls ( n = 42 ) in a 1-year study . In exercisers , absolute increases in HDL ( mg/dL ) were greatest in men with normal-to-high baseline HDL and least in men with low baseline HDL . Specifically , when divided into groups of low ( < or = 37 mg/dL ) , intermediate ( 38 to 47 mg/dL ) , and normal-to-high HDL cholesterol ( > or = 48 mg/dL ) at baseline , the exercisers increased HDL cholesterol by 2.3 + /- 1.9 , 4.9 + /- 1.1 , and 7.0 + /- 1.3 mg/dL , respectively ; HDL2 cholesterol by 0.8 + /- 1.6 , 2.3 + /- 1.2 , and 5.1 + /- 1.3 mg/dL ; and HDL2 mass by 2.8 + /- 5.1 , 9.5 + /- 8.9 , and 31.7 + /- 11.0 mg/dL. Relative increases in HDL cholesterol were more similar in the low ( 7.1 % + /- 6.1 % ) , intermediate ( 12.4 % + /- 3.9 % ) , and normal-to-high men ( 13.2 % + /- 4.0 % ) . Regression analyses were performed to assess whether baseline HDL cholesterol was related to the amount of absolute HDL change per unit of weight loss . In exercisers , the increase in HDL3 cholesterol concentrations was significantly greater in men with low HDL than in those with normal-to-high HDL at entry ( 2.0 + /- 0.8 v 0.2 + /- 0.8 mg/dL per kg/m2 lost ) . ( ABSTRACT TRUNCATED AT 250 WORDS 1 . A prospect i ve r and omized study of two dietary regimens has been started in newly-diagnosed diabetics to determine their effect on circulating metabolites and on diabetic complications . 2 . During the first year of treatment the fasting plasma glucose concentrations on both the low-carbohydrate diet and the high-carbohydrate , modified-fat ( MF ) diet showed a similar decrease . 3 . Plasma cholesterol showed a sustained decrease only in patients recommended a MF diet . Transient changes in plasma triglyceride concentrations occurred in patients on both dietary regimens . 4 . Increased plasma cholesterol levels are associated with atheromatous disease which is common in diabetics in Europe and North America . A MF diet may therefore have an advantage in that it lowers the plasma cholesterol as well as being effective in lowering the plasma glucose CONTEXT Evidence is lacking that a dietary pattern high in vegetables , fruit , and fiber and low in total fat can influence breast cancer recurrence or survival . OBJECTIVE To assess whether a major increase in vegetable , fruit , and fiber intake and a decrease in dietary fat intake reduces the risk of recurrent and new primary breast cancer and all-cause mortality among women with previously treated early stage breast cancer . DESIGN , SETTING , AND PARTICIPANTS Multi-institutional r and omized controlled trial of dietary change in 3088 women previously treated for early stage breast cancer who were 18 to 70 years old at diagnosis . Women were enrolled between 1995 and 2000 and followed up through June 1 , 2006 . INTERVENTION The intervention group ( n = 1537 ) was r and omly assigned to receive a telephone counseling program supplemented with cooking classes and newsletters that promoted daily targets of 5 vegetable servings plus 16 oz of vegetable juice ; 3 fruit servings ; 30 g of fiber ; and 15 % to 20 % of energy intake from fat . The comparison group ( n = 1551 ) was provided with print material s describing the " 5-A-Day " dietary guidelines . MAIN OUTCOME MEASURES Invasive breast cancer event ( recurrence or new primary ) or death from any cause . RESULTS From comparable dietary patterns at baseline , a conservative imputation analysis showed that the intervention group achieved and maintained the following statistically significant differences vs the comparison group through 4 years : servings of vegetables , + 65 % ; fruit , + 25 % ; fiber , + 30 % , and energy intake from fat , -13 % . Plasma carotenoid concentrations vali date d changes in fruit and vegetable intake . Throughout the study , women in both groups received similar clinical care . Over the mean 7.3-year follow-up , 256 women in the intervention group ( 16.7 % ) vs 262 in the comparison group ( 16.9 % ) experienced an invasive breast cancer event ( adjusted hazard ratio , 0.96 ; 95 % confidence interval , 0.80 - 1.14 ; P = .63 ) , and 155 intervention group women ( 10.1 % ) vs 160 comparison group women ( 10.3 % ) died ( adjusted hazard ratio , 0.91 ; 95 % confidence interval , 0.72 - 1.15 ; P = .43 ) . No significant interactions were observed between diet group and baseline demographics , characteristics of the original tumor , baseline dietary pattern , or breast cancer treatment . CONCLUSION Among survivors of early stage breast cancer , adoption of a diet that was very high in vegetables , fruit , and fiber and low in fat did not reduce additional breast cancer events or mortality during a 7.3-year follow-up period . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00003787 BACKGROUND Decreased fat intake with weight loss and increased exercise may reduce the risk of diabetes mellitus in persons with impaired glucose tolerance . This study was undertaken to assess the effects of a low-fat dietary pattern on incidence of treated diabetes among generally healthy postmenopausal women . METHODS A r and omized controlled trial was conducted at 40 US clinical centers from 1993 to 2005 , including 48,835 postmenopausal women aged 50 to 79 years . Women were r and omly assigned to a usual-diet comparison group ( n = 29,294 [ 60.0 % ] ) or an intervention group with a 20 % low-fat dietary pattern with increased vegetables , fruits , and grains ( n = 19,541 [ 40.0 % ] ) . Self-reported incident diabetes treated with oral agents or insulin was assessed . RESULTS Incident treated diabetes was reported by 1303 intervention participants ( 7.1 % ) and 2039 comparison participants ( 7.4 % ) ( hazard ratio , 0.96 ; 95 % confidence interval , 0.90 - 1.03 ; P = .25 ) . Weight loss occurred in the intervention group , with a difference between intervention and comparison groups of 1.9 kg after 7.5 years ( P < .001 ) . Subgroup analysis suggested that greater decreases in percentage of energy from total fat reduced diabetes risk ( P for trend = .04 ) , which was not statistically significant after adjusting for weight loss . CONCLUSIONS A low-fat dietary pattern among generally healthy postmenopausal women showed no evidence of reducing diabetes risk after 8.1 years . Trends toward reduced incidence were greater with greater decreases in total fat intake and weight loss . Weight loss , rather than macronutrient composition , may be the dominant predictor of reduced risk of diabetes OBJECTIVES This study was undertaken to test the effectiveness of the Stanford Nutrition Action Program , an experimental trial to reduce dietary fat intake among low-literacy , low-income adults . METHODS Twenty-four paired adult education classes ( 351 participants , 85 % women , mean age = 31 years ) were r and omly assigned to receive a newly developed dietary fat curriculum ( the Stanford Nutrition Action Program ) or an existing general nutrition curriculum . Food frequency and nutrition-related data , body mass index , and capillary blood cholesterol were collected at baseline and at two postintervention follow-ups . RESULTS The Stanford Nutrition Action Program classes showed significantly greater net improvements in nutrition knowledge ( + 7.7 ) , attitudes ( /0.2 ) , and self-efficacy ( -0.2 ) than the general nutrition classes ; they also showed significantly greater reductions in the percentage of calories from total ( -2.3 % ) and saturated ( -0.9 % ) fat . There were no significant differences in body mass index or blood cholesterol . All positive intervention effects were maintained for 3 months postintervention . CONCLUSIONS The Stanford Nutrition Action Program curriculum , tailored to the cultural , economic , and learning needs of low-literacy , low-income adults , was significantly more effective in achieving fat-related nutritional changes than the general nutrition curriculum The aim of the study was to test the effect of a non-pharmacological weight reduction program on cardiovascular risk factors among overweight hypertensives in a primary health care setting . Forty-nine overweight hypertensive patients completed the 12-month program . The patients were r and omly allocated into either intervention or control groups . The examinations included interviews by a nutritionist , pertinent laboratory tests , and a medical examination . The intervention involved an individually planned energy-restricted diet of 1000 - 1500 kcal per day , weekly discussion s , and various leaflets on diet modification and on increase of physical activity . The mean body weight was reduced by 5 kg in the intervention group , but remained unchanged in the control group . The intervention group reduced their fat intake by 14 g/day while the control group increased it by 9 g/day on the average . In the intervention group , the total serum cholesterol decreased , HDL-cholesterol increased and triglycerides decreased significantly . The systolic blood pressure fell by 8 mm Hg and 15 mm Hg in the intervention and control groups , respectively . The diastolic blood pressure fell on average by 11 mm Hg in both groups . The results demonstrate the comprehensive weight reduction program to be effective in the control of cardiovascular risk factors Background / Objectives : The aim of this study was to analyze the influence of a Mediterranean dietary pattern on plasma total antioxidant capacity ( TAC ) after 3 years of intervention and the associations with adiposity indexes in a r and omized dietary trial ( PREDIMED trial ) with high cardiovascular risk patients .Subjects/ Methods : 187 subjects were r and omly selected from the PREDIMED-UNAV center after they completed 3-year intervention program . Participants were following a Mediterranean-style diet with high intake of virgin olive oil or high intake of nuts , or a conventional low-fat diet . Adiposity indexes were measured at baseline and at year 3 . Plasma TAC was evaluated using a commercially available colorimetric assay kit . Results : Plasma TAC in the control , olive oil and nuts groups was 2.01±0.15 , 3.51±0.14 and 3.02±0.14 mM Trolox , respectively after adjusting for age and sex . The differences between the Mediterranean diet and control groups were statistically significant ( P<0.001 ) . Moreover higher levels of TAC were significantly associated with a reduction in body weight after 3 years of intervention among subjects allocated to the virgin olive oil group ( B=−1.306 ; 95 % CI=−2.439 to −0.173 ; P=0.025 , after adjusting for age , sex and baseline body mass index ) . Conclusions : Mediterranean diet , especially rich in virgin olive oil , is associated with higher levels of plasma antioxidant capacity . Plasma TAC is related to a reduction in body weight after 3 years of intervention in a high cardiovascular risk population with a Mediterranean-style diet rich in virgin olive oil OBJECTIVE To compare the results and cost-effectiveness of a cholesterol lowering protocol implemented by registered dietitians with cholesterol lowering advice by physicians . DESIGN Six month r and omized controlled trial , cost-effectiveness analysis . Subjects included 90 ambulatory care patients ( 60 men , 30 women ) , age range 21 to 65 years , with hypercholesterolemia and not taking hypolipidemic drugs . Patients were r and omly assigned to receive medical nutrition therapy ( MNT ) from dietitians using a NCEP based lowering protocol or usual care ( UC ) from physicians . Outcome measures were plasma lipid profiles , dietary intake , weight , activity , patient satisfaction , and costs of MNT . Changes from baseline for each variable of interest were compared between treatment groups using analysis of covariance controlling for baseline value of the variable and gender . RESULTS MNT achieved a 6 % decrease in total and LDL cholesterol levels at 3 and 6 months compared with a 1 % increase and a 2 % decrease in both values at 3 and 6 months with UC ( P<.001 and P<.05 , respectively ) . Weight loss ( 1.9 vs 0 kg , P<.001 ) and dietary intake of saturated fat ( 7 % of energy vs 10 % , P<.001 ) were better in the MNT than the UC group . The additional costs of MNT were $ 217 per patient to achieve a 6 % reduction in cholesterol and $ 98 per patient to sustain the reduction . The cost-effectiveness ratio for MNT was $ 36 per 1 % decrease in cholesterol and LDL level . APPLICATIONS/ CONCLUSIONS MNT from registered dietitians is a reasonable investment of re sources because it results in significantly better lipid , diet , activity , weight , and patient satisfaction outcomes than UC The Women 's Healthy Eating and Living ( WHEL ) Study is a multisite r and omized controlled trial of the effectiveness of a high-vegetable , low-fat diet , aim ed at markedly raising circulating carotenoid concentrations from food sources , in reducing additional breast cancer events and early death in women with early-stage invasive breast cancer ( within 4 years of diagnosis ) . The study r and omly assigned 3088 such women to an intensive diet intervention or to a comparison group between 1995 and 2000 and is expected to follow them through 2006 . Two thirds of these women were under 55 years of age at r and omization . This research study has a coordinating center and seven clinical sites . R and omization was stratified by age , stage of tumor and clinical site . A comprehensive intervention program that includes intensive telephone counseling , cooking classes and print material s helps shift the dietary pattern of women in the intervention . Through an innovative telephone counseling program , dietary counselors encourage women in the intervention group to meet the following daily behavioral targets : five vegetable servings , 16 ounces of vegetable juice , three fruit servings , 30 g of fiber and 15 - 20 % energy from fat . Adherence assessment s occur at baseline , 6 , 12 , 24 or 36 , 48 and 72 months . These assessment s can include dietary intake ( repeated 24-hour dietary recalls and food frequency question naire ) , circulating carotenoid concentrations , physical measures and question naires about health symptoms , quality of life , personal habits and lifestyle patterns . Outcome assessment s are completed by telephone interview every 6 months with medical record verification . We will assess evidence of effectiveness by the length of the breast cancer event-free interval , as well as by overall survival separately in all the women in the study as well as specifically in women under and over the age of 55 years BACKGROUND Guidelines established by the National Cholesterol Education Program ( NCEP ) promote exercise and weight loss for the treatment of abnormal lipoprotein levels . Little is known , however , about the effects of exercise or the NCEP diet , which is moderately low in fat and cholesterol , in persons with lipoprotein levels that place them at high risk for coronary heart disease . METHODS We studied plasma lipoprotein levels in 180 postmenopausal women , 45 through 64 years of age , and 197 men , 30 through 64 years of age , who had low high-density lipoprotein ( HDL ) cholesterol levels ( < or = 59 mg per deciliter in women and < or = 44 mg per deciliter in men ) and moderately elevated levels of low-density lipoprotein ( LDL ) cholesterol ( > 125 mg per deciliter but < 210 mg per deciliter in women and > 125 mg per deciliter but < 190 mg per deciliter in men ) . The subjects were r and omly assigned to aerobic exercise , the NCEP Step 2 diet , or diet plus exercise , or to a control group , which received no intervention . RESULTS Dietary intake of fat and cholesterol decreased during the one-year study ( P<0.001 ) , as did body weight , in women and men in either the diet group or the diet-plus-exercise group , as compared with the controls ( P<0.001 ) and the exercise group ( P<0.05 ) , in which dietary intake and body weight were unchanged . Changes in HDL cholesterol and triglyceride levels and the ratio of total to HDL cholesterol did not differ significantly among the treatment groups , for subjects of either sex . The serum level of LDL cholesterol was significantly reduced among women ( a decrease of 14.5+/-22.2 mg per deciliter ) and men ( a decrease of 20.0+/-17.3 mg per deciliter ) in the diet-plus-exercise group , as compared with the control group ( women had a decrease of 2.5+/-16.6 mg per deciliter , P<0.05 ; men had a decrease of 4.6+/-21.1 mg per deciliter , P<0.001 ) . The reduction in LDL cholesterol in men in the diet-plus-exercise group was also significant as compared with that among the men in the exercise group ( 3.6+/-18.8 mg per deciliter , P<0.001 ) . In contrast , changes in LDL cholesterol levels were not significant among the women ( a decrease of 7.3+/-18.9 mg per deciliter ) or the men ( 10.8+/-18.8 mg per deciliter ) in the diet group , as compared with the controls . CONCLUSIONS The NCEP Step 2 diet failed to lower LDL cholesterol levels in men or women with high-risk lipoprotein levels who did not engage in aerobic exercise . This finding highlights the importance of physical activity in the treatment of elevated LDL cholesterol levels There is still a need of support for nonpharmacologic treatment of uncomplicated , mild-to-moderate essential hypertension . We investigated whether a low sodium-based diet implemented by a nutritionist could lower blood pressure and affect sympathetic activity . Middle-aged , otherwise healthy men with never-treated essential hypertension ( n = 95 ) were r and omized to an intervention group , a blood pressure control group , and a time control group . The intervention group was advised to use less sodium chloride in their diet , and if necessary , less saturated fat and decrease body weight . They attended regular clinic visits as did the blood pressure control group . After 1 year , the intervention group had achieved on average 72 mmol/24 h lower urinary sodium excretion ( P < .001 ) and a decrease in body weight of 2.7 + /- 0.5 kg ( P < .001 ) . Both supine and st and ing mean blood pressure were on average 8 to 10 mm Hg lower after intervention compared with the two control groups ( P < .001 ) . Arterial plasma epinephrine , measured in all 40-year-old subjects ( n = 30 ) , decreased in parallel in all three groups ( P < .05 ) , indicating some habituation to the invasive procedure and clinic visits . However , the decrease in norepinephrine was significant ( P < .001 ) only in the intervention group ; it correlated with the weight loss ( r = 0.76 , P < .05 ) and was significantly higher ( P < .05 ) than in both control groups . These results suggest that broad dietary advice ( ie , low intake of sodium chloride , saturated fat and energy ) , implemented by a nutritionist , may have a significant blood pressure lowering effect and a favorable sympathicolytic effect in uncomplicated , mild-to-moderate essential hypertension The effects of fruit and vegetables in conjunction with low-energy diet as adjuncts to a prudent diet were compared for 6 months in a r and omized , single blind trial in the management of 202 group A and 204 group B patients with acute myocardial infa rct ion . Dietary intakes were obtained based on weighing of fruit , vegetable and legume intake and weekly diet diaries . After 6 months of follow-up , mean body weight , waist/hip ratio and glucose intolerance fell significantly in patients in group A compared with those in group B. Body weight declined by 5.3 kg in group A versus 2.2 kg in group B ( 95 % confidence interval of difference ( CI ) 1.28 - 4.92 ) , waist/hip ratio decreased by 0.05 in group A and 0.02 in group B ( 95 % CI 0.01 - 0.10 ) , and glucose intolerance decreased by 0.85 mmol/l in group A versus 0.19 mmol/l in group B ( 95 % CI 0.19 - 1.21 ) . There was a significant net decrease in serum triglycerides ( 0.18 mmol/l ) , systolic and diastolic blood pressures ( 7.9/4.7 mmHg ) , and a net increase in high-density lipoprotein cholesterol ( 0.10 mmol/l ) . Underlying these changes , group A patients had 393 g/day net increase in the consumption of fruit and vegetables and 1,160 kJ/day net decrease in energy intake compared to these changes in groups . Those who made greater changes in diet also had greater improvements in central obesity , glucose intolerance and in other associated disturbances UNLABELLED Dietary recommendations for the treatment of hypercholesterolemia ( HC ) emphasize stepwise reductions in fat intake , but there is no agreement on what lower limit is desirable or achievable . These recommendations have applied broadly to persons with HC alone , as well as to those with a combined elevation in triglyceride ( TG ) and cholesterol , even though they may differ in pathophysiological mechanisms and response . In this paper , we describe the design and feasibility of recruiting and r and omizing subjects with HC or combined hyperlipidemia ( CHL ) to an outpatient dietary intervention study of progressively fat-restricted diets . Diets were design ed to contain 30 , 26 , 22 , and 18 % of calories from fat ; 300 , 200 , 100 , and 100 mg cholesterol/day ; and a polyunsaturated/saturated fat ratio of approximately 1.0 . Triglyceride and low-density-lipoprotein cholesterol ( LDL-C ) cutpoints were based on the age-specific 75th percentile value . Over 18 months , 8372 men were screened , yielding 320 HC subjects r and omized to the four diets and 211 CHL subjects r and omized to the first three diets ( because of fewer CHL subjects ) . At baseline , HC and CHL subjects were similar in age , education , lifestyle , dietary intake , and LDL-C , but CHL subjects were heavier , more hyperglycemic , hyperinsulinemic , and hypertensive . CONCLUSIONS Recruiting a large cohort of HC and CHL subjects from an industrial workforce is feasible in a restricted time frame . CHL subjects demonstrate features of the insulin resistance/hypertension syndrome , differing from HC subjects . CHL is sufficiently common relative to HC ( 2:3 ) to permit a comparison of dietary responses between the two conditions . Finally , the r and omization of HC and CHL subjects to the diets yielded statistically indistinguishable groups , permitting a test of the efficacy of the alternative diets within each hyperlipidemic ( HL ) category Phase I of the Trials of Hypertension Prevention was design ed to test the effectiveness and safety of three life-style ( weight loss , sodium restriction , and stress management ) and four nutrition supplement ( calcium , magnesium , potassium , and fish oil ) interventions in reducing diastolic blood pressure ( DBP ) in persons with a high-normal blood pressure . A total of 2182 persons with a DBP between 80 and 89 mm Hg met the eligibility criteria for participation in phase I and were r and omized to one of the active intervention or control treatment groups . Most were white ( 82 % ) , male ( 70 % ) , married ( 76 % ) , nonsmoking ( 88 % ) , college graduate ( 53 % ) , full-time employees ( 91 % ) . The average blood pressure prior to entry into the trial was 124.9 mm Hg systolic and 83.8 mm Hg diastolic . A variety of baseline observations , including sociodemographic characteristics , personal and family medical history , health habits , diet , and biologic measurements , were documented before r and omization and compared among the seven active intervention and control groups . As might be expected in a r and omized trial of this sample size , the distribution of measured baseline characteristics was virtually identical in the treated and control groups . Based on this finding and the knowledge that r and omization procedures were implemented without deviation from the phase I protocol , it is probable that unknown potential confounders were also equally distributed at entry into the study . Given the achievement of high rates of follow-up , subsequent differences in blood pressure are unlikely to have been due to baseline differences between the active treatment and control groups , and can probably be attributed to effects of the active interventions OBJECTIVE Individuals with impaired glucose tolerance ( IGT ) have a high risk of developing NIDDM . The purpose of this study was to determine whether diet and exercise interventions in those with IGT may delay the development of NIDDM , i.e. , reduce the incidence of NIDDM , and thereby reduce the overall incidence of diabetic complications , such as cardiovascular , renal , and retinal disease , and the excess mortality attributable to these complications . RESEARCH DESIGN AND METHODS In 1986 , 110,660 men and women from 33 health care clinics in the city of Da Qing , China , were screened for IGT and NIDDM . Of these individuals , 577 were classified ( using World Health Organization criteria ) as having IGT . Subjects were r and omized by clinic into a clinical trial , either to a control group or to one of three active treatment groups : diet only , exercise only , or diet plus exercise . Follow-up evaluation examinations were conducted at 2-year intervals over a 6-year period to identify subjects who developed NIDDM . Cox 's proportional hazard analysis was used to determine if the incidence of NIDDM varied by treatment assignment . RESULTS The cumulative incidence of diabetes at 6 years was 67.7 % ( 95 % CI , 59.8–75.2 ) in the control group compared with 43.8 % ( 95 % CI , 35.5–52.3 ) in the diet group , 41.1 % ( 95 % CI , 33.4–49.4 ) in the exercise group , and 46.0 % ( 95 % CI , 37.3–54.7 ) in the diet-plus-exercise group ( P < 0.05 ) . When analyzed by clinic , each of the active intervention groups differed significantly from the control clinics ( P < 0.05 ) . The relative decrease in rate of development of diabetes in the active treatment groups was similar when subjects were stratified as lean or overweight ( BMI < or ≥ 25 kg/m2 ) . In a proportional hazards analysis adjusted for differences in baseline BMI and fasting glucose , the diet , exercise , and diet-plus-exercise interventions were associated with 31 % ( P < 0.03 ) , 46 % ( P < 0.0005 ) , and 42 % ( P < 0.005 ) reductions in risk of developing diabetes , respectively . CONCLUSIONS Diet and /or exercise interventions led to a significant decrease in the incidence of diabetes over a 6-year period among those with IGT In this r and omized dietary intervention study ( DI ) we analyzed levels of and rogens , phytoestrogens , and estrogens in 12-h urine sample s of 69 healthy postmenopausal women , 37 of whom followed a traditional Mediterranean diet for 6 months ( intervention group ) as compared to 32 women who followed their regular diet ( control group ) . Circulating levels of both insulin and testosterone ( T ) were also assayed . Overall , enterolactone ( ENL ) was the most prominent phytoestrogen in urines of both control and intervention women , and its levels increased by a 20 % after DI . At the baseline the ENL levels were seen to be significantly associated with both the total and rogens ( TOT-A ) ( r= 0.371 , P= 0.002 ) and the TOT-A/total estrogen ( TOT-E ) ratio ( r= 0.351 , P= 0.005 ) in all 69 postmenopausal women . Furthermore , the DI result ed in a more pronounced negative association of both ENL with insulin ( r=-0.321 , P= 0.05 ) and insulin with TOT-A ( r=-0.421 , P= 0.01 ) . Regarding urinary and rogens , ENL associated with both 3alpha- and rosterone ( 5alpha- and rogen , r= 0.363 , P= 0.002 ) and 3alpha-etiocholanolone ( 5beta- and rogen , r= 0.295 , P= 0.01 ) at baseline , while after DI , circulating insulin and T exhibited a significant negative association with the 5beta- and rogen metabolite etiocholanolone ( r=-0.487 , P= 0.002 ; and r=-0.336 , P= 0.042 , respectively ) . We conclude that lignan components of the Mediterranean diet , notably ENL , are associated with urinary levels of products of and rogen metabolism , including both 5alpha- and 5beta-reductase enzymes , in healthy postmenopausal women . Further studies are necessary to better underst and the interplay of sex hormones with dietary phytoestrogens OBJECTIVES To test whether serum von Willebr and factor ( vWf ) would be lower in men with atherosclerosis who had been consuming a lipid-lowering diet for 3 years than in a control group of men with atherosclerosis who had been following their normal diet . DESIGN A r and omized , population -based case-control study . SETTING A tertiary health care referral centre at a University Hospital . SUBJECTS Men age less than 66 years with angiographically proven coronary atherosclerosis and a cholesterol level > 6 mmol L-1 . Sixty started the study and 50 completed it . INTERVENTIONS Subjects were r and omized to a lipid-lowering diet or to taking their normal diet for approximately 3 years . MAIN OUTCOME MEASURES The components of the subjects ' diets were assessed and blood was obtained for total , low-density lipoprotein ( LDL ) and high-density lipoprotein ( HDL ) cholesterol , triglycerides and for vWf . RESULTS Men on the lipid-lowering diet consumed less total , saturated and monounsaturated fats ( all P < 0.001 ) , cholesterol and retinol ( both P < 0.002 ) but increased polyunsaturated fats ( P < 0.001 ) , fibre , vitamin E ( both P < 0.005 ) and carbohydrate ( P < 0.05 ) . Those on the lipid-lowering diet also had lower serum levels of total and LDL cholesterol ( P < 0.002 and P < 0.05 , respectively ) , triglycerides ( P < 0.02 ) and vWf ( P < 0.05 ) than the men on their normal diet . There was no difference in HDL cholesterol . Levels of vWf correlated with both total cholesterol ( P < 0.005 ) and inversely with dietary polyunsaturated fats ( P < 0.02 ) . CONCLUSION von Willebr and factor , a possible indicator of endothelial cell damage , decreases during long-term compliance with a lipid-lowering diet Objectives : To compare the effects of free access to reduced fat products or their full fat equivalents on fat and energy intake , body weight , plasma lipids and fat-soluble antioxidants concentrations and haemostasis variables . Design : A multicentre open r and omised controlled trial in which intervention and control groups were followed in parallel for six months . Volunteers had free access to 44 different foods either in reduced fat or full fat version , covering between 30 and 40 % of energy intake . The remainder of energy intake was covered by foods bought in regular shops . Setting : Zeist , Wageningen and Maastricht , The Netherl and s . Subjects : Two hundred and forty-one non-obese healthy volunteers who had no intention to lose weight . Main outcome measures : Food intake , body weight , plasma lipid , vitamin E , β-carotene , lycopene and fibrinogen concentrations , plasma factor VII clotting activity , and plasminogen-activator-inhibitor-I antigen level . Results : One hundred and three volunteers in the full fat group and 117 volunteers in the reduced fat group completed the study . Energy and fat intake from the free access products was lower in the reduced fat group , but no difference in energy and fat intake of other products occurred . Body weight , energy- , fat- and vitamin E intake and percentage of energy derived from fat decreased in the reduced fat group . No other statistical significant intervention effects were observed . Blood lipid concentrations , factor VII activity and plasminogen-inhibitor-activator-1 level were reduced after consumption of reduced fat products . Conclusions : When subjects without intention to lose weight limit fat intake by switching from ad libitum consumption of full fat products to reduced fat products body weight gain is prevented , and fat and energy intake are reduced . Such a switch may have beneficial effects on biochemical cardiovascular risk factors . We concluded that reduced fat products will help in a population strategy aim ed at preventing overweight and obesity , they will also be effective in maintaining a lower body weight after slimming . Ad libitum consumption of reduced fat products will be ineffective for those individuals that want to reduce body weight because they are currently overweight or obese . Sponsorship : BACKGROUND Pre clinical and observational studies suggest a relationship between dietary fat intake and breast cancer , but the association remains controversial . We carried out a r and omized , prospect i ve , multicenter clinical trial to test the effect of a dietary intervention design ed to reduce fat intake in women with resected , early-stage breast cancer receiving conventional cancer management . METHODS A total of 2437 women were r and omly assigned between February 1994 and January 2001 in a ratio of 40:60 to dietary intervention ( n = 975 ) or control ( n = 1462 ) groups . An interim analysis was performed after a median follow-up of 60 months when funding for the intervention ceased . Mean differences between dietary intervention and control groups in nutrient intakes and anthropometric variables were compared with t tests . Relapse-free survival was examined using Kaplan-Meier analysis , stratified log-rank tests , and Cox proportional hazards models . Statistical tests were two-sided . RESULTS Dietary fat intake was lower in the intervention than in the control group ( fat grams/day at 12 months , 33.3 [ 95 % confidence interval { CI } = 32.2 to 34.5 ] versus 51.3 [ 95 % CI = 50.0 to 52.7 ] , respectively ; P<.001 ) , corresponding to a statistically significant ( P = .005 ) , 6-pound lower mean body weight in the intervention group . A total of 277 relapse events ( local , regional , distant , or ipsilateral breast cancer recurrence or new contralateral breast cancer ) have been reported in 96 of 975 ( 9.8 % ) women in the dietary group and 181 of 1462 ( 12.4 % ) women in the control group . The hazard ratio of relapse events in the intervention group compared with the control group was 0.76 ( 95 % CI = 0.60 to 0.98 , P = .077 for stratified log rank and P = .034 for adjusted Cox model analysis ) . Exploratory analyses suggested a differential effect of the dietary intervention based on hormonal receptor status . CONCLUSIONS A lifestyle intervention reducing dietary fat intake , with modest influence on body weight , may improve relapse-free survival of breast cancer patients receiving conventional cancer management . Longer , ongoing nonintervention follow-up will address original protocol design plans , which called for 3 years of follow-up after completion of recruitment OBJECTIVE This article investigates the effects of a brief psychological intervention-implementation intentions training-on the reduction of saturated fat intake among patients after myocardial infa rct ion ( MI ) . METHODS One hundred fourteen patients who had experienced a first uncomplicated MI took part in the study . Data were collected at approximately 1 week after MI , 2 weeks after short-term Phase 2 cardiac rehabilitation ( approximately 2 months after MI ) , and 6 months after rehabilitation ( 8 months after MI ) . After data collection at 2 weeks after rehabilitation , patients were r and omly assigned to the control group or the intervention group ( an individually delivered implementation intentions training ) . Daily saturated fat intake was used as the primary outcome ; total fat intake and percentage of calories from fat were secondary outcomes . RESULTS Repeated- measures analysis of variance showed a significant TimexGroup interaction : Compared to time before MI , patients in both groups reported a decrease in saturated fat intake at 2 weeks after rehabilitation . Those who participated in the implementation intentions intervention were able to further decrease saturated fat intake from 22.88 g at 2 months after MI to 19.71 g at 8 months after MI . Patients from the control group maintained the same level of saturated fat intake at 2 months after MI ( mean=22.30 ) and 6 months later ( mean=22.47 ) . CONCLUSIONS An individually delivered implementation intentions intervention may reduce saturated fat intake among patients after MI The growing public concern with the adverse effects on health of a high fat intake has led to a proliferation on the market of reduced fat products . However , no consensus exists on the effectivity of reduced fat products to decrease energy intake . The studies that have investigated this topic have included small numbers of subjects , studied under laboratory conditions and over a relatively short period of time . Therefore , we have executed a long-term study in which volunteers had free access to both reduced fat , commercially available products in the laboratory as well as to products obtained from regular shops . We here report the feasibility of such a type of study and the effects of consumption of reduced fat products on blood levels of cholesterol , haemostasis variables , antioxidants and parameters of the immune system . The study was a multicentre parallel comparison trial of six months ( so-called MSFAT- study ) . 241 volunteers received either reduced fat products or full-fat products and the products were clearly labelled as such . Two months before the start of the study , a 1 month adaptation period was executed to optimize the experimental procedures . Food intake was recorded before the start of the adaptation period and 2 - 4 weeks , 3 months and 6 months after the start of the study . Blood sample s were taken before , after 2 , 4 and 6 months of the study . In addition , a selection of the reduced fat and full-fat products was sensorically evaluated three times during the study by a subgroup of the volunteers . 220 volunteers completed the study . The reduced fat group consumed on average 46 % less fat from the so-called MSFAT-products obtained from the shop at the laboratory than the control group and consumption of these MSFAT-products did not decrease in either of the groups during the time course of the study . The palatability of the reduced fat and full-fat products was similar and as expected , the perceived fattiness of the full-fat products was higher than that of the reduced fat products . No effects were found on blood levels of cholesterol , haemostasis variables , parameters of antioxidant status and immune system characteristics . In conclusion , the experimental manipulation of the fat content of the diet that was achieved and that remained stable throughout the 6 months of the study indicates that this type of set-up is feasible to assess the effects of long-term nutritional intervention in large groups of volunteers under semi-controlled conditions . The regular use of reduced fat products did not positively but also not adversely affect blood cholesterol levels , antioxidant status , haemostasis factors and the body 's immune system BACKGROUND Epidemiologic observations have linked healthy dietary patterns to improved kidney function . STUDY DESIGN We assessed the effects of the Mediterranean diet ( MedDiet ) on kidney function in both a cross-sectional assessment and after a 1-year intervention in a cohort of the PREDIMED ( Prevención con Dieta Mediterránea ) Study , a multicenter 3-arm r and omized clinical trial to determine the efficacy of the MedDiet on primary cardiovascular prevention . SETTING & PARTICIPANTS Community-dwelling men aged 55 - 80 years and women aged 60 - 80 years at high risk of cardiovascular disease from Reus , Spain . INTERVENTION Participants were r and omly assigned to 3 ad libitum diets : a MedDiet supplemented with virgin olive oil ( MedDiet + olive oil ) , a MedDiet supplemented with mixed nuts ( MedDiet + nuts ) , or a control low-fat diet . OUTCOMES Estimated glomerular filtration rate ( eGFR ) and urinary albumin-creatinine ratio ( ACR ) . MEASUREMENTS Nutrient intake , adherence to the MedDiet , lifestyle variables , cardiovascular risk factors , serum urea and creatinine concentrations , eGFR , and urinary ACR were evaluated at baseline and after intervention for 1 year . RESULTS Baseline kidney function markers were similar across quartiles of adherence to the MedDiet in 785 participants ( 55 % women ; mean age , 67 years ) . After a 1-year intervention in 665 participants , the 3 dietary approaches were associated with improved kidney function , with similar average increases in eGFR ( 4.7 [ 95 % CI , 3.2 - 6.2 ] , 3.5 [ 95 % CI , 1.9 - 5.0 ] , and 4.1 [ 95 % CI , 2.8 - 5.5 ] mL/min/1.73 m(2 ) for the MedDiet + olive oil , MedDiet + nuts , and control groups , respectively [ P < 0.001 vs baseline for each ; P = 0.9 for differences among groups ] ) , but no changes in ACRs after adjustment for various confounders . LIMITATIONS Generalization of results to other age groups or ethnicities . GFR was not directly measured . CONCLUSIONS The results do not support the notion that the MedDiet has a beneficial effect on kidney function over and above that of advice for a low-fat diet in elderly individuals at high cardiovascular risk BACKGROUND A r and omized study was conducted to test the feasibility of cholesterol lowering in physician office practice s using the National Cholesterol Education Program Adult Treatment Panel 1 guidelines . METHODS Twenty-two physician practice s in phase 1 and 23 in phase 2 were recruited from communities in Western Pennsylvania and West Virginia . These physicians treated a total of 450 adults in phase 1 ( 190 men and 260 women ) and 480 adults in phase 2 ( 184 men and 296 women ) with hypercholesterolemia . Three models ( Usual Care [ phase 1 ] , Office Assisted [ phase 2 ] , and Nutrition Center [ phase 2 ] ) for implementing the National Cholesterol Education Program Adult Treatment Panel 1 guidelines were tested over an 18-month period . The baseline serum cholesterol levels were as follows : 6.51 mmol/L ( 252 mg/dL ) in the Usual Care Model ; 6.80 mmol/L ( 262 mg/dL ) in the Office Assisted Model ; and 6.96 mmol/L ( 269 mg/dL ) in the Nutrition Center Model . RESULTS In the patients who were not taking lipid-lowering medication , the mean cholesterol response was significantly different between the 3 models ( P < .01 ) . Serum cholesterol levels declined by 0.14 mmol/L ( 5.4 mg/dL ) in the Usual Care Model ; by 0.31 mmol/L ( 12 mg/dL ) in the Office Assisted Model ; and by 0.54 mmol/L ( 20.9 mg/dL ) in the Nutrition Center Model . Two factors-length of time to follow-up measurement and change in weight-were independently related to cholesterol response across all models . African Americans demonstrated a significantly smaller response than whites in the Usual Care Model , while men demonstrated greater declines in serum cholesterol levels than women in the Office Assisted Model . Patient satisfaction was very favorable in both enhanced conditions ; however , those treated in the the Nutrition Center Model were more satisfied ( P < .05 ) with program components . CONCLUSIONS The impact of nutrition intervention delivered through physician practice s on serum cholesterol levels is less than clinical ly desirable , and new approaches with more aggressive therapy should be tested and implemented The effect of a low-fat diet on occurrence of non-melanoma skin cancer was examined in a 2-year dietary intervention trial . A total of 101 skin-cancer patients were r and omized either to a control group that consumed , on average , 38 % of caloric intake as fat , and in which no changes in dietary habits were introduced , or to a low-fat dietary-intervention group , in which patients were instructed to limit their calories from fat to 20 % of total caloric intake . Patients were examined at 4-month intervals by dermatologists blinded to their dietary assignments . Nutrient analyses , conducted at each of the 4-month follow-up visits , indicated that the % calories of fat consumed in the intervention group had been reduced to 21 % at 4 months and remained below this level throughout the 2-year period . There were no significant differences in total calories consumed , or in mean body weights , between the control and the intervention groups . Nor were there significant group differences in P/S ratios until month 24 . Numbers of new skin cancers treated at each examination were analyzed in 8-month periods of the 2-year study . Comparisons of skin-cancer occurrences revealed no significant changes in the control group from baseline values . However , cancer occurrence in the low-fat intervention group declined after the first 8-month period and reached statistical significance by the last 8-month period . Patients in this group had significantly fewer cancers in the last 8-month period than did patients in the control group . In addition , there was a significant reduction in the number of patients developing skin cancer in the last 8-month period , as compared with the first 8-month period , within the low-fat intervention group . There were no significant changes in the control group . These data indicate that a low-fat diet can significantly reduce occurrence of a highly prevalent form of cancer OBJECTIVE To determine whether adoption of dietary patterns consistent with the US Dietary Guidelines for Americans and the Food Guide Pyramid , combined with exercise training , result in significant reductions in cardiovascular risk compared with a regimen of exercise therapy alone . DESIGN A r and omized trial to compare the effects of exercise alone ( n = 17 ) with the effects of exercise and dietary intervention ( n = 15 ) . SETTING McClellan Air Force Base medical clinic ( Sacramento , Calif ) . SUBJECTS Thirty-two members of the Air Force ( 20 men and 12 women ) were recruited at the time they entered a 90-day fitness improvement program . Mean age was 32 years . INTERVENTION All subjects participated in a 90-day fitness program . Half of the group received individualized dietary counseling using the Food Guide Pyramid as a primary educational tool . MAIN OUTCOME MEASURES Changes in body mass index , plasma lipids and lipoprotein levels , aerobic capacity , and dietary intake were selected to evaluate the effectiveness of the intervention . STATISTICAL ANALYSES PERFORMED Outcome measures were evaluated by analysis of variance . A paired t test was performed to compare changes in food-group servings and food-group fat intake from baseline values for the exercise-plus-diet group . RESULTS Percentage of energy from fat decreased from 39 % to 23 % for the exercise-plus-diet group , and servings from each of the food groups changed to reflect current guidelines . This group also had significant reductions in body mass index , total cholesterol level , and low-density lipoprotein level : 2 % ( P = .0001 ) , 9 % ( P = .003 ) , and 13 % ( P = .005 ) , respectively . No change was observed for the exercise-only group . Additionally , a significant improvement in maximum oxygen consumption ( P = .01 ) of 38 % ( vs 14 % for the control group ) was achieved . CONCLUSIONS Dietary modification in accordance with the Food Guide Pyramid and the US Dietary Guidelines results in significant reductions in known cardiovascular risk factors and improves the response to exercise training Coronary artery bypass ( CAB ) patients are older increasingly more often than before . Effectiveness of cardiac rehabilitation among the elderly is not yet adequately known about . The purpose was to describe short-term ( 3-month ) , intermediate ( 6-month ) , and long-term ( 12-month ) effects of health counseling , guidance , and adjustment education in groups on health , health behaviors , and functional abilities among older CAB patients . The study population was r and omized to an intervention group ( IG=49 ) and a control group ( CG=68 ) . Prior to CAB , intervention included one guidance and counseling group session and four sessions within 12 months following CAB . Intervention had positive effects on exercise activities , use of alcohol , and functional abilities among all participants , and on frequency of eating visible fat , fresh greens and vegetables among men . The intervention was effective with some exercise activities and functional abilities persisting for at least 1 year following CAB . Similar interventions may be arranged for older people . Health care professionals need to guide and encourage older people in their efforts to participate in them OBJECTIVE To evaluate the 6-month change in cardiovascular ( coronary heart disease ) risk as a function of diet and drug therapy for mild hypertension . DESIGN Collaborative r and omized , controlled clinical trial to assess the efficacy of alternative regimens in treating mild hypertension . SETTING Three university-based tertiary care centers-the Trial of Antihypertensive Interventions and Management ( T AIM ) . PATIENTS Six hundred and ninety-two men and women ages 21 to 65 years with diastolic blood pressure between 90 and 100 mm Hg and weight between 110 % and 160 % of ideal weight . MEASUREMENTS AND MAIN RESULTS Patients stratified by clinical center and race were r and omized into diet ( usual , low sodium-high potassium , weight loss ) and drug ( placebo , chlorthalidone , and atenolol ) groups result ing in nine diet plus drug combinations . The cardiovascular risk at 6-month follow-up was estimated relative to baseline in 692 participants using the Framingham Study model . Due to the blood pressure reduction , cardiovascular risk declined from baseline for all treatment groups ( except the usual diet plus chlorthalidone group because of increased cholesterol levels ) . The relative cardiovascular risk at 6 months compared to baseline ranged from 0.83 in the weight loss plus atenolol subgroup to 1.03 in the usual diet plus chlorthalidone subgroup . The active drug plus weight loss groups showed the lowest relative cardiovascular risk at 6 months . CONCLUSIONS Mild hypertension was generally reduced to desirable levels within 6 months by monotherapy . Evaluating blood pressure changes together with the risk factors indicated a differential effect on overall cardiovascular risk depending on the diet and drug used . Dietary therapy , particularly weight reduction , was important adjunctive treatment in reducing overall cardiovascular risk OBJECTIVES This paper presents the behavioral results of the Working Well Trial , the largest US work site cancer prevention and control trial to date . METHODS The Working Well Trial used a r and omized , matched-pair evaluation design , with the work site as the unit of assignment and analysis . The study was conducted in 111 work sites ( n = 28,000 workers ) . The effects of the intervention were evaluated by comparing changes in intervention and control work sites , as measured in cross-sectional surveys at baseline and follow-up . The 2-year intervention targeted both individuals and the work-site environment . RESULTS There occurred a net reduction in the percentage of energy obtained from fat consumption of 0.37 percentage points ( P = .033 ) , a net increase in fiber densities of 0.13 g/1000 kcal ( P = .056 ) , and an average increase in fruit and vegetable intake of 0.18 servings per day ( P = .0001 ) . Changes in tobacco use were in the desired direction but were not significant . CONCLUSIONS Significant but small differences were observed for nutrition . Positive trends , but no significant results , were observed in trial-wide smoking outcomes . The observed net differences were small owing to the substantial secular changes in target behaviors Breast cancer is a major cause of death and disability among women in the United States . One in nine women will develop breast cancer at some point in their lives . Over the years , treatment modalities have improved , but mortality from breast cancer has changed little since 1930.1 This observation dictates a need for greater efforts toward disease prevention . One important new prevention strategy to reduce the incidence of breast cancer is dietary intervention Background Physical activity levels among breast cancer survivors are typically low , and knowledge of the correlates of increased physical activity among cancer survivors is limited . The purpose of this study was to examine factors that are associated with physical activity or inactivity among breast cancer survivors . Methods Data from 3088 women participating in the Women ’s Healthy Eating and Living ( WHEL ) Study , collected prior to r and omization , were the focus of the current analyses . Self-reports of physical activity levels , quality of life , depression , and dietary intakes were collected . Pearson correlation analyses were employed to examine the associations among these variables , and multiple regression analyses were performed to examine the relationship between selected health behaviors and physical activity levels , after controlling for demographic , breast cancer-related , and psychosocial variables . Results Demographic and psychosocial variables were related to physical activity levels ( P < 0.001 for all ) . Cancer treatment type and cancer stage were correlated with survivors ’ physical activity levels ( P < 0.01 ) , but the associations were no longer significant after controlling for demographic variables . Physical activity levels were strongly associated with other health behaviors , especially dietary intakes ( P < 0.001 ) , even after controlling for demographic , cancer-related , and psychosocial factors . Conclusion Low physical activity levels in breast cancer survivors are associated with specific behavioral and other factors , which can be considered as indicators of women at higher risk . Findings of significant differences in physical activity levels based on demographic characteristics suggest the importance of promoting physical activity particularly among breast cancer survivors of ethnic minority or lower education levels Self-referred subjects ( N = 227 ) thought to be at risk of developing non-insulin-dependent diabetes mellitus ( NIDDM ) and with fasting plasma glucose ( FPG ) in the range of 5.5 to 7.7 mmol . L-1 on two consecutive tests 2 weeks apart were r and omized to reinforced or basic healthy-living advice . They were simultaneously allocated either to a sulfonylurea group or a control group in a two-by-two factorial design . A total of 201 subjects in three English and two French centers completed 1 year 's follow-up study . Reinforced advice recommending dietary modification and increased exercise was given every 3 months , and basic advice was given once at the initial visit . Glycemia was monitored by FPG , dietary compliance by body weight and food diaries , and fitness compliance by bicycle ergometer assessment and exercise diaries . Both reinforced and basic advice groups had a significant mean reduction in body weight ( 1.5 kg ) at 3 months , although the weight subsequently returned to baseline . After 1 year , subjects allocated to reinforced advice versus basic advice ( 1 ) reported a lower fat intake ( 34.1 % v 35.8 % , P = .04 ) with no difference in lipid profiles , ( 2 ) had improved fitness as shown by increased calculated maximal oxygen uptake ( [ Vo2max ] 2.39 v 2.18 L.min-1 , P = .007 ) with no change in insulin sensitivity , ( 3 ) showed no change in FPG , glucose tolerance , or hemoglobin A1c ( HbA1c ) , and ( 4 ) showed a greater tendency to withdraw from the study ( 16 % v 7 % , P = .03 ) . In conclusion , reinforced healthy-living advice given to self-referred subjects with increased FPG did not encourage sufficiently pronounced life-style changes for significantly greater effects on body weight and glycemia in a 1-year study than basic healthy-living advice OBJECTIVE To determine whether effectiveness of a diet intervention for family members of cardiovascular disease patients varies by participant sex , race/ethnicity , or age because these characteristics have been associated with unique barriers to diet change . DESIGN R and omized controlled trial . SETTING AND PARTICIPANTS University medical center . Healthy adult family members of patients hospitalized with cardiovascular disease ( n = 501 ; 66 % women ; 36 % racial/ethnic minorities ; mean age 48 years ) . INTERVENTION A special screening and educational intervention ( SI ) vs control intervention ( CI ) to reduce dietary saturated fat and cholesterol intake throughout 1 year . MAIN OUTCOME MEASURES Absolute change in MEDFICTS ( meats , eggs , dairy , fried foods , fat in baked goods , convenience foods , fats added at the table and snacks ) diet score , saturated fat , and dietary cholesterol in the SI vs CI from baseline to 1 year . ANALYSIS t tests stratified by sex , race/ethnicity , and age group ; linear regression . Significance set at P < .05 . RESULTS The SI was effective to improve MEDFICTS score independent of sex , race/ethnicity , and age group ( β = -6.7 ; P < .001 ) . There was no interaction between the SI and sex ( β = .9 ; P = .84 ) , race/ethnicity ( β = -1.1 ; P = .81 ) , or age group ( β = -.6 ; P = .89 ) on change in MEDFICTS score or change in saturated fat or dietary cholesterol intake from baseline to 1 year . CONCLUSIONS AND IMPLICATION S Results support the potential for a hospital-based screening and education program to improve diet in diverse population s of cardiovascular disease patient family members Table . SI Units Systematic modification of coronary risk factors is not integrated into the medical care provided to most of the more than 1 million patients treated annually in the United States for acute myocardial infa rct ion by percutaneous transluminal coronary angioplasty or coronary artery surgery . Most of such patients have lipoprotein abnormalities [ 1 ] , and nearly one half smoke [ 2 ] . These risk factors , which contribute to subsequent morbidity and mortality , remain highly prevalent after acute cardiac events . Failure to integrate comprehensive risk factor modification into the st and ard medical care provided to patients after acute cardiac events primarily reflects the lack of an organizational framework or system . This deficiency in re source allocation for preventive and rehabilitative aspects of care in turn reflects the predominant orientation of the U.S. health care system to the management of acute illness [ 3 ] . Several clinical research studies have shown the effectiveness of risk factor modification , especially treatment of lipoprotein abnormalities [ 4 - 7 ] , in achieving regression of coronary artery lesions and reducing the clinical consequences of coronary artery disease [ 6 , 7 ] . However , risk factor interventions shown to be effective in clinical trials may not prove equally effective in clinical practice because of a paucity of re sources , especially nonphysician personnel . The lack of effective management systems limits the expected reduction in morbidity and mortality and the corresponding reduction in medical care costs that motivates current efforts to orient the priorities of the American health care system toward preventive and rehabilitative care . This r and omized , controlled trial compared the effectiveness of a physician-directed , nurse-managed , home-based case-management system for coronary risk factor modification with that of usual medical care . Outcomes were measured in both groups immediately after the end of the first year after acute myocardial infa rct ion . The term case-management system has been used in various context s. As used here , it refers to a system in which a nurse case-manager , working with different health care specialists ( a psychiatrist , a cardiologist , a lipid specialist , a nutritionist , and a nurse coordinator ) , managed coronary risk factors . Methods Enrollment and Orientation Program nurses enlisted patients on hospital day 3 or as soon as their medical condition stabilized . Study participants gave written informed consent to be r and omly assigned to a treatment group . Immediately after r and omization , program nurses introduced patients to the special intervention with the aid of a videotape . Usual Care The 585 patients in our study were cared for by 215 internists and 34 cardiologists in the five participating medical centers who were organized into practice groups of 5 to 10 physicians each . Cardiology consultation was often provided during hospitalization , but primary responsibility for follow-up care was generally assumed by internists . The usual care offered by the Kaiser Permanente Medical Care Program included physician counseling on smoking cessation and nutritionist counseling on dietary change during hospitalization and physician-managed , lipid-lowering drug therapy after hospital discharge . Group outpatient smoking cessation programs were available for a $ 50 fee . Group exercise rehabilitation , not generally provided by the Kaiser Permanente Medical Care Program during this study , was available to patients at various community facilities at an average cost of $ 1800 to $ 2700 for 3 months ' participation . Special Intervention The behavioral interventions in our case-management system , which were offered to the 293 patients in the intervention group in addition to usual care , were derived from social learning theory [ 8 , 9 ] and modified for medical problems [ 10 ] . In this model , persons must learn how to monitor the health habits they seek to change , set attainable sub goals to motivate and direct their efforts , use feedback of progress in ways that promote health , and enlist incentives and social support to sustain the effort needed to succeed [ 8 , 9 ] . In the hospital , patients were instructed on how to complete self-reports [ status reports ] of smoking , dietary intake , and exercise . Scheduled interactions between case managers and patients after discharge took three forms : 1 ) nurse-initiated telephone contacts ; 2 ) computer-generated progress reports mailed to patients based on question naires completed by patients and mailed to the nurses ; and 3 ) visits to the program nurse for treadmill exercise testing , initiation of lipid-lowering drug therapy , if indicated , and a single counseling session after a smoking relapse . The maximum number of treatment contacts during the year , including outcome measurement at 6 and 12 months , was as follows : 14 nurse-initiated telephone contacts , 8 patient visits to the blood chemistry laboratory , and 4 patient visits to the nurse case manager . Smoking Intervention Smoking was defined as the use of cigarettes , cigars , cigarillos , pipe tobacco , or any other form of tobacco in the 6 months before admission . Forty-three percent of patients were smokers . Patients who had smoked during the 6 months before hospitalization received the same intensive smoking cessation intervention during hospitalization ; this intervention has been described previously [ 11 ] . Physicians used a written script that enabled them to provide st and ardized counseling in less than 2 minutes . The hospital-based smoking cessation counseling focused on relapse prevention . Nurses conducted a st and ardized smoking history to evaluate patients ' addiction to smoking . Patients ' reported self-efficacy or confidence to resist smoking in each of 28 potentially high-risk situations was measured ; patients were then counseled on how to manage the situations in which they reported less than 70 % confidence . Patients also received a relapse prevention manual and a relaxation audiotape . They were advised that the nurse would telephone them 48 hours and 1 week after hospital discharge and at monthly intervals for as long as 6 months . Patients who relapsed were offered one additional visit with the nurse for further counseling . Nicotine polacrilex or transdermal nicotine patches were reserved for highly addicted patients who relapsed after hospital discharge . Nutritional Counseling A computer-based expert system developed by the investigators was used to provide nutritional counseling on a National Cholesterol Education Program [ 12 ] Step 2 diet that was low in cholesterol and saturated fat . A food frequency question naire design ed by the investigators was scored using the Cholesterol and Saturated Fat Index developed by Connor and colleagues [ 13 ] . Calculations of cholesterol and saturated fat totals were based on weekly rather than daily average food intakes . Data from the food frequency question naires , mailed by patients to the Stanford coordinating center and entered into a microcomputer , were used to generate progress reports that characterized patients ' dietary patterns , prioritized dietary change goals , and provided guides for managing difficult situations by directing patients to relevant sections of a nutrition workbook entitled Good Eating for Good Health developed by the program nutritionist . Patients in the intervention group completed a food frequency question naire during hospitalization that described their eating habits in the previous month . Patients also completed food frequency question naires 6 , 11 , and 26 weeks after admission . Progress reports were mailed to patients within 48 to 72 hours after the food frequency question naires were received . Detailed strategies for maintenance of dietary change were incorporated into the 26-week progress report . Question naires to evaluate outcomes were also completed at 36 and 52 weeks . Lipid-Lowering Drug Therapy The therapeutic goal of a plasma low-density lipoprotein (LDL)-cholesterol value of 2.46 mmol/L ( 95 mg/dL ) adopted for this trial was based on the mean post-treatment level of LDL cholesterol found in patients in the study by Blankenhorn and colleagues [ 4 ] . Patients with mean plasma LDL cholesterol values ( based on measurements in two separate blood sample s drawn 75 and 90 days after infa rct ion ) that exceeded this value were given initial drug therapy according to the four algorithms shown in Table 1 . Patients unable to tolerate bile acid-binding resin or nicotinic acid because of comorbid conditions or potentially adverse interactions with these agents received lovastatin or gemfibrozil . During a visit 90 days after discharge , the nurses did a brief physical examination and obtained a history relevant to hyperlipidemia . They provided detailed counseling to patients regarding the rationale for lipid-lowering drug therapy and ways to maximize drug efficacy and minimize drug side effects , and they advised patients on the schedule of laboratory visits and nurse-initiated follow-up telephone contacts . Table 1 . Initial Drug Therapy * Changes in drug therapy at 120 , 150 , and 180 days , which were coordinated by nurse-initiated telephone contacts , were based on three types of responses to initial therapy : 1 ) if lipoprotein levels returned to normal , the effective drug therapy was continued ; 2 ) if the response was incomplete , the dose of the effective medication was increased or another drug was added , or both ; and 3 ) if comorbid conditions worsened or blood chemistry abnormalities or intolerable side effects occurred , drug dosage was reduced or the patient was switched to another agent or both . A physician lipid specialist and a Stanford-based senior nurse-coordinator provided telephone consultation to the case managers . Before initiating lipid-lowering drug therapy at 90 days and at each subsequent step , nurses review ed the patients ' blood chemistry and lipoprotein values and elicited any symptoms requiring a change in therapy . The OBJECTIVE : Treatment of elevated cholesterol levels reduces morbidity and mortality from coronary heart disease in high-risk patients , but can be costly . The purpose of this study was to determine whether physician extenders emphasizing diet modification and , when necessary , effective and inexpensive drug algorithms can provide more cost-effective therapy than conventional care . DESIGN : R and omized controlled trial . SETTING : A Department of Veterans Affairs Medical Center . PATIENTS : Two hundred forty-seven veterans with type IIa hypercholesterolemia . INTERVENTIONS : Patients assigned to either a cholesterol treatment program ( CTP ) or usual health care provided by general internists ( UHC ) . CTP included intensive dietary therapy administered by a registered dietitian utilizing individual and group counseling and drug therapy initiated by physician extenders for those failing to achieve goal low-density lipo-protein ( LDL ) levels with diet alone . A drug selection algorithm for CTP subjects utilized niacin as initial therapy followed by bile acid sequestrants and lovastatin . Subjects were followed prospect ively for 2 years . MEASUREMENTS : Primary outcome measurements were effectiveness of therapy defined as reductions in LDL cholesterol ( LDL-C ) , and whether goal LDL-C levels were achieved ; costs of therapy ; and cost-effectiveness defined as the cost per unit reduction in the LDL-C.MAIN RESULTS : Total program costs were higher for CTP patients than for UHC patients ( $ 659±$43 vs $ 477±$42 per patient , p<.001 ) . However , at 24 months the patients in CTP were more likely to achieve LDL goal levels ( 65 % vs 44%,p<.005 ) , and also achieved greater reductions in LDL-C 27%±2 % vs 14%±2 % at 24 months , p<.001 ) . Program costs per unit ( mmol/L ) reduction in the LDL-C , a measure of cost-effectiveness , was significantly lower for CTP ( $ 758±$58 vs $ 1,058±$70,p=.002 ) . CONCLUSIONS : Although more expensive than usual care , the greater effectiveness of physician extenders implementing cholesterol treatment algorithms result ed in more cost-effective therapy Background : The influence of a low-fat dietary pattern on the cardiovascular health of postmenopausal women continues to be of public health interest . Objective : This report evaluates low-fat dietary pattern influences on cardiovascular disease ( CVD ) incidence and mortality during the intervention and postintervention phases of the Women 's Health Initiative Dietary Modification Trial . Design : Participants comprised 48,835 postmenopausal women aged 50 - 79 y ; 40 % were r and omly assigned to a low-fat dietary pattern intervention ( target of 20 % of energy from fat ) , and 60 % were r and omly assigned to a usual diet comparison group . The 8.3-y intervention period ended in March 2005 , after which > 80 % of surviving participants consented to additional active follow-up through September 2010 ; all participants were followed for mortality through 2013 . Breast and colorectal cancer were the primary trial outcomes , and coronary heart disease ( CHD ) and overall CVD were additional design ated outcomes . Results : Incidence rates for CHD and total CVD did not differ between the intervention and comparison groups in either the intervention or postintervention period . However , CHD HRs comparing these groups varied strongly with baseline CVD and hypertension status . Participants without prior CVD had an intervention period CHD HR of 0.70 ( 95 % CI : 0.56 , 0.87 ) or 1.04 ( 95 % CI : 0.90 , 1.19 ) if they were normotensive or hypertensive , respectively ( P-interaction = 0.003 ) . The CHD benefit among healthy normotensive women was partially offset by an increase in ischemic stroke risk . Corresponding HRs in the postintervention period were close to null . Participants with CVD at baseline ( 3.4 % ) had CHD HRs of 1.47 ( 95 % CI : 1.12 , 1.93 ) and 1.61 ( 95 % CI : 1.02 , 2.55 ) in the intervention and postintervention periods , respectively . However , various lines of evidence suggest that results in women with CVD or hypertension at baseline are confounded by postr and omization use of cholesterol-lowering medications . Conclusions : CVD risk in postmenopausal women appears to be sensitive to a change to a low-fat dietary pattern and , among healthy women , includes both CHD benefit and stroke risk . This trial was registered at clinical trials.gov as NCT00000611 BACKGROUND This paper examines participation rates and the association between participation and study outcomes ( % energy from fat ) among participants in the Women 's Health Trial : Feasibility Study in Minority Population s , a r and omized clinical trial to determine if ethnically and socioeconomically diverse women could be recruited and make significant dietary changes . METHODS Women ( n = 2,208 ) were recruited from three clinical centers and r and omized to either an intervention group or a control group . Multiple measures were collected at 6 months . RESULTS Participation rates for follow-up data collection activities were high ( average participation 79 % ) . Hispanics and lower educational groups participated significantly less ( 59 % for Hispanics vs 86 % for blacks and whites ; 78 % for lowest educational group vs 84 % for highest educational group ) . Intervention participation significantly predicted change in percentage energy from fat ( P < 0.001 ) , accounting for an additional 8 % of variance after background variables were controlled for . CONCLUSIONS These data suggest that intervention participation is positively related to dietary change , but they can not rule out the possibility that other factors may influence both of these factors OBJECTIVE To compare and assess the single and joint effect of diet and exercise intervention for 1 year on insulin resistance and the development leading toward the insulin resistance syndrome . RESEARCH DESIGN AND METHODS An unmasked , r and omized 2 × 2 factorial intervention trial was applied with a duration of 1 year for each participant . The trial comprised 219 men and women with diastolic blood pressure of 86–99 mmHg , HDL cholesterol < 1.20 mmol/l , triglycerides > 1.4 mmol/l , total cholesterol of 5.20–7.74 mmol/l , and BMI > 24 kg/m2 . Participants were r and omly allocated to diet group ( n = 35 ) , diet and exercise group ( n = 67 ) , exercise group ( n = 54 ) , and control group ( n = 43 ) . The diet included increased intake of fish and reduced total fat intake . The exercise program entailed supervised endurance exercise three times a week . Baseline cross-sectional changes and 1-year changes in insulin resistance , fasting serum levels of insulin , C-peptide , proinsulin , glucose , and lipids as well as weight , mean blood pressure , and plasminogen activator inhibitor 1 ( PAI-1 ) values were recorded . RESULTS The cross-sectional results at baseline showed significant correlations between the calculated insulin resistance and BMI ( r = 0.54 ) and correlations between the mean blood pressure ( mBP ) ( r = 0.26 ) and PAI-1 ( r = 0.40 ) . The 1-year diet intervention gave a significant decrease in the calculated insulin resistance from 4.6 to 4.2 and a positive correlation between the changes in insulin resistance and changes in BMI ( r = 0.40 ) . The diet and exercise intervention also led to significantly decreased insulin resistance ( from 5.0 to 4.0 ) . The exercise intervention did not significantly change insulin resistance . CONCLUSIONS The cross-sectional and 1-year intervention results supported each other and underscored the important connection between increased BMI and the development leading toward the insulin resistance syndrome We have investigated the effect of fish oil supplementation on the association between serum non-esterified fatty acid ( NEFA ) pattern and atherosclerotic activity . We studied correlations between serum non-esterified very long-chain eicosapentaenoic ( EPA ) , docosahexaenoic acid ( DHA ) and arachidonic acid ( AA ) and biochemical markers of endothelial activation before and after 18-months intervention with fish oil supplementation . The fish oil supplementation consisted of 2.4 g of EPA and DHA per day , with corn oil as placebo . Elderly men ( n = 171 ) with high risk for coronary heart disease were divided into four intervention groups in a factorial design : fish oil supplementation ( n = 44 ) , dietary intervention ( n = 42 ) , fish oil supplementation+dietary intervention ( n = 47 ) or placebo ( n = 38 ) . The composition of fasting NEFA was analysed before and after intervention by GLC . Circulating endothelial markers were analysed by ELISA . A statistically significant positive correlation between the change in serum non-esterified DHA and soluble vascular cell adhesion molecule-1 ( sVCAM-1 ) was found in the pooled group that received fish oil supplementation ( n = 91 ; Spearman 's correlation coefficient r = 0.24 , P = 0.02 ) . No such correlation was found in the pooled group without fish oil supplementation ( n = 80 ) . Furthermore , there was a significant negative correlation between the change in serum non-esterified EPA and the relative change in sVCAM-1 in the group that did not receive fish oil supplementation ( r = -0.34 , P = 0.002 ) . No such correlation was found in the group with fish oil supplementation . We conclude that large increase in serum non-esterified EPA and DHA , which can only be attained by supplementation , might increase inflammation in vascular endothelium . A moderate dietary increase in fish oil intake may , however , have an effect on decreasing inflammatory markers OBJECTIVE To assess the effectiveness of an intervention aim ed to increase adherence to a Mediterranean diet . DESIGN A 12-month assessment of a r and omized primary prevention trial . SUBJECTS/ SETTING S One thous and five hundred fifty-one asymptomatic persons aged 55 to 80 years , with diabetes or > or =3 cardiovascular risk factors . INTERVENTION Participants were r and omly assigned to a control group or two Mediterranean diet groups . Those allocated to the two Mediterranean diet groups received individual motivational interviews every 3 months to negotiate nutrition goals , and group educational sessions on a quarterly basis . One Mediterranean diet group received free virgin olive oil ( 1 L/week ) , the other received free mixed nuts ( 30 g/day ) . Participants in the control group received verbal instructions and a leaflet recommending the National Cholesterol Education Program Adult Treatment Panel III dietary guidelines . MAIN OUTCOME MEASURES Changes in food and nutrient intake after 12 months . STATISTICAL ANALYSES Paired t tests ( for within-group changes ) and analysis of variance ( for between-group changes ) were conducted . RESULTS Participants allocated to both Mediterranean diets increased their intake of virgin olive oil , nuts , vegetables , legumes , and fruits ( P<0.05 for all within- and between-group differences ) . Participants in all three groups decreased their intake of meat and pastries , cakes , and sweets ( P<0.05 for all ) . Fiber , monounsaturated fatty acid , and polyunsaturated fatty acid intake increased in the Mediterranean diet groups ( P<0.005 for all ) . Favorable , although nonsignificant , changes in intake of other nutrients occurred only in the Mediterranean diet groups . CONCLUSIONS A 12-month behavioral intervention promoting the Mediterranean diet can favorably modify an individual 's overall food pattern . The individual motivational interventions together with the group sessions and the free provision of high-fat and palatable key foods customary to the Mediterranean diet were effective in improving the dietary habits of participants in this trial Dietary compliance was studied in 57 women participating for 1 y in a r and omized clinical trial of dietary fat reduction . Nutrient analysis of food records , collected at 0 , 6 , and 12 mo , was compared with changes observed in lipid profiles and with chemical analysis of duplicate diets . Both food records and duplicate meals showed a significant decrease in fat intake ( from 36 to 23 % of total calories , p less than 0.0001 ) and a significant increase in carbohydrate ( from 43 to 56 % of total calories , p less than 0.0001 ) in the intervention group . The calculated nutrient intake from food records tended to overestimate the intake of protein , fat , and carbohydrate compared with the chemically analyzed method . The mean level of plasma cholesterol in the intervention group was significantly reduced ( 7.3 % , p less than 0.01 ) in the first 6 mo after a reduction in dietary fat but the levels observed did not differ significantly between the groups at any time Phase I of the Trials of Hypertension Prevention was a multicenter , r and omized trial of the feasibility and efficacy of seven nonpharmacologic interventions , including sodium reduction , in lowering blood pressure in 30- to 54-year-old individuals with a diastolic blood pressure of 80 to 89 mm Hg . Six centers tested an intervention design ed to reduce dietary sodium to 80 mmol ( 1800 mg)/24 h with a total of 327 active intervention and 417 control subjects . The intervention consisted of eight group and two one-to-one meetings during the first 3 months , followed by less-intensive counseling and support for the duration of the study . The mean net decrease in sodium excretion was 43.9 mmol/24 h at 18 months . Women had lower sodium intake at baseline and were therefore more likely to decrease to less than 80 mmol/24 h. Black subjects were less likely to decrease to less than 80 mmol/d , independent of sex or baseline sodium excretion . The mean ( 95 % confidence interval ) net decrease associated with treatment was -2.1 ( -3.3 , -0.8 ) mm Hg for systolic blood pressure and -1.2 ( -2.0 , -0.3 ) mm Hg for diastolic blood pressure at 18 months ( both P < .01 ) . Multivariate analyses indicated a larger systolic blood pressure effect in women ( -4.44 versus -1.23 mm Hg in men ) , adjusted for age , race , baseline blood pressure , and baseline 24-hour urinary sodium excretion ( P = .02 ) . Dose-response analyses indicated an adjusted decrease of -1.4 mm Hg for systolic blood pressure and -0.9 mm Hg for diastolic blood pressure for a decrease of 100 mmol/24 h in 18-month sodium excretion . These results support the utility of sodium reduction as a population strategy for hypertension prevention and raise questions about possible differences in dose response associated with gender and initial level of sodium intake Abstract 1 . 1 . Ninety-nine male patients between the ages of 20 yr and 50 yr with documented myocardial infa rct ions were r and omly divided into two diet therapy groups . The comparability of these two groups was defined with regard to age , age at time of infa rct ion , family history of coronary heart disease , prevalence of hypertension , degree of angina , height , weight , long-term anti-coagulant therapy , electrocardiographic severity and blood cholesterol level . 2 . 2 . The diet plans for two 30 per cent fat diets , one high in polyunsaturated fatty acid to saturated fatty acid and the second with reciprocal ratio , were outlined . 3 . 3 . Forty-eight subjects who were in the study for one year and maintained or achieved ideal weight were followed on these diet patterns . In the two groups studied , there was no significant difference in cholesterol response . 4 . 4 . Weight loss was comparable prior to beginning either assigned diet . 5 . 5 . The diets utilized in the entire group reduced blood cholesterol levels by 23 mg per 100 ml or 9 per cent over the 12-month period . 6 . 6 . A 30 per cent fat diet , with or without an unsaturated fat supplement , appears to be a satisfactory and palatable regimen for free-living adult males for as prolonged a period as one year . This fact is corroborated by a less than 5 per cent drop-out rate during this period of study . 7 . 7 . There appears to be a relationship between weight reduction and cholesterol change in the group studied In this study , serum lipid and cardiovascular risk levels of 195 military men and women were measured immediately before and 6 months after participation in a coronary artery risk evaluation ( C.A.R.E. ) program . Mean total cholesterol levels decreased from 257 mg/dl to 223 mg/dl ( t(194 ) = -16.76 , p = 0.00 ) , low-density lipoprotein levels decreased from 170 mg/dl to 141 mg/dl ( t(194 ) = -15.22 , p = 0.00 ) , and high-density lipoprotein levels increased from 45 mg/dl to 48 mg/dl ( t(194 ) = 3.27 , p = 0.01 ) . Cardiovascular risk categories ( based on serum lipid levels ) were lowered from high to moderate risk in 54 subjects , high to low risk in 19 subjects , and moderate to low risk in 31 subjects ( chi 2 = 98.28 , p = 0.00 ) . This study demonstrates that health education programs such as the C.A.R.E. Program can have a significant impact on serum lipid levels and cardiovascular risk levels and can potentially improve the health of high-risk population 1 . Changes in serum total and lipoprotein fraction triglyceride and cholesterol levels were studied in 24 adults on home haemodialysis . Half the patients were r and omly allocated to a low cholesterol ( mean 200 mg/day ) , fat-modified diet ( mean polyunsaturated/saturated fat ratio of 1.0 with a mean of 43 % of the total energy content derived from fat ) . 2 . Before dietary manipulation , triglyceride levels in all lipoprotein fractions were significantly higher ( P less than 0.02 ) than in a control group of age and sex matched normal subjects . Total cholesterol , very-low-density-lipoprotein ( VLDL ) and low-density-lipoprotein ( LDL ) cholesterol were also significantly raised ( P less than 0.02 ) , but high-density-lipoprotein ( HDL ) cholesterol was normal . In the patients on a fat-modified diet triglyceride levels did not alter in any of the lipoprotein fractions . Total cholesterol and LDL cholesterol levels fell significantly into the normal range ( P less than 0.002 and less tha 0.001 respectively ) but VLDL and HDL cholesterol levels did not change . 3 . Hypertriglyceridaemia is the most common lipid abnormality in patients with renal failure and a long-term fat-modified diet is , therefore , of limited therapeutic importance in these patients unless there is a low HDL/LDL cholesterol ratio In a r and omized , controlled study of the Treatwell work-site nutrition intervention program , which focused on promoting eating patterns low in fat and high in fiber , 16 work sites from Massachusetts and Rhode Isl and were recruited to participate and r and omly assigned to either an intervention or a control condition . The intervention included direct education and environmental programming tailored to each work site ; control work sites received no intervention . A cohort of workers r and omly sample d from each site was surveyed both prior to and following the intervention . Dietary patterns were assessed using a semiquantitative food frequency question naire . Adjusting for work site , the decrease in mean dietary fat intake was 1.1 % of total calories more in intervention sites than in control sites ( P less than .005 ) . Mean changes in dietary fiber intake between intervention and control sites did not differ . This study provides evidence that a work-site nutrition intervention program can effectively influence the dietary habits of workers Eighteen healthy volunteers consumed very low fat diets ( less than 7 % of daily energy ) enriched with different sources of long chain ( C20 and C22 ) polyunsaturated fatty acids ( PUFA ) . Three diets provided 500 g/day of fish caught in the tropical waters of Australia ( rich in arachidonic acid and docosahexaenoic acid ) , fish caught in the southern waters of Australia ( rich in docosahexaenoic acid ) , or kangaroo meat ( rich in linoleic and arachidonic acids ) . The fourth diet was vegetarian , similarly low in fat but containing no 20- and 22-carbon PUFA . An increase in the percentage of a particular C20 or C22 PUFA in the plasma phospholipid fraction in subjects consuming these low fat diets corresponded to the dietary PUFA composition . This study examined the effect of dietary modification of the level of arachidonic acid in plasma phospholipids on both traditional measures of platelet function and on cold-induced vasoconstriction . The cold pressor response , measured by venous occlusion plethysmography , was depressed in diets which elevated the levels of arachidonic acid in plasma lipids ( kangaroo and tropical fish ) , enhanced after subjects consumed a diet which increased the levels of docosahexaenoic acid and eicosapentaenoic acid ( southern fish diet ) , and was unchanged by the low fat vegetarian diet . There was no effect on bleeding time or platelet responsiveness Abstract In an eight-year controlled clinical trial of a diet high in polyunsaturated vegetable oils and low in saturated fat and cholesterol in preventing complications of atherosclerosis , 846 men were assigned r and omly to a conventional diet or to one similar in all respects except for a substitution of vegetable oils for saturated fat . Fatal atherosclerotic events were more common in the control group ( 70 v .48 ; Social support is inversely associated with heart disease risk . Support may influence heart disease by encouraging health behavior change in high-risk individuals . This study examined the association between spouse support and maintenance of low-fat diets in men with hypercholesterolemia . Participants were 254 men enrolled in a 24-month r and omized trial of lipid-lowering diets initiated in 1985 in Seattle , Washington . The Evaluation of Spouse Support , which assesses the extent to which spouses supported maintenance of lipid-lowering diets , was administered after the last of eight dietary classes and at 3 , 12 , and 24 months postinstruction . Attainment of dietary goals was determined from food records completed at the end of the class and at 3 , 12 , and 24 months . Compared with those in the lowest quartile , those in the highest quartile of support were more likely to attain dietary goals at 3 months ( odds ratio ( OR ) = 4.5 , 95 % confidence interval ( CI ) 1.9 - 10.4 ) , 12 months ( OR = 5.5 , 95 % CI 2.4 - 12.5 ) , and 24 months ( OR = 3.9 , 95 % CI 1.7 - 9.3 ) . Support was not associated with end-of-class dietary goal achievement . Social support may be an important factor in the maintenance of low-fat diets BACKGROUND AND AIM Very low carbohydrate ad libitum diets have been shown to enhance weight loss without increasing cardiometabolic risk factors but no kilojoule-controlled trials have been conducted relative to no intervention . The aim of this study was to compare the changes in weight and other cardiovascular risk factors in 3 isocaloric energy-restricted diets to no-intervention control after 1 year . METHODS AND RESULTS One hundred and thirteen subjects ( age 47 ± 10 years , BMI 32 ± 6 kg/m(2 ) with one additional cardiovascular risk factor ) were r and omly allocated to one of three isocaloric diets ( VLC-very low carbohydrate , 60 % fat , 4 % carbohydrate , n=30 ; VLF-very low fat , 10 % fat , n = 30 ; HUF-high unsaturated fat , 30 % fat , n = 30 ) with intensive support for 3 months followed by minimal support for 12 months compared to a control group ( no intervention , n = 23 ) . The estimated weight change was -3.0 ± 0.2 kg for VLC , -2.0 ± 0.1 kg for VLF , -3.7 ± 0.01 kg for HUF and 0.8 ± 0.5 kg for controls ( P=0.065 ) . After correcting for baseline values , decreases in body weight and diastolic blood pressure in the diet groups ( -2.9 ± 5.2 ) were significantly different to the increase in the control group ( 0.8 ± 5.0 ) ( P<0.05 ) . No differences in cardiovascular risk factors were observed between the diet groups . CONCLUSION Significant cardiometabolic risk factor reduction was observed equally with VLC , VLF and HUF diets after 15 months , compared to an exacerbation of risk factors in the control group . At a modest level of adherence , 3 months of intensive support on these dietary patterns confer an improvement in cardiometabolic profile compared to no dietary intervention after 15 months OBJECTIVES To determine whether a reduced-fat diet consumed ad libitum can achieve the recommended intakes of other macronutrients , fiber , and cholesterol and whether such a diet affects intake of other important micronutrients such as fat-soluble vitamins . DESIGN Twelve-month , r and omized , controlled trial of a reduced-fat , ad libitum diet vs usual diet . SUBJECTS One hundred ten adults older than 40 years with glucose intolerance ( 2-hour blood glucose concentration = 7.0 to 11.0 mmol/L ) who were selected from a previous workforce survey . INTERVENTION Monthly small-group meetings aim ed at identifying sources of dietary fat and ways to reduce fat consumption . MAIN OUTCOME MEASURES Nutrient intakes derived from 3-day food diaries at the beginning and end of the study . Blood levels of retinol , alpha-tocopherol , and beta carotene at the end of the study . STATISTICAL ANALYSES PERFORMED Unpaired t tests for determining changes in nutrient intake and antioxidant vitamin concentrations . Separate analyses were conducted with users of mineral and vitamin supplements and people who changed smoking status to reduce potential confounding . RESULTS Fat intake decreased from 35 % to 26 % of energy in the reduced-fat diet group compared with a 2 % decrease in the control group ( P < .0001 ) . Total energy intake also decreased in the 2 groups ( -362 vs -59 kcal/day , P < .02 ) . Those changes were reflected in a 3.1 + /- 4.7 kg ( mean + /- st and ard deviation ) weight loss in the intervention group compared with a 0.4 + /- 3.0 kg weight gain in the control group ( P < .0001 ) . There were no differences between groups in the changes in micronutrient intakes , except for an energy-adjusted increase in beta carotene intake in the reduced-fat diet group . Serum retinol and alpha-tocopherol concentrations were not different between the groups , but the reduced-fat diet group had higher beta carotene concentrations ( P = .009 ) . APPLICATIONS A reduced-fat , ad libitum diet can be prescribed to improve overall macronutrient intake and achieve modest weight loss without sacrificing micronutrient intakes OBJECTIVE --To test whether a fat reduced diet rich in soluble dietary fibre , antioxidant vitamins , and minerals reduces complications and mortality after acute myocardial infa rct ion . DESIGN --R and omised , single blind , controlled trial . SETTING -- Primary and secondary care research centre for patients with myocardial infa rct ion . SUBJECTS--505 patients with suspected acute myocardial infa rct ion . Those with definite or possible acute myocardial infa rct ion and unstable angina based on World Health Organisation criteria were assigned to diet A ( n = 204 ) or diet B ( n = 202 ) within 24 - 48 hours of infa rct ion . INTERVENTIONS --Both groups were advised to follow a fat reduced diet . Group A was also advised to eat more fruit , vegetables , nuts , and grain products . MAIN OUTCOME MEASURES --Mortality from cardiac disease and other causes . Serum lipid concentrations and compliance with diet . RESULTS --Blood lipoprotein concentrations and body weight fell significantly in patients in group A compared with those in group B ( cholesterol fell by 0.74 mmol/l in group A v 0.32 mmol/l in group B , 95 % confidence interval of difference 0.14 to 0.70 , and weight by 7.1 v 3.0 kg , 0.52 to 7.68 ) . The incidence of cardiac events was significantly lower in group A than group B ( 50 v 82 patients , p less than 0.001 ) . Group A also had lower total mortality ( 21 v 38 died , p less than 0.01 ) than group B. CONCLUSIONS --Comprehensive dietary changes in conjunction with weight loss immediately after acute myocardial infa rct ion may modulate blood lipoproteins and significantly reduce complications and mortality after one year CONTEXT Nonpharmacologic interventions are frequently recommended for treatment of hypertension in the elderly , but there is a paucity of evidence from r and omized controlled trials in support of this recommendation . OBJECTIVE To determine whether weight loss or reduced sodium intake is effective in the treatment of older persons with hypertension . DESIGN R and omized controlled trial . PARTICIPANTS A total of 975 [ corrected ] men and women aged 60 to 80 years with systolic blood pressure lower than 145 mm Hg and diastolic blood pressure lower than 85 mm Hg while receiving treatment with a single antihypertensive medication . SETTING Four academic health centers . INTERVENTION The 585 obese participants were r and omized to reduced sodium intake , weight loss , both , or usual care , and the 390 nonobese participants were r and omized to reduced sodium intake or usual care . Withdrawal of antihypertensive medication was attempted after 3 months of intervention . MAIN OUTCOME MEASURE Diagnosis of high blood pressure at 1 or more follow-up visits , or treatment with antihypertensive medication , or a cardiovascular event during follow-up ( range , 15 - 36 months ; median , 29 months ) . RESULTS The combined outcome measure was less frequent among those assigned vs not assigned to reduced sodium intake ( relative hazard ratio , 0.69 ; 95 % confidence interval [ CI ] , 0.59 - 0.81 ; P<.001 ) and , in obese participants , among those assigned vs not assigned to weight loss ( relative hazard ratio , 0.70 ; 95 % CI , 0.57 - 0.87 ; P<.001 ) . Relative to usual care , hazard ratios among the obese participants were 0.60 ( 95 % CI , 0.45 - 0.80 ; P<.001 ) for reduced sodium intake alone , 0.64 ( 95 % CI , 0.49 - 0.85 ; P=.002 ) for weight loss alone , and 0.47 ( 95 % CI , 0.35 - 0.64 ; P<.001 ) for reduced sodium intake and weight loss combined . The frequency of cardiovascular events during follow-up was similar in each of the 6 treatment groups . CONCLUSION Reduced sodium intake and weight loss constitute a feasible , effective , and safe nonpharmacologic therapy of hypertension in older persons 21 patients with severe persistent cyclical mastopathy of at least 5 years ' duration were r and omised to a control group who received general dietary advice or to an intervention group who were taught how to reduce the fat content of their diet to 15 % of calories while increasing complex carbohydrate consumption to maintain caloric intake . Both groups were followed for 6 months with food records and measurement of plasma hormone and lipid levels . Severity of symptoms was recorded with daily diaries and patients were assessed at the beginning and end of the study by a physician who was unaware of their dietary regimen . After 6 months there was a significant reduction in the intervention group in the severity of premenstrual breast tenderness and swelling . Physical examination showed reduced breast swelling , tenderness , and nodularity in 6 of 10 patients in the intervention group and 2 of 9 patients in the control group OBJECTIVE To describe the development of a computer-based system for dietary management of hyperlipidemia and to evaluate its efficacy for lowering plasma cholesterol level . DESIGN Using a stepwise approach , we developed and tested a three-part self-management system in five consecutive clinical studies . Each study assessed plasma cholesterol levels before and after dietary intervention using the system . These studies enabled progressive refinement of ( a ) a food frequency question naire used to assess food intake in the preceding month ; ( b ) computer-generated progress reports , based on question naire responses , offering dietary change sub goals and strategies for change ; and ( c ) a dietary workbook providing detailed information on how to achieve goals . SUBJECTS/ SETTING Persons with hyperlipidemia ( n=814 ) were enrolled from worksite and clinical setting s in the San Francisco Bay area of California . The attrition rate after r and omization was 5 % . INTERVENTION Elements of the dietary intervention evolved in response to the results of five clinical studies . In each study , patients underwent a form of baseline assessment of dietary intake followed by counseling/instruction by various means . Follow-up dietary assessment s were provided at specific intervals to facilitate subjects ' progress toward their dietary goals . A dietary workbook provided the detailed instruction required to implement the recommendations contained in the periodic progress reports . STATISTICAL ANALYSES PERFORMED Changes in plasma cholesterol level were measured by paired and unpaired t tests . The relationship between the reported reduction in dietary fat and cholesterol level assessed by food frequency question naires and the directly measured change in plasma cholesterol level was measured by multiple linear regression . RESULTS The three major elements of the final computerized system ( food frequency question naires , computer-generated progress reports , and dietary workbook ) were developed and refined in the course of the five clinical studies . Reductions in total plasma cholesterol level of 5.0 % to 6.5 % achieved by participants in all five studies were consistent with self-reported reductions in intake of dietary saturated fat and cholesterol . Therefore , the computerized self-management system appears to be an effective tool for reducing plasma cholesterol levels . APPLICATIONS/ CONCLUSIONS A computer-based system for dietary self-management of hyperlipidemia , implemented by mail , was effective in short-term studies . This self-management system can potentially provide health-promoting services to large numbers of people at low cost Preliminary evidence from a case control study of healthy postmenopausal women living in Palermo , Sicily , is presented to investigate the potential impact of a traditional Mediterranean diet on the risk of developing breast cancer . Of the 230 women who fulfilled specific eligibility criteria , 115 were enrolled in the study based on serum testosterone values equal to or greater than the median population value ( 0.14 microg/ml ) . Women were then individually r and omized into a diet intervention ( n = 58 ) and a control ( n = 55 ) group . Women in the intervention group attended a weekly " cooking course " for 1 year , being trained by professional chefs in the correct use of the natural ingredients of the traditional Mediterranean diet , including whole cereals , legumes , seeds , fish , cruciferous vegetables , and many others . The intervention group was subsequently instructed to follow the learned diet at home , while the control group was only advised to increase the consumption of fruits and vegetables , as recommended by WHO . The following measures were taken at the beginning , middle , and end of the study : ( a ) fasting blood and 12-hour urine sample s to assay defined hormonal endpoints ; ( b ) height , weight , and circumference of the waist and hip ; and ( c ) a food frequency and computerized 24-hour dietary recall question naire . After 1 year , both the control and the intervention groups showed satisfactory compliance rates ( 81 and 85 % , respectively ) . In addition , preliminary results so far obtained reveal an unequivocal trend towards weight loss , a strong reduction in cholesterol levels , and a psychophysical feeling of well-being by women adopting the Mediterranean diet . The study is currently ongoing to verify the association of changes in serum and urine hormone levels and breast cancer risk in the intervention group BACKGROUND Detrimental effects of consumption of industrial trans fatty acids ( TFA ) from partially hydrogenated vegetable oils ( PHVO ) on cardiovascular disease ( CVD ) risk factors are well documented . However , very little information is available on the effect of natural sources of TFA coming from milk fat , dairy products and ruminant meat . In fact , due to the naturally low level of TFA in milk fat , it is almost impossible to conduct a clinical trial with a limited number of subjects ( < 200 ) . METHODOLOGY To compare the effects of industrial and natural dietary sources of TFA , two specific test fats have been design ed and produced . A substantial amount of milk fat ( 130 kg ) enriched in TFA has been produced by modification of the cow 's diet and selection of cows with the highest TFA content . The level obtained was approximately 4- to 7-fold higher than typically present in milk fat ( approximately 20 instead of 3 - 6 g/100 g of total fatty acids ) . The control fat is composed of PHVO balanced in saturated fatty acids ( lauric , myristic and palmitic ) . Both experimental fats contain about 20 - 22 % of monounsaturated TFA and the volunteers ' daily experimental fat intake ( 54 g ) , will represent about 12.0 g/day of TFA or 5.4 % of the daily energy ( based on 2000 kcal/day ) . These two test fats have been incorporated into food items and will be provided to 46 healthy subjects under a r and omised , double blind , controlled , cross-over design . The primary outcome is high-density lipoprotein cholesterol ( HDL-C ) , which is an independent risk factor for CVD . Other parameters such as low-density lipoprotein cholesterol ( LDL-C ) , very low-density lipoprotein cholesterol ( VLDL-C ) , and HDL-C level and subclasses will be also to be evaluated . CONCLUSION We have shown that it is technically feasible to perform a clinical trial on the comparative effects of natural and industrial sources of TFA isomers on CVD risk factors . Results are expected by mid-2006 Diverging results from studies of marine oil supplementation to western diets initiated the undertaking of a double-blind crossover study , with administration to healthy volunteers for 4 weeks of either 10 g of fish oil or 10 g of vegetable oil . Each oil containing approx . 40 % of n-3 and n-6 polyunsaturated fatty acids ( PUFA ) respectively . During the n-3 PUFA period , systolic blood pressure , plasma total lipids , triglycerides and VLDL concentrations fell significantly whereas plasma antithrombin-III ( AT-III ) rose . Cutaneous bleeding time increased significantly . In contrast only AT-III rose during the n-6 PUFA feeding , however , more marked than during the n-3 oil period . It is concluded that a n-3 PUFA oil supplement to the western diet exerts an effect that generally is considered as beneficial in terms of the risk of developing cardiovascular diseases . It is in this respect superior to that of n-6 PUFA , stressing the necessity of a more differentiated approach to advice on dietary PUFA enrichment than presently is exerted BACKGROUND Diet is an essential part of the nonpharmacological management of hypertension . The aim of this study was to investigate in a primary health care setting the effect of intensified diet counseling on the diet of hypertensive subjects . METHODS A total of 715 free-living subjects , ages 25 - 74 years , with systolic blood pressure 140 - 179 mm Hg and /or diastolic blood pressure 90 - 109 mm Hg and /or drug treatment for hypertension participated in an open r and omized trial with a 2-year follow-up at health centers in eastern Finl and . The intervention group ( n = 360 ) was advised to reduce their total fat , saturated fat , and salt intake and to increase monounsaturated and polyunsaturated fat intake as well as to reduce weight and to use alcohol in moderation if at all . The usual care group ( n = 355 ) continued with their usual primary health care . The subjects filled out a 4-day food record , and 24-h urine sample s were collected at baseline and at 1- and 2-year examinations . RESULTS The 2-year net changes ( change in intervention minus change occurring in usual care group ) in total fat intake [ -2.7 E% ( 95 % CI -4.0 , -1.6 ; P < 0.0005 ) ] , in saturated fatty acid intake [ -1.7 E% ( 95 % CI -2.3 , -1.1 ; P < 0.0005 ) ] , and in body weight [ -1.4 kg ( 95 % CI -2.0 , -0.8 ; P < 0.0005 ) ] were significant . Furthermore , the 2-year net change in daily sodium intake was significant , -9 mmol ( 95 % CI -17 , -2 ; P = 0.021 ) , but the 24-h urinary sodium excretion showed no difference between the study groups . CONCLUSION The intensified diet counseling in primary health care result ed in dietary changes interpreted as being of benefit in the long-term treatment of hypertension and prevention of atherosclerotic vascular diseases OBJECTIVES This study assessed stages of change in fat intake , physical activity , and cigarette smoking during a r and omized controlled trial of behavioral counseling . METHODS Twenty general practice s ( primary health care centers ) were r and omized to lifestyle counseling by behavioral methods or to usual health promotion . A total of 883 patients were selected for the presence of 1 or more of the following risk factors : cigarette smoking , high cholesterol , or a combination of a high body mass index and low physical activity . Stage of change ( precontemplation , contemplation , preparation , and action/maintenance ) was assessed at baseline and after 4 and 12 months . RESULTS The odds of moving to action/maintenance for behavioral intervention vs control patients at 4 months were 2.15 ( 95 % confidence interval [ CI ] = 1.30 , 3.56 ) for fat reduction , 1.89 ( 95 % CI = 1.07 , 3.36 ) for increased physical activity , and 1.77 ( 95 % CI = 0.76 , 4.14 ) for smoking cessation . The likelihood of achieving action/maintenance was related to baseline stage for all 3 behaviors . CONCLUSIONS Brief behavioral counseling based on advice matched to stage of readiness for change may be valuable in encouraging healthy lifestyles among patients in primary care at raised risk of cardiovascular disease The Women 's Health Trial : Feasibility Study in Minority Population s ( WHT : FSMP ) , a r and omized trial of 2208 women , was conducted to investigate three questions . First , can women from minority and low-socioeconomic-status population s be recruited in numbers sufficient to evaluate a dietary intervention design ed to lower fat intake . Second , the efficacy of a low fat , increased fruit/vegetable/ grain product intervention for reducing fat consumption . Third , will participation in the intervention lower plasma cholesterol and estradiol levels relative to the controls . The baseline results showed that an adequate number of minority and low SES women could be recruited to test the study hypotheses . A diverse study population of postmenopausal women consuming a high fat diet was recruited : 28 % of participants were Black , 16 % were Hispanic , 11 % had less than a high school level of education , and 15.5 % had household incomes of < $ 15,000 CONTEXT Obesity is an independent risk factor for cardiovascular disease , which may be mediated by increased secretion of proinflammatory cytokines by adipose tissue . OBJECTIVE To determine the effect of a program of changes in lifestyle design ed to obtain a sustained reduction of body weight on markers of systemic vascular inflammation and insulin resistance . DESIGN AND SETTING R and omized single-blind trial conducted from February 1999 to February 2002 at a university hospital in Italy . PATIENTS One hundred twenty premenopausal obese women ( body mass index > or = 30 ) aged 20 to 46 years without diabetes , hypertension , or hyperlipidemia . INTERVENTIONS The 60 women r and omly assigned to the intervention group received detailed advice about how to achieve a reduction of weight of 10 % or more through a low-energy Mediterranean-style diet and increased physical activity . The control group ( n = 60 ) was given general information about healthy food choices and exercise . MAIN OUTCOME MEASURES Lipid and glucose intake ; blood pressure ; homeostatic model assessment of insulin sensitivity ; and circulating levels of interleukin 6 ( IL-6 ) , interleukin 18 ( IL-18 ) , C-reactive protein ( CRP ) , and adiponectin . RESULTS After 2 years , women in the intervention group consumed more foods rich in complex carbohydrates ( 9 % corrected difference ; P<.001 ) , monounsaturated fat ( 2 % ; P = .009 ) , and fiber ( 7 g/d ; P<.001 ) ; had a lower ratio of omega-6 to omega-3 fatty acids ( -5 ; P<.001 ) ; and had lower energy ( -310 kcal/d ; P<.001 ) , saturated fat ( -3.5 % ; P = .007 ) , and cholesterol intake ( -92 mg/d ; P<.001 ) than controls . Body mass index decreased more in the intervention group than in controls ( -4.2 ; P<.001 ) , as did serum concentrations of IL-6 ( -1.1 pg/mL ; P = .009 ) , IL-18 ( -57 pg/mL ; P = .02 ) , and CRP ( -1.6 mg/L ; P = .008 ) , while adiponectin levels increased significantly ( 2.2 microg/mL ; P = .01 ) . In multivariate analyses , changes in free fatty acids ( P = .008 ) , IL-6 ( P = .02 ) , and adiponectin ( P = .007 ) levels were independently associated with changes in insulin sensitivity . CONCLUSION In this study , a multidisciplinary program aim ed to reduce body weight in obese women through lifestyle changes was associated with a reduction in markers of vascular inflammation and insulin resistance To evaluate the incremental effectiveness of a worksite cholesterol control management program when added to an established , comprehensive health promotion program at the worksite , we conducted a r and omized , controlled trial including both blue- and white-collar employees at four geographically dispersed worksites . One hundred twenty-seven employees with serum cholesterol levels of 240 mg/dL or greater were assigned to receive an enhanced intervention program ( the IMPACT program ) while 125 were assigned to a regular screening and referral group , which included a comprehensive worksite health promotion program . One hundred eighteen program and 116 control subjects had one-year follow-up measures recorded . We used venipuncture specimens to obtain st and ardized baseline and follow-up cholesterol measures . Program subjects experienced a mean decline of 16.6 mg/dL as compared to a decline of 10.0 mg/dL in control subjects . The crude intergroup difference was 6.6 mg/dL ( 95 % confidence internal [ CI ] = 1.1 , 14.3 ) , while the adjusted difference was 6.9 mg/dL ( 95 % CI = 0.5 , 14.3 ) . Neither difference was significant at the .05 level . The percentage of program subjects who reduced their cholesterol level to below 240 mg/dL ( 36 % ) was significantly greater than the corresponding percentage among control subjects ( 21 % ) . The enhanced worksite cholesterol control program provided incremental benefit in the percentage of individuals with elevated cholesterol in a population already exposed to a comprehensive worksite health promotion program that includes regular cholesterol screening , referral , and education activities Questions remain concerning the effect of variations in cholesterol intake on plasma cholesterol concentration , as well as on the role of factors modulating the metabolic impact of this dietary intervention . To define the impact of wide variations in dietary cholesterol intake on plasma total and low-density lipoprotein ( LDL ) cholesterol concentrations , as well as testing the hypothesis that resistance to insulin-mediated glucose disposal would accentuate the increase in plasma total and LDL cholesterol concentrations in response to a given increment in dietary cholesterol intake , we performed a prospect i ve , r and omized study comparing diets varying in cholesterol content in 65 healthy , postmenopausal women , 31 defined as insulin-resistant and 34 as insulin-sensitive . The changes in total and LDL cholesterol in response to increments in dietary cholesterol of up to approximately 800 mg/day were modest in magnitude , without evidence of a statistically significant diet-induced increase in cholesterol concentration , or of any difference in the responses of insulin-resistant as compared with insulin-sensitive women . These results indicate that relatively large increments in dietary cholesterol intake had little effect on total or LDL cholesterol concentrations in healthy , postmenopausal women , irrespective of whether they were insulin-resistant or insulin-sensitive BACKGROUND Relatives of patients with coronary heart disease have a heightened risk of cardiovascular disease . Attendance at a family-based screening clinic after an acute cardiac event could motivate patients and relatives to modify their lifestyles . AIMS The Family Atherosclerosis Risk Intervention Study ( FARIS ) aim ed to determine ( i ) whether a high proportion of patients and relatives would attend a special screening and prevention programme ; ( ii ) whether the risk factor profiles of relatives would be worse than those in the general community ; and ( iii ) whether ongoing management of patients and families together in a special clinic would improve risk factor profiles . METHODS Consecutive patients , together with spouse , siblings and offspring , aged 18 to 69 years , were r and omly allocated three months after an acute cardiac event to attend a special outpatient clinic , a screening and advice group , or a control group . Risk factor measures were total cholesterol , HDL cholesterol ( HDLC ) , systolic blood pressure ( SBP ) , body mass index ( BMI ) and smoking behaviour . This paper presents the risk factor profiles of all FARIS attenders and compares those of family members , age adjusted , with risk factors measured in a multicentre urban cross-sectional survey conducted in the same period . Differences between groups were compared using t-tests for numerical variables and ANOVA and chi-square for categorical variables . RESULTS Six hundred and twenty-eight patients and 1723 family members were enrolled , representing 85.9 % and 82.7 % of eligible patients and relatives respectively . Risk factors were significantly worse amongst family members than among those in the population survey BACKGROUND Increasing concern over long-term drug treatment of mild hypertension has stimulated several studies of weight reduction . Phase I of the Trial of Antihypertensive Interventions and Management demonstrated a short-term effect of weight loss on blood pressure control in overweight persons with mild hypertension , who were either taking placebo or taking low-dose monotherapy . Phase II investigates the long-term benefit of weight loss on the ability to maintain blood pressure control . METHODS From 10148 community-based screenees , 587 persons ( 5.8 % ) , aged 21 to 65 years , entered a multicenter , r and omized drug ( double-blind , placebo-controlled ) and diet trial . Participants had a diastolic blood pressure between 90 and 100 mm Hg and were at 110 % to 160 % of their ideal weight . They were r and omized to a usual diet ( n = 296 ) or to a weight loss diet ( n = 291 ) and within each diet group to placebo , chlorthalidone , 25 mg/d , or atenolol , 50 mg/d . Treatment failure was defined as using additional antihypertensive medications if diastolic blood pressure rose above 90 mm Hg according to protocol -specified criteria . RESULTS At baseline , mean diastolic blood pressure was 93 mm Hg ; systolic blood pressure , 143 mm Hg ; weight , 88 kg ; percent ideal weight , 137 % ; age , 48 years ; 56 % were men ; and 33 % were black . Mean follow-up was 4.5 years . There was a net loss of 2 to 3 kg with weight loss diet compared with usual diet over most of the follow-up period . The 5-year incidence of treatment failure was 56.7 per 100 participants with usual diet and 49.8 per 100 with weight loss . Long-term weight loss decreased failure of blood pressure control for those receiving placebo or low-dose diuretic or beta-blocker by 23 % . The results were similar in direction in each drug group . CONCLUSIONS The Trial of Antihypertensive Interventions and Management demonstrated that weight reduction is an effective long-term therapy for maintaining blood pressure in the normal range when used as monotherapy or in combination with either thiazide diuretics or beta-blockers . Consequently , weight loss should be recommended for the management of obese individuals with mild hypertension The Dietary Modification ( DM ) component of the Women ’s Health Initiative ( WHI ) is a r and omized controlled evaluation of a low-fat diet that is high in fruits , vegetables , and grains . This low-fat dietary pattern is hypothesized to reduce the risk of breast and colorectal cancer and secondarily , coronary heart disease , in postmenopausal women . To test these hypotheses , 48,836 postmenopausal women were r and omly assigned to either the lowfat eating pattern ( 40 % ) or self-selected dietary behavior ( 60 % ) . The nutrition goals for women in the intervention arm are to reduce energy from fat to 20 % and energy from saturated fat to 7 % , and to increase fruit and vegetable intake to at least five servings per day and grains to at least six servings per day . Participants will be followed for an average of 8.5 years . The DM was motivated by animal studies ( 1 , 2 ) , international ecologic studies of diet and disease ( 3 , 4 ) , migrant studies ( 5–7 ) , and epidemiologic studies ( 8) indicating that the diet , particularly lower levels of fat intake , has the potential to reduce risk of breast cancer , colon cancer , and heart disease . Within-country analytic BACKGROUND The Mediterranean dietary pattern is thought to reduce the risk of cancer in addition to being cardioprotective . However , no trial has been conducted so far to prove this belief . METHODS We compared overall survival and newly diagnosed cancer rate among 605 patients with coronary heart disease r and omized in the Lyon Diet Heart Study and following either a cardioprotective Mediterranean-type diet or a control diet close to the step 1 American Heart Association prudent diet . RESULTS During a follow-up of 4 years , there were a total of 38 deaths ( 24 in controls vs 14 in the experimental group ) , including 25 cardiac deaths ( 19 vs 6 ) and 7 cancer deaths ( 4 vs 3 ) , and 24 cancers ( 17 vs 7 ) . Exclusion of early cancer diagnoses ( within the first 24 months after entry into the trial ) left a total of 14 cancers ( 12 vs 2 ) . After adjustment for age , sex , smoking , leukocyte count , cholesterol level , and aspirin use , the reduction of risk in experimental subjects compared with control subjects was 56 % ( P=.03 ) for total deaths , 61 % ( P=.05 ) for cancers , and 56 % ( P=.01 ) for the combination of deaths and cancers . The intakes of fruits , vegetables , and cereals were significantly higher in experimental subjects , providing larger amounts of fiber and vitamin C ( P<.05 ) . The intakes of cholesterol and saturated and polyunsaturated fats were lower and those of oleic acid and omega-3 fatty acids were higher ( P<.001 ) in experimental subjects . Plasma levels of vitamins C and E ( P<.05 ) and omega-3 fatty acids ( P<.001 ) , measured 2 months after r and omization , were higher and those of omega-6 fatty acids were lower ( P<.001 ) in experimental subjects . CONCLUSIONS This r and omized trial suggests that patients following a cardioprotective Mediterranean diet have a prolonged survival and may also be protected against cancer . Further studies are warranted to confirm the data and to explore the role of the different lipids and fatty acids in this protection Background / Objectives : Short-term studies have suggested beneficial effects of a Palaeolithic-type diet ( PD ) on body weight and metabolic balance . We now report the long-term effects of a PD on anthropometric measurements and metabolic balance in obese postmenopausal women , in comparison with a diet according to the Nordic Nutrition Recommendations (NNR).Subjects/ Methods : Seventy obese postmenopausal women ( mean age 60 years , body mass index 33 kg/m2 ) were assigned to an ad libitum PD or NNR diet in a 2-year r and omized controlled trial . The primary outcome was change in fat mass as measured by dual-energy X-ray absorptiometry . Results : Both groups significantly decreased total fat mass at 6 months ( −6.5 and −2.6 kg ) and 24 months ( −4.6 and −2.9 kg ) , with a more pronounced fat loss in the PD group at 6 months ( P<0.001 ) but not at 24 months ( P=0.095 ) . Waist circumference and sagittal diameter also decreased in both the groups , with a more pronounced decrease in the PD group at 6 months ( −11.1 vs−5.8 cm , P=0.001 and −3.7 vs−2.0 cm , P<0.001 , respectively ) . Triglyceride levels decreased significantly more at 6 and 24 months in the PD group than in the NNR group ( P<0.001 and P=0.004 ) . Nitrogen excretion did not differ between the groups . Conclusions : A PD has greater beneficial effects vs an NNR diet regarding fat mass , abdominal obesity and triglyceride levels in obese postmenopausal women ; effects not sustained for anthropometric measurements at 24 months . Adherence to protein intake was poor in the PD group . The long-term consequences of these changes remain to be studied The effects of plasma lipid reduction on the progression of femoral atherosclerosis have been studied in 24 hyperlipidaemic patients with stable intermittent claudication . The patients were r and omized into treatment or ‘ usual‐care ’ groups , the former receiving lipid‐lowering therapy by diet and drugs , and the latter no such treatment . Biplanar femoral arteriography was performed before and after a mean period of 19 months . In the treatment group plasma total cholesterol was decreased by a mean of 25 per cent and plasma triglyceride by more than 40 per cent . Plasma lipids were unchanged in the usual‐care group . Significantly fewer arterial segments showed detectable progression in the treatment group ( P < 0·01 ) . In addition , the mean increment in plaque area ( mm2 per segment per year ) in the treatment group was only 34 per cent of that in the usual‐care group ( P = 0.06 ) Ninety-one middle-aged men and women with untreated mild hypertension were allocated to a nopharmacological treatment group or to a control group . Members of the treatment group were instructed to reduce daily sodium intake to less than 70 mmol , to reduce the intake of saturated fat , to lose weight if necessary and to perform regular physical exercise and relaxation training . Adherence to and effects of the programme on blood pressure and serum lipids were monitored for 12 months . In the treatment group , daily sodium excretion decreased to and remained at 50 % of its original level ( P less than 0.001 ) , and there was a significant reduction in saturated fat intake . The average weight reduction was modest . Adherence to physical exercise and relaxation training regimens was poor . The net decreases ( difference in changes between treatment and control group ) in blood pressure were greatest during the first 3 months : in men the decrease in systolic blood pressure was 11.3 mmHg ( P less than 0.001 ) and in diastolic blood pressure 8.3 mmHg ( P less than 0.001 ) ; in women the decrease in systolic blood pressure was 10.8 mmHg ( P less than 0.01 ) and in diastolic blood pressure 6.4 mmHg ( P less than 0.01 ) . However , this decrease diminished during the last 3 months to approximately one half owing to blood pressure reduction in controls . Low density lipoprotein cholesterol levels decreased significantly in treated men and women OBJECTIVE To determine whether a fat- and energy-reduced diet rich in antioxidant vitamins C and E , beta carotene , and soluble dietary fiber reduces free-radical stress and cardiac enzyme level and increases plasma ascorbic acid level 1 week after acute myocardial infa rct ion . DESIGN R and omized , single blind , controlled study . SETTING Primary - and secondary -care research center for patients with myocardial infa rct ion . SUBJECTS All subjects with suspected acute myocardial infa rct ion ( n = 505 ) were considered for entry to the study . Subjects with definite or possible acute myocardial infa rct ion and unstable angina ( according to World Health Organization criteria ) were assigned to either an intervention diet ( n = 204 ) or a control diet ( n = 202 ) within 48 hours of symptoms of infa rct ion . INTERVENTIONS Intervention and control groups were advised to consume a fat-reduced , oil-substituted diet . The intervention group was also advised to eat more fruits , vegetable soup , pulses , and crushed almonds and walnuts mixed with skim milk . MAIN OUTCOME MEASURES Reduction in plasma lipid peroxide and lactate dehydrogenase cardiac enzyme levels , increase in plasma ascorbic acid level , and compliance with diet , especially with vitamin C intake as determined by chemical analysis . STATISTICAL ANALYSIS A two- sample t test using one-way analysis of variance for comparison of data . RESULTS Plasma lipid peroxide level decreased significantly in the intervention group compared with the control group ( 0.59 pmol/L in the intervention group and 0.10 pmol/L in the control group ; 95 % confidence interval of difference = 0.19 to 0.83 ) . Lactate dehydrogenase level increased less in the intervention group than in the control group ( 427.7 vs 561.2 U/L ; confidence interval of difference = 82.9 to 184.7 ) . Plasma ascorbic acid level increased more in the intervention group than in the control group ( 23.38 vs 7.95 mumol/L ; confidence interval of difference = 12.85 to 26.13 ) . APPLICATIONS/ CONCLUSIONS Consumption of an antioxidant-rich diet may reduce the plasma levels of lipid peroxide and cardiac enzyme and increase the plasma level of ascorbic acid . Antioxidant-rich foods may reduce myocardial necrosis and reperfusion injury induced by oxygen free radicals PURPOSE To describe PREMIER , a r and omized trial to determine the effects of multi-component lifestyle interventions on blood pressure ( BP ) . METHODS Participants with above optimal BP through stage 1 hypertension were r and omized to : 1 ) a behavioral lifestyle ( BLS ) intervention that implements established recommendations , 2 ) a BLS intervention that implements established recommendations plus the DASH diet , or 3 ) an advice only st and ard of care group . The two BLS interventions consist of group and individual counseling sessions for 18 months . The primary outcome is systolic BP at 6 months . Additional outcomes include diastolic BP and homocysteine at 6 months ; systolic and diastolic BP at 18 months ; fasting lipids , glucose and insulin at 6 and 18 months ; and effects in subgroup . CONCLUSION Results from the PREMIER trial will provide scientific rationale for implementing multi-component behavioral lifestyle intervention programs to control BP and prevent CVD OBJECTIVE The association of dairy food consumption with the risk for developing cardiovascular disease ( CVD ) has been investigated in many studies , but results often have been contradictory . The aim of the present study was to determine whether genetic polymorphisms are associated with interindividual variation in the response of CVD risk biomarker values after milk consumption . METHODS Fourteen single nucleotide polymorphisms ( SNPs ) in nine genes related to lipid metabolism were examined in 161 volunteers r and omly allocated to consume either 500 mL/d of skimmed ( S ) or semi-skimmed ( SS ) milk for 1 year in addition to their usual diets . Total cholesterol/high-density lipoprotein cholesterol ( TC/HDL-C ) and low-density lipoprotein/HDL-C ratios were used as biomarkers of CVD risk . Three-way repeated- measures analysis of variance was used to examine the effect of time , treatment ( S or SS ) , and genotype on these biomarkers . RESULTS A TT genotype for the proliferator-activated receptor alpha polymorphism ( PPARA rs135549 SNP ) was significantly associated with a reduction in the TC/HDL and LDL/HDL ratios after 12 mo of S milk intake ( mean reduction -0.29 , 95 % confidence interval [ CI ] , -0.63 to 0.05 ; P = 0.0015 and -0.31 , 95 % CI , -0.58 to -0.03 ; P = 0.0005 , respectively ) . However , no differences were observed after consuming either S or SS milk in the C allele carriers . CONCLUSIONS Saturated fatty acid consumption has long been linked to an increased risk for CVD ; indeed , the consumption of saturated fat-free products is recommended as a means of reducing this risk . However , the present results suggest that many individuals might not benefit from such general recommendations . Genetic analysis of PPARA rs135549 might help identify those individuals who are more likely to benefit from reducing the saturated fatty acid content of their diet A r and omised controlled trial with a factorial design was done to examine the effects of dietary intervention in the secondary prevention of myocardial infa rct ion ( MI ) . 2033 men who had recovered from MI were allocated to receive or not to receive advice on each of three dietary factors : a reduction in fat intake and an increase in the ratio of polyunsaturated to saturated fat , an increase in fatty fish intake , and an increase in cereal fibre intake . The advice on fat was not associated with any difference in mortality , perhaps because it produced only a small reduction ( 3 - 4 % ) in serum cholesterol . The subjects advised to eat fatty fish had a 29 % reduction in 2 year all-cause mortality compared with those not so advised . This effect , which was significant , was not altered by adjusting for ten potential confounding factors . Subjects given fibre advice had a slightly higher mortality than other subjects ( not significant ) . The 2 year incidence of reinfa rct ion plus death from ischaemic heart disease was not significantly affected by any of the dietary regimens . A modest intake of fatty fish ( two or three portions per week ) may reduce mortality in men who have recovered from MI OBJECTIVE To report the rationale , recruitment , design , dietary intervention and baseline characteristics of participants in the Medi-RIVAGE study ( Mediterranean Diet , Cardiovascular Risks and Gene Polymorphisms ) . DESIGN A r and omised , parallel trial comparing a new nutritional programme with a conventional programme . SETTING Centre for Detection and Prevention of Arteriosclerosis , Timone University Hospital , Marseille , France , and collaborating teams . SUBJECTS Two hundred and twelve male and female volunteers with at least one cardiovascular risk factor . INTERVENTION A Mediterranean-type diet characterised mainly by the quality of fatty acids , amount of fish , vegetable foodstuffs and fibre was proposed and compared with a usually prescribed , low-fat/cholesterol diet . Body mass index , fasting lipids and lipoproteins , apolipoproteins , glucose , insulin and homocysteine were the main outcome measures . Gene polymorphisms of interest were determined . RESULTS Characteristics of men in the two arms were comparable with regard to sociodemographic variables , and clinical and biological cardiovascular risk factors . There were few differences between the groups of women ( cholesterol-related parameters , P<0.05 ) . There was no difference between arms in allelic distribution of the gene polymorphisms studied . Saturated fat and protein intakes were high while carbohydrate and fibre intakes were low , but with no difference between arms . Overall , the nutritional markers were comparable in both arms with few exceptions . Correlations between nutritional intakes and plasma nutrient levels ranged from 0.19 ( beta-carotene ) to 0.47 ( folate ) . CONCLUSIONS The comparability of the two arms is notable and warrants a low risk of biases . Current diet departs from the traditional Mediterranean one . The assessment of nutritional intake is vali date d by correlations obtained between dietary intake and relevant biomarkers . This will be important to estimate participant compliance and to analyse intervention data BACKGROUND Phase 1 of the Trials of Hypertension Prevention was a collaborative , r and omized controlled clinical trial design ed to determine the feasibility and efficacy of selected nonpharmacologic interventions in reducing or preventing an increase in diastolic blood pressure . METHODS Participants aged 30 to 54 years who had a high-normal diastolic blood pressure ( 80 to 89 mm Hg ) , and were between 115 % and 165 % of their desirable body weight , were r and omly assigned to either an 18-month weight loss intervention ( n = 308 ) or a usual-care control condition ( N = 256 ) . Intervention consisted of 14 weekly group meetings followed by monthly maintenance sessions . Intervention participants received training in behavioral self-management technique and were asked to make life-style changes aim ed at achieving a moderate reduction in energy intake and an increase in physical activity . RESULTS The average weight losses in the intervention group at 6 , 12 , and 18 months of follow-up were 6.5 , 5.6 , and 4.7 kg for men and 3.7 , 2.7 , and 1.6 kg for women . The mean ( + /- SE ) change in diastolic blood pressure for intervention participants compared with controls at termination was -2.8 + /- 0.6 mm Hg for men and -1.1 + /- 0.9 mm Hg for women . For systolic blood pressure , the corresponding change was -3.1 + /- 0.7 mm Hg for men and -2.0 + /- 1.3 mm Hg for women . Blood pressure reductions were greater for those who lost larger amounts of weight . Sex-related differences in blood pressure response were largely due to the smaller amount of weight lost by women , and sex differences in weight loss could be accounted for by differences in baseline body weight . CONCLUSIONS During an 18-month follow-up period , this weight reduction program was shown to be an effective nonpharmacologic intervention for reducing blood pressure in overweight adults with high-normal blood pressure OBJECTIVE The aim of the study was to determine if multiple patient-centred lifestyle counselling sessions would be of interest to patients at risk of coronary heart disease ( CHD ) , in a primary care setting , and if such sessions would result in changes in physical activity and diet , and health status . A r and omised trial was conducted to compare the counselling intervention with usual care ( health promotion leaflet ) , among 334 mostly obese patients . METHODS Patients were r and omised into an intervention group that received st and ard exercise and nutrition information plus up to five face-to-face counselling sessions with a Physical Activity Specialist ( PAS ) and Registered Dietitian ( RD ) over a 6-month period or to a control group that only received the st and ard information . RESULTS Of those invited , patients r and omised tended to be more obese , older and female . The mean ( S.D. ) sessions attended was 2.0 ( 1.6 ) with 50 % attending at least 3 . At 6 months , the counselling group were more active , particularly with respect to walking , and had reduced weight , blood pressure and cholesterol , but had not changed their diet , compared with the control group . Furthermore , those who did more sessions had greater increases in activity and reductions in weight , blood pressure and cholesterol . CONCLUSION Attending multiple sessions of client-centred counselling in primary care was of interest to patients , and generally reduced CHD risk factors . PRACTICE IMPLICATION S The primary care setting can be used effectively to promote particularly walking , using physical activity specialists and dietitians trained to use an adapted motivational interviewing ( MI ) counselling style BACKGROUND Epidemiologic evidence of associations between the high intake of fat and low intake of dietary fiber , beta carotene , and other dietary constituents and the risk of colorectal neoplasia has been inconsistent and has not provided a sufficient basis for recommendations concerning the dietary prevention of large-bowel cancer in humans . PURPOSE We conducted a clinical trial to assess the effects on the incidence of adenomas of reducing dietary fat to 25 % of total calories and supplementing the diet with 25 g of wheat bran daily and a capsule of beta carotene ( 20 mg daily ) . METHODS We performed a r and omized , partially double-blinded , placebo-controlled factorial trial in which half the patients were assigned to each intervention , result ing in seven intervention groups and one control group . Eligibility criteria included histologic confirmation of at least one colorectal adenoma and confidence expressed by the colonoscopist that all polyps had been removed . Dietary changes were individually initiated and monitored by dietitians and research nurses . At surveillance colonoscopy , the size and location of all polyps were recorded , and their histology was later central ly review ed . Among 424 patients who were r and omly assigned in the trial , 13 were found to be ineligible upon histologic review . Among the remaining 411 , complete outcome data were collected from 390 at 24 months and from 306 at 48 months . All P values are from two-sided tests of statistical significance . RESULTS There was no statistically significant prevention of total new adenomas with any of the interventions . We found a statistically non-significant reduced risk of large adenomas ( > or = 10 mm ) with the low-fat intervention : At 24 months , the odds ratio ( OR ) adjusted for potential confounders = 0.4 and 95 % confidence interval ( CI ) = 0.1 - 1.1 ; at 48 months , OR = 0.3 and 95 % CI = 0.1 - 1.0 . Less and statistically nonsignificant reductions in the risk of large adenomas were found with wheat bran : At 24 months , OR = 0.8 and 95 % CI = 0.3 - 2.2 ; at 48 months , OR = 0.8 and 95 % CI = 0.3 - 2.5 . Patients on the combined intervention of low fat and added wheat bran had zero large adenomas at both 24 and 48 months , a statistically significant finding ( P = .03 ) . CONCLUSIONS Because only small numbers of patients were studied , our finding that the combination of fat reduction and a supplement of wheat bran reduced the incidence of large adenomas in this r and omized , controlled trial must be treated with caution . The results do suggest , however , that these interventions may reduce the transition from smaller to larger adenomas , a step that may critically define those adenomas most likely to progress to malignancy Saturated fatty acids and cholesterol in the diet raise the plasma cholesterol concentration , and a reduction in these constituents is recommended widely . However , there is not general agreement as to which nutrients should replace saturated fatty acids . Several different substitute nutrients are possible . In this study , three cholesterol-lowering diets were compared in nine men living in a domiciliary . On a typical American diet at baseline , cholesterol levels were in the normal range . One replacement diet was high in polyunsaturated fatty acids ( High Poly ) ; another had 30 % fat and corresponded to the American Heart Association 's ( AHA ) recommended diet for the general public ( AHA phase I ) ; the third diet had 20 % fat , equivalent to the AHA phase III diet for treatment of hypercholesterolemia . Compared with baseline levels , all diets caused similar reductions in total cholesterol and low-density lipoprotein cholesterol levels , but the High Poly and AHA phase III diets lowered the high-density lipoprotein cholesterol level more than the AHA phase I diet . Thus , for the limited number of patients in this study , the diet recommended for the general public appeared as effective for lowering of cholesterol levels as diets containing more polyunsaturates or more carbohydrates BACKGROUND Nutrients can exert healthy effects through nutrigenomic modulation . Data are scarce concerning the in vivo effect of a sustained traditional Mediterranean diet ( TMD ) pattern on the whole transcriptomic response . OBJECTIVE We explored the overall nutrigenomic effect associated with a TMD . DESIGN We focused on biological pathways related to cardiovascular disease ( CVD ) in a sub sample ( n = 34 ) of the Prevención Con Dieta Mediterránea ( PREDIMED ) study , which was a large , parallel-group , multicenter , r and omized controlled trial that aim ed to assess the effects of TMD on the primary prevention of CVD in individuals with high cardiovascular risk . Participants were r and omly assigned to a low-fat diet control group or TMD intervention groups [ traditional Mediterranean diet supplemented with virgin olive oil ( TMD+VOO ) or traditional Mediterranean diet supplemented with nuts ( TMD+Nuts ) ] in equal proportions . Three-month changes in whole genome peripheral blood mononuclear cells were assessed by using whole transcriptome microarray analyses . RESULTS A functional annotation analysis was performed on 241 selected responder genes after the TMD+VOO ( 139 upregulated and 102 downregulated genes ) , 312 selected responder genes after the TMD+Nuts ( 165 upregulated and 147 downregulated genes ) , and 145 selected responder genes after the low-fat ( 100 upregulated and 45 downregulated genes ) diets . Of 18 cardiovascular canonical pathway analyses , 12 pathways were differentially expressed , and 43 % of pathways were modulated by both TMDs ; the most prevalent pathways were related to atherosclerosis and hypertension . After simultaneous testing adjustment , 9 pathways were modulated by the TMD+VOO diet , and 4 pathways were modulated by the TMD+Nuts diet . CONCLUSION One of the mechanisms by which TMD , particularly if supplemented with virgin olive oil , can exert health benefits is through changes in the transcriptomic response of genes related to cardiovascular risk . This trial was registered at the London-based Current Controlled Trials register as IS RCT N35739639 The beFIT study tested whether teaching the NCEP step II diet ( < 30 % of calories from total fat and < 7 % from saturated fat ) is an effective therapy in hypercholesterolemic women and men with or without elevated triglycerides after 6 months . Hypercholesterolemic subjects had two LDL cholesterol measurements above the age- and sex-specific 75th percentile , and combined hyperlipidemic subjects additionally had similarly elevated triglyceride . Subjects were r and omized to receive dietary intervention ( eight weekly classes ) immediately or 6 months later . Follow-up visits were quarterly , with lipid measurements and 4-day food records . Subjects r and omized to delayed intervention did not report diet changes or experience lipid changes ; the immediate intervention group significantly reduced fat and cholesterol intake , result ing in significant LDL cholesterol lowering . Six months after diet instruction , 178 women and 231 men reported total and saturated fat intakes of approximately 25 % and 7.5 % kcal LDL cholesterol was significantly reduced in women ( 7.6 % and 8.1 % ) and men ( 8.8 % and 8.1 % ) with hypercholesterolemia and combined hyperlipidemia , respectively , but was not different by sex or lipid disorder . C and i date s for drug therapy were reduced from between 27 % and 37 % to 20 % . HDL cholesterol was significantly decreased in women ( -6.4 % and -4.7 % ) but not in men ( -1.3 % and -2.7 % ) . The 6.4 % reduction in hypercholesterolemic women was significantly different from that of men . The significance of the HDL cholesterol reduction in women is unknown . LDL cholesterol response was similar between women and men and between hypercholesterolemic and combined hyperlipidemic subjects . LDL cholesterol lowering by diet can significantly reduce the number of hyperlipidemic persons requiring drug therapy We studied separately the influence of two methods for losing fat weight on the levels of plasma lipids and lipoproteins in overweight sedentary men -- decreasing energy intake without increasing exercise ( diet ) , and increasing energy expenditure without altering energy intake ( exercise , primarily running)--in a one-year r and omized controlled trial . As compared with controls ( n = 42 ) , dieters ( n = 42 ) had significant loss of total body weight ( -7.8 + /- 0.9 kg [ mean + /- SE ] ) , fat weight ( -5.6 + /- 0.8 kg ) , and lean ( non-fat ) weight ( -2.1 + /- 0.5 kg ) ( P less than 0.001 for each variable ) , and exercisers ( n = 47 ) had significant loss of total body weight ( -4.6 + /- 0.8 kg ) and fat weight ( -3.8 + /- 0.7 kg ) ( P less than 0.001 for both variables ) but not lean weight ( -0.7 + /- 0.4 kg ) . Fat-weight loss did not differ significantly between dieters and exercisers . All subjects were discouraged from altering their diet composition ; however , dieters and exercisers had slight reductions in the percentage of kilojoules derived from fat . As compared with the control group , both weight-loss groups had significant increases ( P less than 0.01 ) in plasma concentrations of high-density lipoprotein ( HDL ) cholesterol ( diet vs. exercise , 0.13 + /- 0.03 vs. 0.12 + /- 0.03 mmol per liter ) , HDL2 cholesterol ( 0.07 + /- 0.02 vs. 0.07 + /- 0.02 mmol per liter ) , and HDL3 cholesterol ( 0.07 + /- 0.02 vs. 0.06 + /- 0.02 mmol per liter ) and significant decreases ( P less than 0.05 ) in triglyceride levels ( diet vs. exercise , -0.35 + /- 0.14 vs. -0.24 + /- 0.12 mmol per liter ) . Levels of total and low-density lipoprotein cholesterol were not significantly changed , relative to values in controls . None of these changes were significantly different between dieters and exercisers . Thus , we conclude that fat loss through dieting or exercising produces comparable and favorable changes in plasma lipoprotein concentrations BACKGROUND Weight loss reduces body fat and lean mass , but whether these changes are influenced by macronutrient composition of the diet is unclear . OBJECTIVE We determined whether energy-reduced diets that emphasize fat , protein , or carbohydrate differentially reduce total , visceral , or hepatic fat or preserve lean mass . DESIGN In a subset of participants in a r and omized trial of 4 weight-loss diets , body fat and lean mass ( n = 424 ; by using dual-energy X-ray absorptiometry ) and abdominal and hepatic fat ( n = 165 ; by using computed tomography ) were measured after 6 mo and 2 y. Changes from baseline were compared between assigned amounts of protein ( 25 % compared with 15 % ) and fat ( 40 % compared with 20 % ) and across 4 carbohydrate amounts ( 35 % through 65 % ) . RESULTS At 6 mo , participants lost a mean ( ±SEM ) of 4.2 ± 0.3 kg ( 12.4 % ) fat and 2.1 ± 0.3 kg ( 3.5 % ) lean mass ( both P < 0.0001 compared with baseline values ) , with no differences between 25 % and 15 % protein ( P ≥ 0.10 ) , 40 % and 20 % fat ( P ≥ 0.34 ) , or 65 % and 35 % carbohydrate ( P ≥ 0.27 ) . Participants lost 2.3 ± 0.2 kg ( 13.8 % ) abdominal fat : 1.5 ± 0.2 kg ( 13.6 % ) subcutaneous fat and 0.9 ± 0.1 kg ( 16.1 % ) visceral fat ( all P < 0.0001 compared with baseline values ) , with no differences between the diets ( P ≥ 0.29 ) . Women lost more visceral fat than did men relative to total-body fat loss . Participants regained ~40 % of these losses by 2 y , with no differences between diets ( P ≥ 0.23 ) . Weight loss reduced hepatic fat , but there were no differences between groups ( P ≥ 0.28 ) . Dietary goals were not fully met ; self-reported contrasts were closer to 2 % protein , 8 % fat , and 14 % carbohydrate at 6 mo and 1 % , 7 % , and 10 % , respectively , at 2 y. CONCLUSION Participants lost more fat than lean mass after consumption of all diets , with no differences in changes in body composition , abdominal fat , or hepatic fat between assigned macronutrient amounts . This trial was registered at clinical trials.gov as NCT00072995 16 202 men , aged 40 - 49 years , were screened for coronary risk factors , Of these , 1232 healthy , normotensive men at high risk of coronary heart disease ( CHD ) were selected for a 5-year r and omised trial to show whether lowering of serum lipids and cessation of smoking could reduce the incidence of CHD . Men were admitted to the trial if they had serum cholesterol levels of 7.5 - 9.8 mmol/l ( 290 - 380 ) mg/dl ) , coronary risk scores ( based on cholesterol levels , smoking habits , and blood pressure ) in the upper quartile of the distribution , and systolic blood pressures below 150 mm Hg ( mean of two measurements ) . The men in the intervention group were recommended to lower their blood lipids by change of diet and to stop smoking . Mean serum cholesterol concentrations were approximately 13 % lower in the intervention group than in the control group during the trial ( based on the difference between the mean of 3 prer and omisation values and the mean of yearly values during the trial ) . Mean fasting serum triglycerides fell by 20 % in the intervention group compared with controls . 80 % of the men in both groups smoked tobacco daily at the start of the study . The mean tobacco consumption per man decreased by 45 % more in the intervention group than in the control group . However , only 25 % of the smokers in the intervention group completely stopped smoking compared with 17 % in the control group . Diagnosis of events of cardiovascular disease during the study was made blindly according to predefined criteria by two cardiologists not involved in the study . At the end of the observation period the incidence of myocardial infa rct ion ( fatal and non-fatal ) and sudden death was 47 % lower in the intervention group than in the controls ( p = 0.028 , two-tailed log rank test ) . When the incidence of strokes was added , the difference between the groups was still significant . It is concluded that in healthy middle-aged men at high risk of CHD advice to change eating habits and to stop smoking significantly reduced the incidence of the first event of myocardial infa rct ion and sudden death . Statistical analysis , by Cox 's proportional hazards model shows that the reduction in incidence in the intervention group is correlated with the reduction in total cholesterol and to a lesser extent with smoking reduction In a r and omized , single-blind intervention trial , 406 patients 24 to 48 hours after acute myocardial infa rct ion ( AMI ) were assigned to either diet A ( 204 patients , group A ) or B ( 202 patients , group B ) for 6 weeks . At entry to the study , mean age , male sex , risk factors , complications , possible and definite AMI , and drug therapy were comparable between the 2 groups . Dietary adherence to intervention and control diets was checked by question naire , and drug therapy by tablet count . Group A received significantly lower calories , a higher percentage of calories from complex carbohydrates , vegetable/fish proteins , polyunsaturated fatty acids , and a higher polyunsaturated/saturated fat ratio diet than did group B ( higher total calories and saturated fatty acids ) . Group A also received less dietary cholesterol , salt and caffeine , and higher soluble dietary fiber , vitamins and minerals than did group B. After 6 weeks , group A had a significant decrease in mean serum total ( -20.5 vs -8.6 mg/dl ) and low-density lipoprotein ( -16.6 vs -6.4 mg/dl ) cholesterols , and triglycerides ( -15.5 vs -7.6 mg/dl ) , with no decrease in high-density lipoprotein cholesterol ( -1.5 vs -1.3 mg/dl ) compared with the initial levels and changes in group B. Group A also had a greater decrease in mean body weight ( 3.4 vs 1.3 kg ) than that of group B. ( ABSTRACT TRUNCATED AT 250 WORDS The purpose of this study was to investigate the effect of 1-year diet intervention , exercise intervention and both combined on blood pressure ( BP ) in normotensives and mild hypertensives . Two hundred and nineteen sedentary middle aged men and women with slightly deranged coronary heart disease ( CHD ) risk factors were r and omised to a control , a diet , an exercise and a diet + exercise group . Based on baseline diastolic BP , participants were divided into tertiles , giving baseline average BP of 141.4/96.7 in tertile 1 , 130.7/87.6 in tertile 2 and 121.9/79.0 in tertile 3 . The 1-year net-difference in BP between the intervention groups and the control group decreased across the tertiles ; in tertile 1 being -11.2/-6.7 ( p < 0.05 ) , -11.3/-6.7 ( p < 0.05 for systolic BP only ) and -7.0/-5.1 ( NS ) in the combined , diet and exercise group respectively . Triglycerides , HDL cholesterol , and insulin variables were significantly and favourably changed , the changes being most marked in the combined group . The results show that diet and diet + exercise are about equally effective in reducing BP , and the effects may be dependent on the baseline level . Within the upper tertile of baseline BP , the decline in BP in the combined intervention and the diet group are almost comparable to those obtained with drug treatment . In addition , other important CHD risk factors were all changed in a beneficial direction BACKGROUND Fatty acids that contain a trans double bond are consumed in large amounts as hydrogenated oils , but their effects on serum lipoprotein levels are unknown . METHODS We placed 34 women ( mean age , 26 years ) and 25 men ( mean age , 25 years ) on three mixed natural diets of identical nutrient composition , except that 10 percent of the daily energy intake was provided as oleic acid ( which contains one cis double bond ) , trans isomers of oleic acid , or saturated fatty acids . The three diets were consumed for three weeks each , in r and om order . RESULTS On the oleic acid diet , the mean ( + /- SD ) serum values for the entire group for total , low-density lipoprotein ( LDL ) , and high-density lipoprotein ( HDL ) cholesterol were 4.46 + /- 0.66 . 2.67 + /- 0.54 , and 1.42 + /- 0.32 mmol per liter ( 172 + /- 26 , 103 + /- 21 , and 55 + /- 12 mg per deciliter ) , respectively . On the trans-fatty-acid diet , the subjects ' mean HDL cholesterol level was 0.17 mmol per liter ( 7 mg per deciliter ) lower than the mean value on the diet high in oleic acid ( P less than 0.0001 ; 95 percent confidence interval , 0.13 to 0.20 mmol per liter ) . The HDL cholesterol level on the saturated-fat diet was the same as on the oleic acid diet . The LDL cholesterol level was 0.37 mmol per liter ( 14 mg per deciliter ) higher on the trans-fatty-acid diet than on the oleic acid diet ( P less than 0.0001 ; 95 percent confidence interval , 0.28 to 0.45 mmol per liter ) and 0.47 mmol per liter ( 18 mg per deciliter ) higher on the saturated-fat diet ( P less than 0.001 ; 95 percent confidence interval , 0.39 to 0.55 mmol per liter ) than on the oleic acid diet . The effects on lipoprotein levels did not differ between women and men . CONCLUSIONS The effect of trans fatty acids on the serum lipoprotein profile is at least as unfavorable as that of the cholesterol-raising saturated fatty acids , because they not only raise LDL cholesterol levels but also lower HDL cholesterol levels One hundred young male out patients with coronary disease who were under dietary management with a 28 % fat diet were group-matched to a non-dietary-managed group in regard to age , age at infa rct ion , number of infa rct ions , prevalence of hypertension , degree of angina , and value of serum cholesterol , among other factors . The diet-managed group experienced a significant reduction in serum cholesterol value , while the non-dietary-managed group did not . No significant differences were noted between the two groups in levels for serum total lipids , phospholipids , and triglycerides . Under the experimental conditions employed , the degree of unsaturation of the diet did not appear to influence serum cholesterol value or mortality . The non-dietary-managed group had a 160 % higher recurrent infa rct ion rate and a 233 % higher mortality rate than did the dietary-managed group during the first five years of observation OBJECTIVES This study evaluated the effectiveness of a low-intensity dietary intervention in primary care practice in lowering dietary fat intake and raising dietary fiber intake . METHODS A r and omized controlled trial of 28 physician practice s in six primary care clinics enrolled , by telephone , adult patients who had appointments for nonurgent nonacute visits . Of 3490 eligible patients contacted , 2111 completed baseline interview ; 86.1 % also completed a 12-month follow-up . Physicians gave intervention participants a self-help booklet and a brief motivational message . Changes in fat and fiber from baseline to 12-month follow-up were evaluated . RESULTS Intervention and control groups both reported a decrease in fat intake and an increase in fiber intake . The differential change and 95 % confidence interval ( CI ) for the percentage of energy obtained from fat was -1.2 ( CI = -0.71 , -1.7 ) ( P = .0015 ) , for grams fiber/1000 kcal 0.32 ( CI = -0.066 , 0.71 ) ( P = .086 ) , for fat score -0.044 ( CI = -0.016 , -0.072 ) ( P = .010 ) , and for fiber score 0.036 ( CI = 0.011 , 0.061 ) ( P = .014 ) , with greater reductions in fat and greater increase in fiber in the intervention group . CONCLUSIONS This low-intensity intervention was effective in dietary behavior change Summary To evaluate the feasibility of using a low-fat diet ( i.e. 20–25 % of energy ( E% ) as fat ) as a component of adjuvant therapy for breast cancer patients , 240 females aged 50–65 years and operated for a stage I-II breast cancer were entered into a r and omized study . The intervention group ( n = 121 ) was to reduce dietary fat intake to 20–25 E% and to increase the intake of carbohydrates . Dietary counselling complemented other adjuvant treatments and the patients were followed for two years . No dietary advice was given to patients in the control group ( n = 119).There was no significant difference between the groups in terms of base-line nutrient intake except for higher energy intake in the control group ( p < 0.05 ) . Only 52 % of the patients in the intervention group followed through with the dietary regimen for two years , and 89 % of the patients in the control group had a two-year follow-up . Energy intake decreased in both groups after two years , and the difference between the two groups remained ( p < 0.01 ) . Total fat intake decreased from 36.2 E% to 22.2 E% after one year in the intervention group and remained at that level after two years . Total fat intake in the control group decreased by 3.6 E% after two years . The low compliance raises concern about the protocol design . The study nevertheless indicates that a long-term reduction of dietary fat intake can be implemented in breast cancer patients Compliance with dietary recommendations and the effect of intensified dietary therapy on energy and nutrient intakes and fatty acid composition of serum lipids were studied in 86 obese subjects ( aged 40 to 64 years ) with recently diagnosed non-insulin-dependent diabetes mellitus ( NIDDM ) . After three months of basic education , the subjects were r and omly separated into an intervention group ( n = 40 ) and a conventional treatment group ( n = 46 ) . Members of the intervention group participated in 12 months of intensified education ; those in the conventional group visited local health centers . Compliance with dietary instructions was monitored through food records . Intensified dietary therapy result ed in greater weight loss , better metabolic control , and a less atherogenic lipid profile than conventional treatment . Intake of energy and saturated fatty acids tended to decline in the intervention group . A higher percentage of patients in the intervention group had a total fat intake of 30 % of energy or less after 15 months ( 32.5 % [ 12 of 38 ] vs 17.4 % [ 8 of 46 ] ) . Similarly , more patients in the intervention group had a saturated fatty acid intake of 10 % or less of total energy intake at the end of the study ( 35.0 % [ 13 of 38 ] vs 8.7 % [ 4 of 46 ] ) . The mean dietary cholesterol intake was within recommendations in both groups at the end of the study . The relative percentage of linoleic acid of serum lipids increased significantly and the relative percentage of palmitic acid of serum triglycerides , phospholipids , and cholesterol esters decreased in the intervention group . These changes indicate that intensified dietary therapy improved the quality of fat in the diet of patients with NIDDM In a one-year , double-blind clinical trial , 45 patients with peripheral vascular disease ( PVD ) were r and omly assigned to either the American Heart Association Hyperlipidemia Diet C ( n = 20 ) or a low-fat , high-fiber , complex carbohydrate diet similar to the Pritikin Maintenance Diet ( n = 25 ) . Vascular status and blood lipid levels were monitored at 0 , 2 , 4 , 6 , and 12 months . Walking distance increased significantly in both groups , with no difference between groups . No vascular parameters changed significantly , suggesting that increased walking distance was due to improved metabolic capacity of the muscle . A trend toward lower blood lipid values was observed , with no significant differences within or between groups . We conclude that while patients with PVD benefit from a program of diet and exercise , there is no apparent advantage to the more difficult complex carbohydrate diet Context Can adults make sustained changes in unhealthy lifestyle behaviors ? Content In this multicenter trial , 810 adult volunteers with prehypertension or stage 1 hypertension were r and omly assigned to a multicomponent behavioral intervention group , a group combining the behavioral intervention plus the Dietary Approaches to Stop Hypertension ( DASH ) diet , or an advice only group . At 18 months , participants in both behavioral intervention groups had less hypertension , more weight loss , and better reduction in sodium and fat intake than those receiving advice only . The participants in the DASH diet group also increased their intake of fruits , vegetables , and fiber . Implication s Motivated adults can sustain several lifestyle changes over 18 months , which might reduce their risk for cardiovascular disease . The Editors The public health burden of chronic diseases related to suboptimal diet and physical inactivity is enormous . It has been estimated that these lifestyle factors contribute to approximately 20 % of deaths in the United States ( 1 ) . Incidence of atherosclerotic cardiovascular disease , overweight and obesity , elevated blood pressure and lipid levels , diabetes , osteoporosis , and cancer is increased by unhealthy lifestyles ( 2 - 8 ) . Multiple lifestyle factors , such as physical inactivity ; excessive intake of calories , sodium , saturated fat , and cholesterol ; and inadequate intake of fruits , vegetables , and low-fat dairy products , are etiologically related to the development of these diseases ( 4 , 5 , 8 - 10 ) . To reduce the burden of chronic disease , increased physical activity and changes in diet are needed , yet few intervention studies have attempted to achieve many lifestyle changes simultaneously . The PREMIER r and omized trial tested the effects of 2 multicomponent behavioral interventions on blood pressure ( 11 ) . Both interventions promoted increased physical activity , weight loss , and reduced sodium intake , each of which is recommended by the 2005 Dietary Guidelines Scientific Advisory Committee ( 12 ) . One intervention also added the Dietary Approaches to Stop Hypertension ( DASH ) diet ( 13 ) . This diet , which is high in fruits , vegetables , and low-fat dairy products and low in saturated fat , total fat , and cholesterol , meets each of the major nutrient recommendations that were established by the Institute of Medicine ( 14 - 18 ) . We report the effects of the PREMIER interventions on lifestyle changes and blood pressure status at 18 months . The main results of PREMIER , namely change in blood pressure at 6 months , were reported previously ( 11 ) . Methods The PREMIER study design and rationale ( 19 ) and intervention methods ( 11 ) have been described previously . The institutional review boards at each clinical center ; an external protocol review committee appointed by the National Heart , Lung , and Blood Institute ( NHLBI ) ; and the NHLBI review ed and approved the protocol ( available at www.kpchr.org/public/premier/intervention/default.asp ) . The NHLBI also appointed a data and safety monitoring board to monitor the trial . Each participant provided written informed consent . The trial was conducted from January 2000 through November 2002 . Study Participants Participants were generally healthy adults , age 25 years or older , who had prehypertension or stage 1 hypertension and met the Joint National Committee VI ( JNC VI ) criteria for a 6-month trial of nonpharmacologic therapy ( 2 ) . Targeted recruitment methods were used to ensure adequate representation of clinical ly important subgroups , in particular , African-American persons . Specific methods varied from site to site but included direct mailings , radio and newspaper advertisements , and networking within the local African-American communities . Eligibility criteria included not taking antihypertensive medication and having a systolic blood pressure of 120 to 159 mm Hg and a diastolic blood pressure of 80 to 95 mm Hg , based on the average of 3 screening visits . Persons with prehypertension ( systolic blood pressure of 120 to 139 mm Hg or diastolic blood pressure of 80 to 89 mm Hg ) were included because of the excess risk for cardiovascular disease in those with blood pressure within this range ( 20 ) . Major exclusion criteria were a body mass index less than 18.5 kg/mg2 or greater than 45.0 kg/m2 , use of antihypertensive drugs or other drugs that affect blood pressure , JNC VI risk category C ( target organ damage or diabetes ) , use of prescription weight loss medications , previous cardiovascular event , congestive heart failure , angina , cancer , and consumption of more than 21 alcoholic drinks per week . Trial Conduct Eligible participants were r and omly assigned , with equal probability , to 1 of 3 groups : an advice only comparison group ( advice only ) ; an intervention group that targeted established , guideline -recommended lifestyle recommendations ( established ) ( 2 ) ; or an intervention group targeting the established recommendations and adding the DASH dietary pattern ( established plus DASH ) ( 13 ) . Computer-generated treatment assignments were stratified by clinic and hypertension status and were assigned in blocks of varying sizes to provide balance over time . The actual assignments were administered by using a password-protected , Web-based application developed by the coordinating center and accessible only by authorized individuals . All clinic measurement staff were blinded to treatment assignment , and all intervention staff were blinded to clinic measurements . Hypertension was defined by using the JNC VI criteria for hypertension treatment : an average systolic blood pressure of 140 mm Hg , a diastolic blood pressure greater than 90 mm Hg , or use of antihypertensive medication . Normal blood pressure was defined as systolic blood pressure less than 120 mm Hg , diastolic blood pressure less than 80 mm Hg , and no use of antihypertensive medication ( 21 ) ( Figure ) . Intervention was provided by master 's degreelevel counselors ( dietitians and health educators trained in behavioral methods ) . The counselors were central ly trained before the start of the study , attended annual 3-day training sessions , and participated in monthly conference calls . Figure . Flow diagram of enrollment , measurements , and visit completion . Advice Only Group Participants in the advice group received advice to follow the National High Blood Pressure Education Program lifestyle recommendations for blood pressure control ( 2 ) . Lifestyle recommendations included reducing weight ( if overweight ) , following a reduced-sodium diet , engaging in regular moderate-intensity physical activity , and eating a heart-healthy diet , including the DASH diet . This advice was provided in two 30-minute individual sessions , 1 immediately after r and om assignment and 1 after the 6-month data collection visit . A PREMIER counselor review ed the guidelines with the participant and provided printed educational material s and information about community re sources . This intervention did not include advice to keep a food or exercise diary . Behavioral Interventions in the Established and Established plus DASH Groups Participant goals for the established and established plus DASH groups included weight loss of at least 6.8 kg ( 15 lb ) for those with a body mass index of 25 kg/m2 or greater , at least 180 minutes per week of moderate-intensity physical activity , no more than 100 mmol per day of dietary sodium , and alcohol consumption of no more than 30 mL ( 1 oz ) per day ( 2 drinks ) for men and 15 mL ( 0.5 ) oz per day ( 1 drink ) for women . Participants assigned to the established plus DASH group ( but not those in the established group ) also received counseling on the DASH diet , with goals for increased consumption of fruits and vegetables ( 9 to 12 servings/d ) and low-fat dairy products ( 2 to 3 servings/d ) and reduced consumption of saturated fat ( 7 % of energy ) and total fat ( 25 % of energy ) . The intervention format , contact pattern , and behavior change strategies for the established and established plus DASH groups were identical . During the first 6 months , participants in both behavioral intervention groups attended 14 group sessions and 4 individual sessions ; during months 7 to 18 , they attended monthly group sessions supplemented with 3 individual counseling sessions . Throughout the trial , participants in the established and established plus DASH groups ( but not those in the advice group ) kept food diaries , monitored dietary calorie and sodium intakes , and recorded minutes of physical activity . Self-monitoring was used to provide individualized feedback , reinforcement , problem solving , and support . Social support for initial behavior changes and maintenance of change was provided during the group sessions . More detailed descriptions of the behavorial intervention methods are available ( 22 ) . Measurements Blood pressure was assessed twice at each measurement , and systolic and diastolic blood pressures were calculated by using the mean of all available measurements ( 4 sets before r and om assignment , 3 sets at 6 and 18 months , and 1 set at 3 and 12 months ) . For 4 participants who were started on antihypertensive drug therapy between the 12- and 18-month visits , we obtained an official set of blood pressure measurements before initiation of therapy and used these as our 18-month blood pressure values for analysis . A similar procedure was used to obtain the 6-month blood pressure value for the 1 participant who began taking antihypertensive drugs between the 3- and 6-month visits . Two 24-hour dietary recalls , 1 obtained on a weekday and the other obtained on a weekend , were collected at baseline and at 6 and 18 months by telephone interview ( 23 ) . Intakes of nutrients and food groups were calculated by using the Nutrition Data System for Research , version NDS-R 1998 ( University of Minnesota , Minneapolis , Minnesota ) . Urinary excretion of sodium ( reflecting salt intake ) and potassium ( reflecting fruit and vegetable intake ) was obtained from 24-hour urinary collection s at baseline Under experimental clinical conditions diet modification has been shown to reduce serum cholesterol levels . This paper reports such a positive response to a nonpharmacologic , behavioral education program at the worksite . Employees at the New York Telephone Company corporate headquarters were assigned r and omly to treatment and control groups . Treatment consisted of an 8-week group cholesterol reduction program conducted during employee lunch hours . It comprised a multiple-treatment approach -- food behavior change techniques combined with nutrition education , physical activity planning , and self-management skills . The treatment group showed substantial change compared with the control group at the program 's completion . Those treated displayed a significant 6.4 % reduction in total serum cholesterol ( 266 mg% average at baseline ) as compared with control subjects with a corresponding decrease in high-density lipoprotein levels . A significant increase in nutrition knowledge and moderate weight loss were also documented for this group . The magnitudes of a participant 's baseline serum cholesterol level and his/her reduction in percentage of ideal body weight were positively and independently correlated with percentage changes in serum cholesterol levels . Over the same period , decreases in high-density lipoprotein levels and no changes in serum cholesterol , weight , and nutrition knowledge were observed for the control group . Overall , participants in the treatment program successfully reduced the coronary heart disease risk factors of elevated cholesterol and weight . Directions for future study are suggested We utilized data from the comparison group of the Women ’s Healthy Eating and Living r and omized trial to investigate an “ a priori ” hypothesis suggested by CYP2D6 studies that hot flashes may be an independent predictor of tamoxifen efficacy . A total of 1551 women with early stage breast cancer were enrolled and r and omized to the comparison group of the WHEL multi-institutional trial between 1995 and 2000 . Their primary breast cancer diagnoses were between 1991 and 2000 . At study entry , 864 ( 56 % ) of these women were taking tamoxifen , and hot flashes were reported by 674 ( 78 % ) . After 7.3 years of follow-up , 127 of those who took tamoxifen at baseline had a confirmed breast cancer recurrence . Women who reported hot flashes at baseline were less likely to develop recurrent breast cancer than those who did not report hot flashes ( 12.9 % vs 21 % , P = 0.01 ) . Hot flashes were a stronger predictor of breast cancer specific outcome than age , hormone receptor status , or even the difference in the stage of the cancer at diagnosis ( Stage I versus Stage II ) . These findings suggest an association between side effects , efficacy , and tamoxifen metabolism . The strength of this finding suggests that further study of the relationship between hot flashes and breast cancer progression is warranted . Additional work is warranted to clarify the mechanism of hot flashes in this setting A r and omized intervention trial of dietary fat reduction to 15 % of total calories was initiated in 1987 for women at high risk for breast cancer to determine the feasibility of recruiting and maintaining them on a low-fat diet . The study has enrolled 194 women between the ages of 18 and 67 years who met at least one of three eligibility criteria : 1 ) a first-degree relative with breast cancer , 2 ) a P2 or DY Wolfe mammographic pattern , and 3 ) a prior breast biopsy demonstrating epithelial hyperplasia with or without atypia . Eligible women must also have had diets that contained > or = 30 % of calories from fat at entry . Women were r and omized to a nonintervention usual diet vs. a 15 % low-fat diet . Recruitment was sought through physicians , personal mailings , breast cancer patients , and the news media . Two study sites participated : a large urban hospital affiliated with a university medical center and a community oncology private practice . The results from both institutions were similar and demonstrated that a low-fat dietary plan could be effectively conducted in private as well as academic setting s with recruitment tailored to the community where the trial is being conducted . Reduction in dietary fat intake was maximal during the first three months of the dietary intervention and remained stable throughout 12 months of follow-up . Reductions in total calories , weight loss , and percent body fat were minimal . The nonintervention group experienced no major change in their diet . We conclude that it is feasible to recruit women who are at high risk for breast cancer into a dietary intervention trial and with sufficient dietary counseling and motivation on the part of participants , reduction in dietary fat intake can be achieved and maintained . More in-depth analyses of these data will be presented in subsequent reports Women diagnosed as suffering from premenstrual syndrome and symptom free controls were compared on hormonal parameters , glucose tolerance , mineralocorticoids , cholesterols , triglycerides , apolipoprotein ( a ) , magnesium and calcium in the follicular and luteal phases of the menstrual cycle . The effect of treatment with essential fatty acids on the biochemical variables was also evaluated in a r and omized , double‐blind crossover design . The results showed that the hormonal and biochemical profiles of women with PMS and symptom free controls were markedly similar , except for aldosterone which was lower in the follicular and luteal phases and cholesterol which was higher in the follicular phase in women with PMS . No effects of treatment with essential fatty acids were found for any of the biochemical variables studied The effectiveness of lovastatin was compared with both a high-fat vs low-fat diet . Hypercholesterolemic subjects were studied under metabolic ward conditions for diet periods of 3 weeks while receiving lovastatin ( 40 mg/d ) or placebo . Multiple lipoprotein levels were measured during the final week of each diet period . Nineteen subjects completed the study on the high-fat ( 43 % of kilojoules ) diet and 16 on the low-fat ( 25 % of kilojoules ) diet . Lovastatin reduced total cholesterol by 23 % and low-density lipoprotein cholesterol by 30 % , compared with placebo on both diets , with no significant diet-drug interaction . High-density lipoprotein cholesterol was raised by 7 % to 8 % on the diet regimens . Addition of lovastatin to the low-fat diet permitted 80 % of subjects on this diet , but less than 50 % of those on the high-fat diet , to achieve current guidelines . Although lovastatin produces a comparable percentage reduction in lipoprotein profiles on either diet , the accompanying low-fat diet remains advisable for additional reduction of low-density lipoprotein cholesterol levels to specified goals BACKGROUND Our aim was to investigate whether a nurse-coordinated multidisciplinary , family-based preventive cardiology programme could improve st and ards of preventive care in routine clinical practice . METHODS In a matched , cluster-r and omised , controlled trial in eight European countries , six pairs of hospitals and six pairs of general practice s were assigned to an intervention programme ( INT ) or usual care ( UC ) for patients with coronary heart disease or those at high risk of developing cardiovascular disease . The primary endpoints-measured at 1 year-were family-based lifestyle change ; management of blood pressure , lipids , and blood glucose to target concentrations ; and prescription of cardioprotective drugs . Analysis was by intention to treat . The trial is registered as IS RCT N 71715857 . FINDINGS 1589 and 1499 patients with coronary heart disease in hospitals and 1189 and 1128 at high risk were assigned to INT and UC , respectively . In patients with coronary heart disease who smoked in the month before the event , 136 ( 58 % ) in the INT and 154 ( 47 % ) in the UC groups did not smoke 1 year afterwards ( difference in change 10.4 % , 95 % CI -0.3 to 21.2 , p=0.06 ) . Reduced consumption of saturated fat ( 196 [ 55 % ] vs 168 [ 40 % ] ; 17.3 % , 6.4 to 28.2 , p=0.009 ) , and increased consumption of fruit and vegetables ( 680 [ 72 % ] vs 349 [ 35 % ] ; 37.3 % , 18.1 to 56.5 , p=0.004 ) , and oily fish ( 156 [ 17 % ] vs 81 [ 8 % ] ; 8.9 % , 0.3 to 17.5 , p=0.04 ) at 1 year were greatest in the INT group . High-risk individuals and partners showed changes only for fruit and vegetables ( p=0.005 ) . Blood-pressure target of less than 140/90 mm Hg was attained by both coronary ( 615 [ 65 % ] vs 547 [ 55 % ] ; 10.4 % , 0.6 to 20.2 , p=0.04 ) and high-risk ( 586 [ 58 % ] vs 407 [ 41 % ] ; 16.9 % , 2.0 to 31.8 , p=0.03 ) patients in the INT groups . Achievement of total cholesterol of less than 5 mmol/L did not differ between groups , but in high-risk patients the difference in change from baseline to 1 year was 12.7 % ( 2.4 to 23.0 , p=0.02 ) in favour of INT . In the hospital group , prescriptions for statins were higher in the INT group ( 810 [ 86 % ] vs 794 [ 80 % ] ; 6.0 % , -0.5 to 11.5 , p=0.04 ) . In general practice s in the intervention groups , angiotensin-converting enzyme inhibitors ( 297 [ 29 % ] INT vs 196 [ 20 % ] UC ; 8.5 % , 1.8 to 15.2 , p=0.02 ) and statins ( 381 [ 37 % ] INT vs 232 [ 22 % ] UC ; 14.6 % , 2.5 to 26.7 , p=0.03 ) were more frequently prescribed . INTERPRETATION To achieve the potential for cardiovascular prevention , we need local preventive cardiology programmes adapted to individual countries , which are accessible by all hospitals and general practice s caring for coronary and high-risk patients To identify diets that are more effective than existing ones in reducing lipoprotein-mediated risk of atherosclerotic heart disease , the serum lipids and lipoprotein response to three modified diets was studied in twelve normal men living in an institution . The " Western " reference diet ( 40 % energy from fat , P/S ratio 0.27 ) was compared in Latin square design with a fat-modified diet ( diet B , 27 % energy from fat , P/S 1.0 , reduced cholesterol content ) ; with a fat-modified diet supplemented with fruit , vegetable , and cereal fibre ( diet C ) ; and with a diet providing 40 % energy from fat , having P/S ratio 1.0 and supplemented by fibre ( diet D ) . The effects of fat modification and fibre-supplementation ( diets C and D ) were strongly additive-a fall serum cholesterol by 24 - 29 % , in low-density-lipoprotein ( LDL ) cholesterol by 31 - 34 % , and in serum triglyceride by 21 - 26 % ; and the reduction , by diet C , of the ratio of serum cholesterol to high-density-lipoprotein (HDL)-cholesterol by 21 % , and that of LDL-cholesterol to HDL2-cholesterol by 26 % . The additive effects of multiple changes in nutrient intake , each moderate in extent , permits the design of diets which are remarkably effective in reducing serum-cholesterol level Diet is important in the prevention of cardiovascular disease , and it has been suggested that a high-MUFA diet is more cardioprotective than a low-fat diet . We hypothesised that the postpr and ial thrombotic risk profile is improved most favourably by a high-MUFA diet compared with a low-fat diet . This was tested in a parallel intervention trial on overweight individuals ( aged 28.4 ( SD 4.7 ) years ) r and omly assigned to a MUFA-diet ( 35 - 45 % of energy as fat ; > 20 % as MUFA , n = 21 ) or a low-fat ( LF ) diet ( 20 - 30 % of energy as fat , n = 22 ) for 6 months after a weight loss of ~10 % . All foods were provided free of charge from a purpose -built supermarket . Meal tests design ed after the same principles were performed before and after the dietary intervention , and blood sample s were collected at 8.00 h ( fasting ) , 12.00 h , and 18.00 h and analysed for factor VII coagulant activity ( FVII : C ) , activated FVII , fibrinogen , prothrombin fragment 1 + 2 ( F1 + 2 ) , D-dimer , plasminogen activator inhibitor ( PAI : Ag ) , and thrombin activatable fibrinolysis inhibitor . There were significant postpr and ial increases in F1 + 2 and D-dimer before and after dietary intervention , with significantly lower values after 6 months . No significant differences were observed between the postpr and ial changes induced by the two diets . The postpr and ial decrease in FVII : C and PAI : Ag did not differ before and after intervention , irrespective of the diets . Our findings suggest postpr and ial coagulation activation in overweight subjects with more pronounced acute than long-term effects . We observed similar effects of the MUFA diet and the LF diet on the postpr and ial prothrombotic risk profile Bei gesunden Versuchspersonen wurden unter fettreich/kohlenhydratarmer und unter fettarm/kohlenhydratreicher Kost ( rd . 60 bzw . rd . 5 % Fettcalorien ) nach peroraler Zufuhr von 1 g Olivenol/kg Korpergewicht die Triglyceride i m Serum bestimmt . Unter fettreich/kohlenhydratarmer Kost stiegen die Triglyceride postcenal von tiefem Nuchternniveau aus hoch an , wahrend sie unter fettarm/kohlenhydratreicher Kost von hohem Nuchternniveau aus kaum oder gar nicht anstiegen In a prospect i ve , r and omised single-blinded secondary prevention trial we compared the effect of a Mediterranean alpha-linolenic acid-rich diet to the usual post-infa rct prudent diet . After a first myocardial infa rct ion , patients were r and omly assigned to the experimental ( n = 302 ) or control group ( n = 303 ) . Patients were seen again 8 weeks after r and omisation , and each year for 5 years . The experimental group consumed significantly less lipids , saturated fat , cholesterol , and linoleic acid but more oleic and alpha-linolenic acids confirmed by measurements in plasma . Serum lipids , blood pressure , and body mass index remained similar in the 2 groups . In the experimental group , plasma levels of albumin , vitamin E , and vitamin C were increased , and granulocyte count decreased . After a mean follow up of 27 months , there were 16 cardiac deaths in the control and 3 in the experimental group ; 17 non-fatal myocardial infa rct ion in the control and 5 in the experimental groups : a risk ratio for these two main endpoints combined of 0.27 ( 95 % CI 0.12 - 0.59 , p = 0.001 ) after adjustment for prognostic variables . Overall mortality was 20 in the control , 8 in the experimental group , an adjusted risk ratio of 0.30 ( 95 % CI 0.11 - 0.82 , p = 0.02 ) . An alpha-linolenic acid-rich Mediterranean diet seems to be more efficient than presently used diets in the secondary prevention of coronary events and death Abstract To study the effect of long-term feeding of a diet high in unsaturated fat , low in saturated fat , low in cholesterol , and high in plant sterol on cholelithiasis in man , we review ed autopsy records from the Los Angeles Veterans Administration controlled clinical trial of dietary prevention of complications of atherosclerosis . Autopsied men who ate more than 33 per cent of the experimental meals served from entry into the trial to death were more likely to have gallstones ( 34 per cent ) than control subjects ( 14 per cent ) ( p less than 0.01 ) . The proportion of men in the experimental diet group with gallstones at autopsy was directly correlated with number of trial meals eaten ( p less than 0.05 ) . Gallstones were more common ( p less than 0.01 ) at autopsy in men 9.1 kg or more overweight ( 43 per cent ) than in the remaining men ( 16 per cent ) in both diet groups . The data suggest that some property of the experimental diet ( high ratio of polyunsaturated fat to saturated fat or high ratio of plant sterol PURPOSE To evaluate the feasibility of integrating a program based on dietary fat intake reduction into adjuvant treatment strategies for postmenopausal women receiving therapy for early breast cancer . PATIENTS AND METHODS Two hundred ninety postmenopausal women with localized ( stage I to IIIa ) breast cancer receiving conventional systemic therapy provided informed consent and were r and omized in a multicenter trial to either a dietary intervention group receiving a program of individualized instruction for reducing total fat intake or a dietary control group with minimal dietary counseling . RESULTS Significantly reduced ( P < .001 ) fat intake ( in terms of percent calories derived from fat ) was observed in the intervention group versus the control group at 3 months ( 20.3 % + /- 2.4 % v 31.5 % + /- 2.6 % , mean + /- SD , respectively ) and maintained throughout 24 months of observation . The 50 % reduction in daily fat-gram intake ( from 66 + /- 23 to 33 + /- 14 g , P < .001 ) seen at 6 months was associated with reduced saturated fat , monounsaturated fat , polyunsaturated fat , and linoleic acid ( P < .001 ) . Significantly lower body weight was also seen in intervention compared with control patients at all observation periods , result ing in a 3.3-kg weight difference 18 months after r and omization ( P < .001 ) . CONCLUSION Substantial and sustained dietary fat reduction with associated weight change can be achieved at relatively low cost within the context of conventional multimodality clinical management of postmenopausal women with localized breast cancer . This result supports the feasibility of conducting a full-scale evaluation of the influence of dietary fat intake reduction on the clinical outcome of breast cancer patients OBJECTIVES The objective was to analyse whether a favourable change in risk factors , caused by a comprehensive risk factor modification programme , affected intima-media thickness ( IMT ) in the common carotid artery , and whether any such change was associated with a change in cardiovascular events during a 6-year follow-up . DESIGN Patients were r and omized 1 : 1 to special intervention or usual care . SETTING Hypertension Unit at university hospital . SUBJECTS A total of 164 patients were r and omized . Inclusion criteria were male , aged 50 - 72 years ( at r and omization ) and one or more of the following : Serum cholesterol level > 6.5 mmol L(-1 ) , smoking or diabetes mellitus . All patients were prescribed antihypertensive treatment since many years . In 142 men good quality ultrasound recording of the common carotid IMT were achieved at baseline , 119 were re-examined after 3.3 years , and 97 patients were available for examination after mean follow-up time of 6.2 years . Cardiovascular events were available for all r and omized patients . INTERVENTIONS The nonpharmacological special intervention programme was based on one information meeting followed by five weekly 2-h sessions with participation of patients and spouses . The diet recommendations were similar to established guidelines . Overweight patients were instructed to lose weight , and diabetic patients were systematic ally taught self-monitoring of blood glucose . Smokers were invited to a smoking cessation programme with five weekly meetings . Follow-up visits were thereafter scheduled every 6 months . Lipid lowering drugs were recommended in the intervention group if the treatment goals using nonpharmacological measures were not achieved . Patients in the usual care group were told to quit smoking and to lower their consumption of fat and glucose . Antihypertensive treatment ( i.e. , selection of drugs ) was on purpose kept similar in the two groups . MAIN OUTCOME MEASURES The IMT of the common carotid artery as measured by ultrasound . Cardiovascular events during follow-up . RESULTS Significant net reductions were seen for serum cholesterol , triglycerides , fasting glucose and smoking . No difference in change in IMT was observed during follow-up between the two r and omization groups . The explanation was that patients with positive plaque status at baseline had a much larger increase in IMT over time than patients with negative plaque status , and that patients with positive plaque status more often survived and were available for re-examination after 6 years in the intervention group than in the usual care group . Total mortality was lower in the intervention group , compared with the usual care group , 13 and 29 % , respectively ( P=0.028 ) . CONCLUSIONS In high risk population s , long-term studies with surrogate endpoints may be misleading because of missing data in patients where a large increase in IMT would have been observed , had they been re-examined . Another important conclusion from our study was that the gloomy prognosis for this patient category may be improved by a dedicated risk factor intervention programme . The improved prognosis was observed mainly in those patients at highest risk judged from history of cardiovascular disease or positive ultrasound plaque status at baseline Abstract The mortality from coronary heart-disease ( C.H.D. ) and other causes was studied in two mental hospitals during a long-term ( twelve-year ) controlled preventive trial . The trial was cross-over in design . In one of the hospitals a serum-cholesterol-lowering diet was introduced and the other hospital using a normal diet served as the control . After six years the diets were reversed , and the trial was continued for six more years . In men , the use of the cholesterol-lowering diet was associated with considerably and significantly reduced mortality from C.H.D. Total mortality also was consistently lower on this diet , although the differences were too small for statistical significance . In women , the mortality from C.H.D. also appeared to be lower during the diet period , but the differences were small and not significant . In female total mortality no appreciable differences were found Diet intervention trials are currently testing whether reduced fat intake can reduce the risk and progression of breast cancer . Energy from dietary fat is generally replaced by energy from carbohydrate in these studies , and altering the proportion of energy from dietary carbohydrate and fat has been shown to affect plasma lipid concentrations in controlled feeding studies . The purpose of this study was to examine the effect of increased carbohydrate and reduced fat intakes on plasma lipids in a r and omized , controlled trial that is testing the effect of diet modification on risk for recurrence and survival in women previously treated for breast cancer . Plasma concentrations of lipids and related factors were measured at enrollment and 1-y follow-up in 393 women enrolled in the trial . Dietary goals for the intervention group focused on an increase in vegetable , fruit and fiber intakes , and reduced fat intake . Women assigned to the intervention group significantly reduced fat intake ( from 28.1 to 21.0 % of energy ) , and significantly increased intakes of carbohydrate ( from 56.9 to 65.3 % of energy ) and fiber ( from 21.0 to 29.6 g/d ) ( P < 0.05 ) . Body weight did not change significantly in either study group . A small but significant increase in fasting plasma triacylglycerol concentration , and decreases in HDL cholesterol and apoprotein-A1 concentrations , were observed in the intervention group ( P < 0.05 ) but not in the comparison group . Changes in total cholesterol , LDL cholesterol , apoprotein-B , lipoprotein ( a ) , and insulin concentrations , and in the LDL cholesterol/HDL cholesterol ratio , were not observed in either group . The lipid responses that were observed in this study provide biological evidence that vali date s the self-reported change in dietary intakes of fat and carbohydrate in response to the intervention efforts . The degree of change in these lipid concentrations was small and does not suggest increased cardiovascular disease risk OBJECTIVE To examine the dietary habits of patients with ischemic heart disease 1 year after they received either dietary advice on using the Plate Model and how to increase intakes of fruits and vegetables in a 10-minute session ( brief counseling group , BCG ) or dietary advice primarily based on the National Cholesterol Education Program Step I diet provided in 2 individually tailored 50-minute sessions held 3 months apart ( comprehensive counseling group , CCG ) . DESIGN A r and omized study that included dietary intake evaluation on basis of 7-day weighed food records completed at 3 occasions : immediately before counseling ( week zero ) , 12 weeks after counseling , and 52 weeks after counseling . SUBJECTS BCG was composed of 15 men and 2 women and CCG was composed of 16 men and 3 women with ischemic heart disease age 70 years or younger recruited from the Department of Cardiology , Odense University Hospital , Odense , Denmark . STATISTICAL ANALYSES PERFORMED ANOVA , unpaired t tests , and multiple regression analysis , as well as nonparametric statistical analyses were carried out . RESULTS The comprehensive counseling result ed in significant improvements from week 0 to 52 in the percent of energy from fat ( 33 % to 28 % ) , saturated fat ( 12 % to 9 % ) and carbohydrate ( 51 % to 54 % ) consumed by the subjects . The corresponding values in BCG did not differ significantly ( 31 % to 32 % , 11 % to 12 % , 53 % to 52 % respectively ) . Differences from week 0 to 52 between groups were significant for fat , saturated fat , and carbohydrate intake . In CCG , median intakes of fish , fruits , and vegetables were 44 g/day , 172 g/day , and 315 g/day , respectively , at week 52 . The corresponding values in BCG were 44 g/day , 129 g/day , and 224 g/day . There was no significant difference either within or between the groups . CONCLUSION This study suggests that sustained improvements in dietary behavior require individualized and reinforced counseling in patients with ischemic heart disease . Changes in intakes of fish , fruits , and vegetables need to be specifically targeted AIM To evaluate the effectiveness of lifestyle interventions in people with impaired glucose tolerance ( IGT ) . METHODS Participants with IGT ( n=78 ) , diagnosed on two consecutive oral glucose tolerance tests ( OGTTs ) , were r and omly assigned to a 2-year lifestyle intervention or to a control group . Main outcome measures were changes from baseline in : nutrient intake ; physical activity ; anthropometry , glucose tolerance and insulin sensitivity . Measurements were repeated at 6 , 12 and 24 months follow-up . RESULTS After 24 months follow-up , there was a significant fall in total fat consumption ( difference in change between groups ( Delta intervention-Delta control)= -17.9 , 95 % confidence interval ( CI ) -33.6 to -2.1g/day ) as a result of the intervention . Body mass was significantly lower in the intervention group compared with controls after 6 months ( -1.6 , 95 % CI -2.9 to -0.4 kg ) and 24 months ( -3.3 , 95 % CI -5.7 to -0.89 kg ) . Whole body insulin sensitivity , assessed by the short insulin tolerance test ( ITT ) , improved after 12 months in the intervention group ( 0.52 , 95 % CI 0.15 - 0.89%/min ) . CONCLUSIONS These findings complement the findings of the Finnish Diabetes Prevention Study and the American Diabetes Prevention Study , both of which tested intensive interventions , by showing that pragmatic lifestyle interventions result in improvements in obesity and whole body insulin sensitivity in individuals with IGT , without change in other cardiovascular risk factors Phase I of the Trials of Hypertension Prevention ( TOHP ) was a National Heart , Lung , and Blood Institute-sponsored , 3-year , national , multicenter , r and omized , controlled trial design ed to test the feasibility and efficacy of three life-style ( weight loss , sodium restriction , and stress management ) and four nutrition supplement ( calcium , magnesium , fish oil , and potassium ) interventions aim ed at lowering diastolic blood pressure in those whose blood pressure was initially in the high normal range ( 80 to 89 mm Hg ) . A total of 2182 volunteers were recruited and allocated to the various treatment arms , such that each hypothesis was tested with a power of 85 % or higher to detect a diastolic blood pressure treatment effect of 2 mm Hg . The four nutrition supplement interventions were delivered in a double-blinded fashion and the three life-style interventions , single ( observed ) -blinded . Phase I was design ed to provide a rigorous test of short-term lowering of blood pressure for each of the seven treatments chosen and provides the basis for planning of a subsequent long-term trial of hypertension prevention The effect of plasma lipid reduction on the progression of femoral atherosclerosis was studied in hyperlipidaemic patients with stable intermittent claudication . 24 patients were r and omly assigned to treatment and usual-care groups , the former receiving dietary advice and cholestyramine , nicotinic acid , or clofibrate depending on their lipoprotein phenotype . Biplanar arteriography was performed when the study began and after a mean period of 19 months . Angiograms were assessed visually , with blinding , and by computerised image analysis . Therapy reduced mean plasma total cholesterol by 25 % , mean low density lipoprotein ( LDL ) cholesterol by 28 % , and mean plasma triglycerides by 45 % . Significantly fewer arterial segments showed detectable progression of atherosclerosis in the treatment group . The mean increase in plaque area ( mm2/segment/year ) in the treatment group was only one third of that in the usual-care group . The mean increase in edge irregularity index ( a measure of the severity of disease ) in the treatment group was only 40 % of that in the usual care group . Twice as many arterial segments showed improvement in the treatment group . In both groups changes in edge irregularity index were directly related to plasma LDL cholesterol concentration . This study , the first r and omised controlled trial of its type , provides evidence that effective treatment of hyperlipidaemia favourably influences the natural history of symptomatic peripheral atherosclerosis It has previously been shown that fish oil supplementation , compared to olive oil , reduces plasma fibrinogen . Presented here are the results of a r and omized , double-blind , crossover controlled trail that compared the effects of dietary n-3 and n-6 fatty acid supplementation on plasma fibrinogen levels in 10 patients with hyperlipoproteinemia types IIb or IV . Plasma fibrinogen levels showed statistically significant reductions during both the fish oil and corn oil treatment periods . Other variables related to hemostasis which showed no significant changes from baseline included tissue plasminogen activator activity and inhibitor , protein C antigen , antithrombin III activity , bleeding time , and platelet counts . These data confirm the two previous reports that fish oil supplementation is associated with reductions in plasma fibrinogen levels , thereby modifying a potential nonlipid risk factor for cardiovascular disease . Unlike previous reports , however , n-6 polyunsaturated fatty acids were also associated with significant reductions in fibrinogen levels . Therefore , it is premature to conclude that the fibrinogen-lowering effects of dietary fish oil are unique to n-3 polyunsaturated fatty acids OBJECTIVE To test the short-term feasibility and efficacy of seven nonpharmacologic interventions in persons with high normal diastolic blood pressure . DESIGN R and omized control multicenter trials . SETTING Volunteers recruited from the community , treated and followed up at special clinics . PARTICIPANTS Of 16,821 screenees , 2182 men and women , aged 30 through 54 years , with diastolic blood pressure from 80 through 89 mm Hg were selected . Of these , 50 did not return for follow-up blood pressure measurements . INTERVENTIONS Three life-style change groups ( weight reduction , sodium reduction , and stress management ) were each compared with unmasked nonintervention controls over 18 months . Four nutritional supplement groups ( calcium , magnesium , potassium , and fish oil ) were each compared singly , in double-blind fashion , with placebo controls over 6 months . MAIN OUTCOME MEASURES Primary : change in diastolic blood pressure from baseline to final follow-up , measured by blinded observers . Secondary : changes in systolic blood pressure and intervention compliance measures . RESULTS Weight reduction intervention produced weight loss of 3.9 kg ( P less than .01 ) , diastolic blood pressure change of -2.3 mm Hg ( P less than .01 ) , and systolic blood pressure change of -2.9 mm Hg ( P less than .01 ) . Sodium reduction interventions lowered urinary sodium excretion by 44 mmol/24 h ( P less than .01 ) , diastolic blood pressure by 0.9 mm Hg ( P less than .05 ) , and systolic blood pressure by 1.7 mm Hg ( P less than .01 ) . Despite good compliance , neither stress management nor nutritional supplements reduced diastolic blood pressure or systolic blood pressure significantly ( P greater than .05 ) . CONCLUSIONS Weight reduction is the most effective of the strategies tested for reducing blood pressure in normotensive persons . Sodium reduction is also effective . The long-term effects of weight reduction and sodium reduction , alone and in combination , require further evaluation OBJECTIVE Past research efforts to determine the influence of the diet on cardiovascular ( CV ) health have focused on the individual roles of specific dietary components with debatable success . Awareness of the impact and complexity of nutrient interactions has exp and ed in recent years to include assessment of dietary patterns as they contribute to lower CV disease risk . RESEARCH METHODS AND PROCEDURES In a series of multicenter studies , we compared a comprehensive , prepared meal plan , formulated to meet recommended intake levels of macro- and micronutrients , with a self-selected diet based on the exchange system . The three studies comprised adult participants with hypertension , hyperlipidemia , and type 2 diabetes ( n = 560 , 251 , and 330 , respectively ) . The first two studies ( 10 weeks ) varied by the amount of contact with study personnel , and the third study assessed long-term effects over 52 weeks . Outcome measures included : blood pressure , lipid and lipoprotein levels , glycemic control , homocysteine , compliance , quality of life , and weight . RESULTS The first study demonstrated significant improvements in all measures , with greater improvements with the prepared meal plan compared with the self-selected diet . The second study , design ed to parallel the contact frequency that would occur in a real world clinical setting , also produced significant improvements in multiple CV risk factors . In the long-term study , in addition to sustained improvements in risk factors , significant weight loss was achieved and maintained over the 52 weeks . DISCUSSION These trials demonstrate that regular consumption of a nutritionally complete diet offers multiple , concurrent clinical benefits for reducing CV disease risk and body weight OBJECTIVE To assess the effects of a diet restricted in fat , saturated fat , and cholesterol , under weight-maintenance and ad libitum conditions on body weight and plasma lipid levels in hypercholesterolemic subjects . DESIGN Dietary intervention study . SETTING AND PARTICIPANTS Twenty-seven free-living , healthy middle-aged and elderly men ( n = 13 , age range , 41 to 81 years ) and women ( n = 14 , age range , 52 to 79 years ) with moderate hypercholesterolemia ( low-density lipoprotein cholesterol [ LDL-C ] > or = 3.36 mmol/L [ 130 mg/dL ] ) participated in the study . INTERVENTION Subjects underwent three dietary phases . First , subjects were provided with a diet similar to the average US diet ( baseline diet ; 35.4 % total fat , 13.8 % to 14.1 % saturated fat , and 30 to 35 mg/1000 kJ [ 128 to 147 mg/1000 kcal ] cholesterol ) . During the second dietary phase , subjects consumed a low-fat diet ( 15.1 % total fat , 5.0 % saturated fat , 17 mg/1000 kJ [ 73 mg/1000 kcal ] cholesterol ) . During the baseline and low-fat diet phases , which lasted 5 to 6 weeks each , the energy intake was adjusted to keep body weight constant . During the third diet phase ( low-fat ad libitum diet ) subjects were given the same low-fat diet for 10 to 12 weeks , but could adjust their intake between 66 % and 133 % of the energy required to maintain body weight . MAIN OUTCOME MEASURES Body weight and plasma lipid levels . RESULTS Consumption of the low-fat diet under weight-maintenance conditions had significant lowering effects on plasma total cholesterol ( TC ) , LDL-C , and high-density lipoprotein cholesterol ( HDL-C ) levels ( mean change , -12.5 % , -17.1 % , and -22.8 % , respectively ) . This diet significantly increased plasma triglyceride levels ( + 47.3 % ) and the TC/HDL-C ratio ( + 14.6 % ) . In contrast , consumption of the low-fat ad libitum diet was accompanied by significant weight loss ( 3.63 kg ) , by a mean decrease in LDL-C ( 124.3 % ) , and by mean triglyceride levels and TC/HDL-C ratio that were not significantly different from values obtained at baseline . CONCLUSIONS Our results indicate that a low-fat ad libitum diet promotes weight loss and LDL-C lowering without adverse effects on triglycerides or the TC/HDL-C ratio in middle-aged and elderly men and women with moderate hypercholesterolemia High levels of fibrinogen , factor ( F ) VIIc , plasminogen activator inhibitor-1 ( PAI-1 ) , and plasma viscosity are associated with an increased coronary risk . As positive correlations of these parameters with triglycerides have been shown , the increased coronary risk associated with high levels of triglycerides may be assumed to be due to alterations within the hemostatic system . To reduce the coronary risk to which hypertriglyceridemic patients are exposed , dietary treatment is recommended ; the optimal composition of such a diet is , however , a matter of debate . With regard to the effects on hemostasis , we compared in a sequential approach two diets for treatment of 25 nonobese male patients ( age , mean+/-S.D. , 40.4+/-8.7 years ) with fasting triglycerides > 2.3 mmol/l . The first diet ( high fat ) was rich in monounsaturated fatty acids ( MUFA ) and marine n-3 polyunsaturated fatty acids ( PUFA ) , whereas the second diet ( low-fat ) was rich in complex carbohydrates and dietary fiber . The high-fat diet induced a significant lowering of FIIc , FIXc , FXc , FVIIc , FVIIa , FXIIa , PAI-1 , plasma viscosity , and platelet activity , but led to an increase in fibrinogen , whereas the low-fat diet lowered FXIIc values and induced a nonsignificant decrease in fibrinogen . Prob and s on this diet had a slightly higher FVIIa and platelet activity than those on the high-fat diet . However , as all changes appeared to be within the normal range of each hemostatic parameter , it remains to be clarified whether the likely beneficial effects of the high-fat diet on most hemostatic factors are outweighed by the small increase in fibrinogen levels The Trial of Antihypertensive Intervention and Management evaluated nine diet-drug combinations in 878 mildly hypertensive , moderately obese participants using a 3 x 3 factorial design . Drugs evaluated were placebo , diuretic ( chlorthalidone ) , and beta-blocker ( atenolol ) ; diets were usual ( no intervention ) , weight reduction , and low sodium/high potassium ( Na/K ) . This article reports 6-month dietary changes and the effect of dietary change on blood pressure . Six-month mean weight change was -4.7 kg in the weight reduction group , -0.3 kg in the Na/K group , and -0.5 kg in the usual-diet group . At 6 months , daily electrolyte excretion had changed in the Na/K intervention group . Daily sodium excretion decreased from 138.0 to 112.0 mmol in the Na/K group and increased from 134.1 to 138.4 mmol in the weight reduction group and from 129.1 to 137.0 mmol in the usual-diet group . Daily potassium output increased from 58.7 to 71.4 mmol in the Na/K group , from 57.0 to 60.5 mmol in the weight reduction group , and from 55.3 to 59.1 mmol in the usual diet group . Analysis of 3-day food records indicated that sodium intake decreased from 141.1 to 85.8 mmol and potassium intake increased from 76.4 to 90.5 mmol . Our results indicate that the goal for weight reduction was more easily achieved than the goal for electrolyte modification The Type II Coronary Intervention Study ( Type II Study ) is a double-blind , r and omized , placebo-controlled clinical trial conducted by the Division of Intramural Research of the National Heart , Lung , and Blood Institute of Bethesda , Maryl and . The study was design ed to evaluate the 5-year treatment effect of cholestyramine on low density lipoprotein ( LDL ) cholesterol and on lesions in the coronary arteries . One hundred forty-three patients with Type II hyperlipoproteinemia ( elevated LDL cholesterol ) and coronary artery disease ( CAD ) were entered into the study between 1972 and 1976 . Patients were stratified by sex and extent of coronary disease as defined angiographically and were r and omly allocated to a daily dosage of 24 g cholestyramine and diet ( treatment group ) or placebo and diet ( control group ) . Changes in the coronary arteries were evaluated by sequential coronary angiography carried out before and after five years of treatment . This report describes the trial design and baseline characteristics of the study patients OBJECTIVES The purpose of this study was to assess the costs and impact of a nutrition education program following a cholesterol screening . METHODS Forty work-sites were r and omly assigned to one of two educational interventions : a " usual " intervention of 5 minutes of counseling , or a " special " intervention of 2 hours of behaviorally based education on dietary changes to lower serum cholesterol . Costs were monitored , and cholesterol levels were retested 6 and 12 months later . RESULTS The total per-person cost for screening and the educational intervention was about $ 50 . Cholesterol levels differed little between the two intervention groups 6 months after screening , but after 12 months those in the special intervention worksites showed a 6.5 % drop in cholesterol , whereas those at the usual intervention worksites showed a drop of only 3.0 % . Hence a 3.5 % cholesterol reduction was attributable to the special intervention . CONCLUSIONS A behaviorally based nutrition education program following cholesterol screening can have a meaningful impact on long-term cholesterol levels at a low cost . Nutrition education in work-sites may therefore be a useful way to lower the risk of heart disease in communities BACKGROUND The apolipoprotein A5 gene ( APOA5 ) is a major gene that regulates lipid metabolism and is modulated by dietary factors . A novel variant rs964184 in APOA5 was identified to be associated with lipids in genome-wide association studies . OBJECTIVE We examined whether this variant modified changes in lipid concentrations in response to a 2-y weight-loss diet intervention in a r and omized trial . DESIGN The current analyses were secondary analyses of a data set from the Pounds Lost Trial . We genotyped APOA5 rs964184 in 734 overweight or obese adults who were r and omly assigned to one of 4 diets that differed in percentages of energy derived from fat , protein , and carbohydrate for 2 y. We evaluated changes in fasting serum concentrations of total cholesterol ( TC ) , LDL cholesterol , HDL cholesterol , and triglyceride from baseline to 2 y of follow-up . RESULTS After a 2-y dietary intervention , we showed significant interactions between the APOA5 rs964184 polymorphism and dietary fat intake ( low compared with high ) in the determination of changes in TC , LDL cholesterol , and HDL cholesterol ( P-interaction = 0.007 , 0.017 , and 0.006 , respectively ) . In the low-fat intake group ( 20 % of energy derived from fat ) , carriers of the risk allele ( G allele ) exhibited greater reductions in TC and LDL cholesterol than did noncarriers ( P = 0.036 and 0.039 , respectively ) , whereas in the high-fat diet group ( 40 % of energy derived from fat ) , participants with the G allele had a greater increase in HDL cholesterol than did participants without this allele ( P = 0.038 ) . CONCLUSION Our data showed better improvement in lipid profiles from long-term low-fat diet intake in the APOA5 rs964184 risk allele BACKGROUND Many older adults with hyperlipidemia or hypertension participate in the Older Americans Act Nutrition Program , which serves meals in community setting s and delivers meals to homes . However , there is little information regarding whether therapeutic meals design ed around Dietary Approach to Stop Hypertension ( DASH ) principles have a beneficial effect on the diets of these older adults . OBJECTIVE The objective of this study was to determine the degree to which dietary change is influenced by providing 7 home-delivered therapeutic meals weekly to adults aged > or = 60 y. DESIGN We conducted a 1-y r and omized controlled trial in 298 persons with hyperlipidemia or hypertension , in which 50 % of participants received 7 therapeutic meals per week for 12 mo . Those in need of dietary change at baseline ( n = 210 ) were examined . Changes in intermediate DASH accordance , DASH accordance , and the nutrients that make up the DASH diet were measured by using 24-h food recalls at baseline , 6 mo , and 12 mo . Chi-square tests , t tests , and multiple regression were used to examine the association between receipt of meals and dietary change over time . RESULTS Participants who received meals were 20 % ( P = 0.001 ) more likely to reach intermediate DASH accordance at 6 mo and were 18 % ( P = 0.007 ) more likely to meet saturated fat accordance at 12 mo than were those who did not receive meals . When stratified by race and income , gains were marginally larger for whites and higher-income individuals . CONCLUSION Delivery of 7 DASH meals per week was found to increase compliance with dietary recommendations among noncompliant older adults with cardiovascular disease Two hundred women with breast cysts proven by aspiration were entered into a r and omized double-blind trial of Efamol ( evening primrose oil ) at a dose of 6 capsules daily or equivalent placebo dose for a year . Cysts were categorized by initial electrolyte composition , and follow-up continued for 1 year posttherapy . Recurrent cyst formation in the first year was slightly ( but not significantly ) lower in the Efamol group compared with the placebo-treated group . The Efamol treatment was well tolerated as the dropout rate was only 7 % and equal in both the active and placebo groups . The initial electrolyte composition did not predict for cyst recurrence The fat in the normal diet of 19 apparently well men was partly replaced by linoleic acid . This produced striking changes in many platelet-function tests , suggesting decreased platelet activation . Twenty controls maintaining their normal diet showed no change . It is concluded that normal people have a degree of platelet activation which can be decreased . This may be relevant to the benefits attributed to a diet containing polyunsaturated fats Altogether 160 free living subjects ( aged 30 - 60 years ) most of whom had moderate hypercholesterolemia were r and omised into the following diet groups to find out long-term effects of different fat-modified diets : ( 1 ) control diet 35/14:10:4 ( energy percents from fat/saturated : monounsaturated : polyunsaturated fatty acids in actual diets ) ; ( 2 ) AHA type diet 32/10:8:8 ; ( 3 ) monoene-enriched diet 34/11:11:5 ; ( 4 ) reduced-fat diet 30/12:8:3 . LDL cholesterol fell equally with the AHA type diet ( 4.54 + /- 0.97 vs. 4.21 + /- 0.89 mmol/l ( mean + /- S.D. , 0 vs. 6 months ) , P = 0.001 ) and with the monoene-enriched diet ( 4.55 + /- 0.95 vs. 4.25 + /- 0.95 mmol/l , P = 0.004 ) during the 6-month study . Moderate amounts of polyenes or monoenes as part of natural diets did not decrease HDL cholesterol level in the long term . Serum lipid values remained unchanged with the reduced-fat diet . Analysis by apolipoprotein E phenotypes showed a decrease in LDL cholesterol only in subjects with phenotype 3/3 in the monoene-enriched group ( -8.6 + /- 8.7 vs. + 1.3 + /- 15.4 , percent change in LDL cholesterol E 3/3 vs. E 4/3 + 4/4 ) , but in the AHA type group LDL cholesterol decreased similarly in phenotypes E 3/3 and E 4/3 + 4/4 ( -6.9 + /- 10.1 vs -6.9 + /- 16.5 ) Purpose . This study tested the efficacy of a computer-assisted counseling intervention to reduce diet-related cancer risk . Design . R and omized controlled trial . Subjects . Healthy women HMO members ( n = 616 ) aged 40 to 70 . Intervention . Participants were r and omly assigned to nutrition intervention or an attention-control intervention unrelated to diet . Intervention consisted of two 45-minute counseling sessions plus two 5- to 10-minute follow-up telephone contacts . Counseling sessions included a 20-minute , interactive , computer-based intervention using a touchscreen format . Intervention goals were reducing dietary fat and increasing consumption of fruit , vegetables , and whole grains . Measures . Twenty-four hour diet recalls and the Fat and Fiber Behavior Question naire ( FFB ) . Results . Four-month follow-up data were collected from 94 % of the intervention participants and 91 % of the controls . Testing with a multivariate general linear models analysis showed improvements on all dietary outcome variables . Compared to the control , intervention participants reported significantly less fat consumption ( 2.35 percentage points less for percentage of energy from fat ) , significantly greater consumption of fruit and vegetables combined ( 1.04 servings per day ) , and a significant reduction in a behavioral measure of fat consumption ( .24 point change in the FFB ) . Conclusions . These 4-month results are comparable to several other moderate-intensity studies showing that , in the appropriate circumstances , moderate-intensity dietary interventions can be efficacious . Study limitations include the short follow-up period and the use of self-reported outcome measures CONTEXT Multiple epidemiologic studies and some trials have linked diet with cardiovascular disease ( CVD ) prevention , but long-term intervention data are needed . OBJECTIVE To test the hypothesis that a dietary intervention , intended to be low in fat and high in vegetables , fruits , and grains to reduce cancer , would reduce CVD risk . DESIGN , SETTING , AND PARTICIPANTS R and omized controlled trial of 48,835 postmenopausal women aged 50 to 79 years , of diverse background s and ethnicities , who participated in the Women 's Health Initiative Dietary Modification Trial . Women were r and omly assigned to an intervention ( 19,541 [ 40 % ] ) or comparison group ( 29,294 [ 60 % ] ) in a free-living setting . Study enrollment occurred between 1993 and 1998 in 40 US clinical centers ; mean follow-up in this analysis was 8.1 years . INTERVENTION Intensive behavior modification in group and individual sessions design ed to reduce total fat intake to 20 % of calories and increase intakes of vegetables/fruits to 5 servings/d and grains to at least 6 servings/d . The comparison group received diet-related education material s. MAIN OUTCOME MEASURES Fatal and nonfatal coronary heart disease ( CHD ) , fatal and nonfatal stroke , and CVD ( composite of CHD and stroke ) . RESULTS By year 6 , mean fat intake decreased by 8.2 % of energy intake in the intervention vs the comparison group , with small decreases in saturated ( 2.9 % ) , monounsaturated ( 3.3 % ) , and polyunsaturated ( 1.5 % ) fat ; increases occurred in intakes of vegetables/fruits ( 1.1 servings/d ) and grains ( 0.5 serving/d ) . Low-density lipoprotein cholesterol levels , diastolic blood pressure , and factor VIIc levels were significantly reduced by 3.55 mg/dL , 0.31 mm Hg , and 4.29 % , respectively ; levels of high-density lipoprotein cholesterol , triglycerides , glucose , and insulin did not significantly differ in the intervention vs comparison groups . The numbers who developed CHD , stroke , and CVD ( annualized incidence rates ) were 1000 ( 0.63 % ) , 434 ( 0.28 % ) , and 1357 ( 0.86 % ) in the intervention and 1549 ( 0.65 % ) , 642 ( 0.27 % ) , and 2088 ( 0.88 % ) in the comparison group . The diet had no significant effects on incidence of CHD ( hazard ratio [ HR ] , 0.97 ; 95 % confidence interval [ CI ] , 0.90 - 1.06 ) , stroke ( HR , 1.02 ; 95 % CI , 0.90 - 1.15 ) , or CVD ( HR , 0.98 ; 95 % CI , 0.92 - 1.05 ) . Excluding participants with baseline CVD ( 3.4 % ) , the HRs ( 95 % CIs ) for CHD and stroke were 0.94 ( 0.86 - 1.02 ) and 1.02 ( 0.90 - 1.17 ) , respectively . Trends toward greater reductions in CHD risk were observed in those with lower intakes of saturated fat or trans fat or higher intakes of vegetables/fruits . CONCLUSIONS Over a mean of 8.1 years , a dietary intervention that reduced total fat intake and increased intakes of vegetables , fruits , and grains did not significantly reduce the risk of CHD , stroke , or CVD in postmenopausal women and achieved only modest effects on CVD risk factors , suggesting that more focused diet and lifestyle interventions may be needed to improve risk factors and reduce CVD risk . CLINICAL TRIALS REGISTRATION Clinical Trials.gov Identifier : NCT00000611 Objective To investigate how weight loss by different diets impacts postpr and ial levels of glucagon-like peptide 1 ( GLP-1 ) , glucose-dependent insulinotropic polypeptide ( GIP ) and glucagon . Methods In this single-centre , parallel group 2-year trial , 70 healthy postmenopausal obese women were r and omised to the Paleolithic diet or a healthy control diet based on Nordic Nutrition Recommendations . Both diets were without calorie restriction . The primary outcome was the change in fat mass . Here , secondary analyses on GLP-1 , GIP and glucagon measured during an OGTT are described . Results In the Paleolithic diet group , mean weight loss compared to baseline was 11 % at 6 months and 10 % at 24 months . In the control diet group , mean weight loss was 6 % after 6 and 24 months ( P = 0.0001 and P = 0.049 for the comparison between groups at 6 and 24 months respectively ) . Compared to baseline , the mean incremental area under the curve ( iAUC ) for GLP-1 increased by 34 and 45 % after 6 and 24 months in the Paleolithic diet group and increased by 59 % after 24 months in the control diet group . The mean iAUC for GIP increased only in the Paleolithic diet group . The area under the curve ( AUC ) for glucagon increased during the first 6 months in both groups . The fasting glucagon increase correlated with the β-hydroxybutyrate increase . Conclusions Weight loss caused an increase in postpr and ial GLP-1 levels and a further rise occurred during weight maintenance . Postpr and ial GIP levels increased only after the Paleolithic diet . Reduced postpr and ial glucagon suppression may be caused by a catabolic state Objective To create a data base of long-term r and omised controlled trials ( RCTs ) comparing higher with lower omega-3 , omega-6 or total polyunsaturated fatty acid ( PUFA ) , regardless of reported outcomes , and to develop methods to assess effects of increasing omega-6 , alpha-linolenic acid ( ALA ) , long-chain omega-3 ( LCn3 ) and total PUFA on health outcomes . Design Systematic review search , methodology and meta-analyses . Data sources Medline , Embase , CENTRAL , WHO International Clinical Trials Registry Platform , Clinical trials.gov and trials in relevant systematic review s. Eligibility criteria RCTs of ≥24 weeks ' duration assessing effects of increasing ALA , LCn3 , omega-6 or total PUFAs , regardless of outcomes reported . Data synthesis Methods included r and om-effects meta-analyses and sensitivity analyses . Funnel plots were examined , and subgrouping assessed effects of intervention type , replacement , baseline diabetes risk and use of diabetic medications , trial duration and dose . Quality of evidence was assessed using Grading of Recommendations Assessment , Development and Evaluation ( GRADE ) . Results Electronic search es generated 37 810 hits , de-duplicated to 19 772 titles and abstract s. We assessed 2155 full-text papers , conference abstract s and trials registry entries independently in duplicate . Included studies were grouped into 363 RCTs comparing higher with lower omega-3 , omega-6 and /or total PUFA intake of at least 6 months ’ duration —the Data base . Of these 363 included RCTs , 216 RCTs were included in at least one of our review s of health outcomes , data extracted and risk of bias assessed in duplicate . Ninety five RCTs were included in the Data base but not included in our current review s. Of these 311 completed trials , 27 altered ALA intake , 221 altered LCn3 intake and 16 trials altered omega-3 intake without specifying whether ALA or LCn3 . Forty one trials altered omega-6 and 59 total PUFA.The remaining 52 trials are ongoing though 13 ( 25 % ) appear to be outst and ing , or constitute missing data . Conclusions This extensive data base of trials is available to allow assessment of further health outcomes ABSTRACT Background The preferred macronutrient dietary composition , and the health consequences of dietary fat reduction specifically , have been debated for decades . Here we provide a comprehensive overview of long-term health outcomes in the Women 's Health Initiative Dietary Modification ( DM ) trial . Objective The DM trial aim ed to examine whether a low-fat dietary pattern would reduce the risk of invasive breast cancer , colorectal cancer , and , secondarily , coronary heart disease ( CHD ) , with various other health outcomes also considered . Methods The DM trial is a r and omized controlled trial conducted at 40 centers in the US , among 48,835 postmenopausal women aged 50–79 y with baseline intake of ≥32 % energy from fat . Participants were r and omly assigned to a low-fat dietary pattern intervention group or to a usual-diet comparison group , during 1993–1998 . Intervention goals were to reduce fat intake from ∼35 % to 20 % of total energy , in conjunction with increasing vegetables and fruit to 5 servings/d and grains to 6 servings/d . Results Over an 8.5-y ( median ) intervention period , intervention and comparison group differences included lower fat by 8–10 % , and higher carbohydrate by 8–10 % , of total energy , in conjunction with higher consumption of vegetables , fruit , and grains . Time-to- outcome analyses did not show significant differences between intervention and comparison groups for invasive breast cancer , colorectal cancer , or CHD , either over the intervention period or over longer-term cumulative follow-up . Additional analyses showed significant intervention group benefits related to breast cancer , CHD , and diabetes , without adverse effects . Over a 19.6-y ( median ) follow-up period , HRs ( 95 % CIs ) were 0.84 ( 0.74 , 0.96 ) for breast cancer followed by death , and 0.87 ( 0.77 , 0.98 ) for diabetes requiring insulin . Conclusions Reduction in dietary fat with corresponding increase in vegetables , fruit , and grains led to benefits related to breast cancer , CHD , and diabetes , without adverse effects , among healthy postmenopausal US women . This trial was registered at clinical trials.gov as NCT00000611 The role of nutrition in preventing peripheral artery disease ( PAD ) remains elusive.1 Mediterranean diets reduce the risk of myocardial infa rct ion and stroke.2,3 They also may reduce the risk of PAD , but this hypothesis has never been tested in a r and omized trial . We assessed the association of Mediterranean diets with the occurrence of symptomatic PAD in an exploratory , nonprespecified analysis of a r and omized trial BACKGROUND A Mediterranean-type diet could play a role in decreasing serum uric acid concentrations due to its antioxidant and anti-inflammatory properties . The aim of this study was to evaluate whether better adherence to the Mediterranean diet ( MeDiet ) reduced or prevented the development of hyperuricemia . METHODS Cross-sectional and prospect i ve analysis in 4,449 elderly participants at high cardiovascular risk from the PREvención con DIeta MEDiterránea trial r and omized to two MeDiet interventions ( supplemented with either olive oil or nuts ) or a control diet . A vali date d 14-item question naire was used to assess adherence to the MeDiet . Hyperuricemia was considered to be present when serum uric acid was higher than 7mg/dL in men or higher than 6mg/dL in women . RESULTS After a median follow-up of 5 years , 756 individuals of the 3,037 ( 24.9 % ) who did not have hyperuricemia at baseline developed hyperuricemia , whereas 422 of the 964 hyperuricemic individuals at baseline ( 43.8 % ) reverted this condition . In cross-sectional analyses , an inverse association was observed between increasing levels of adherence to the 14-item MeDiet score and decreasing hyperuricemia ( p trend < .001 ) . Baseline consumption of red meat , fish and seafood , and wine were associated with a higher prevalence of hyperuricemia . Reversion of hyperuricemia was significantly higher ( multivariable-adjusted odds ratio = 1.73 ; 95 % confidence interval : 1.04 - 2.89 ) in the highest category of baseline adherence to the MeDiet as compared with the lowest . No association was found between baseline adherence to MeDiet and the incidence of hyperuricemia . The three intervention diets had similar effects in the reduction of hyperuricemia . CONCLUSIONS Higher baseline adherence to the MeDiet is associated with lower risk of hyperuricemia Background / Objectives : Our objective was to investigate changes in liver fat and insulin sensitivity during a 2-year diet intervention . An ad libitum Paleolithic diet ( PD ) was compared with a conventional low-fat diet (LFD).Subjects/ Methods : Seventy healthy , obese , postmenopausal women were r and omized to either a PD or a conventional LFD . Diet intakes were ad libitum . Liver fat was measured with proton magnetic resonance spectroscopy . Insulin sensitivity was evaluated with oral glucose tolerance tests and calculated as homeostasis model assessment -insulin resistance (HOMA-IR)/liver insulin resistance ( Liver IR ) index for hepatic insulin sensitivity and oral glucose insulin sensitivity (OGIS)/Matsuda for peripheral insulin sensitivity . All measurements were performed at 0 , 6 and 24 months . Forty-one women completed the examinations for liver fat and were included . Results : Liver fat decreased after 6 months by 64 % ( 95 % confidence interval : 54–74 % ) in the PD group and by 43 % ( 27–59 % ) in the LFD group ( P<0.01 for difference between groups ) . After 24 months , liver fat decreased 50 % ( 25–75 % ) in the PD group and 49 % ( 27–71 % ) in the LFD group . Weight reduction between baseline and 6 months was correlated to liver fat improvement in the LFD group ( rs=0.66 , P<0.01 ) but not in the PD group ( rs=0.07 , P=0.75 ) . Hepatic insulin sensitivity improved during the first 6 months in the PD group ( P<0.001 for Liver IR index and HOMA-IR ) , but deteriorated between 6 and 24 months without association with liver fat changes . Conclusions : A PD with ad libitum intake had a significant and persistent effect on liver fat and differed significantly from a conventional LFD at 6 months . This difference may be due to food quality , for example , a higher content of mono- and polyunsaturated fatty acids in the PD . Changes in liver fat did not associate with alterations in insulin sensitivity Whether a Mediterranean-style diet reduces cardiovascular events and mortality more than a low-fat diet is uncertain . The objectives of this study were to actively compare low-fat and Mediterranean-style diets after first myocardial infa rct ion ( MI ) in a r and omized , controlled clinical trial and to compare dietary intervention per se with usual care in a case-control analysis . First MI survivors were r and omized to a low-fat ( n = 50 ) or Mediterranean-style ( n = 51 ) diet . The 2 diets were low in saturated fat ( < or = 7 % kcal ) and cholesterol ( < or = 200 mg/day ) ; the Mediterranean-style diet was distinguished by greater omega-3 fat intake ( > 0.75 % kcal ) . Participants received individual dietary counseling sessions , 2 within the first month and again at 3 , 6 , 12 , 18 , and 24 months , along with 6 group sessions . Combined dietary intervention groups ( cases , n = 101 ) were compared with a usual-care group ( controls , n = 101 ) matched for age , gender , MI type and treatment , and status of diabetes mellitus and hypertension . Primary - outcome -free survival ( a composite of all-cause and cardiac deaths , MI , hospital admissions for heart failure , unstable angina pectoris , or stroke ) did not differ between low-fat ( 42 of 50 ) and Mediterranean-style ( 43 of 51 ) diet groups over a median follow-up period of 46 months ( range 18 to 72 ; log-rank p = 0.81 ) . Patients receiving dietary intervention had better primary - outcome -free survival ( 85 of 101 ) than usual-care controls ( 61 of 101 ) ( log-rank p < 0.001 ) , with unadjusted and adjusted odds ratios of 0.33 ( 95 % confidence interval 0.18 to 0.60 , p < 0.001 ) and 0.28 ( 95 % confidence interval 0.13 to 0.63 , p = 0.002 ) , respectively . In conclusion , active intervention with either a low-fat or a Mediterranean-style diet similarly and significantly benefits overall and cardiovascular-event-free survival after MI Older adults tend to require fewer energy content and higher levels of nutrients to promote and maintain optimal health . Regrettably , dietary variety and quality are known to decline with advancing age . We conducted a 2-year prospect i ve , r and omised , dietary intervention trial where we asked free-living elderly subjects ( 63 - 79 years ) on self-selected habitual diets to incorporate walnuts daily into their diet ( 15 % energy ) . We then compared their nutrient intake with that of a similar group of concurrent participants on self-selected habitual diets but abstaining from walnut consumption ( control ) . No recipes or advice on use of nuts were provided . Dietary intake was assessed by multiple unannounced 24-h telephone dietary recalls . On average , walnut supplement consumption was 43 g/d or 1171·5 kJ ( 281 kcal ) . The mean daily energy intake was 954 kJ ( 228 kcal ) higher in the walnut group than in the control group ( P<0·001 ) . Compared with control , participants in the walnut group reported significantly higher intake of total protein , vegetable protein , total PUFA and n-3 and n-6 PUFA ; and significantly lower intake of total carbohydrate , animal protein , SFA , and Na . An estimated 19 % of total energy and 25 % of total fat from other food sources was displaced . Displacement of MUFA and total PUFA was 21 and 16 % , respectively . Thus adding a daily supplement of walnuts to an ad libitum diet of older adults can induce favourable modifications to the nutrient profile in a way that addresses declining nutrient intake associated with aging Only a few studies have analyzed the effects of the potential interaction between the -174G/C polymorphism of IL6 gene and the adherence to the Mediterranean diet ( MD ) on adiposity indexes . Our aim was to investigate the interplay between the -174G/C polymorphism of the IL6 gene and a Mediterranean-style diet on body weight changes after 3 years of nutritional intervention in a high cardiovascular risk population . A total of 737 participants , aged 55 - 80 years were assigned to a low-fat diet or to a Mediterranean-style diet group with high intake of virgin olive oil ( VOO ) or nuts . Anthropometric measurements were taken at baseline and after 3-year follow-up . The -174G/C polymorphism of the IL6 gene was genotyped . Minor allele frequency ( C ) was 0.39 . At baseline , the CC genotype was associated with higher measures of adiposity . After 3 years , a significant interaction ( p=0.028 ) was found between the polymorphism ( GG+GC versus CC ) and the nutritional intervention : CC subjects following the MD+VOO had the lowest body weight gain . In conclusion , at baseline , CC subjects for the -174G/C polymorphism of IL6 had the highest body weight and BMI . However , after 3 years of nutritional intervention with MD+VOO , these subjects were predicted to have the greatest reduction in body weight Abstract Objective To assess the effect of brief interventions during the “ watchful waiting ” period for hypertension . Design Factorial trial . Setting General practice . Methods 296 patients with blood pressure > 160/90 mm Hg were r and omised to eight groups defined by three factors : an information booklet ; low sodium , high potassium salt ; prompt sheets for high fruit , vegetable , fibre ; and low fat . Main outcome measures Blood pressure ( primary outcome ) ; secondary outcomes of diet , weight , and dietary biomarkers ( urinary sodium : potassium ( Na : K ) ratio ; carotenoid concentrations ) . Results Blood pressure was not affected by the booklet ( mean difference ( diastolic blood pressure ) at one month 0.2 , 95 % confidence interval 1.6 to 2.0 ) , salt ( 0.13 ; 1.7 to 2.0 ) , or prompts ( 0.52 ; 1.3 to 2.4 ) . The salt decreased Na : K ratio ( difference 0.32 ; 0.08 to 0.56 , P = 0.01 ) , and the prompts helped control weight ( difference 0.39 ( 0.85 to 0.05 ) kg at one month , P = 0.085 ; 1.2 ( 0.1 to 2.25 ) kg at six months , P = 0.03 ) . Among those with lower fruit and vegetable consumption ( < 300 g per day ) , prompts increased fruit and vegetable consumption and also carotenoid concentrations ( difference 143 ( 16 to 269 ) mmol/l , P < 0.03 ) but did not decrease blood pressure . Conclusion During watchful waiting , over and above the effect of brief advice and monitoring , an information booklet , lifestyle prompts , and low sodium salt do not reduce blood pressure . Secondary analysis suggests that brief interventions —particularly lifestyle prompts — can make useful changes in diet and help control weight , which previous research indicates are likely to reduce the long term risk of stroke The hypothesis that 6 months after acute myocardial infa rct ion , adoption of secondary prevention activities would be higher , quality of life better , and blood cholesterol lower in patients r and omly allocated to a mail-out intervention program than in those receiving usual care was tested . Patients were aged < 70 years , admitted to hospitals in and around Newcastle , Australia with a suspected heart attack and discharged alive from the hospital . Cluster r and omization , based on the patient 's family practitioner , was used to allocate consenting patients to an intervention or usual care group . A low-cost mail-out program was design ed to help patients reduce dietary fat , obtain regular exercise by walking and ( for smokers only ) to quit smoking . Supplementary telephone contact was also used . In addition , a letter was sent to the family doctor regarding the benefit of aspirin and beta blockers for secondary prevention . Of eligible patients , 71 % participated , and 79 % of the 213 intervention subjects and 87 % of the 237 usual care ones returned a 6-month follow-up question naire . Self-reported fat intake was significantly lower , an " emotional " score obtained from a quality -of-life question naire was significantly higher in the intervention than in the usual care group , and " physical " and " social " scores for quality of life were slightly higher . Blood cholesterol level and other variables were not different between the groups at 6 months . Simple low-cost programs providing support and advice on lifestyle change may be beneficial , particularly in improving patients ' perceived quality of life BACKGROUND A diet high in vegetables , fruit , and fiber and low in fat decreased additional risk of secondary breast cancer events in women without hot flashes ( HF- ) compared with that in women with hot flashes ( HF+ ) , possibly through lowered concentrations of circulating estrogens . OBJECTIVE The objective was to investigate the intervention effect by baseline quartiles of dietary pattern among breast cancer survivors in the HF- subgroup of the Women 's Healthy Eating and Living Study . DESIGN A r and omized controlled trial compared a putative cancer prevention diet with a diet of 5 servings of vegetables and fruit daily in early-stage breast cancer survivors . Participants did not experience hot flashes at baseline ( n = 896 ) . We confirmed cancer status for 96 % of participants approximately 7.3 y after enrollment . RESULTS The study intervention achieved a large between-group difference in dietary pattern that , at 4 y , was not significantly different across baseline quartiles of dietary pattern . The intervention group experienced fewer breast cancer events than did the comparison group for all of the baseline quartiles . This difference was significant only in upper baseline quartiles of intake of vegetables , fruit , and fiber and in the lowest quartile of fat . A significant trend for fewer breast cancer events was observed across quartiles of vegetable-fruit and fiber consumption . CONCLUSIONS The secondary analysis showing the decreased risk in the HF- subgroup was not explained by amount of change in dietary pattern achieved . The difference was strongest in the quartile with the most putatively cancer-preventive dietary pattern at baseline BACKGROUND Previous research has found that African American ( AA ) vegetarians/vegans have a significantly lower body mass index and risk of hypertension compared to omnivores . OBJECTIVES The Nutritious Eating with Soul ( NEW Soul ) study partnered with local soul food restaurants/chefs to deliver two behavioral nutrition interventions to AA adults . NEW Soul examines the impact of two different culturally tailored diets ( vegan and omnivorous low-fat ) on changes in risk factors for cardiovascular disease ( CVD ) . METHODS AA adults with overweight or obesity are recruited from the community in the Midl and s of South Carolina . Eligible participants are r and omized to follow one of two different culturally-adapted , soul food diets : a vegan diet emphasizing minimally-processed whole foods from plants or a low-fat omnivorous diet . Participants attend weekly group classes for the first six months , bi-weekly for the next six months , and monthly meetings for the last year . In addition to face-to-face content , participants also have access to private Facebook groups for their diet , podcasts , and online newsletters starting at six months . Primary outcomes include changes in body weight and CVD risk factors ( lipids , blood pressure , glucose , and insulin ) at 12 months . Secondary outcomes include changes in dietary intake . Participants complete assessment s at baseline and at months 6 , 12 , and 24 . CONCLUSIONS The NEW Soul study is an innovative intervention aim ed at improving dietary intake while maintaining traditional AA cultural food choices . Primary outcomes are expected by 2021 |
14,016 | 28,475,791 | Conclusions A 4-component strategy was the most effective intervention to prevent MDR-GNB acquisition . | Background This study evaluated the relative efficacy of strategies for the prevention of multidrug-resistant gram-negative bacteria ( MDR-GNB ) in adult intensive care units ( ICUs ) . | BACKGROUND This study was undertaken to determine the temporal relationship between implementation of different interventions in an intensive care unit ( ICU ) and control of endemic nosocomial acquisition of extended-spectrum β-lactamase Enterobacteriaceae ( ESBLE ) . METHODS This was a prospect i ve observational study with time-series analysis of the monthly incidence of ESBLE and its predictors . In November 2007 , after a 14-month baseline period , an intervention consisting of restriction of third-generation cephalosporins ( 3 GC ) and increased use of alcohol-based h and rubs was implemented . In January 2008 , an increased health care worker (HCW):patient ratio was also implemented . In March 2010 , the ICU was closed , and patients were moved to a clean ICU . RESULTS The first intervention result ed in global reduction in 3 GC and increased use of alcohol-based h and rub . A significant change in ESBLE incidence was observed in a full segmented univariate regression analysis ( mean change in level , -0.91 ± 0.19 ; P < .0001 ) . After ICU closure , there was a dramatic reduction in ESBLE acquisition . According to the multivariate model , the ICU closure was the main protective factor . Before ICU closure , an increase in the HCW : patient ratio of 0.1 point tended to be associated with a decreased risk of ESBLE acquisition ( relative risk , 0.28 ; 95 % confidence interval , 0.06 - 1.25 ; P = .09 ) . CONCLUSIONS This study shows that ICU closure was associated with , but not necessarily the reason for , control of ESBLE cross-transmission in a nonoutbreak setting . Environmental ESBE sources may play a role in cross-transmission ABSTRACT Beginning in 1992 , a sustained outbreak of multiresistantAcinetobacter baumannii infections was noted in our 1,000-bed hospital in Barcelona , Spain , result ing in considerable overuse of imipenem , to which the organisms were uniformly susceptible . In January 1997 , carbapenem-resistant (CR)A. baumannii strains emerged and rapidly disseminated in the intensive care units ( ICUs ) , prompting us to conduct a prospect i ve investigation . It was an 18-month longitudinal intervention study aim ed at the identification of the clinical and microbiological epidemiology of the outbreak and its response to a multicomponent infection control strategy . From January 1997 to June 1998 , clinical sample s from 153 ( 8 % ) of 1,836 consecutive ICU patients were found to contain CR A. baumannii . Isolates were verified to be A. baumannii by restriction analysis of the 16S-23S ribosomal genes and the intergenic spacer region . Molecular typing by repetitive extragenic palindromic sequence-based PCR and pulsed-field gel electrophoresis showed that the emergence of carbapenem resistance was not by the selection of resistant mutants but was by the introduction of two new epidemic clones that were different from those responsible for the endemic . Multivariate regression analysis selected those patients with previous carriage of CR A. baumannii(relative risk [ RR ] , 35.3 ; 95 % confidence interval [ CI ] , 7.2 to 173.1 ) , those patients who had previously received therapy with carbapenems ( RR , 4.6 ; 95 % CI , 1.3 to 15.6 ) , or those who were admitted into a ward with a high density of patients infected with CR A. baumannii ( RR , 1.7 ; 95 % CI , 1.2 to 2.5 ) to be at a significantly greater risk for the development of clinical colonization or infection with CR A. baumannii strains . In accordance , a combined infection control strategy was design ed and implemented , including the sequential closure of all ICUs for decontamination , strict compliance with cross-transmission prevention protocol s , and a program that restricted the use of carbapenem . Subsequently , a sharp reduction in the incidence rates of infection or colonization with A. baumannii , whether resistant or susceptible to carbapenems , was shown , although an alarming dominance of the carbapenem-resistant clones was shown at the end of the study Purpose Antibiotic de-escalation is promoted to limit prolonged exposure to broad-spectrum antibiotics , but proof that it prevents the emergence of resistance is lacking . We evaluated determinants of antibiotic de-escalation in an attempt to assess whether the latter is associated with a lower emergence of antimicrobial resistance . Methods Antibiotic treatments , starting with empirical beta-lactam prescriptions , were prospect ively documented during 2013 and 2014 in a tertiary intensive care unit ( ICU ) and categorized as continuation , de-escalation or escalation of the empirical antimicrobial treatment . Determinants of the de-escalation or escalation treatments were identified by multivariate logistic regression ; the continuation category was used as the reference group . Using systematic ally collected diagnostic and surveillance cultures , we estimated the cumulative incidence of antimicrobial resistance following de-escalation or continuation of therapy , with adjustment for ICU discharge and death as competing risks . Results Of 478 anti-pseudomonal antibiotic prescriptions , 42 ( 9 % ) were classified as escalation of the antimicrobial treatment and 121 ( 25 % ) were classified as de-escalation , mainly through replacement of the originally prescribed antibiotics with those having a narrower spectrum . In multivariate analysis , de-escalation was associated with the identification of etiologic pathogens ( p < 0.001 ) . The duration of the antibiotic course in the ICU in de-escalated versus continued prescriptions was 8 ( range 6–10 ) versus 5 ( range 4–7 ) days , respectively ( p < 0.001 ) . Mortality did not differ between patients in the de-escalation and continuation categories . The cumulative incidence estimates of the emergence of resistance to the initial beta-lactam antibiotic on day 14 were 30.6 and 23.5 % for de-escalation and continuation , respectively ( p = 0.22 ) . For the selection of multi-drug resistant pathogens , these values were 23.5 ( de-escalation ) and 18.6 % ( continuation ) respectively ( p = 0.35 ) . Conclusion The emergence of antibiotic-resistant bacteria after exposure to anti-pseudomonal beta-lactam antibiotics was not lower following de-escalation Introduction Although early use of broad-spectrum antimicrobials in critically ill patients may increase antimicrobial adequacy , uncontrolled use of these agents may select for more-resistant organisms . This study investigated the effects of early use of broad-spectrum antimicrobials in critically ill patients with hospital-acquired pneumonia . Methods We compared the early use of broad-spectrum antimicrobials plus subsequent de-escalation ( DE ) with conventional antimicrobial treatment ( non-de-escalation , NDE ) in critically ill patients with hospital-acquired pneumonia ( HAP ) . This open-label , r and omized clinical trial was performed in patients in a tertiary-care center medical intensive care unit ( MICU ) in Korea . Patients ( n = 54 ) r and omized to the DE group received initial imipenem/cilastatin plus vancomycin with subsequent de-escalation according to culture results , whereas patients r and omized to the NDE group ( n = 55 ) received noncarbapenem , nonvancomycin empiric antimicrobials . Results Between November 2004 and October 2006 , 109 MICU patients with HAP were enrolled . Initial antimicrobial adequacy was significantly higher in the DE than in the NDE group for Gram-positive organisms ( 100 % versus 14.3 % ; P < 0.001 ) , but not for Gram-negative organisms ( 64.3 % versus 85.7 % ; P = 0.190 ) . Mean intensive care unit ( ICU ) stay , and 14-day , 28-day , and overall mortality rates did not differ in the two groups . Among culture-positive patients , mortality from methicillin-resistant Staphylococcus aureus ( MRSA ) pneumonia was higher in the DE group , even after early administration of vancomycin . Multidrug-resistant organisms , especially MRSA , were more likely to emerge in the DE group ( adjusted hazard ratio for emergence of MRSA , 3.84 ; 95 % confidence interval , 1.06 to 13.91 ) . Conclusions The therapeutic advantage of early administration of broad-spectrum antimicrobials , especially with vancomycin , was not evident in this study Background We determined the effects of two antibiotic policies ( predominance of either β-lactam antibiotics or fluroquinolones ) on acquisition with third-generation cephalosporin-resistant Enterobacteriaceae ( CRE ) and fluoroquinolone-resistant CRE ( FCRE ) in two ICUs , with monitoring of other variables that may influence acquisition . Methods After an 8-month baseline period , units were r and omized to a predominant β-lactam antibiotic regimen ( weekly cycling of ceftriaxone , amoxicillin – clavulanic acid and fluroquinolones ) or a fluoroquinolone regimen for 3 months , with cross-over for another 3 months . Acquisition of CRE and FCRE was determined by microbiological surveillance . Results During baseline , acquisition rates for CRE and FCRE were 14/1,000 and 2/1,000 patient days at risk , respectively . Cross-transmission of CRE accounted for ≤25 % of acquisitions , and CRE acquisition was associated with the use of β-lactam antibiotics ( amoxicillin – clavulanic acid in particular ) . As compared to baseline , β-lactam antibiotic use [ in defined daily dose (DDD)/1,000 patient days ] was reduced from 854 to 526 ( −39 % ) and 555 ( −35 % ) during both intervention periods . Fluoroquinolone use was increased from 150 and 129 DDD/1,000 patient days in baseline and the β-lactam period to 514 DDD/1,000 patient days ( + 243 % ) in the fluoroquinolone period . Reductions in β-lactam use were not associated with reduced CRE acquisition [ adjusted HRs were 1.0 ( 95 % CR : 0.5–2.2 ) and 1.1 ( 95 % CI : 0.5–2.5 ) during both periods , respectively ] . Increased use of fluoroquinolones was associated with increased acquisition of FCRE [ adjusted HR 4.1 ( 95 % CI : 1.4–11.9 ; p < 0.01 ] . Infection control variables remained comparable during all periods . Conclusion A 35–39 % reduction of β-lactam exposure was not associated with reduced acquisition of CRE , whereas a 243 % increase of fluoroquinolone use increased acquisition of FCRE Mixed treatment comparison ( MTC ) meta- analysis is a generalization of st and ard pairwise meta- analysis for A vs B trials , to data structures that include , for example , A vs B , B vs C , and A vs C trials . There are two roles for MTC : one is to strengthen inference concerning the relative efficacy of two treatments , by including both ' direct ' and ' indirect ' comparisons . The other is to facilitate simultaneous inference regarding all treatments , in order for example to select the best treatment . In this paper , we present a range of Bayesian hierarchical models using the Markov chain Monte Carlo software WinBUGS . These are multivariate r and om effects models that allow for variation in true treatment effects across trials . We consider models where the between-trials variance is homogeneous across treatment comparisons as well as heterogeneous variance models . We also compare models with fixed ( unconstrained ) baseline study effects with models with r and om baselines drawn from a common distribution . These models are applied to an illustrative data set and posterior parameter distributions are compared . We discuss model critique and model selection , illustrating the role of Bayesian deviance analysis , and node-based model criticism . The assumptions underlying the MTC models and their parameterization are also discussed Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more Objective To study the effect of selective digestive tract decontamination by erythromycin-base on the incidence of carriage and infection with MREnterobacteriaceae producing an extended spectrum beta-lactamase ( ESB ) . Design After a 10-week prospect i ve survey to ascertain the baseline incidence in two bays ( 1 and 3 ) of the same ICU , bay 1 was compared with bay 3 during a further survey of 6 moths . The patients in bya 1 . received erythromycin-base . Setting Two non-contiguous bays , 1 and 3 , of 4 beds , in the same polyvalent ICU of a university hospital . PatientConsecutive patients with unit stay longer than 2 days ; 34 patients were included during the control period , 43 in bay 1 ( decontamination ) and 46 in bay 3 ( control ) during the trial period . InterventionErythromycin-base , 1 g t.i.d . in powder form administered by gastric tube to patients in bay 1 from admission to discharge . Measurements and results Digestive tract carriage was monitored by cultures of gastric and rectal swab specimens , sample d twice a week . Enterobacteriaceae were isolated on Drigalski agar with incorporated ceftazidime ( 4 mg/l ) . In bay 1 there was a decrease in ESB producingEnterobacteriaceae ( 23 % vs 10%,p=0.0004 ) from rectal swab , especially inK. pneumoniae ( 15 % vs 2%,p=10−5 ) , during the decontamination period in comparison to the control period . During the trial period the only differences observed between bays 1 and 3 were in the gastric sample s : K. pneumoniae were less often isolated in bay 1 than in bay 3 ( 0 % vs 3%,p=0.03 ) . Intestinal carriage with multiresistantEnterobacteriaceae occurred in 28 % patients in bay 1 and 30 % patients in bay 3 during the trial period ( p=0.79 ) . Erythromycin-base did not delay the carriage by patients in bay 1 ( log rank testp=0.42 ) . Conclusion Erythromycin-base was not effective in preventing digestive tract carriage due toEnterobacteriaceae resistant to third generation cephalosporin by production of chromosomal cephalosporinase . The decrease in isolates containingK. pneumoniae in bay 1 can not be definitively attributed to erythromycin-base , since the number of this species in bay 3 was low STUDY OBJECTIVE To study the efficacy of intestinal decontamination by oral nonabsorbable antibiotic agents to control a nosocomial outbreak of intestinal colonization and infection with multiresistant Enterobacteriaceae , and to examine its effects on endemic nosocomial infection rates . DESIGN A 10-week prospect i ve incidence study ( group 1 ) , and then an 8-week r and omized , open trial of intestinal decontamination ( groups 2 and 3 ) . SETTING A medical intensive care unit of a tertiary care university hospital . PATIENTS Consecutive patients with unit stay of over 2 days and a severity score at admission of more than 2 ; 124 patients were included in group 1 , 50 in group 2 ( control ) , and 36 in group 3 ( intestinal decontamination ) . INTERVENTIONS Neomycin , polymyxin E , and nalidixic acid were given to group 3 patients throughout their stay in the unit . MEASUREMENTS AND MAIN RESULTS Intestinal colonization with multiresistant strains occurred in 19.6 % of patients in group 1 , at a mean of 16 days after admission , and preceded detection in clinical sample s by a mean of 11 days . During the decontamination trial , intestinal colonization rates decreased to 10 % ( group 2 ) , and 3 % ( group 3 ) ( P = 0.12 and P less than 0.01 , compared with group 1 , respectively ) . Corresponding infection rates were 9 % ( group 1 ) , 3 % ( group 2 ) , and 0 ( group 3 ) . No new cases were detected in the following 4 months . The intestinal colonization rate with gram-positive cocci was higher in group 3 than group 2 ( P less than 0.001 ) . The overall rate of nosocomial infections was at 28 % ( group 1 ) , 33 % ( group 2 ) , and 32 % ( group 3 ) . CONCLUSIONS Intestinal decontamination can help to control an outbreak of intestinal colonization and infection with multiresistant gram-negative bacilli in the intensive care unit , but should not be recommended for routine prevention of endemic nosocomial infections We investigated the effects of replacing third-/fourth-generation cephalosporins with piperacillin-tazobactam on the rate of acquisition of extended spectrum beta-lactamase-producing Klebsiella pneumoniae and Escherichia coli by patients hospitalized in a Department of Respiratory Medicine . This 9-month , prospect i ve , non-controlled , intervention study comprised two phases : a 3-month pre-intervention phase ( Phase I ) and a 6-month intervention phase ( Phase II ) , during which the use of third-/forth-generation cephalosporins was restricted and replaced by piperacillin-tazobactam . Rectal swabs were obtained within 24 h after admission ( baseline screening ) , weekly , and 48 h before discharge during Phase I and the last 3 months of Phase II ( Phase IIb ) . Swabs were tested for E. coli and K. pneumoniae , and extended spectrum beta-lactamase production was detected with the double disc test . Use of third/fourth-generation cephalosporins decreased by 63.0 % and 100 % , respectively ; while the use of piperacillin-tazobactam increased by 28-fold . The rate of acquisition of extended spectrum beta-lactamase-producing E. coli and K. pneumoniae together in rectal swab specimens decreased in Phase IIb as compared with Phase I ( 19.5 % vs 29.5 % ) . Few rectal swab specimens were positive for extended spectrum beta-lactamases-producing K. pneumoniae , and no substantial decrease in the rate of its acquisition was observed INTRODUCTION Acinetobacter baumanii is a Gram-negative coccobacillus that is normally a commensal pathogen but can be a nosocomial pathogen . An epidemiologic study was performed to investigate an outbreak of A baumanii that occurred in our medical intensive care unit ( MICU ) from March to September 1995 . METHODS A case-control study was performed by retrospective chart review , comparing case patients to r and omly selected patients who were mechanically ventilated in the MICU for at least 1 week during the outbreak . A case patient was defined as any patient with an Acinetobacter infection in which the epidemic strain was considered to be a pathogen . The epidemic strain was defined by its antibiogram . Case patients and control patients were compared for age , gender , underlying disease , acute physiology and chronic health evaluation III score , length of MICU stay , prior antibiotic use , presence of fever , sepsis , type of pulmonary infiltrate , and outcome . Environmental and h and -washing studies also were performed during the period of the outbreak . Molecular typing was performed on available bloodstream isolates . RESULTS There were 15 cases of A baumanii nosocomial pneumonia . Fifty percent were bacteremic ; one chart was unavailable for review . Twenty-nine patients were identified as control patients . The mean age for case patients was 50 ( range , 21 to 84 ) . The mean duration of time from admission to the ICU to infection was 12.8 days ( range , 4 to 40 ) . Sepsis developed in 35 % of the case patients . Forty-three percent of the case patients died during their hospitalization , with two of those deaths attributed to Acinetobacter infection . Univariate analysis showed that prior use of ceftazidime was associated with infection with Acinetobacter ( 11/14 case patients compared to 11/29 control patients ; p < 0.01 ) . Pulsed-field gel electrophoresis revealed two strains to be responsible for the outbreak . H and washing was performed before patient contact by only 10 % of health-care workers , and only 32 % washed their h and s after patient contact . CONCLUSION The use of ceftazidime was associated with an increased risk of nosocomial pneumonia with resistant strains of Acinetobacter . Health-care workers need to improve compliance with h and -washing recommendations OBJECTIVES To identify risk factors for the respiratory acquisition of extended-spectrum beta-lactamase (ESBL)-producing Klebsiella pneumoniae among patients admitted to a neurosurgical intensive care unit ( NSICU ) and to modify them without changing general infection control measures . DESIGN Nested case-control and intervention study . SETTING A 1,200-bed , tertiary-care teaching hospital with a 17-bed NSICU . METHODS Sputa of all patients admitted to the NSICU were cultured weekly during the study . From October 2002 through February 2003 , 29 case- patients from whose sputum ESBL-producing K. pneumoniae was isolated were detected and 59 controls- patients were r and omly selected among patients without any positive isolate of ESBL-producing K. pneumoniae . After analyzing the risk factors , we intervened to modify them and compared the acquisition rate of ESBL-producing K. pneumoniae before ( October 2002 to February 2003 ) and after ( April to August 2003 ) the intervention . RESULTS Multivariate analysis showed that prior exposure to third-generation cephalosporins ( TGCs ) ( OR , 6.0 ; CI95 , 1.9 to 18.6 ; P = .002 ) was an independent risk factor of ESBL-producing K. pneumoniae acquisition . The neurosurgical team was notified of the result , and the infectious diseases specialist visited the NSICU three times a week to regulate TGC use during the intervention period . Patients admitted before the intervention were older than patients admitted after . The respiratory acquisition of ESBL-producing K. pneumoniae per 1,000 patient-days ( 13.5 [ CI95 , 8.9 to 18.1 ] vs 2.7 [ CI95 , 0.9 to 4.6 ] ) and the antimicrobial use density of TGCs ( 38.2 + /- 5.0 vs 17.3 + /- 2.6 ; P < .001 ) decreased significantly after the intervention . CONCLUSION Prior exposure to TGCs was an independent risk factor for the respiratory acquisition of ESBL-producing K. pneumoniae , and less use of TGCs was associated with a decrease in acquisition ABSTRACT Risk factors for the nosocomial occurrence of imipenem-resistant Acinetobacter baumannii ( IRAB ) were determined . A case-control study design was used for a comparison of two groups of A. baumannii-positive patients with control patients . Nosocomial IRAB was isolated from the first group of A. baumannii-positive patients , and imipenem-susceptible A. baumannii ( ISAB ) was isolated from the second group . The control patients were r and omly selected in a 4:1 ratio from the same medical or surgical services from which the A. baumannii-positive patients were receiving care when the isolation of IRAB occurred . Risk factors analyzed included demographic variables , comorbid conditions , variables related to hospitalization , and the antimicrobials used . IRAB was isolated from 104 patients , and ISAB was isolated from 387 patients between January and December 2000 . The risk factors for IRAB were a previous intensive care unit ( ICU ) stay ( odds ratio [ OR ] , 21.54 ; 95 % confidence interval [ CI ] , 10.73 to 43.23 ) and prior exposure to imipenem ( OR , 9.18 ; 95 % CI , 3.99 to 21.13 ) or third-generation cephalosporins ( OR , 2.11 ; 95 % CI , 1.13 to 3.95 ) . Risk factors for ISAB were a previous ICU stay ( OR , 8.05 ; 95 % CI , 5.67 to 11.44 ) and exposure to third-generation cephalosporins ( OR , 2.07 ; 95 % CI , 1.47 to 2.91 ) . Our results suggest that the nosocomial occurrence of IRAB or ISAB is strongly related to an ICU stay , and IRAB occurrence may be favored by the selection pressure of imipenem OBJECTIVE To describe , during a 6-year period , multidrug-resistant bacterial carriage in an intensive care unit ( ICU ) . DESIGN Prospect i ve survey of 2235 ICU patients with methicillin-resistant Staphylococcus aureus ( MRSA ) and extended-spectrum beta-lactamase-producing Enterobacteriaceae ( ESBL-E ) . SETTING A surgical ICU in a tertiary-care teaching hospital . PATIENTS All admitted patients . INTERVENTIONS Nasal and rectal swabs were performed at admission and weekly thereafter . There was nasal application of mupirocin for MRSA carriers and selective digestive decontamination with local antibiotics for ESBL-E carriers . RESULTS The swab compliance rate was 82 % at admission and 51 % during ICU stay . The rates of MRSA carriage or infection were 4.2 new cases per 100 admissions and 7.9 cases per 1000 patient-days during ICU stay . The rates of ESBL-E carriage or infection were 0.4 new case per 100 admissions and 3.9 cases per 1000 patient-days during ICU stay . Importation of MRSA increased significantly over time from 3.2 new cases per 100 admissions during the first 3 years to 5.5 during the last 3 years . The rate of ICU-acquired ESBLE decreased from 5.5 cases per 1000 patient-days during the first 3 years to 1.9 cases during the last 3 years . Nasal and digestive decontamination had low efficacy in eradicating carriage . CONCLUSIONS MRSA remained poorly controlled throughout the hospital and was not just a problem in the ICU . MRSA thus requires more effective measures throughout the hospital . ESBL-E was mainly an ICU pathogen and our approach result ed in a clear decrease in the rate of acquisition in the ICU over time BACKGROUND Selective decontamination of the digestive tract ( SDD ) is an infection-prevention regimen used in critically ill patients . We assessed the effects of SDD on intensive-care-unit ( ICU ) and hospital mortality , and on the acquisition of resistant bacteria in adult patients admitted to intensive care . METHODS We did a prospect i ve , controlled , r and omised , unblinded clinical trial . 934 patients admitted to a surgical and medical ICU were r and omly assigned oral and enteral polymyxin E , tobramycin , and amphotericin B combined with an initial 4-day course of intravenous cefotaxime ( SDD group n=466 ) , or st and ard treatment ( controls n=468 ) . Primary endpoints were ICU and hospital mortality and the acquisition of resistant bacteria . FINDINGS In the SDD group 69 ( 15 % ) patients died in the ICU compared with 107 ( 23 % ) in the control group ( p=0.002 ) . Hospital mortality was lower in the SDD groups than in the control group ( 113 [ 24 % ] vs 146 [ 31 % ] , p=0.02 ) . During their stay in intensive care , colonisation with gram-negative bacteria resistant to ceftazidime , ciprofloxacin , imipenem , polymyxin E , or tobramycin occurred in 61 ( 16 % ) of 378 SDD patients and in 104 ( 26 % ) of 395 patients in the control group ( p=0.001 ) . Colonisation with vancomycin-resistant enterococcus occurred in five ( 1 % ) SDD patients and in four ( 1 % ) controls ( p=1.0 ) . No patient in either group was colonised with meticillin-resistant Staphylococcus aureus . INTERPRETATION In a setting with low prevalence of vancomycin-resistant enterococcus and meticillin-resistant S aureus , SDD can decrease ICU and hospital mortality and colonisation with resistant gram-negative aerobic bacteria Objectives : In a multicenter , placebo-controlled , r and omized , double-blind trial , we showed that acquired infections in intubated patients were reduced by the combination of topical polymyxin plus tobramycin and nasal mupirocin plus chlorhexidine body wash . Because intubated patients are particularly at risk for acquired infections , we reassessed the impact of this protocol as a routine procedure to control acquired infections in the ICU . Design : Nonr and omized study comparing acquired infections in ICU patients during two 1-year periods : the last year before ( group A , n = 925 ) and the first year after the implementation of the protocol ( group B , n = 1,022 ) . Acquired infections were prospect ively recorded . Setting : Polyvalent medical ICU at a university-affiliated hospital . Patients : All patients admitted to the ICU . Interventions : Administration of polymyxin/tobramycin/amphotericin B in the oropharynx and the gastric tube plus a mupirocin/chlorhexidine regimen in intubated patients and st and ard care in the other patients . Measurements and Main Results : The comparison of acquired infection rates between groups was adjusted for differences at baseline . Infection rates were lower in group B compared with group A ( 5.3 % vs 11.0 % ; p < 0.001 ) , as were the incidence rates of total acquired infections ( 9.4 vs 23.6 per 1,000 patient-days ; p < 0.001 ) , intubation-related pneumonia ( 5.1 vs 17.1 per 1,000 ventilator-days ; p < 0.001 ) , and catheter-related bloodstream infections ( 1.0 vs 3.5 per 1,000 catheter-days ; p = 0.03 ) . There were fewer acquired infections caused by ceftazidime-resistant Enterobacteriaceae ( 0.8‰ vs 3.6‰ ; p < 0.001 ) , ciprofloxacin-resistant Enterobacteriaceae ( 0.8‰ vs 2.5‰ ; p = 0.02 ) , ciprofloxacin-resistant Pseudomonas aeruginosa ( 0.5‰ vs 1.6‰ ; p = 0.05 ) , and colistin-resistant Gram-negative bacilli ( 0.7‰ vs 1.9‰ ; p = 0.04 ) . Fewer patients got acquired infections due to multidrug-resistant aerobic Gram-negative bacilli ( p = 0.008 ) . Conclusions : In intubated patients , the use of topical polymyxin/tobramycin/amphotericin B plus mupirocin/chlorhexidine was associated with the reduction of all-cause ICU-acquired infections . Long-term emergence of multidrug-resistant organisms deserves further investigation BACKGROUND Chlorhexidine bathing has been associated with reductions in healthcare-associated bloodstream infection . To determine the impact and sustainability of the effect of chlorhexidine bathing on central venous catheter-associated bloodstream infection , we performed a prospect i ve , 3-phase , multiple-hospital study . METHODS In the medical intensive care unit and the respiratory care unit of a tertiary care hospital and the medical-surgical intensive care units of 4 community hospitals , rates of central venous catheter-associated bloodstream infection were collected prospect ively for each period . Pre-intervention ( phase 1 ) patients were bathed with soap and water or nonmedicated bathing cloths ; active intervention ( phase 2 ) patients were bathed with 2 % chlorhexidine gluconate cloths with the number of baths administered and skin tolerability assessed ; post-intervention ( phase 3 ) chlorhexidine bathing was continued but without oversight by research personnel . Central venous catheter-associated bloodstream infection rates were compared over study periods using Poisson regression . RESULTS Compared with pre-intervention , during active intervention there were significantly fewer central venous catheter-associated bloodstream infections ( 6.4/1000 central venous catheter days vs 2.6/1000 central venous catheter days , relative risk , 0.42 ; 95 % confidence interval , 0.25 - 0.68 ; P<.001 ) , and this reduction was sustained during post-intervention ( 2.9/1000 central venous catheter days ; relative risk , 0.46 ; 95 % confidence interval , 0.30 - 0.70 ; P<.001 ) . During the active intervention period , compliance with chlorhexidine bathing was 82 % . Few adverse events were observed . CONCLUSION In this multiple-hospital study , chlorhexidine bathing was associated with significant reductions in central venous catheter-associated bloodstream infection , and these reductions were sustained post-intervention when chlorhexidine bathing was unmonitored . Chlorhexidine bathing was well tolerated and is a useful adjunct to reduce central venous catheter-associated bloodstream infection Summary Background Intensive care units ( ICUs ) are high-risk areas for transmission of antimicrobial-resistant bacteria , but no controlled study has tested the effect of rapid screening and isolation of carriers on transmission in setting s with best-st and ard pre caution s. We assessed interventions to reduce colonisation and transmission of antimicrobial-resistant bacteria in European ICUs . Methods We did this study in three phases at 13 ICUs . After a 6 month baseline period ( phase 1 ) , we did an interrupted time series study of universal chlorhexidine body-washing combined with h and hygiene improvement for 6 months ( phase 2 ) , followed by a 12–15 month cluster r and omised trial ( phase 3 ) . ICUs were r and omly assigned by computer generated r and omisation schedule to either conventional screening ( chromogenic screening for meticillin-resistant Staphylococcus aureus [ MRSA ] and vancomycin-resistant enterococci [ VRE ] ) or rapid screening ( PCR testing for MRSA and VRE and chromogenic screening for highly resistant Enterobacteriaceae [ HRE ] ) ; with contact pre caution s for identified carriers . The primary outcome was acquisition of resistant bacteria per 100 patient-days at risk , for which we calculated step changes and changes in trends after the introduction of each intervention . We assessed acquisition by microbiological surveillance and analysed it with a multilevel Poisson segmented regression model . We compared screening groups with a likelihood ratio test that combined step changes and changes to trend . This study is registered with Clinical Trials.gov , number NCT00976638 . Findings Seven ICUs were assigned to rapid screening and six to conventional screening . Mean h and hygiene compliance improved from 52 % in phase 1 to 69 % in phase 2 , and 77 % in phase 3 . Median proportions of patients receiving chlorhexidine body-washing increased from 0 % to 100 % at the start of phase 2 . For trends in acquisition of antimicrobial-resistant bacteria , weekly incidence rate ratio ( IRR ) was 0·976 ( 0·954–0·999 ) for phase 2 and 1·015 ( 0·998–1·032 ) for phase 3 . For step changes , weekly IRR was 0·955 ( 0·676–1·348 ) for phase 2 and 0·634 ( 0·349–1·153 ) for phase 3 . The decrease in trend in phase 2 was largely caused by changes in acquisition of MRSA ( weekly IRR 0·925 , 95 % CI 0·890–0·962 ) . Acquisition was lower in the conventional screening group than in the rapid screening group , but did not differ significantly ( p=0·06 ) . Interpretation Improved h and hygiene plus unit-wide chlorhexidine body-washing reduced acquisition of antimicrobial-resistant bacteria , particularly MRSA . In the context of a sustained high level of compliance to h and hygiene and chlorhexidine bathings , screening and isolation of carriers do not reduce acquisition rates of multidrug-resistant bacteria , whether or not screening is done with rapid testing or conventional testing . Funding European Commission The prevalence of skin colonisation with Acinetobacter baumannii ( ACBA ) on admission to the medical intensive care unit ( MICU ) was studied in an institution endemic for ACBA bloodstream infections ( BSIs ) . The impact of 4 % chlorhexidine gluconate ( 4 % CG ) whole-body washing on the patients ' ACBA skin colonisation was also determined . A prospect i ve cohort trial in a MICU during March 2002 to December 2003 was performed , with a comparison between the prevalence and incidence of ACBA-BSIs obtained after intervention and retrospectively . During the intervention period , ACBA skin-screening swabs were taken from all patients on admission and periodically until discharge . Patients underwent whole-body disinfection with 4 % CG immediately after obtaining the initial cultures . Disinfection was carried out on a daily basis until discharge , regardless of colonisation status . Of the 320 patients at ward admission , 55 ( 17 % ) yielded ACBA . The prevalence of ACBA colonisation among the remaining MICU patients was 5.5 % at 24h and 1 % at 48h following the disinfection regimen ( P=0.002 , OR : 2.4 ) . Following a second screen , 80 % of colonised patients were decolonised . Prevalence of ACBA-BSIs decreased from 4.6 to 0.6 per 100 patients ( P < or = 0.001 ; OR : 7.6 ) and incidence decreased from 7.8 to 1.25 ( 85 % reduction ) . We conclude that daily whole-body disinfection with 4 % CG significantly reduced ACBA skin colonisation . This regimen may be considered in addition to well-known infection control measures , particularly in institutions with endemic rates of multidrug-resistant ACBA-BSIs BACKGROUND We sought to determine the long-term effect of a multifaceted infection-control intervention to reduce the incidence of p and rug-resistant Acinetobacter baumannii infection in a Thai tertiary care center . METHODS A 3-year , prospect i ve , controlled , quasi-experimental study was conducted in medical intensive care , surgical intensive care , and coronary care units for a 1-year period before intervention ( period 1 ) , a 1-year period after intervention ( period 2 ) , and a 1-year follow-up period ( period 3 ) . The interventions in period 2 included strictly implementing contact isolation pre caution s and appropriate h and hygiene , active surveillance , cohorting patients who were colonized or infected with p and rug-resistant A. baumannii , and environmental cleaning with 1:100 sodium hypochlorite solution . All interventions were continued in period 3 , but environmental cleaning solutions were changed to detergent and phenolic agents . RESULTS Before the intervention , the rate of p and rug-resistant A. baumannii colonization and /or infection was 3.6 cases per 1000 patient-days . After the intervention , the rate of p and rug-resistant A. baumannii colonization and /or infection decreased by 66 % in period 2 ( to 1.2 cases per 1000 patient-days ; P < .001 ) and by 76 % in period 3 ( to 0.85 cases per 1000 patient-days ; P < .001 ) . The monthly hospital antibiotic cost of treating p and rug-resistant A. baumannii colonization and /or infection and the hospitalization cost for each patient in the intervention units were also reduced by 36%-42 % ( P < .001 ) and 25%-36 % ( P < .001 ) , respectively , during periods 2 and 3 . CONCLUSIONS A multifaceted intervention featuring active surveillance and environmental cleaning result ed in sustained reductions in the rate of p and rug-resistant A. baumannii colonization and infection , the cost of antibiotic therapy , and the cost of hospitalization among intensive care unit patients in a developing country We evaluated the impact of infection control interventions to reduce nosocomial extended-spectrum beta-lactamase ( ESBL ) transmission in a non-outbreak setting . This study was conducted at a tertiary 1200-bed hospital in Canada . The incidence of ESBLs was based on recovery of clinical isolates and assessed prospect ively from 1999 to 2005 . The incidence increased significantly from 0.28 to 0.67 per 1000 admissions during this period ( P<0.001 ) , reflecting an increase in the regional ESBL incidence from 1.32 to 9.28 per 100 000 population ( P<0.001 ) . Despite this increase , nosocomial ESBL rates increased only marginally , suggesting that infection control measures had an impact on nosocomial transmission . Infection control measures consisted of isolating all ESBL patients , as well as implementing the use of contact pre caution s for those with a high risk for transmission . The cost of these measures was CN$138 046.00 per year and CN$3191.83 per case admitted . A combination of control measures including active surveillance cultures , contact pre caution s for all colonized or infected patients and antimicrobial stewardship is required to significantly reduce the incidence of ESBLs The objective of this prospect i ve cohort study was to determine whether admission to an intensive care unit ( ICU ) room previously occupied by a patient with multidrug-resistant ( MDR ) Gram-negative bacilli ( GNB ) increases the risk of acquiring these bacteria by subsequent patients . All patients hospitalized for > 48 h were eligible . Patients with MDR GNB at ICU admission were excluded . The MDR GNB were defined as MDR Pseudomonas aeruginosa , Acinetobacter baumannii and extended spectrum β-lactamase ( ESBL ) -producing GNB . All patients were hospitalized in single rooms . Cleaning of ICU rooms between two patients was performed using quaternary ammonium disinfectant . Risk factors for MDR P. aeruginosa , A. baumannii and ESBL-producing GNB were determined using univariate and multivariate analysis . Five hundred and eleven consecutive patients were included ; ICU-acquired MDR P. aeruginosa was diagnosed in 82 ( 16 % ) patients , A. baumannii in 57 ( 11 % ) patients , and ESBL-producing GNB in 50 ( 9 % ) patients . Independent risk factors for ICU-acquired MDR P. aeruginosa were prior occupant with MDR P. aeruginosa ( OR 2.3 , 95 % CI 1.2 - 4.3 , p 0.012 ) , surgery ( OR 1.9 , 95 % CI 1.1 - 3.6 , p 0.024 ) , and prior piperacillin/tazobactam use ( OR 1.2 , 95 % CI 1.1 - 1.3 , p 0.040 ) . Independent risk factors for ICU-acquired A. baumannii were prior occupant with A. baumannii ( OR 4.2 , 95 % CI 2 - 8.8 , p < 0.001 ) , and mechanical ventilation ( OR 9.3 , 95 % CI 1.1 - 83 , p 0.045 ) . Independent risk factors for ICU-acquired ESBL-producing GNB were tracheostomy ( OR 2.6 , 95 % CI 1.1 - 6.5 , p 0.049 ) , and sedation ( OR 6.6 , 95 % CI 1.1 - 40 , p 0.041 ) . We conclude that admission to an ICU room previously occupied by a patient with MDR P. aeruginosa or A. baumannii is an independent risk factor for acquisition of these bacteria by subsequent room occupants . This relationship was not identified for ESBL-producing GNB PURPOSE The study aim ed to determine whether improvements in intensive care unit ( ICU ) structural environment affect the incidence of ICU-acquired infections ( IAIs ) , particularly those caused by multidrug-resistant pathogens . METHODS The incidence of IAI and the number of infections caused by organisms during the 6 months immediately before ICU renovation and during the 6 months immediately after ICU renovation were compared . The observational duration was prolonged for an additional 1 year after recruiting the after-renovation data to observe if the found effect of ICU structural renovation is maintained . The relevant data were prospect ively gathered . RESULTS The overall IAI incidence and distribution of infection site showed no difference in both periods . In IAI-causing pathogens , no considerable difference was found between before and after renovation , except for Acinetobacter baumannii . In comparison of the major pathogens ' identification rate between the entire hospital and the renovated ICU during the study periods , only A baumannii cases in the renovated ICU significantly decreased . However , the reduction of the IAI cases by A baumannii was not sustained for more than 1 year . CONCLUSIONS These results suggest that structural ICU renovations only may not improve overall IAI incidence , except for transient decrease in IAI by A baumannii BACKGROUND Previously , we assessed selective digestive tract decontamination ( SDD ) and selective oropharyngeal decontamination ( SOD ) on survival and prevention of bacteraemia in patients in intensive-care units . In this analysis , we aim ed to assess effectiveness of these interventions for prevention of respiratory tract colonisation and bacteraemia with highly resistant microorganisms acquired in intensive-care units . METHODS We did an open-label , clustered group-r and omised , crossover study in 13 intensive-care units in the Netherl and s between May , 2004 , and July , 2006 . Participants admitted to intensive-care units with an expected duration of mechanical ventilation of more than 48 h or an expected stay of more than 72 h received SOD ( topical tobramycin , colistin , and amphotericin B in the oropharynx ) , SDD ( SOD antibiotics in the oropharynx and stomach plus 4 days ' intravenous cefotaxime ) , or st and ard care . The computer-r and omised order of study regimens was applied by an independent clinical pharmacist who was masked to intensive-care-unit identity . We calculated crude odds ratios ( 95 % CI ) for rates of bacteraemia or respiratory tract colonisation with highly resistant microorganisms in patients who stayed in intensive-care units for more than 3 days ( ie , acquired infection ) . This trial is registered at http://is rct n.org , number IS RCT N35176830 . FINDINGS Data were available for 5927 ( > 99 % ) of 5939 patients , of whom 5463 ( 92 % ) were in intensive-care units for more than 3 days . 239 ( 13 % ) of 1837 patients in st and ard care acquired bacteraemia after 3 days , compared with 158 ( 9 % ) of 1758 in SOD ( odds ratio 0·66 , 95 % CI 0·53 - 0·82 ) , and 124 ( 7 % ) of 1868 in SDD ( 0·48 , 0·38 - 0·60 ) . Eight patients acquired bacteraemia with highly resistant microorganisms during SDD , compared with 18 patients ( with 19 episodes ) during st and ard care ( 0·41 , 0·18 - 0·94 ; rate reduction [ RR ] 59 % , absolute risk reduction [ ARR ] 0·6 % ) and 20 during SOD ( 0·37 , 0·16 - 0·85 ; RR 63 % , ARR 0·7 % ) . Of the patients staying in intensive-care units for more than 3 days , we obtained endotracheal aspirate cultures for 881 ( 49 % ) patients receiving st and ard care , 886 ( 50 % ) receiving SOD , and 828 ( 44 % ) receiving SDD . 128 ( 15 % ) patients acquired respiratory tract colonisation with highly resistant microorganisms during st and ard care , compared with 74 ( 8 % ) during SDD ( 0·58 , 0·43 - 0·78 ; RR 38 % , ARR 5·5 % ) and 88 ( 10 % ) during SOD ( 0·65 , 0·49 - 0·87 ; RR 32 % , ARR 4·6 % ) . Acquired respiratory tract colonisation with Gram-negative bacteria or cefotaxime-resistant and colistin-resistant pathogens was lowest during SDD . INTERPRETATION Widespread use of SDD and SOD in intensive-care units with low levels of antibiotic resistance is justified . FUNDING None OBJECTIVE To determine the effectiveness of daily bathing with 2 % chlorhexidine-impregnated washcloths in preventing multidrug-resistant ( MDR ) gram-positive bacterial colonization and bloodstream infection . METHODS A r and omized , open-label controlled trial was conducted in 4 medical intensive care units ( ICUs ) in Thail and from December 2013 to January 2015 . Patients were r and omized to receive cleansing with non-antimicrobial soap ( control group ) or 2 % chlorhexidine-impregnated washcloths used to wipe the patient 's body once daily ( chlorhexidine group ) . Swabs were taken from nares , axilla , antecubital , groin , and perianal areas on admission and on day 3 , 5 , 7 , and 14 . The 5 outcomes were ( 1 ) favorable events ( all sample s negative throughout ICU admission , or initially positive sample s with subsequent negative sample s ) ; ( 2 ) MDR bacteria colonization-free time ; ( 3 ) hospital-acquired infection ; ( 4 ) length of ICU and hospital stay ; ( 5 ) adverse skin reactions . RESULTS A total of 481 patients were r and omly assigned to the control group ( 241 ) or the chlorhexidine group ( 240 ) . Favorable events at day 14 were observed in 34.8 % of patients in the control group and 28.6 % in the chlorhexidine group ( P=.79 ) . Median MDR bacteria colonization-free times were 5 days in both groups . The incidence rate of hospital-acquired infection and the length of the ICU and hospital stay did not differ significantly between groups . The incidence of adverse skin reactions in the chlorhexidine group was 2.5 % . CONCLUSION The effectiveness of 2 % chlorhexidine-impregnated washcloths for the prevention of MDR gram-negative bacteria colonization and hospital-acquired infection in adult patients in ICU was not proven . TRIAL REGISTRATION Clinical Trials.gov identifier : NCT01989416 |
14,017 | 27,456,962 | Discussion This will be the first systematic review of studies to establish the change in BMI required to improve metabolic health status in obese children and adolescents . | Background Childhood obesity is one of the most serious , global , public health challenges and has adverse health consequences in both the short- and long-term .
The purpose of this study is to establish the change in body mass index ( BMI ) needed to achieve improvements in metabolic health status in obese children and adolescents attending lifestyle treatment interventions . | The evaluation of child growth trajectories and the interventions design ed to improve child health are highly dependent on the growth charts used . The U.S. CDC and the WHO , in May 2000 and April 2006 , respectively , released new growth charts to replace the 1977 NCHS reference . The WHO charts are based for the first time on a prescriptive , prospect i ve , international sample of infants selected to represent optimum growth . This article compares the WHO and CDC curves and evaluates the growth performance of healthy breast-fed infants according to both . As expected , there are important differences between the WHO and CDC charts that vary by age group , growth indicator , and specific Z-score curve . Differences are particularly important during infancy , which is likely due to differences in study design and characteristics of the sample , such as type of feeding . Overall , the CDC charts reflect a heavier , and somewhat shorter , sample than the WHO sample . This results in lower rates of undernutrition ( except during the first 6 mo of life ) and higher rates of overweight and obesity when based on the WHO st and ards . Healthy breast-fed infants track along the WHO st and ard 's weight-for-age mean Z-score while appearing to falter on the CDC chart from 2 mo onwards . Shorter measurement intervals in the WHO st and ards result in a better tool for monitoring the rapid and changing rate of growth in early infancy . Their adoption would have important implication s for the assessment of lactation performance and the adequacy of infant feeding and would bring coherence between the tools used to assess growth and U.S. national guidelines that recommend breast-feeding as the optimal source of nutrition during infancy |
14,018 | 27,756,263 | Conclusions It is clear that very little trans-disciplinary research has been done with the majority of studies still being discipline specific .
It also appears that certain low and middle income countries seem to focus on domain-specific interventions . | Background Although linkages have been found between agricultural interventions and nutritional health , and the development of clean fuels and improved solid fuel stoves in reducing household air pollution and adverse health effects , the extent of the potential of combined household interventions to improve health , nutrition and the environment has not been investigated .
A systematic review was conducted to identify the extent and type of community-based agricultural and household interventions aim ed at improving food security , health and the household environment in low and middle income countries . | Diarrhoea and respiratory infections remain the biggest killers of children under 5 years in developing countries . We conducted a 5-month household r and omised controlled trial among 566 households in rural Rw and a to assess uptake , compliance and impact on environmental exposures of a combined intervention delivering high-performance water filters and improved stoves for free . Compliance was measured monthly by self-report and spot-check observations . Semi-continuous 24-h PM2.5 monitoring of the cooking area was conducted in a r and om sub sample of 121 households to assess household air pollution , while sample s of drinking water from all households were collected monthly to assess the levels of thermotolerant coliforms . Adoption was generally high , with most householders reporting the filters as their primary source of drinking water and the intervention stoves as their primary cooking stove . However , some householders continued to drink untreated water and most continued to cook on traditional stoves . The intervention was associated with a 97.5 % reduction in mean faecal indicator bacteria ( Williams means 0.5 vs. 20.2 TTC/100 mL , p<0.001 ) and a median reduction of 48 % of 24-h PM2.5 concentrations in the cooking area ( p = 0.005 ) . Further studies to increase compliance should be undertaken to better inform large-scale interventions . Trial registration : Clinical trials.gov ; NCT01882777 ; http:// clinical trials.gov/ct2/ results ? term = NCT01882777 & Search = Background Household water treatment can improve the microbiological quality of drinking water and may prevent diarrheal diseases . However , current methods of treating water at home have certain shortcomings , and there is evidence of bias in the reported health impact of the intervention in open trial design s. Methods and Findings We undertook a r and omised , double-blinded , placebo-controlled trial among 240 households ( 1,144 persons ) in rural Democratic Republic of Congo to assess the field performance , use and effectiveness of a novel filtration device in preventing diarrhea . Households were followed up monthly for 12 months . Filters and placebos were monitored for longevity and for microbiological performance by comparing thermotolerant coliform ( TTC ) levels in influent and effluent water sample s. Mean longitudinal prevalence of diarrhea was estimated among participants of all ages . Compliance was assessed through self-reported use and presence of water in the top vessel of the device at the time of visit . Over the 12-month follow-up period , data were collected for 11,236 person-weeks of observation ( 81.8 % total possible ) . After adjusting for clustering within the household , the longitudinal prevalence ratio of diarrhoea was 0.85 ( 95 % confidence interval : 0.61–1.20 ) . The filters achieved a 2.98 log reduction in TTC levels while , for reasons that are unclear , the placebos achieved a 1.05 log reduction ( p<0.0001 ) . After 8 months , 68 % of intervention households met the study 's definition of current users , though most ( 73 % of adults and 95 % of children ) also reported drinking untreated water the previous day . The filter maintained a constant flow rate over time , though 12.4 % of filters were damaged during the course of the study . Conclusions While the filter was effective in improving water quality , our results provide little evidence that it was protective against diarrhea . The moderate reduction observed nevertheless supports the need for larger studies that measure impact against a neutral placebo . Trial Registration Current Controlled Trials IS RCT To assess the impact on child growth of the nutrition-counseling component of the Integrated Management of Childhood Illnesses ( IMCI ) strategy , a r and omized trial was implemented . All 28 government health centers in a Southern Brazil city were paired according to baseline nutritional indicators . One center from each pair was r and omly selected and its doctors received 20-h training in nutrition counseling . Thirty-three doctors were included and 12 - 13 patients < 18 mo of age from each doctor were recruited . The study included testing the knowledge of doctors , observing consultations and visiting the children at home 8 , 45 and 180 d after the initial consultation . Maternal knowledge , practice s and adherence to nutritional recommendations were assessed , and anthropometric measurements were taken . Day-long dietary intake was evaluated on a sub sample of children . Doctors in the intervention group had better knowledge of child nutrition and improved assessment and counseling practice s. Maternal recall of recommendations was higher in the intervention than in the control group , as was satisfaction with the consultation . Reported use of recommended foods was also increased . Daily fat intake was higher in the intervention than in the control group ; mean daily intakes of energy and zinc also tended to improve . Children 12 mo of age or older had improved weight gain and a positive but nonsignificant improvement in length . Nutrition-counseling training improved doctors ' performances , maternal practice s and the diets and weight gain of children . The r and omized design with blind outcome evaluation strongly supports a causal link . These results should be replicated in other setting Lack of access to safe water and sanitation contributes to diarrhoea moribidity and mortality in developing countries . We evaluated the impact of household water treatment , latrines , shallow wells , and rainwater harvesting on diarrhoea incidence in rural Kenyan children . We compared diarrhoea rates in 960 children aged < 5 years in 556 households in 12 r and omly selected intervention villages and six r and omly selected comparison villages during weekly home visits over an 8-week period . On multivariate analysis , chlorinating stored water [ relative risk ( RR ) 0.44 , 95 % confidence interval ( CI ) 0.28 - 0.69 ] , latrine presence ( RR 0.71 , 95 % CI 0.54 - 0.92 ) , rainwater use ( RR 0.70 , 95 % CI 0.52 - 0.95 ) , and living in an intervention village ( RR 0.31 , 95 % CI 0.23 - 0.41 ) , were independently associated with lower diarrhoea risk . Diarrhoea risk was higher among shallow well users ( RR 1.78 , 95 % CI 1.12 - 2.83 ) . Chlorinating stored water , latrines , and rainwater use all decreased diarrhoea risk ; combined interventions may have increased health impact Point of use drinking water treatment with the BioS and filter ( BSF ) allows people to treat their water in the home . The purpose of this research was to document the ability of the Hydraid plastic-housing BSF to reduce diarrheal disease in households who received a BSF in a r and omized controlled trial . The trial of the Hydraid plastic-housing BSF was carried out in rural , mountainous communities in Copan , Honduras during April of 2008 to February of 2009 . A logistic regression adjusting for clustering showed that the incidence of diarrheal disease in children under 5 years was reduced by approximately 45 % ( odds ratio = 0.55 , 95 % confidence interval = 0.28 , 1.10 ) in households that had a BSF compared with those households without a BSF , but this finding fluctuated depending on season and was not statistically significant . Households with a BSF had significantly better drinking water quality regardless of water source or season In developing countries , the burden of diarrhoea is still enormous . One way to reduce transmission of pathogens is by water quality interventions . Solar water disinfection ( SODIS ) is a low-cost and simple method to improve drinking water quality on household level . This paper evaluates the implementation of SODIS in slum areas of Yaoundé , Cameroon . Promoters trained 2,911 households in the use of SODIS . Two surveys with r and omly selected households were conducted before ( N=2,193 ) and after ( N=783 ) the intervention . Using a question naire , interviewers collected information on the health status of children under five , on liquid consumption , hygiene and other issues . Prior to the intervention , diarrhoea prevalence amounted to 34.3 % among children . After the intervention , it remained stable in the control group ( 31.8 % ) but dropped to 22.8 % in the intervention group . Households fully complying with the intervention exhibited even less diarrhoea prevalence ( 18.3 % ) and diarrhoea risk could be reduced by 42.5 % . Multivariate analyses revealed that the intervention effects are also observed when other diarrhoea risk factors , such as hygiene and cleanliness of household surroundings , are considered . According to the data , adoption of the method was associated with marital status . Findings suggest health benefits from SODIS use . Further promotional activities in low-income setting s are recommended Vitamin A deficiency ( VAD ) persists in Ug and a and the consumption of β-carotene-rich orange sweet potato ( OSP ) may help to alleviate it . Two large-scale , 2-y intervention programs were implemented among Ug and an farmer households to promote the production and consumption of OSP . The programs differed in their inputs during year 2 , with one being more intensive ( IP ) and the other being reduced ( RP ) . A r and omized , controlled effectiveness study compared the impact of the IP and RP with a control on OSP and vitamin A intakes among children aged 6 - 35 mo ( n = 265 ) and 3 - 5 y ( n = 578 ) , and women ( n = 573 ) , and IP compared with control on vitamin A status of 3- to 5-y-old children ( n = 891 ) and women ( n = 939 ) with serum retinol < 1.05 μmol/L at baseline . The net OSP intake increased in both the IP and RP groups ( P < 0.01 ) , accounting for 44 - 60 % of vitamin A intake at follow-up . The prevalence of inadequate vitamin A intake was reduced in the IP and RP groups compared with controls among children 6 - 35 mo of age ( > 30 percentage points ) and women ( > 25 percentage points ) ( P < 0.01 ) , with no differences between the IP and RP groups of children ( P = 0.75 ) or women ( P = 0.17 ) . There was a 9.5 percentage point reduction in prevalence of serum retinol < 1.05 μmol/L for children with complete data on confounding factors ( n = 396 ; P < 0.05 ) . At follow-up , vitamin A intake from OSP was positively associated with vitamin A status ( P < 0.05 ) . Introduction of OSP to Ug and an farming households increased vitamin A intakes among children and women and was associated with improved vitamin A status among children The impact on vitamin A deficiency ( VAD ) , wasting malnutrition , and excessive childhood mortality of two alternative approaches-nutrition education and mega-dose capsule distribution ( 6 - 12-month-olds : 100,000 IU ; 1 - 5-year-olds : 200,000 IU)-in communities in Nepal are compared . Approximately 40,000 children from 75 locations in seven districts in two ecological setting s ( lowl and and hills ) took part in the study and were r and omly allocated to intervention cohorts or a control group . At 24 months after the implementation of the project the reduction of risk for xerophthalmia was greater among children whose mothers were able to identify vitamin-A-rich foods ( relative risk ( RR ) = 0.25 ; 95 % confidence interval ( CI ) = 0.10 - 0.62 ) than among the children who received mega-dose capsules ( RR = 0.59 ; 95 % CI = 0.41 - 0.84 ) . The risk of mortality at 2 years was reduced for both the nutrition education ( RR = 0.64 ; 95 % Cl = 0.48 - 0.86 ) and capsule distribution ( RR = 0.57 ; 95 % CI = 0.42 - 0.77 ) cohorts . The nutrition education programme was , however , more expensive to deliver than the capsule distribution programme . High rates of participation for children in the supplementation programme were achieved quickly . The nutrition education messages also spread rapidly throughout the study population ( regardless of intervention cohort assignment ) . Practice s , however , were slower to change . In communities where maternal literacy was low and channels of communication were limited the capsule distribution programme appeared to be more economical . However , there are economies of scale for nationwide education programmes that do not exist for capsule distribution programmes . Although nutrition education provides economies of scale and the promise of long-term sustainability , a comprehensive national programme requires both dietary supplementation and nutrition education components Abstract Objective : To evaluate the effect of a nutrition improvement project based on home garden production and nutrition education on morbidity from acute respiratory infection and diarrhoeal disease in preschool children . Design : The morbidity survey comprised five data collection s undertaken by trained interviewers to ascertain the incidence and severity of respiratory infections and the incidence of diarrhoeal disease in children in two communes . Setting : A project commune and a control commune in Vietnam . Subjects : Preschool children to 6 years of age living in the project commune Khai Xuan ( average 469 children ) and the control commune Ching Cong ( average 251 children ) . Main outcome measures : Differences between the two communes over time in the incidence and severity of respiratory infections and the incidence of diarrhoeal disease . Results : In Khai Xuan there was a significant reduction ( P<0.0001 ) in the incidence of respiratory infections ( from 49.5 % to 11.2 % ) and diarrhoeal infections ( 18.3 % to 5.1 % ) ; the incidence of pneumonia and severe pneumonia was also significantly reduced ( P<0.0001 ) . In Ching Cong there was no significant change in the incidence and severity of respiratory disease nor in the incidence of diarrhoeal disease . Conclusions : These findings emphasise the successful health outcome of a nutrition project based on household food production and nutrition education and the value of evaluating nutrition projects by reference to measurable health outcomes . Key messages Deficiencies of protein energy and a number of micronutrients compromise the immune system and , in many cases , the integrity of epithelial tissues , which lowers defences to pathogenic invasion The implementation of a nutrition project , focusing on household food production and nutrition education , significantly reduced the incidence and severity of acute respiratory infections and the incidence of diarrhoeal disease in preschool children in a rural commune in Vietnam Nutrition improvement should be widely adopted as a strategy for infectious disease control in international and national development programmes , especially in those countries where respiratory and diarrhoeal infections are the major cause of morbidity and mortality in young |
14,019 | 23,597,822 | CONCLUSIONS Most interventions targeted physical activity and /or diet behavioral modification in Latinas and were led by bicultural/bilingual professionals . | CONTEXT Latinos have one of the highest prevalences of obesity in the U.S. Efforts to address U.S. Latino health have exp and ed to include obesity prevention and treatment initiatives .
The objectives of this review were to ( 1 ) conduct a systematic review of obesity-related treatment interventions targeting U.S. Latino adults and ( 2 ) develop evidence -based recommendations to inform culturally relevant strategies for obesity treatment targeting U.S. Latino adults . | OBJECTIVE : To evaluate the effectiveness of a culturally appropriate lifestyle intervention combined with orlistat in producing weight loss with obese Mexican-American women . SUBJECTS : Mexican-American women ( N=108 ) , aged 21–65 y , with a body mass index ( BMI ) ≥27 kg/m2 were r and omized to 1 y of treatment with orlistat and a culturally tailored lifestyle modification intervention ( OLM ; n=56 ) or a wait-list control group ( WLC ; n=52 ) . DESIGN : A r and omized , controlled , open-label 12-month study . Orlistat was dosed at 120 mg , three times per day . The OLM intervention included behavior modification , a low-fat ( ≤30 % of total daily calories ) diet , and moderate physical activity ( ≥150 min/week).MEASUREMENT : Primary outcomes included changes in body weight ( kg ) , BMI , waist circumference , blood pressure , glucose , and lipids . RESULTS : A total of 72 ( 37 OLM , 35 WLC ) and 66 participants ( 32 OLM , 34 WLC ) completed the 6- and 12-month follow-ups , respectively . Repeated- measures ANOVA demonstrated a significant time × treatment interaction ( Wilks ' λ=12.61 ; P<0.001 ) , indicating that OLM-treated patients achieved significant weight loss relative to the WLC group during the study ( mean percentage weight loss±s.e.m . ; −8.1%±1.2 vs −1.6%±0.7 at 6 months and −8.8%±1.5 vs −0.2%±1.0 at 12 months , respectively ) . OLM-treated patients also experienced significant reductions in waist circumference , low-density-lipoprotein , and total cholesterol . CONCLUSIONS : This study demonstrates the effectiveness of an intervention combining orlistat and lifestyle modification with Mexican-American women , a population with substantial risk for obesity PURPOSE The purpose of this study was to evaluate the effects of a culturally sensitive diabetes education program for Hispanics with type 2 diabetes . METHODS This study is a prospect i ve cohort study to test the impact of a comprehensive diabetes education program on blood glucose control on Hispanics with type 2 diabetes . The educational program focused on maintaining glycemic control and general aspects of managing diabetes and complications . The study participants were recruited by flyers placed in Hispanic markets and in ambulatory care clinics . A total of 34 Hispanic male and female subjects with type 2 diabetes participated in the study . The concentrations of glucose , insulin , hemoglobin A1c ( HbA1c ) , total cholesterol , triglycerides , low-density lipoprotein and high-density lipoprotein ( HDL ) cholesterol were analyzed at baseline and at 3 months . RESULTS A significant mean change was observed for HbA1c , fasting plasma glucose , cholesterol/HDL ratio , and HDL after 3 months of education compared with baseline . There were significant reductions in weight , total fat , percent fat , trunk fat , and waist-to-hip ratio compared with baseline . After 3 months , subjects showed a significant positive correlation between changes in body mass index and insulin and weight , total fat , trunk fat , and fat free mass and insulin . CONCLUSIONS A culturally sensitive program conducted in Spanish had a significant impact on important clinical parameters in Hispanic subjects with diabetes in a relatively short time period . The study demonstrates the importance of design ing education intervention studies that are sensitive to cultural diversity , particularly in at-risk diabetic subjects This study tested the effects of an exercise and diet modification training program for weight loss among Latinas . Forty four obese women were assigned to an experimental training group ( n = 22 ) or a control ( n = 22 ) , at r and om . One session per week for eight weeks included instruction for diet modification and walking for exercise , and all women were led in 20 min of walking during each session . Instruction was provided by a bi-cultural Spanish-speaking physician . Statistically significant ( P < 0.05 ) decreases , relative to controls , were obtained for Body Mass Index , waist to hip ratio , and serum cholesterol . Significant increases were obtained for fitness , exercise rate and frequency , and diet/exercise knowledge . Results suggest that the training was effective for decreasing obesity and increasing fitness among Low SES , Mexican-American women . Implication s for weight control and disease prevention among under-served population s are discussed The increasing prevalence of diabetes and obesity , growing health disparities , and shortage of bilingual and culturally trained health care professionals underscore the role of trained community health workers ( CHWs ) to provide economically sustainable and culturally relevant services . This prospect i ve r and omized design evaluated the relative effectiveness of a CHW intervention among Hispanic persons with newly diagnosed type 2 diabetes , as compared with usual clinic practice in three inner-city health centers . In sum , 189 Hispanic patients newly diagnosed with type 2 diabetes were r and omly assigned to one of three 6-month diabetes management approaches — CHW , case management , and st and ard provider care— and assessed for diabetes-related health measures and clinical indicators at baseline and postintervention . Participants in the CHW group achieved greater improvements than did the controls in program measures : health status , emergency department utilization , dietary habits , physical activity , and medication adherence . They also had 2.9 times greater odds of decreasing body mass index OBJECTIVE To examine associations of diet with acculturation among Hispanic immigrants from Mexico to Washington state and to compare dietary patterns of Hispanic with non-Hispanic white residents . DESIGN Data are part of the baseline assessment for a community-r and omized cancer prevention trial . The Fat-Related Diet Habits question naire and the National 5-A-Day for Better Health program dietary assessment instruments were used to collect data on fat and fruit and vegetable intake , respectively . Data were also collected on demographic characteristics and acculturation status . SUBJECTS/ SETTING A total of 1,689 adult Hispanic and non-Hispanic white residents of 20 communities in the Yakima Valley , WA , completed in-person interviews . STATISTICAL ANALYSES PERFORMED Mixed model regression analyses tested associations of acculturation with diet . These models compared the fat and the fruit and vegetable intake of Hispanics vs non-Hispanic white residents . Additional analyses compared the diets of highly acculturated Hispanics with low-acculturated Hispanics . All models included age , sex , income , and education and were also adjusted for the r and om effect of community . RESULTS Dietary patterns varied by ethnicity and acculturation status . On average , compared with non-Hispanic white residents , Hispanics consumed one more serving of fruits and vegetables per day ( P<.001 ) . Dietary habits changed as Hispanics acculturated to the United States . Highly acculturated Hispanics ate fewer servings of fruits and vegetables per day compared with those not highly acculturated ( P<.05 ) . Highly acculturated Hispanics had slightly higher , but not statistically significant , scores on the Fat-Related Diet Habits question naire , which corresponds to a higher fat intake , compared with low-acculturated Hispanics . The early dietary changes made on acculturation included adding fat at the table to breads and potatoes . APPLICATIONS/ CONCLUSIONS Nutrition professionals should encourage their Hispanic clients to maintain their traditional dietary practice s , such as a high intake of fruits and vegetables and eating bread and potatoes without added fat OBJECTIVES Our community-academic partnership employed community-based participatory research to develop and pilot a simple , peer-led intervention to promote weight loss , which can prevent diabetes and eliminate racial/ethnic disparities in incident diabetes among overweight adults with prediabetes . METHODS We recruited overweight adults at community sites , performed oral glucose tolerance testing to identify persons with blood glucose levels in the prediabetes range , and r and omized eligible people to a peer-led lifestyle intervention group or delayed intervention in 1 year . Outcomes , including weight , blood pressure , and health behaviors , were measured at baseline and 3 , 6 , and 12 months . RESULTS More than half of those tested ( 56 % , or 99 of 178 ) had prediabetes and enrolled in the study . Participants were predominantly Spanish-speaking , low-income , undereducated women . The intervention group lost significantly more weight than the control group and maintained weight loss at 12 months ( 7.2 versus 2.4 pounds ; P < .01 ) . One fourth ( 24 of 99 ) of participants progressed to diabetes . CONCLUSIONS In underserved minority communities , prediabetes prevalence may be higher than previously reported . Low-cost , community-based interventions can succeed in encouraging weight loss to prevent diabetes Background Diabetes outcomes are worse for underserved patients from certain ethnic/racial minority population s. Telephonic disease management is a cost-effective strategy to deliver self-management services and possibly improve diabetes outcomes for such patients . Objective We conducted a trial to test the effectiveness of a supplemental telephonic disease management program compared to usual care alone for patients with diabetes cared for in a community health center . Design R and omized controlled trial . Participants All patients had type 2 diabetes , and the majority was Hispanic or African American . Most were urban-dwelling with low socioeconomic status , and nearly all had Medicaid or were uninsured . Measurements Clinical measures included glycemic control , blood pressure , lipid levels , and body mass index . Vali date d surveys were used to measure dietary habits and physical activity . Results A total of 146 patients were r and omized to the intervention and 149 to the control group . Depressive symptoms were highly prevalent in both groups . Using an intention to treat analysis , there were no significant differences in the primary outcome ( HbA1c ) between the intervention and control groups at 12 months . There were also no significant differences for secondary clinical or behavioral outcome measures including BMI , systolic or diastolic blood pressure , LDL cholesterol , smoking , or intake of fruits and vegetables , or physical activity . Conclusions A clinic-based telephonic disease management support for underserved patients with diabetes did not improve clinical or behavioral outcomes at 1 year as compared to patients receiving usual care alone The beneficial effects of moderate-intensity exercise on cardiorespiratory fitness and body composition are well documented , with the greatest health benefits reported in sedentary individuals who engage in moderate levels of exercise . The published literature contains no quantification of the threshold of lower limits of beneficial exercise or estimates of benefits derived from lower exercise levels . The specific aim of this study was to compare the effects of two walking frequencies , holding intensity and duration constant , on blood lipids , body composition , and exercise maintenance regimens of Mexican American women . A quasi-experimental design , with two treatment groups and one comparison group , was used to explore the dose-response effects of low-intensity exercise on cardiovascular outcomes . Significant interactions were found between walking and total serum cholesterol and skin-fold sums . This study demonstrated the clinical efficacy of a low-intensity exercise regimen on cardiovascular risk factors and exercise adherence A pilot study was conducted to determine if a nutritional intervention aim ed at portion control leads to significant weight loss in a community of low-income Mexican American women . Nineteen low-income Mexican American women were r and omized to a st and ard care group or an intervention group in portion control . The trial was 20 weeks in length , and the intervention included four 2-hour classes . Both interventions were administered by a certified nurse-midwife ( CNM ) and a promotora de salud ( i.e. , lay health advisor ) . Women in the intervention group lost more weight than women in the st and ard care group , though this difference was not statistically significant . The mean weight loss in the intervention group was 6.57 pounds ( 2.9 kg ) compared to a mean weight loss of 2.8 pounds ( 1.3 kg ) in the st and ard care group ( P = .47 ) . Mean weight loss , regardless of group , was significantly greater when participants reported self-weighing ( P = .02 ) . This pilot study in portion control for low-income Mexican American women merits further study Current knowledge is scarce on Latino dietary practice s. This study compared the dietary practice s , alcohol consumption , and smoking behavior of Latinos and non-Latino whites in two r and omly selected sample s. Telephone surveys of adults 35 - 74 years of age from the Kaiser Permanente Medical Care Program ( Latinos = 844 ; non-Latino whites = 510 ) and from census tract-based areas ( Latinos = 806 ; non-Latino whites = 436 ) were conducted in the San Francisco Bay Area . Latino ethnicity was a significant predictor of dietary and alcohol consumption practice s in multivariate logistic regression models after adjustment for sex , education , age , employment , health insurance , martial status , county of residence , and self-perceived health status . Compared with non-Latino whites , Latinos were significantly less likely to report eating vegetables and more likely to eat rice , beans , and fried foods and to drink whole milk . Less acculturated Latinos were more likely to eat fruits , rice , beans , meat , and fried foods and to drink whole milk than more acculturated Latinos . Latino men were significantly more likely to be binge drinkers , and Latina women were significantly more likely to abstain from drinking alcohol during the month prior to the interview . As Latina women acculturate to the U.S. mainstream , they report more cigarette smoking and alcohol consumption . Although Latinos reported higher levels of selected high-fiber foods , the low consumption of vegetables , widespread use of saturated fat , and the heavy drinking and smoking among Latino men , which are associated with the level of acculturation , may increase the risk for cancer . Educational messages targeting less acculturated Latinos should focus on maintaining their current healthy dietary practice s of eating fruits , rice , and beans and decreasing their fat consumption . For more acculturated Latinos , emphasis should be placed on resuming the traditional diet OBJECTIVES This report presents health statistics from the 2007 National Health Interview Survey ( NHIS ) for the civilian noninstitutionalized adult population , classified by sex , age , race and ethnicity , education , family income , poverty status , health insurance coverage , marital status , and place and region of residence . Estimates are presented for selected chronic conditions and mental health characteristics , functional limitations , health status , health behaviors , health care access and utilization , and human immunodeficiency virus testing . Percentages and percent distributions are presented in both age adjusted and unadjusted versions . SOURCE OF DATA NHIS is a household , multistage probability sample survey conducted annually by interviewers of the U.S. Census Bureau for the Centers for Disease Control and Prevention 's National Center for Health Statistics . In 2007 , data were collected on 23,393 adults in the Sample Adult question naire . The conditional response rate was 78.3 % , and the final response rate was 67.8 % . The health information for adults in this report was obtained from one r and omly selected adult per family . In very rare instances where the sample adult was not able to respond for him- or herself , a proxy was used . HIGHLIGHTS In 2007 , 61 % of adults 18 years of age or over reported excellent or very good health . Sixty-one percent of adults never participated in any type of vigorous leisure-time physical activity , and 15 % of adults did not have a usual place of health care . Eleven percent of adults had been told by a doctor or health professional that they had heart disease , and 23 % had been told on two or more visits that they had hypertension . Twenty percent of all adults were current smokers and 21 % were former smokers . Based on estimates of body mass index , 35 % of adults were overweight and 26 % were obese Mexican Americans are more likely to be obese than non-Hispanic whites , yet little research has been conducted on the treatment of obesity in Mexican Americans . The purpose of this study was to compare a family-based intervention with a traditional program oriented to the individual for achieving weight loss by obese Mexican American women . A total of 168 obese women were r and omly assigned to one of three groups . Group 1 served as a comparison group and received only printed material s on nutrition , exercise , and behavioral principles for weight loss . Subjects in the individual group ( group 2 ) received the same printed information , but they also attended classes led by bilingual registered dietitians . Subjects in the family group ( group 3 ) received material s and attended classes that emphasized a family-oriented approach to making changes in eating habits and exercise behavior . Spouses and children attended classes with subjects in this group . Results revealed a significant linear trend in both body mass index and weight reduction across the groups , with losses greatest in the family group , followed by the individual group , and least in the comparison group . Both the individual and the family groups lost significantly more weight than the comparison group , although the difference between these two groups was not statistically significant . The results suggest that a culturally and linguistically appropriate program can achieve significant weight reduction among Mexican Americans . More research should be conducted on the effects of family and other types of social support on weight loss by Mexican Americans OBJECTIVE To evaluate a culturally appropriate intervention to increase activity in overweight Mexican American women . METHODS Participants were r and omly assigned to a physical activity program or wait-list control . RESULTS Treated participants were not more active than controls at 6 or 12 months . In addition , we found no significant differences in the proportion of individuals who met an objective criterion for physical activity from baseline to 6 months in the treatment or control groups . CONCLUSION The intervention did not increase physical activity in this population . Differences in baseline activity and contamination of the control group may partially account for the outcome |
14,020 | 19,956,160 | Results : We found some evidence that interventions delivered to individuals modestly increase cancer awareness in the short term and insufficient evidence that they promote early presentation .
We found limited evidence that public education campaigns reduce stage at presentation of breast cancer , malignant melanoma and retinoblastoma .
Conclusions : Interventions delivered to individuals may increase cancer awareness .
Interventions delivered to communities may promote cancer awareness and early presentation , although the evidence is limited | Background : Low cancer awareness contributes to delay in presentation for cancer symptoms and may lead to delay in cancer diagnosis .
The aim of this study was to review the evidence for the effectiveness of interventions to raise cancer awareness and promote early presentation in cancer to inform policy and future research . | BACKGROUND Rates of malignant melanoma are rising , with those people with sun-sensitive skin most at risk . Health education interventions are needed to help people protect themselves by detecting early signs of melanoma and by protecting their skin from sunburn . This study aim ed to evaluate the impact of an interactive multimedia intervention " Skinsafe " on patients ' knowledge about melanoma and on their skin protective behaviors . METHODS In this cluster-r and omized , controlled trial conducted in Nottinghamshire , UK , doctors and nurses in 5 family practice s prescribed Skinsafe to patients with higher risk skin characteristics . Measures of melanoma knowledge , perceived risk of melanoma and reported skin protective behaviors were obtained at baseline and at 6-month follow-up from 259 patients receiving the intervention and 330 patients with higher risk skin characteristics in 5 matched control practice s. RESULTS AND DISCUSSION Participants had low levels of melanoma knowledge at baseline . At follow-up , the intervention group had higher knowledge scores than control ( 3.71 vs. 3.03 , P < or = 0.001 ) , reported more protective skin behaviors ( 5.36 vs. 5.06 , P = 0.007 ) and were more likely to report mole checking ( odds ratio 1.67 , 95 % CI 1.04 to 2.70 , P = 0.035 ) . The Skinsafe intervention was evaluated positively by patients and could be used to support melanoma health education within clinical setting OBJECTIVES This study assessed whether the Learn , Share & Live breast cancer education program result ed in favorable , replicable , and sustainable outcomes . METHODS The program was implemented at index ( year 1 ) and replication ( year 2 ) sites . Baseline interviews ( year 1 ; n = 240 ) and 2 follow-up telephone interviews ( years 2 and 3 ; n = 337 and 323 ) were used to assess postintervention changes . RESULTS From baseline to year 2 , mammography adherence and stage of adoption improved at the index site relative to the replication site . Knowledge scores and percentages of respondents reporting that a friend had spoken with them about mammography improved significantly . Improvements were sustained through year 3 ( 2 years postintervention ) . In year 3 , replication participants showed improvements in regard to knowledge and perceived mammography benefits , and there was a trend toward increased adherence . Site differences in postintervention adherence may have stemmed from respective choices of follow-up activities . CONCLUSIONS The study outcomes affirm the impact of Learn , Share & Live , indicating a replicated and sustained program effect . Future studies should continue longer follow-up and explore the importance of providing mammography opportunities along with education Objective : We aim ed to develop and vali date a measurement tool to assess cancer awareness in the general population : the cancer awareness measure ( CAM ) . Methods : Items assessing awareness of cancer warning signs , risk factors , incidence , screening programmes and attitudes towards help seeking were extracted from the literature or generated by expert groups . To determine reliability , the CAM was administered to a university participant panel ( n=148 ) , with a sub- sample ( n=94 ) completing it again 2 weeks later . To establish construct validity , CAM scores of cancer experts ( n=12 ) were compared with those of non-medical academics ( n=21 ) . Finally , university students ( n=49 ) were r and omly assigned to read either a cancer information leaflet or a leaflet with control information before completing the measure , to ensure the CAM was sensitive to change . Results : Cognitive interviewing indicated that the CAM was being interpreted as intended . Internal reliability ( Cronbach 's α=0.77 ) and test – retest reliability ( r=0.81 ) were high . Scores for cancer experts were significantly higher than those for non-medical academics ( t(31)=6.8 , P<0.001 ) . CAM scores were higher among students who received an intervention leaflet than the control leaflet ( t(47)=4.8 , P<0.001 ) . Conclusions : These studies show the psychometric properties of the CAM and support its validity as a measure of cancer awareness in the general population BACKGROUND The objective was to determine the impact of a multimedia device offering information about malignant melanoma on public knowledge , attitudes , and behaviors . METHODS Two municipalities in Sweden , Dalby and S S and by , were chosen . The population of Dalby was exposed to the multimedia program during 1994 - 97 , whereas the S S and by population was not . A question naire was sent to r and om sample s of the population s ( 10 % of those aged 20 - 59 years ) before ( 1994 , n = 373 and n = 409 , respectively ) and after the intervention ( 1996 , n = 375 and n = 418 , respectively ) . Response rates were 74 - 89 % . RESULTS The groups were well balanced at baseline . In both areas women scored higher both at baseline and in 1996 . Dalby women showed less fear of skin cancer in 1996 than in 1994 ( 2.13 vs 2.27 , p < 0.01 ) . This was not so in the controls . There was no major change in " sun behavior " in Dalby , whereas there was a negative change in S S and by . After the intervention Dalby men had more " knowledge " ( from 2.64 to 2.70 , p < 0.05 ) and a tendency to better " sun behavior " ( from 1.77 to 1.85 , p = 0.076 ) . There was no significant change over time in the S S and by men . CONCLUSIONS The multimedia program had a modest effect . The population in Dalby had more knowledge and changed its attitudes in a sun-protective direction . In the control area , the two-year follow-up sun behavior score was lower than at baseline . There was also significantly less fear of skin cancer after the intervention Is no evidence better than any evidence when controlled studies are unethical ? Rigorous evidence on the health effects of social interventions is scarce1 2 despite calls for more evidence from r and omised studies .3 One reason for the lack of such experimental research on social interventions may be the perception among research ers , policymakers , and others that r and omised design s belong to the biomedical world and that their application to social interventions is both unethical and simplistic.4 Applying experimental design s to social interventions may be problematic but is not always impossible and is a desirable alternative to uncontrolled experimentation.3 However , even when r and omised design s have been used to evaluate social interventions , opportunities to incorporate health measures have often been missed.5 For example , income supplementation is thought to be a key part of reducing health inequalities,6 but rigorous evidence to support this is lacking because most r and omised controlled trials of income supplementation have not included health measures .5 Current moves to increase uptake of benefits offer new opportunities to establish the effects of income supplements on health . In attempting to design such a study , however , we found that r and omised or other controlled trials were difficult to justify ethically , and our eventual design was rejected by funders . # # # # Box 1 Attendance allowance A pilot study carried out by one of us ( RH ) showed substantial health gains among elderly people after receipt of attendance allowance . We therefore decided to pursue a full scale study of the health effects of income supplementation . Men over the age of 45 present with thicker , more advanced melanomas than younger people . A r and omised trial was conducted in this group to evaluate whether an educational brochure would increase knowledge about melanoma and the ability to recognise and discriminate between pigmented skin lesions . Men in an industrial complex were allocated to an intervention group ( n = 110 ) and two control groups ( n = 96 and n = 108 ) . The intervention group was given two educational brochures about melanoma . Their effect on knowledge and ability to detect pigmented lesions was assessed by a question naire and a self-examination body chart given before the brochure , and at four weeks and three months after return of the brochure . The control groups did not receive any educational material , but control group 2 received the question naire and chart . At the end of the study all participants were examined for pigmented lesions by doctors , whose counts were compared with those of the participants . There was a significant ( 19.8 per cent ) increase in knowledge about melanoma in the intervention group ( but not in the control groups ) , except for discrimination of photos of benign and malignant lesions . The educational material did not improve the ability of those in the intervention group to recognise and count their pigmented lesions nor to discriminate between benign and malignant pigmented lesions . The increased knowledge about melanoma was retained for at least three months BACKGROUND Since it is widely accepted that the earlier cancer is detected , the better the chances of treatment and survival , people should be encouraged to create positive intentions toward early detection of several types of cancer , for instance , skin cancer , breast cancer , and colon cancer . This can be done by being alert to the warning signs of cancer and seeking help once a cancer symptom is detected . METHODS A r and omized controlled study ( n = 1,500 ) assessed the effects of computer-tailored information and general information on determinants and intentions to engage in early detection behaviors ( i.e. , passive detection and help seeking ) compared with those in a control group . Possible negative side effects , like increased chronic fear of cancer and more fatalistic attitudes toward cancer , were studied as well . RESULTS Shortly after the intervention , differences between the study groups were found in intention , several social psychological determinants , and knowledge . Six months after the intervention , there were still differences between the tailored information group and the control group in intentions toward help seeking . Neither of the interventions result ed in increased chronic fear nor more fatalistic attitudes toward cancer . CONCLUSIONS It is concluded that there were positive effects of the tailored intervention on determinants , passive detection , and help-seeking intentions in the short-term , but additional research is needed to assess ways of maintaining these effects in the long-term CONTEXT Although evidence -based guidelines recommend that physicians inform men about prostate cancer screening , the most efficient way to do this is not known . OBJECTIVE To evaluate whether a mailed educational pamphlet affected men 's knowledge about early detection of prostate cancer . DESIGN R and omized , controlled trial . SETTING Primary care clinic of the Minneapolis VA Medical Center . PATIENTS 342 men at least 50 years of age who responded to a mailed survey ( overall response rate , 68 % ) and did not report a history of prostate cancer . INTERVENTION " Early Prostate Cancer " pamphlet mailed to patients in the intervention group 1 week before their scheduled clinic appointments . OUTCOME MEASURES Patients ' responses to a survey mailed 1 week after their clinic appointments ; prostate-specific antigen ( PSA ) testing determined from electronic medical records . RESULTS Respondents were predominantly elderly white men ( mean age , 71 years ; 90 % white ) with chronic illnesses ( 48 % described their health as " fair " or " poor " ) . Men who received the educational pamphlet were better informed than men in the usual care group , as measured by correct responses to the following three questions about prostate cancer screening : the natural history of prostate cancer ( 32 % vs. 24 % ; P = 0.10 ) , whether treatment lengthens lives of men with early prostate cancer ( 56 % vs. 44 % ; P = 0.04 ) , and accuracy of PSA testing ( 46 % vs. 27 % ; P < 0.008 ) . The overall proportion of correctly answered questions was greater in the intervention group ( 45 % vs. 32 % ; P < 0.001 ) . Testing for PSA in the year after the index clinic appointments did not differ significantly between the intervention group and the usual care group ( 31 % vs. 37 % ; P > 0.2 ) . CONCLUSIONS Male veterans are poorly informed about the potential benefits and risks of prostate cancer screening . Although our mailed educational pamphlet enhanced knowledge only modestly , it was an inexpensive and easily implemented intervention Study aim was to determine the influence of a patient information leaflet ( PIL ) on mouth cancer to improve knowledge , reduce distress and increase intention to accept a mouth screen over a 2-month period . The design was a r and omised controlled trial . Two dental practice s in the northwest of Engl and participated . St and ardised multi-item scales of the three outcome measures were employed . The PIL was given to a r and omised intervention group of patients in waiting room . Single sheet question naire was completed by both groups of patients at baseline in waiting room ( immediately following leaflet administration in intervention arm of study ) . Repeat question naire completion at 8 weeks by all patients through postal system . Mann-Whitney U-tests comparing outcome variables between patients with and without access to the leaflet at baseline and 8 weeks were performed . Multiple logistic regression was used to predict re-reading of the leaflet at home . Useable replies were received from 317 patients ( 60 % response rate ) . All measures showed some benefit of immediate exposure to the leaflet at follow up . Older patients , less initial knowledge , and self-reported smoking positively predicted the re-reading of the leaflet . The introduction of a mouth cancer PIL into dental practice may help to inform patients about oral cancer , moderate distress and encourage acceptance of an oral health screen As part of its strategy to identify cancer cases in a rural population , the cancer registry of Barshi , India , has developed a methodology which includes education of the population about likely symptoms of cancer , and motivation of symptomatic individuals to undergo medical investigation . Patients with cervical cancer from the registry area who attended Barshi Cancer Hospital ( 84 % of the total ) showed a significant improvement in stage at diagnosis between 1988 - 1989 ( 38 % in stages I and II ) and 1990 - 1992 ( 51 % in stages I and II ) . No change was observed in those attending the same hospital from a control area ( 38 % vs. 34 % ) . Among a r and om sample of the population of the registry area , 76 % of women were aware of the symptoms of cervical cancer , compared with 25 % of the population of control areas . It is suggested that action to raise awareness of symptoms of cancer , and to encourage medical consultation , should form an important initial component of cervical-cancer control programmes BACKGROUND Most women are not getting regular mammograms , and there is confusion about several mammography-related issues , including the age at which women should begin screening . Numerous groups have called for informed decision making about mammography , but few programs have result ed . Our research is intended to fill this gap . METHODS We conducted a r and omized controlled trial , which ran from 1997 to 2000 . Women aged 40 to 44 and 50 to 54 , who were enrolled in Blue Cross Blue Shield of North Carolina , were r and omly assigned to one of three groups : usual care ( UC ) , tailored print ( TP ) material s , or TP plus tailored telephone counseling ( TP+TC ) . We assessed the impact of tailored interventions on knowledge about breast cancer and mammography , accuracy of breast cancer risk perceptions , and use of mammography at two time points after intervention-12 and 24 months . RESULTS At 12 and 24 months , women who received TP+TC had significantly greater knowledge and more accurate breast cancer risk perceptions . Compared to UC , they were 40 % more likely to have had mammograms ( odds ratio=0.9 - 2.1 ) . The effect was primarily for women in their 50s . TP had significant effects for knowledge and accuracy , but women who received TP were less likely to have had mammography . CONCLUSIONS Decision-making interventions , comprised of two tailored print interventions ( booklet and newsletter ) , delivered a year apart , with or without two tailored telephone calls , significantly increased knowledge and accuracy of perceived breast cancer risk at 12 and 24 months post-intervention . The effect on mammography use was significant in bivariate relationships but had a much more modest impact in multivariate analyses We report the first multisite , multicomponent community intervention trial to focus on cancer prevention in African Americans . The project explored the potential of historically black medical schools to deliver health information to their local communities and used a community-based participatory research approach . The intervention consisted of culturally sensitive messages at appropriate educational levels delivered over an 18-month period and tested in predominantly black census tracts in Nashville , TN and Atlanta , GA . Chattanooga , TN and Decatur , GA served as comparison cities . Results were evaluated by pre- and postintervention r and om-digit dial telephone surveys . The intervention cities showed an increase in reported contact with or knowledge of the project . There was little or no effect on knowledge or attitudes in the intervention cities . Compared to Chattanooga , Nashville showed an increase in percentage of women receiving Pap smears . Compared to Decatur , Atlanta showed an increase in percentage of age-appropriate population s receiving digital rectal exams , colorectal cancer screenings and mammograms . The results of this community intervention trial demonstrated modest success and are encouraging for future efforts of longer duration |
14,021 | 24,477,489 | Cortisol levels are high for at least 7 days after stroke .
Elevated cortisol after stroke is associated with dependency , morbidity , and mortality ; however , there is insufficient evidence to conclude that these relationships are independent of stroke severity | Studies in non-stroke patients have shown an association between dysregulation of the hypothalamic – pituitary – adrenal axis and morbidity and mortality .
We conducted a systematic review to evaluate cortisol levels in acute stroke and their associations with outcome . | Introduction Subarachnoid haemorrhage ( SAH ) may damage the hypothalamo-pituitary-adrenal gl and ( HPA ) axis and disturb cortisol metabolism . There are no available data that relates to the response of the HPA axis in the acute phase of SAH . We aim ed to characterise the behavior of serum adrenocorticotropic hormone ( ACTH ) , total cortisol , stimulated total cortisol and free cortisol concentrations in acute aneurysmal SAH . Methods A prospect i ve cohort study was conducted of patients with acute aneurysmal SAH ( n = 30 ) admitted to a tertiary university hospital . Patients admitted for elective aneurysmal surgery ( n = 16 ) served as the control group . An ACTH stimulation test was performed twice during the first week and at three months . The main outcome measure was description of the ACTH-cortisol response by calculating serum free cortisol and measuring total cortisol and ACTH concentrations . A mixed models method was used for testing between the groups , allowing heterogeneity between the groups . Results Patients with SAH had higher initial serum total cortisol ( mean + /- SD ; 793 + /- 312 nmol/L ) and free cortisol concentrations ( 83 + /- 55 nmol/L ) than control patients ( 535 + /- 193 nmol/L , p = 0.001 and 33 + /- 18 nmol/L , p < 0.001 , respectively ) . Thereafter , there were no differences in this respect . Serum free and total cortisol concentrations correlated but were unaffected by the severity of SAH . ACTH concentrations were comparable between SAH and control groups . Patients with Hunt-Hess grade s IV to V had higher ACTH concentrations at day one ( 10.7 + /- 7.1 pmol/l/L ) and day five ( 8.2 + /- 7.7 pmol/L ) than patients with grade I-III ( day one : 3.8 + /- 2.0 pmol/L , p = 0.002 ; day five : 4.7 + /- 1.8 pmol/L , p = 0.04 ) . Conclusions Calculation of serum free cortisol concentration was not helpful in identifying patients with potential hypocortisolism . SAH severity did not affect cortisol concentrations , possibly indicating relative pituitary-adrenal insufficiency in patients with more severe bleeding . Trial registration Clinical Trials.gov Identifier NCT00614887 Background Neuroendocrine changes have been reported after ischemic stroke , subarachnoid hemorrhage , and brain trauma . As there are no corresponding data in patients with intracerebral hemorrhage ( ICH ) we analyzed various neuroendocrine parameters to investigate possible alterations in hormone profiles of patients with ICH . Methods Twenty patients with ICH were prospect ively enrolled in the study . Patients were a priori parted into two groups : Ten non-ventilated patients treated on the stroke-unit ( hemorrhage volumes < 20 ml , “ small ICH ” ) , and 10 ventilated patients treated on the neurocritical care unit ( hematoma volumes > 20 ml with possible additional ventricular involvement ( “ large ICH ” ) . Neuroendocrine parameters were compared between both groups referring to reference values . The following parameters were obtained over a period of 9 days in 20 patients with spontaneous supratentorial ICH : thyrotropin , free thiiodothyronine and thyroxine , human growth hormone , insulin-like growth factor 1 , luteinizing hormone , follicle-stimulating hormone , testosterone , prolactin , adrenocorticotropic hormone , and cortisol . Results Small ICH patients were in a median 71 ( 54–88 ) years old and had a mean ICH volume of 9.5 ± 6.5 ml , whereas large ICH patients were 65 ( 47–80 ) years old and showed a mean volume of 56 ± 30.2 ml . None of the patients revealed pathological alterations for thyrotropin , free thiiodothyronine , thyroxine , human growth hormone , insulin-like growth factor 1 , and testosterone . There was only a mild decrease of adrenocorticotropic hormone and cortisol on day 3 in large ICH patients . Small ICH patients showed pathologically elevated levels of luteinizing and follicle-stimulating hormone throughout the observation period . Large ICH patients showed a marked increase of prolactin that developed during the course . Conclusions Overall , neuroendocrine changes in ICH patients are not as profound as reported for ischemic stroke or subarachnoid hemorrhage . The clinical significance of increased LH and FSH levels in small ICH is unclear , whereas elevation of prolactin in large ICH was anticipated . Future r and omized controlled trials should also focus on neuroendocrine parameters to clarify the impact of possible hormonal alterations on functional outcome Background and Purpose — & agr;-Melanocyte stimulating hormone ( & agr;-MSH ) is an endogenously produced neuropeptide derived from the same precursor as adrenocorticotropic hormone . & agr;-MSH has profound immunomodulatory properties and may also be neuroprotective . Nothing is known about & agr;-MSH and changes in its plasma concentrations in patients with acute ischemic stroke . Methods — In this prospect i ve observational study , plasma concentrations of & agr;-MSH , adrenocorticotropic hormone , cortisol , and interleukin 6 were assessed longitudinally over the course of 1 year after stroke onset in 111 patients . Logistic regression was used to the effect of initial plasma & agr;-MSH , adrenocorticotropic hormone , cortisol , and interleukin 6 on long-term outcome . Results — There was an early decrease in plasma & agr;-MSH in patients with severe stroke ( National Institutes of Health Stroke Scale ≥17 ) that normalized over the course of the year ; these same patients evidence d elevations in plasma cortisol and interleukin 6 . Higher initial plasma & agr;-MSH , but not adrenocorticotropic hormone , cortisol , or interleukin 6 , was independently predictive of good long-term outcome . Conclusions — This research is the first to study endogenous changes in plasma & agr;-MSH after stroke . The independent effect of early plasma & agr;-MSH on stroke outcome , as well as a growing body of experimental data demonstrating improved stroke outcome with exogenous & agr;-MSH administration , suggests a potential therapeutic role for & agr;-MSH in the treatment of stroke Altered hypothalamo-pituitary-adrenal axis was reported in stroke patients ; however , mechanisms responsible for this phenomenon are barely understood . Acute cerebral ischemia triggers interleukin-6 ( IL-6 ) release into blood . Circulating IL-6 can stimulate hypothalamo-pituitary-adrenal axis . The goal of our study was to assess a relationship between serum IL-6 and cortisol in acute ischemic stroke . Twenty two patients with ischemic stroke and 17 controls were included . Serum sample s were collected on the 2nd day of stroke at 6:00 , 10:00 18:00 , 22:00 h and at the same time points in control group . Cytokines and cortisol levels were measured using ELISA method . Serum IL-6 and cortisol levels were higher in stroke patients than in controls . Cortisol displayed diurnal variations in both stroke patients and controls . In contrast with control subjects , serum IL-6 levels did not display diurnal variations in stroke patients . In stroke patients , but not in controls , IL-6 level correlated significantly with cortisol level and morning serum IL-6 level independently predicted evening/night cortisol level . In conclusion , brain ischemia could stimulate IL-6 release in blood and in this way modulate hypothalamo-pituitary-adrenal axis Background and Purpose : Experimental and clinical data suggest that overactivation of the sympathetic nerve system ( SNS ) is an essential mediator of stroke-induced immunodepression , which in turn increases susceptibility to post-stroke infections . In a post hoc analysis of the PANTHERIS ( Preventive Antibacterial Treatment in Acute Stroke ) trial , we investigated the impact of distinct lesion patterns on SNS activation , immunodepression , and frequency of post-stroke infections . Methods : Stroke volume , stress hormone levels , and immune function were determined on day 1 after stroke onset . Stroke localization was grade d using the Alberta Stroke Programme Early CT score ( ASPECTS ) . In univariate analysis , we investigated the impact of clinical ( National Institutes of Health Stroke Scale , NIHSS ) and imaging stroke characteristics ( lesion volume , lateralization , localization grading ) on autonomous nervous system activity ( norepinephrine , cortisol ) , immune competence ( monocytic HLA-DR expression ) , and the frequency of post-stroke infections . In a logistic regression model , we tested for independent factors that might increase susceptibility to post-stroke infections . Results : In a single-factor analysis , large stroke volume , lesions affecting distinct regions of the MCA cortex , and SNS activation ( elevated norepinephrine levels ) were associated with an impaired immune function ( reduced mHLA-DR expression ) and a higher susceptibility to post-stroke infections . Multivariate analysis identified increased levels of norepinephrine and infa rct ion of the anterior MCA cortex as independent risk factors of post-stroke infections . Neither stroke severity nor stroke volume was independently associated with post-stroke infections . Conclusions : Apart from sympathetic activation , our data suggest that ischemic lesion in the anterior MCA cortex may be a major determinant of stroke-associated infection . This finding has to be confirmed in larger prospect i ve studies Assessment s of mood disturbance and “ vegetative ” ( appetite or sleep ) disturbance as well as a single‐dose dexamethasone suppression test ( DST ) were carried out in 25 r and omly selected stroke patients and in 13 nonstroke control patients hosptalized in a rehabilitation center . Prevalence rates of moderate‐to‐sever depression of mood and vegetative disturbance were significantly higher in stroke patients than controls ( 48 % and 52 % versus 0 % and 8 % , respectively ) , as was the prevalence of abnormal DST results ( 52 % versus 8 % ) . Abnormal DST results were associated with the occurrence of moderate to severe mood , appetite , and sleep disturbances among all patients . In 2 stroke patients , repeated DST results paralleled the clinical course . The DST may be useful as an adjunct to the diagnosis and in monitoring the progress of the common and potentially reversible mood and vegetative disturbances occurring after stroke Background / Aim : The cause of elevated blood pressure ( BP ) in acute stroke is unknown . Stress is often suggested as a main contributing factor . We aim ed to investigate the relationship between BP and stress in patients with acute stroke . Methods : 58 patients with clinical symptoms of stroke were recruited prospect ively after exclusion of haemorrhage by CT scan within 14 h and 15 min ( mean ) after symptom onset ( range 2 h and 45 min–23 h and 40 min ) . The mean age of the patients was 66 years ( range 39–86 years ) , and the mean National Institute of Health Stroke Scale score was 7 ( range 1–26 ) . BP and pulse rate were recorded by non-invasive automatic monitoring hourly for 24 h. Stress was evaluated by testing the level of salivary cortisol . Four sample s of saliva were obtained at inclusion , on the evening of the inclusion day ( 20.00–22.00 h ) , on the morning of the next day ( 7.00–9.00 h ) and on the afternoon of the inclusion day/next day ( 15.00–17.00 h ) within 24 h after inclusion in the study . Logarithmic transformation was done for cortisol levels . Results : The 24-hour mean cortisol level ( geometric mean 13.6 nmol/l ) was related to 24-hour mean systolic BP [ SBP ; r = 0.36 , p = 0.01 , multivariate p = 0.02 ] , mean night-time ( 22.00–6.00 h ) SBP ( r = 0.43 , p = 0.001 , multivariate p < 0.005 ) and mean night-time diastolic BP ( r = 0.31 , p = 0.02 , multivariate p = 0.02 ) . Cortisol levels at inclusion ( r = 0.31 , p = 0.02 , multivariate p = 0.05 for 24-hour SBP ) and in the evening were also statistically significantly related to the above BP variables . The morning cortisol ( r = 0.28 , p = 0.04 , multivariate p = 0.04 ) was related to night-time SBP . Conclusions : Salivary cortisol was positively correlated with 24-hour SBP and night-time BP , suggesting that stress is a contributing factor for high BP in acute stroke BACKGROUND Hippocampal volume reduction , declarative memory deficits , and cortisol elevations are reported in persons with major depressive disorder ; however , data linking cortisol elevations with hippocampal atrophy are lacking . Prescription corticosteroid-treated patients offer an opportunity to examine corticosteroid effects on hippocampal volume and biochemistry and memory in humans . METHODS Seventeen patients on long-term prescription corticosteroid therapy and 15 controls of similar age , gender , ethnicity , education , height , and medical history were assessed with magnetic resonance imaging and proton magnetic resonance spectroscopy , the Rey Auditory Verbal Learning Test , Stroop Color Word Test and other neurocognitive measures , the Hamilton Rating Scale for Depression , Young Mania Rating Scale , and Brief Psychiatric Rating Scale . RESULTS Compared with controls , corticosteroid-treated patients had smaller hippocampal volumes and lower N-acetyl aspartate ratios , lower scores on the Rey Auditory Verbal Learning Test and Stroop Color Word Test , and higher Hamilton Rating Scale for Depression and Brief Psychiatric Rating Scale scores . CONCLUSIONS Patients receiving chronic corticosteroid therapy have smaller hippocampal volumes , lower N-acetyl aspartate ratios , and declarative memory deficits compared with controls . These findings support the idea that corticosteroid exposure appears to be associated with changes in hippocampal volume and functioning in humans Recent reports suggest adrenal insufficiency in critically ill patients is common . We found only one case of de novo adrenal insufficiency using admission ACTH injection in 70 selected intensive care unit ( ICU ) patients . R and om serum cortisol levels correlated positively with illness severity in ICU patients using proven methods for assessing illness severity . Those with the highest r and om serum cortisol levels ( greater than 60 micrograms/dl ) had the greatest mortality , while those with lower r and om cortisol levels which stimulated to more than 18 micrograms/dl after ACTH injection had improved outcomes . Based on our results , routine screening for adrenal insufficiency in ICU patients is not warranted . If it is suspected , the cosyntropin test should be performed since low r and om cortisol levels ( even to 5 micrograms/dl ) are not diagnostic of adrenal insufficiency BACKGROUND The adrenal glucocorticoid stress response in humans causes catabolism , increasing blood glucose and heart rate , and possibly potentiates ischaemic damage to neurons . These effects could induce secondary brain damage in acute stroke . MATERIAL S AND METHODS This prospect i ve study was based on a single determination of s-cortisol in 172 patients included within 24 h of stroke onset , 50 % within 12 h of stroke onset . All patients were admitted to hospital within 6 h of stroke onset . We investigated the relations of s-cortisol to neurological deficit measured by Sc and inavian Stroke Scale ( SSS ) , lesion volume on CT-scan , blood glucose on admission , pulse rate , blood pressure , body temperature , deteriorating stroke , cytokines and cytokine receptors , and outcome . RESULTS In a multivariate logistic regression analysis , s-cortisol was independently related to death within 7 days of stroke onset , odds ratio ( OR ) Cortisol(+100 nmol/l ) 1.9 ( 95 % CI 1.01 - 3.8 ) ; serum-cortisol was , however , not a predictor of death or dependency within 3 months . S-cortisol correlated to SSS ( rho=-0.45 , p<0.001 ) , body temperature ( rho=0.27 , p<0.001 ) , pulse rate ( rho=0.26 , p<0.001 ) , and lesion volume ( rho=0.33 , p<0.001 ) . S-cortisol was related to the presence of insular damage . CONCLUSION Acute stroke mortality related to increasing serum-cortisol levels . S-cortisol was associated with stroke severity and markers reflecting stroke severity BACKGROUND Subarachnoid hemorrhage ( SAH ) is a potential cause of hypopituitarism . Most of the studies regarding the relationship between SAH and anterior pituitary function were retrospective and hormonal assessment was performed several months after SAH . AIM To prospect ively evaluate the prevalence of anterior pituitary hormone deficiencies in the acute phase after spontaneous SAH and their possible correlation with clinical and radiological parameters . METHODS Pituitary function was tested in 60 patients within 72 h after spontaneous SAH . RESULTS 56.9 % of the patients showed at least one anterior pituitary hormone deficiency : gonadotropin and GH secretion failure represented the most prevalent hormonal deficiencies ( 33.3 and 22.0 % , respectively ) , whereas ACTH and TSH deficiency was less frequent ( 7.1 and 1.8 % , respectively ) . With the exception of secondary hypogonadism , the prevalence of other pituitary hormone deficiencies is in agreement with previous studies , which evaluated pituitary function on longterm follow up after SAH . No correlation was found between hypopituitarism and clinical status , as assessed with Hunt-Hess and Glascow Coma Scales . Moreover , no correlation was found between hypopituitarism and bleeding severity evaluated with Fisher 's scale . CONCLUSIONS We demonstrated a high prevalence of anterior pituitary hormone deficiencies acutely after SAH . Although part of GH and gonadotropin deficiencies might be a consequence of functional alteration due to SAH itself , the finding of low cortisol levels in this stressful condition strongly suggests the presence of true hypocortisolism . Therefore , an evaluation of pituitary function shortly after SAH might be useful to identify a subset of patients who deserve a more accurate follow-up CONTEXT Evidence for the association of cortisol with mortality or disease events is mixed , possibly due to a failure to consider diurnal cortisol patterns . OBJECTIVE Our objective was to examine the association of diurnal cortisol patterns throughout the day with cardiovascular and noncardiovascular mortality in a community-dwelling population . DESIGN This was a prospect i ve cohort study among 4047 civil servants , the Whitehall II study , United Kingdom . We measured diurnal cortisol patterns in 2002 - 2004 from six saliva sample s obtained over the course of a normal weekday : at waking , + 30 min , + 2.5 h , + 8 h , + 12 h , and bedtime . Participants were subsequently followed for all-cause and cause-specific mortality until January 2010 . PARTICIPANTS Participants included 4047 men and women aged 61 yr on average at baseline . OUTCOMES We assessed all-cause , cardiovascular , and noncardiovascular death . RESULTS There were 139 deaths , 32 of which were deaths due to cardiovascular disease , during a mean follow-up period of 6.1 yr . Flatter slopes in cortisol decline across the day were associated with increased risk of all-cause mortality ( hazard ratio for 1 sd reduction in slope steepness 1.30 ; 95 % confidence interval ( CI ) = 1.09 - 1.55 ) . This excess mortality risk was mainly driven by an increased risk of cardiovascular deaths ( hazard ratio = 1.87 ; 95 % confidence interval = 1.32 - 2.64 ) . The association with cardiovascular deaths was independent of a wide range of covariates measured at the time of cortisol assessment . There was no association between morning cortisol , the cortisol awakening response , and mortality outcomes . CONCLUSIONS These findings demonstrate , for the first time , the relationship between a flatter slope in cortisol levels across the day and an increased risk of cardiovascular disease mortality in a non clinical population |
14,022 | 23,975,736 | Posaconazole had the highest probability of being the most effective agent in reducing IFI risk and all-cause mortality .
CONCLUSIONS IFI prophylaxis has a positive effect on IFI risk reduction .
However , its effect on all-cause mortality is not as pronounced .
The analysis has additionally pinpointed posaconazole as potentially the most effective IFI prophylaxis in neutropenic patients | OBJECTIVES Patients receiving therapy for haematological malignancies have a higher risk of invasive fungal infections ( IFIs ) .
Antifungal prophylaxis is an effective strategy against IFIs , but relative effectiveness estimates across agents are inconclusive .
A mixed treatment comparison ( MTC ) was conducted to estimate the relative effectiveness of all agents for a number of outcomes of interest . | ABSTRACT Invasive fungal infection remains the most common cause of infectious death in acute leukemia . In this open-label , r and omized study , we compared the efficacy and safety of caspofungin with that of intravenous itraconazole for antifungal prophylaxis in patients undergoing induction chemotherapy for acute myelogenous leukemia or myelodysplastic syndrome . Of 200 patients , 192 were evaluable for efficacy ( 86 for itraconazole , 106 for caspofungin ) . Duration of prophylaxis ( median , 21 days [ range , 1 to 38 days ] ) , demographics , and prognostic factors were similar in both groups . Ninety-nine patients completed antifungal prophylaxis without developing fungal infection ( 44 [ 51 % ] with itraconazole , 55 [ 52 % ] with caspofungin ) . Twelve patients developed documented invasive fungal infections , five in the itraconazole group ( four with c and idemia and one with Aspergillus pneumonia ) , and seven in the caspofungin group ( two with c and idemia , two with disseminated trichosporon species , two with Aspergillus pneumonia , and one with disseminated Fusarium spp ) . Two patients in the itraconazole group and four in the caspofungin group died of fungal infection ( P = 0.57 ) . Grade 3 to 4 adverse event rates were comparable between groups ; the most common event in both was reversible hyperbilirubinemia . No evidence of cardiovascular toxicity from intravenous itraconazole was noted among patients older than 60 . In conclusion , intravenous itraconazole and caspofungin provided similar protection against invasive fungal infection during induction chemotherapy , and both drugs were well tolerated Invasive fungal infection ( IFI ) is a serious threat after allogeneic hematopoietic cell transplant ( HCT ) . This multicenter , r and omized , double-blind trial compared fluconazole ( N = 295 ) versus voriconazole ( N = 305 ) for the prevention of IFI in the context of a structured fungal screening program . Patients undergoing myeloablative allogeneic HCT were r and omized before HCT to receive study drugs for 100 days , or for 180 days in higher-risk patients . Serum galactomannan was assayed twice weekly for 60 days , then at least weekly until day 100 . Positive galactomannan or suggestive signs triggered m and atory evaluation for IFI . The primary endpoint was freedom from IFI or death ( fungal-free survival ; FFS ) at 180 days . Despite trends to fewer IFIs ( 7.3 % vs 11.2 % ; P = .12 ) , Aspergillus infections ( 9 vs 17 ; P = .09 ) , and less frequent empiric antifungal therapy ( 24.1 % vs 30.2 % , P = .11 ) with voriconazole , FFS rates ( 75 % vs 78 % ; P = .49 ) at 180 days were similar with fluconazole and voriconazole , respectively . Relapse-free and overall survival and the incidence of severe adverse events were also similar . This study demonstrates that in the context of intensive monitoring and structured empiric antifungal therapy , 6-month FFS and overall survival did not differ in allogeneic HCT recipients given prophylactic fluconazole or voriconazole . This trial was registered at www . clinical trials.gov as NCT00075803 To evaluate the efficacy of itraconazole capsules in prophylaxis for fungal infections in neutropenic patients , we conducted a prospect i ve , double-blind , placebo-controlled , r and omized trial . Patients with hematologic malignancies or those who received autologous bone marrow transplants were assigned either a regimen of itraconazole ( 100 mg orally twice daily ; n=104 ) or of placebo ( n=106 ) . Overall , fungal infections ( superficial or systemic ) occurred more frequently in the placebo group ( 15 % vs. 6 % ; P=.03 ) . There were no differences in the empirical use of amphotericin B or systemic fungal infections . Among patients with neutropenia that was profound ( < 100 neutrophils/mm3 ) and prolonged ( for at least 7 days ) , those receiving itraconazole used less empirical amphotericin B ( 22 % vs. 61 % ; P=.0001 ) and developed fewer systemic fungal infections ( 6 % vs. 19 % ; P=.04 ) . For patients with profound and prolonged neutropenia , itraconazole capsules at the dosage of 100 mg every 12 h reduce the frequency of systemic fungal infections and the use of empirical amphotericin Fungal infections are a major problem in patients with hematologic malignancy . Attempts to reduce their frequency with antifungal agents have not been successful . A double-blind , controlled , single-center trial was conducted with 96 consecutive patients undergoing 154 episodes of chemotherapy . Patients received 400 mg of fluconazole or placebo until bone marrow recovery or initiation of intravenous amphotericin B infusions . End points were amphotericin B use , fungal infection , stable neutrophil count > 0.5 x 10(9)/L , toxicity precluding further fluconazole use , and death . By Kaplan-Meier estimation , the time to initiation of amphotericin B therapy was shorter in 76 patients treated with placebo than in 75 treated with fluconazole ( P = .003 ) . Also , fluconazole reduced the number of febrile days by 20 % ( P = .002 ) and prevented oropharyngeal c and idiasis ( 1/75 vs. 9/76 , P = .018 ) . The frequency of deep mycoses ( 8/76 vs. 8/75 ) and outcome were unaffected . Fluconazole did not have a favorable effect on infection-related health care costs and was associated with prolonged severe neutropenia ( P = .01 ) Liposomal amphotericin ( AmBisome ) 2 mg/kg three times weekly was compared with placebo as prophylaxis against fungal infection in patients undergoing chemotherapy or bone marrow transplantation ( BMT ) for haematological malignancies . Prophylaxis began on day 1 of chemotherapy and continued until neutrophils regenerated or infection was suspected . Of 161 evaluable patients , 74 received AmBisome and 87 received placebo . Proven fungal infections developed in no patients on AmBisome and in three on placebo ( 3.4 % ) ( P = NS ) . Suspected fungal infections requiring intervention with systemic antifungal therapy ( usually amphotericin B ) occurred in 31 patients on AmBisome ( 42 % ) and in 40 on placebo ( 46 % ) ( P = NS ) . Suspected deep-seated infections developed in 21 ( 28.3 % ) and 31 ( 35.6 % ) patients , respectively ( P = NS ) . Time to develop a suspected or proven deep-seated infection showed a trend in favour of AmBisome ( P = 0.11 ) . Fifty patients had fungal colonisation ( 48 with C and ida spp , two with Aspergillus spp ) of at least one body site during prophylaxis ; 15 patients while receiving AmBisome ( 20 % ) and 35 while on placebo ( 40 % ) ( P < 0.01 ) . time to colonisation was significantly delayed in the group receiving ambisome ( P < 0.05 ) . treatment-related toxicity was modest and no additional toxicity was observed in patients receiving ambisome . ambisome 2 mg/kg three times weekly is safe and reduces fungal colonisation in patients receiving intensive chemotherapy or bmt . however , despite encouraging trends , prophylactic ambisome did not lead to a significant reduction in fungal infection or in requirement for systemic antifungal therapy Mixed treatment comparison ( MTC ) meta- analysis is a generalization of st and ard pairwise meta- analysis for A vs B trials , to data structures that include , for example , A vs B , B vs C , and A vs C trials . There are two roles for MTC : one is to strengthen inference concerning the relative efficacy of two treatments , by including both ' direct ' and ' indirect ' comparisons . The other is to facilitate simultaneous inference regarding all treatments , in order for example to select the best treatment . In this paper , we present a range of Bayesian hierarchical models using the Markov chain Monte Carlo software WinBUGS . These are multivariate r and om effects models that allow for variation in true treatment effects across trials . We consider models where the between-trials variance is homogeneous across treatment comparisons as well as heterogeneous variance models . We also compare models with fixed ( unconstrained ) baseline study effects with models with r and om baselines drawn from a common distribution . These models are applied to an illustrative data set and posterior parameter distributions are compared . We discuss model critique and model selection , illustrating the role of Bayesian deviance analysis , and node-based model criticism . The assumptions underlying the MTC models and their parameterization are also discussed Invasive fungal infection is a problem in patients undergoing bone marrow transplantation ( BMT ) . To determine if a liposomal formulation of amphotericin B ( Ambisome ) is safe and can prevent fungal infection we performed a placebo controlled double-blind r and omized prophylactic trial . Study drug was administered from when neutrophil count had decreased to < 0.5 x 10(9)/l and was continued until neutrophils recovered to this level or an infection or toxicity end-point was reached . Thirty-six patients received 1 mg/kg/day of ambisome and 40 patients received placebo daily . There were no statistical differences in characteristics or clinical course between the two groups . Fungal colonization decreased in the ambisome group while it increased in the placebo group . By the end of prophylaxis 8 of 24 ( 33 % ) patients receiving ambisome were colonized compared with 18 of 29 ( 62 % ) placebo patients ( p = 0.05 ) . Five and 7 patients on ambisome or placebo , respectively , were withdrawn due to a presumed fungal infection ( NS ) . There was no statistical reduction of autopsy-proven fungal infection . Proven fungal infection occurred in one patient receiving ambisome ( C. guillermondi ) compared with three patients receiving placebo ( C. guillermondi , 2 ; C. albicans , 1 ) . Ambisome was well tolerated at the dose of 1 mg/kg/day but in three patients allergic reactions were observed OBJECTIVES This trial studied the efficacy and safety of itraconazole and fluconazole in the prevention of invasive fungal infections in neutropenic patients with haematological malignancies . PATIENTS AND METHODS An 8 week , open-label , r and omized , parallel-group , multicentre trial comparing itraconazole oral solution ( 2.5 mg/kg twice daily ; N=248 ) with fluconazole oral solution or capsules ( 400 mg daily ; N=246 ) in 494 patients with anticipated profound neutropenia ( i.e. neutrophil count expected to be < 500 cells/mm3 for at least 10 days ) from tertiary care centres . RESULTS Invasive fungal infections were reported for 4 out of 248 patients ( 1.6 % ) in the itraconazole group and 5 out of 246 patients ( 2.0 % ) in the fluconazole group . Invasive Aspergillus infections were proven for 2 out of 248 patients ( 0.8 % ) in the itraconazole group and 3 out of 246 patients ( 1.2 % ) in the fluconazole group . For both the ITT and profoundly neutropenic population s , no differences were detected between treatment groups in proven or suspected invasive fungal infections or other endpoints . The mortality rates owing to proven invasive fungal infections were 2 out of 248 patients ( 0.8 % ) for the itraconazole group and 3 out of 246 patients ( 1.2 % ) for the fluconazole group . There was also no difference between treatment groups in the number of patients who recovered from neutropenia or in the duration of neutropenia . More discontinuation of drug intake owing to nausea and more hypokalaemia occurred in the itraconazole group , other adverse events and the total number of adverse events were similar in both groups . CONCLUSIONS In this study there were no differences in the efficacy and safety of itraconazole and fluconazole prophylaxis in neutropenic patients with haematological malignancies Purpose To compare the efficacy and safety of voriconazole with itraconazole as prophylaxis in leukemia patients . Methods Open-label , r and omized study . Patients with acute myelogenous leukemia or high-risk myelodysplastic syndrome undergoing induction chemotherapy or first salvage were eligible . Patients received voriconazole ( 400 mg intravenous ( IV ) every 12 h for two doses , followed by 300 mg BID ) or itraconazole ( 200 mg IV twice daily for 2 days , followed by 200 mg IV daily ) . Results A total of 127 patients were enrolled . Four were excluded because they did not receive study drug ( n = 3 ) or received two antifungal agents during the first week on study ( n = 1 ) , leaving 123 patients for analysis . None of the 71 patients receiving voriconazole developed proven or probable invasive fungal infection , compared to two ( 4 % ) of the 52 patients receiving itraconazole ( P = 0.17 ) . Drug discontinuation because of adverse events occurred in 15 patients ( 21 % ) receiving voriconazole and six ( 11 % ) receiving itraconazole ( P = 0.23 ) . Conclusions Voriconazole is a good alternative for prophylaxis in patients with leukemia . Elevated baseline bilirubin levels were associated with a higher risk of side effects in patients receiving IV voriconazole or IV itraconazole . Monitoring of liver function and drug levels should be considered for some patients BACKGROUND We performed a prospect i ve , r and omized , open-label trial to evaluate the efficacy of low-dose liposomal amphotericin B ( L-AmB ) to reduce the incidence of invasive fungal infections ( IFI ) in patients with hematological malignancies and prolonged neutropenia ( > 10 days ) following intensive chemotherapy . PATIENTS AND METHODS In 219 neutropenic episodes ( NE ) of 132 patients r and omization was performed . Patients received either 50 mg L-AmB every other day ( arm A ) or no systemic antifungal prophylaxis ( arm B ) . RESULTS In the first NE of each patient the incidence of proven or probable IFI ( primary end point ) was five of 75 patients ( 6.7 % ) in arm A and 20 of 57 patients ( 35 % ) in arm B ( P=0.001 ) . Invasive aspergillosis occurred less frequently in patients receiving L-AmB-prophylaxis ( P=0.0057 ) , whereas the reduction of invasive c and idiasis did not reach statistical significance ( P=0.0655 ) . In all NE the incidence of IFI was five of 110 NE ( 4.6 % ) in arm A versus 22 of 109 NE ( 20.2 % ) in arm B ( P<0.01 ) . Adverse events , possibly related to L-AmB , were observed in five NE ( 4.6 % ) and L-AmB was discontinued in three NE ( 2.8 % ) . No grade 3 or 4 toxicities were observed . CONCLUSIONS Antifungal prophylaxis with low-dose L-AmB proved to be feasible and effective in our trial We performed a r and omized , controlled study comparing the prophylactic effects of capsule forms of fluconazole ( n = 110 ) and itraconazole ( n = 108 ) in patients with acute myeloid leukemia ( AML ) or myelodysplastic syndromes ( MDS ) during and after chemotherapy . There were 4 cases with possible systemic fungal infection in the itraconazole group , and there were 8 possible and 3 probable cases in the fluconazole group . Adverse events did not significantly differ in the 2 groups . In patients with MDS or in the remission-induction phase of chemotherapy , the numbers of cases with probable or possible infections were lower in the itraconazole group than in the fluconazole group , whereas no difference was seen in patients with AML or in the consolidation phase of therapy . In patients with neutrophil counts of < 0.1 * 109/L lasting for more than 4 weeks , the frequency of infection in the fluconazole group ( 5 of 9 patients ) was significantly higher than in the itraconazole group ( 0 of 7 patients ; P = .03 ) . Our results suggest that both drugs were well tolerated in patients with AML or MDS who received chemotherapy and that the efficacy of itraconazole for prophylaxis against systemic fungal disease is not inferior to that of fluconazole This study was carried out on 70 patients with haematological or solid malignancies who were receiving chemotherapy and /or radiotherapy . Forty-one patients were r and omly assigned to receive fluconazole , 400 mg/day , while they were neutropenic . Systemic fungal infection developed in four of the 41 patients ( 9 % ) receiving prophylaxis in comparison to nine of 29 patients ( 31 % ) not receiving prophylaxis . The incidence of systemic fungal infection was significantly different between the groups receiving prophylaxis and those not receiving it ( p < 0.05 ) . Fluconazole was found to be effective for preventing systemic fungal infections in neutropenic patients with cancer A prospect i ve r and omized clinical trial assessed the efficacy and tolerance of micafungin compared with that of st and ard fluconazole treatment in patients undergoing hematopoietic stem cell transplantation ( HSCT ) . Adult patients ( n = 106 ) were r and omly assigned to receive prophylaxis with either micafungin 150 mg ( n = 52 ) , or fluconazole 400 mg ( n = 52 ) . Success was defined as the absence of suspected , proven , or probable invasive fungal infection ( IFI ) through the end of therapy and the absence of proven or probable IFI through the end of the 4-week period following treatment . The overall efficacy of micafungin was comparable to that of fluconazole ( 94 vs. 88 % ; difference 6.0 % ; 95 % confidence interval , −5.4 to + 17.4 % ; P = 0.295 ) . A total of 2 ( 4.0 % ) of 50 patients in the micafungin arm and 6 ( 12.0 % ) of 50 patients in the fluconazole arm received empirical antifungal therapy ( P = 0.06 ) . Micafungin treatment did not result in increasing adverse effects and had a safe profile as fluconazole in neutropenic patients . This r and omized trial indicates that the efficacy and tolerance of micafungin 150 mg was comparable to that of fluconazole 400 mg , suggesting that micafungin at 150 mg daily represents a valuable new treatment option for antifungal prophylaxis in HSCT recipients Fluconazole antifungal prophylaxis is st and ard care in allogeneic hematopoietic stem cell transplant ( HSCT ) recipients , but this drug lacks anti-Aspergillus activity , the primary cause of invasive fungal infection ( IFI ) in many transplantation centers . We performed a r and omized trial to compare itraconazole vs fluconazole , for prevention of IFIs in patients with acute leukemia ( AL ) and HSCT recipients . One hundred and ninety-five patients were r and omly assigned to either fluconazole or itraconazole antifungal prophylaxis , after stratification into high-risk and low-risk groups . Antifungal prophylaxis was started at the beginning of chemotherapy and continued until resolution of neutropenia , or until amphotericin B treatment was started . IFI occurred in 11 ( 11 % ) of itraconazole , and in 12 ( 12 % ) fluconazole recipients . Invasive c and idiasis ( IC ) developed in two ( 2 % ) itraconazole and one ( 1 % ) fluconazole recipients , while invasive aspergillosis ( IA ) developed in nine ( 9 % ) itraconazole and 11(11 % ) fluconazole recipients . There was no difference in the incidence of total IFI , IC and IA between the two study arms . However , there was a nonsignificant trend towards reduced mortality among patients who developed IA while receiving itraconazole prophylaxis ( 3/9=33 % vs 8/11=73 % , P=0.095 ) A r and omized , double-blind , placebo-controlled trial assessed the efficacy and toxicity of 400 mg/day fluconazole in preventing fungal infections during the first 75 days after marrow transplantation . During prophylaxis , systemic fungal infections occurred in 10 ( 7 % ) of 152 fluconazole-treated patients compared with 26 ( 18 % ) of 148 placebo-treated patients ( P = .004 ) . There were no C and ida albicans infections in fluconazole recipients compared with 18 in placebo recipients ( P < .001 ) and no significant increase in C and ida infections other than C. albicans . Fluconazole also significantly reduced the incidence of superficial fungal infections ( P < .001 ) , fungal colonization ( P = .037 ) , and empiric amphotericin B use ( P = .005 ) . The probability of survival was improved in fluconazole recipients , in whom 31 deaths occurred up to day 110 after transplantation compared with 52 deaths in placebo recipients ( P = .004 ) . No clinical ly significant toxicity was detected with fluconazole use . Prophylactic fluconazole was safe and significantly reduced systemic fungal infections with other benefits , including improved survival at day 110 after marrow transplantation BACKGROUND AND METHODS Superficial and systemic fungal infections are a major problem among severely immunocompromised patients who undergo bone marrow transplantation . We performed a double-blind , r and omized , multicenter trial in which patients receiving bone marrow transplants were r and omly assigned to receive placebo or fluconazole ( 400 mg daily ) . Fluconazole or placebo was administered prophylactically from the start of the conditioning regimen until the neutrophil count returned to 1000 per microliter , toxicity was suspected , or a systemic fungal infection was suspected or proved . RESULTS By the end of the treatment period , 67.2 percent of the 177 patients assigned to placebo had a positive fungal culture of specimens from any site , as compared with 29.6 percent of the 179 patients assigned to fluconazole . Among these , superficial infections were diagnosed in 33.3 percent of the patients receiving placebo and in 8.4 percent of the patients receiving fluconazole ( P less than 0.001 ) . Systemic fungal infections occurred in 28 patients who received placebo as compared with 5 who received fluconazole ( 15.8 percent vs. 2.8 percent , P less than 0.001 ) . Fluconazole prevented infection with all strains of c and ida except C and ida krusei . Fluconazole was well tolerated , although patients who received it had a higher mean increase in alanine aminotransferase levels than patients who received placebo . Although there was no significant difference in overall mortality between the groups , fewer deaths were ascribed to acute systemic fungal infections in the group receiving fluconazole than in the group receiving placebo ( 1 of 179 vs. 10 of 177 , P less than 0.001 ) . CONCLUSIONS Prophylactic administration of fluconazole to recipients of bone marrow transplants reduces the incidence of both systemic and superficial fungal infections We studied the efficacy and safety of itraconazole for the prevention of fungal infection in neutropenic patients given cytotoxic chemotherapy for hematologic malignancies . Patients were r and omly allocated to receive either itraconazole ( 200 mg bd ) or placebo in addition to oral amphotericin B until the patient either developed fungal infection or had completed antileukemic treatment . Forty six patients ( 83 neutropenic episodes ) treated with itraconazole and 46 placebo treated patients ( 84 neutropenic episodes ) were evaluable . No specific toxicity was noted . Nine fungal infections developed in the itraconazole group , of which four were histologically or microbiologically proven and 15 in the patients given placebo ( eight proven ) ( p < 0.12 ) . All these patients received IV amphotericin B. The incidence of C and ida albicans infections tended to be lower in the itraconazole group , but overall , there was no measurable improvement in the prevention of fungal infections and mortality by itraconazole To evaluate the efficacy and safety of itraconazole oral solution for preventing fungal infections , a r and omized , placebo-controlled , double-blind , multicenter trial was conducted : 405 neutropenic patients with hematologic malignancies were r and omly assigned to receive either itraconazole , 2.5 mg/kg every 12 hours ( 201 patients ) , or placebo ( 204 patients ) . Proven and suspected deep fungal infection occurred in 24 % of itraconazole recipients and in 33 % of placebo recipients , a difference of 9 percentage points ( 95 % confidence interval [ CI ] , 0.6 % to 22.5 % ; P = .035 ) . Fungemia due to C and ida species was documented in 0.5 % of itraconazole recipients and in 4 % of placebo recipients , a difference of 3.5 percentage points ( 95 % CI , 0.5 % to 6 % ; P = .01 ) . Deaths due to c and idemia occurred in none of the itraconazole recipients compared with 4 placebo recipients , a difference of 2 percentage points ( 95 % CI , 0.05 % to 4 % ; P = .06 ) . Aspergillus infection was documented in four itraconazole recipients ( one death ) and one placebo recipient ( one death ) . Side effects causing drug interruption occurred in 18 % of itraconazole recipients and 13 % of placebo recipients . Itraconazole oral solution was well-tolerated and effectively prevented proven and suspected deep fungal infection as well as systemic infection and death due to C and ida species BACKGROUND Invasive aspergillosis ( IA ) is a leading cause of infection-related mortality following hematopoietic cell transplantation ( HCT ) . The aim of this study was to determine the probability of survival and prognostic factors associated with outcomes over a long period of time . METHODS Cases of proven and probable IA diagnosed in HCT recipients at the Fred Hutchinson Cancer Research Center from 1 January 1990 through 31 December 2004 were included . Patient data were collected from a prospect ively maintained data base and by retrospective clinical chart review . Survival was estimated using Kaplan-Meier curves , and Cox regression models were used for multivariable analyses . RESULTS Four hundred five cases were identified . The probability of survival at 90 days after diagnosis was higher for patients identified as having IA between 2002 and 2004 than for patients whose IA was diagnosed in preceding years ( 45 % vs. 22 % ; P<.001 ) . Risk factors independently associated with all-cause mortality include impairment in pulmonary function before HCT , receipt of human leukocyte antigen-mismatched stem cells , neutropenia , elevated bilirubin and creatinine levels , receipt of corticosteroids at > or = 2 mg/kg per day , disseminated and proven IA , and IA occurring > 40 days after HCT . Factors associated with a decreased risk of all-cause mortality included receipt of nonmyeloablative conditioning and peripheral blood stem cells . In a sub analysis of attributable mortality restricted to patients receiving antifungal therapy , receipt of voriconazole was independently associated with protection from IA-related death . CONCLUSIONS There has been a significant decrease in mortality in patients with a diagnosis of IA following HCT in recent years , coinciding with multiple changes in transplantation practice s , including use of nonmyeloablative conditioning regimens , receipt of peripheral blood stem cells , more prompt diagnosis of IA , and use of voriconazole BACKGROUND Fungal infections still represent a major clinical problem in neutropenic patients ; the recent availability of active imidazole derivatives , particularly fluconazole and itraconazole , has increased interest in prophylaxis . MATERIAL S AND METHODS Fifty-nine consecutive bone marrow transplant ( BMT ) recipients were r and omized to receive either itraconazole 400 mg/day or fluconazole 300 mg/day as oral antimycotic prophylaxis during the pancytopenic phase ; they were retrospectively compared with a historical control group of 30 patients who had received fluconazole 50 mg/day . Every febrile episode was treated with the same empirical antibiotic combination ; amphotericin-B was added after 4 - 5 days in the case of persistent fever . Proven or suspected mycotic infections and the empirical use of amphotericin-B were considered as failures of prophylaxis . RESULTS There were no differences in the number of febrile episodes in the three groups . Five patient died of bacterial sepsis : two in the fluconazole 300 , two in the itraconazole and one in the fluconazole 50 group . The addition of amphotericin-B was required in 12 , 16 and 11 cases , respectively , in the three groups . There were four documented fungal infections in the intraconazole and one in both fluconazole groups ; three suspected fungal infections were observed in the fluconazole 300 group and two in both the itraconazole and the fluconazole 50 group . None of the differences were statistically significant . CONCLUSIONS The present results indicate that high-dose fluconazole and itraconazole are equivalent ; neither of them was superior to low-dose fluconazole , which is regarded as being devoid of prophylactic activity against systemic mycoses Objective : The objective of this study was to determine the clinical features associated with c and idemia caused by non-albicans C and ida spp . and with potentially fluconazole-resistant C and ida spp . ( C. glabrata and C. krusei ) among c and idemic intensive care unit patients . Design : The authors conducted a nationwide prospect i ve cohort study . Setting : The study was conducted in Australian intensive care units . Patients : All patients with intensive care unit-acquired c and idemia over a 3-yr period were included in the study . Measurements : Clinical risk factors occurring up to 30 days before c and idemia , C and ida spp . associated with c and idemia , and outcomes were determined . Risk factors associated with either non-albicans C and ida spp . or with potentially fluconazole-resistant C and ida spp . ( C. glabrata or C. krusei ) were assessed using multivariate logistic regression . Main Results : Among 179 episodes of intensive care unit-acquired c and idemia , C. albicans accounted for 62 % , C. glabrata 18 % , C. krusei 4 % , and other C and ida spp . 16 % . Independently significant variables associated with non-albicans C and ida bloodstream infection included recent prior gastrointestinal surgery ( adjusted odds ratio , 2.87 ; 95 % confidence interval , 1.68–4.91 ) and recent prior systemic antifungal exposure ( 4.6 ; 1.36–15.53 ) . Those associated with potentially fluconazole-resistant c and idemia included recent prior gastrointestinal surgery ( 3.31 ; 1.79–6.11 ) and recent prior fluconazole exposure ( 5.47 ; 1.23–24.32 ) . No significant differences in outcomes were demonstrated for non-albicans or potentially fluconazole-resistant c and idemia . Conclusions : Among c and idemic intensive care unit patients , prior gastrointestinal surgery and systemic antifungal exposure were significantly associated with both a non-albicans C and ida spp . and a potentially fluconazole-resistant C and ida spp . LEARNING OBJECTIVES On completion of this article , the reader should be able to : List clinical features discriminating between c and idemia caused by C. albicans and those caused by other species . Describe predisposing factors that help discriminate between c and idemia which are potentially fluconazole-resistant . Use this information in a clinical setting .Dr . Playford has disclosed that he was a consultant/advisor for Pfizer and Merck ; was on the advisory board for Schering-Plough ; and is a recipient of grant/ research funds from Pfizer and Merck . Dr. Marriott has disclosed that she was/is a recipient of grant/ research funds from Pfizer ; was/is a consultant/advisor for Merck , Sharpe & Dohme and Sanofi-Pasteur ; and was/is on the advisory board for Roche . Dr. Nguyen has disclosed that he has no financial relationships with or interests in any commercial companies pertaining to this educational activity . Dr. Chen has disclosed that she was a recipient of grant/ research funds from Pfizer ; is a recipient of grant/ research funds from Gilead Sciences , Inc. ; and is on the advisory board for Gilead Sciences , Inc. and Pfizer Australia . Dr. Ellis has disclosed that he was/is a recipient of grant/ research funds from Pfizer Australia , Merck , Sharpe & Dohme Australia , Gilead Sciences Australia , and Schering-Plough Australia ; was/is a consultant/advisor for Pfizer Australia , Merck , Sharpe & Dohme Australia , Gilead Sciences Australia , and Schering-Plough Australia ; and was/is on the speaker 's bureau for Pfizer Australia , Merck , Sharpe & Dohme Australia , Gilead Sciences Australia , and Schering-Plough Australia . Dr. Slavin has disclosed that she was/is a recipient of grant/ research funds from Pfizer Inc. , Gilead Sciences , Schering-Plough , and Merck and Co. ; and was/is on the advisory board for Pfizer Inc. , Gilead Sciences , Schering-Plough , and Merck and Co. Dr. Sorrell has disclosed that she was/is a recipient of grant/ research funds from Merck , Sharpe & Dohme Australia , Pfizer , and Gilead ; and was/is a consultant/advisor for Pfizer , Merck , Gilead , and Schering-Plough . All faculty and staff in a position to control the content of this CME activity have disclosed that they have no financial relationship with , or financial interests in , any commercial companies pertaining to this educational activity . Lippincott CME Institute , Inc. , has identified and resolved all faculty conflicts of interest regarding this educational activity . Visit the Critical Care Medicine Web Site ( www.ccmjournal.org ) for information on obtaining continuing medical education credit Infections continue to be common causes of morbidity and mortality in neutropenic patients undergoing chemotherapy for acute leukemia [ 1 , 2 ] . Although bacteria are usually the primary pathogens in neutropenic patients , most bacterial infections can now be treated successfully with currently available antibacterial drugs [ 3 , 4 ] . In contrast , fungal infections , often documented only at autopsy , are increasing in frequency in patients with acute leukemia and are now responsible for most fatal infections [ 5 - 7 ] . C and ida species are the predominant fungal pathogens , followed by Aspergillus species , the zygomycetes , and several newly recognized opportunistic fungi . Survival from invasive fungal infections has generally been poor in neutropenic patients with acute leukemia . In many cases , this poor survival can be linked to delays in diagnosis . Obstacles to the rapid diagnosis of invasive fungal infection include difficulty in isolation of fungi in cultures , inability to perform biopsies or other invasive diagnostic procedures in patients with disorders of coagulation , and the nonavailability of reliable serologic tests [ 8 ] . Because of these difficulties , amphotericin B is frequently administered empirically to patients with neutropenia and persistent fever refractory to antibacterial therapy [ 3 , 9 , 10 ] . This approach , however , is limited by the toxicity of amphotericin B , especially in patients receiving other nephrotoxic drugs . The problems associated with effective therapy of serious fungal infections in neutropenic patients with acute leukemia have been the stimulus for using antifungal drugs for prophylaxis . Unfortunately , prophylaxis with oral agents such as nystatin , clotrimazole , and ketoconazole has produced inconsistent results either due to lack of efficacy or poor patient compliance [ 11 ] . Similarly , prophylaxis with parenteral drugs like intravenous miconazole or amphotericin B has been used only on a limited basis because of concerns about toxicity and overall effectiveness [ 12 , 13 ] . Thus , there is currently no uniformly accepted or proven approach for prevention of fungal infections in neutropenic patients with acute leukemia . Fluconazole is a new triazole antifungal agent with activity against many common fungal pathogens causing infection in patients with acute leukemia [ 14 ] . Fluconazole has a favorable pharmacokinetic profile that includes a long serum half-life , making once-daily administration possible , more consistent absorption from the gastrointestinal tract than that of ketoconazole , excellent penetration into the cerebrospinal fluid , and elimination predominantly by renal mechanisms . Significant side effects related to fluconazole have been uncommon and occur less frequently than those associated with amphotericin B. Fluconazole is currently approved for treatment of C and ida and cryptococcal infections [ 15 , 16 ] . Studies in neutropenic animal models also suggest that fluconazole may be effective for prevention of C and ida infection and for treatment of invasive aspergillosis when given at high doses [ 17 , 18 ] . Similar studies in neutropenic bone marrow transplants found that prophylactic fluconazole prevents both systemic and superficial fungal infections [ 19 ] . For these reasons , we did a double-blind , placebo-controlled trial of prophylactic fluconazole in neutropenic patients undergoing chemotherapy for acute leukemia . Methods Patients Patients were eligible for the study if they satisfied the following criteria : 1 ) undergoing chemotherapy for acute leukemia or the blast crisis of chronic myelogenous leukemia ; 2 ) 13 years of age or older ; 3 ) anticipated neutropenia of less than 500 neutrophils per mm3 for 7 or more days ; 4 ) no clinical evidence of fungal infection at time of study entry ; 5 ) no systemic antifungal therapy within the 2 weeks before r and omization ; and 6 ) no allergy to the imidazoles or azoles . Patients with moderate or severe liver disease ( aspartate aminotransferase [ AST ] , alanine aminotransferase [ ALT ] , or alkaline phosphatase greater than five times the upper limit of normal or a total bilirubin greater than 43 mol/L ) and patients with renal insufficiency ( creatinine clearance of less than 0.83 mL/s ) were excluded from the study . Our trial involved 18 oncology centers . Informed consent approved by the institutional review board at each center was obtained from each patient . Study Drugs Eligible patients were r and omly assigned to receive either prophylactic fluconazole or placebo in a double-blind fashion . The fluconazole or placebo was begun at the time of initiation of chemotherapy and administered in identically appearing capsules . A capsule contained 100 mg of fluconazole , and each patient received four capsules ( 400 mg ) as a single daily dose . For patients unable to tolerate oral capsules , the fluconazole or placebo was administered intravenously . The intravenous dose of fluconazole was 200 mg every 12 hours and was infused over 1 hour . The daily dose of fluconazole was reduced in patients who developed renal failure [ 20 ] . Prophylaxis with the study drug was continued through the course of chemotherapy and neutropenia and until 7 days after the neutrophil count reached 1000 cells per mm3 or greater . The maximum duration of prophylaxis was 10 weeks . Prophylaxis was discontinued if one of the following events occurred : 1 ) development of a documented invasive fungal infection ; 2 ) initiation of empiric systemic antifungal therapy ( amphotericin B ) for clinical ly suspected invasive fungal infection ; 3 ) adverse side effects related to the study drug ; or 4 ) patient 's inability to continue in the study due to noncompliance or death . Patients who developed a documented superficial fungal infection could be treated with topical clotrimazole while continuing to receive the study drug . Laboratory Procedures Complete blood counts , prothrombin times , blood urea nitrogen levels , serum creatinine and electrolyte determinations , urinalyses , and liver function studies ( AST , ALT , alkaline phosphatase , and total bilirubin ) were obtained at the time of study entry , once or twice weekly during the study , and at the end of prophylaxis to assess patients for drug-related side effects . Patients were also examined at least twice weekly for clinical symptoms and signs of adverse effects related to the study drugs . A serum pregnancy test was done on all women of child-bearing potential before the study began . Surveillance cultures of the nasopharynx , oropharynx , axillae , urine , perirectal area , and stool were done at the time of study entry , once weekly during the study , and at the end of prophylaxis to determine the presence of fungal colonization . Cultures of blood and other suspected sites of fungal infection were obtained during the study whenever a patient 's clinical condition suggested the possibility of fungal infection . Amphotericin B therapy was initiated in accordance with previously established guidelines when a reasonable clinical suspicion of systemic fungal infection existed [ 3 , 9 , 10 ] . Definition of Fungal Colonization and Infection Fungal colonization was defined as the presence of a fungus in one or more surveillance cultures in the absence of any clinical symptoms or signs of infection . Superficial fungal infections were diagnosed by the isolation of a fungus from the skin , oropharynx , or gastrointestinal tract in association with signs of inflammation , ulcerations , plaques , or exu date s not explainable by other pathogens . Invasive fungal infections were diagnosed by the presence of fungus in the blood , pulmonary tissue or secretions , sinuses , soft tissues , or other organ structures in association with symptoms and signs of infection not explainable by other pathogens . Data Collection and Statistical Analysis Data required by the study protocol were collected and recorded in case report forms by the investigators at each oncology center . Barton and Polansky Associates independently review ed all case report forms for accuracy and compliance with the protocol by comparing the case report forms with patients ' medical and pharmacy records . The case report forms were then su bmi tted to clinical research personnel at Pfizer Central Research for review and entry of data into computer programs . All review s , classifications of infections , and data entry were done blindly before the statistical analyses were performed . Proven fungal infections were required to meet the definitions of infection established by the protocol and approved by the Federal Drug Administration before the study . There was no interim analysis . All statistical tests were performed as two-tailed tests . The Fisher exact test was used to compare differences in proportions , whereas the e quality of two distributions was compared by the Wilcoxon rank-sum test . Univariate comparisons of times to specific events were performed by using Kaplan-Meier estimates of survival distributions and the Gehan generalized Wilcoxon test [ 21 ] . The SAS procedure LIFETEST was used for these comparisons [ 22 ] . The Cochran-Mantel-Haenszel chi-square test was used to check the e quality of mean scores of ordinal response variables adjusted for center effect . Except for one placebo patient who did not receive the study drug and one fluconazole patient with invasive fungal infection at baseline , all patients were included in the efficacy analysis ( intent-to-treat analysis ) . Center by treatment interactions were tested by using the Breslow-Day test of homogeneity of odds ratio [ 23 ] . Results Patient Characteristics Two hundred fifty-seven patients were enrolled into the study . One patient r and omized to the placebo group did not receive the study drug and was excluded from all analyses . The characteristics of the other 256 patients are summarized in Table 1 . One hundred thirty-two patients received placebo , and 124 patients were given fluconazole . The two groups of patients were similar in terms of age , sex , underlying disease , and baseline fungal Context Fungal infections after allogeneic hematopoietic stem-cell transplantation are a serious problem . Current prophylactic regimens are limited by toxicity and the emergence of resistant infections . Contribution This open-label r and omized trial of 140 patients undergoing stem-cell transplantation found that prophylaxis with itraconazole for 100 days after transplantation prevented more invasive fungal infections than did prophylaxis with fluconazole ( absolute difference , 16 percentage points [ 95 % CI , 29 to 5 percentage points ] ) . More fungal pathogens were resistant to fluconazole . Nausea , vomiting , diarrhea , and abdominal pain were more common in patients receiving itraconazole . Implication s Itraconazole is better than fluconazole for preventing invasive fungal infections in allogeneic stem-cell transplant recipients but causes more gastrointestinal side effects . The Editors Fungal infections have become an increasing cause of morbidity and death after allogeneic hematopoietic stem-cell transplantation . Indeed , with better prevention of cytomegalovirus disease , invasive fungal infections are now the leading cause of death from infection at many transplantation centers ( 1 , 2 ) . Consequently , antifungal agents are often used for prophylaxis in allogeneic hematopoietic stem-cell transplant recipients . An amphotericin B formulation or fluconazole has been most commonly used ( 3 - 11 ) . Each of these agents , however , has substantial limitations for prophylaxis . The amphotericin B formulations are limited by toxicity , and the lipid preparations of amphotericin B can be expensive . Furthermore , the prophylactic efficacy of st and ard amphotericin B and the newer lipid formulations of amphotericin has not been consistently demonstrated in r and omized , controlled trials ( 1 , 5 - 11 ) . Routine use of fluconazole for prophylaxis has been associated with the emergence of fluconazole-resistant C and ida infections ( 12 - 14 ) . Fluconazole also lacks reliable activity against Aspergillus species , which have now become the primary cause of invasive fungal infection at many transplantation centers ( 15 , 16 ) . Itraconazole is an azole antifungal agent that may overcome some of the limitations of fluconazole and the amphotericin B formulations as prophylactic agents in allogeneic hematopoietic stem-cell transplant recipients . Itraconazole has excellent in vitro activity against many opportunistic fungi that are resistant to fluconazole , including Aspergillus and some C and ida species ( 17 , 18 ) . Itraconazole is less toxic than the amphotericin B formulations . It is now available in an oral hydroxypropyl -- cyclodextrin solution as well as an intravenous formulation . Compared with itraconazole capsules , itraconazole oral solution is much better absorbed and has been used successfully for antifungal prophylaxis in neutropenic patients who had not received an allogeneic hematopoietic stem-cell transplant ( 19 - 21 ) . Intravenous itraconazole is the only azole approved for empirical antifungal therapy in febrile neutropenic patients ( 22 ) . We performed a r and omized trial to compare intravenous and oral itraconazole with intravenous and oral fluconazole for prevention of fungal infections in allogeneic hematopoietic stem-cell transplant recipients . Methods Patients Patients of either sex who were 13 years of age or older and undergoing allogeneic hematopoietic stem-cell transplantation were eligible for the study if they had no history of an invasive yeast or mold infection within 8 weeks before initiation of therapy with the study drug . Because of the paucity of efficacy and safety data on the use of intravenous and oral itraconazole in children at the time this study was initiated , patients younger than 13 years of age were excluded . Patients with liver enzyme values greater than five times the upper limit of normal , a bilirubin level greater than 85.5 mol/L ( 5.0 mg/dL ) , an allergy to imidazoles or azoles , or a body temperature greater than 38.0 C within 48 hours of starting therapy with the study drug were also excluded . Similarly , patients who had received a previous bone marrow or peripheral stem-cell transplant and patients requiring concomitant therapy with drugs ( rifampin , rifabutin , phenobarbital , phenytoin , carbamazepine , midazolam , triazolam , cisapride , terfenadine , or astemizole ) having potential interactions with azole antifungal agents were not eligible for the study . Women were required to have a negative result on a pregnancy test . Informed consent was obtained from each patient or appropriate relative in a manner approved by the institutional review board at each study center . Study Drugs and Design Eligible patients were r and omly assigned to receive prophylaxis with either itraconazole or fluconazole . We used blocked r and omization , which was done in a 1:1 ratio and stratified by study center . The r and omization process was performed by the pharmacy department at each study site . The study design was open label because blinding of intravenous and oral itraconazole against intravenous and oral fluconazole was technologically impossible at the time the study was conducted . Prophylaxis with each study medication was started on the first day after transplantation . Because a previous trial had shown both a reduction in fungal infections and improved survival when prophylactic fluconazole was used for 75 days after transplantation ( 4 ) , use of the study drug was continued until day 100 after transplantation . Patients r and omly assigned to receive itraconazole were initially given intravenous itraconazole at a loading dose of 200 mg every 12 hours for 2 days , followed by 200 mg every 24 hours for 12 days . Patients were then switched to oral itraconazole solution at a dose of 200 mg every 12 hours until day 100 after transplantation . Similarly , patients r and omly assigned to receive fluconazole were initially given intravenous fluconazole at a dose of 400 mg once daily for 14 days and were then switched to oral fluconazole tablets at a dose of 400 mg once daily until day 100 after transplantation . If patients could not take or tolerate oral medications , they resumed prophylaxis with the intravenous form of the study drug . The dose of itraconazole was not adjusted in patients with renal failure . However , if the serum creatinine level increased to greater than 354 mol/L ( 4.0 mg/dL ) during treatment with intravenous itraconazole , patients were changed to itraconazole oral solution because of the prolonged elimination rate of intravenous hydroxypropyl -- cyclodextrin with severe renal impairment . The daily dose of fluconazole was decreased by 50 % for a creatinine clearance of 0.33 to 0.84 mL/s ( 20 to 50 mL/min ) and by 75 % for a creatinine clearance of less than 0.33 mL/s ( 20 mL/min ) . After transplantation , prophylaxis with the study drug was discontinued if an invasive fungal infection was documented , a serious adverse event definitely related to the study drug occurred , or the patient died . Patients with a documented superficial fungal infection could be treated with a topical antifungal agent while continuing prophylaxis with the study drug . Use of the study drug was temporarily discontinued when empirical therapy with amphotericin B was administered for suspected but undocumented fungal infection . After the empirical amphotericin B therapy was stopped , prophylaxis with the study drug was resumed . Transplantation Regimen Investigators at each study center were allowed to use the preparative regimens of chemoradiation therapy and the immunosuppressive agents for prophylaxis and treatment of graft-versus-host disease that were considered st and ard practice at their institutions . Similarly , each study center used its own st and ard agents to prevent and treat bacterial and viral infections . The criteria used to diagnose and grade graft-versus-host disease have been previously published ( 23 , 24 ) . Laboratory Procedures We obtained complete blood counts with differential leukocyte count and platelet count , blood urea nitrogen levels , serum creatinine and electrolyte determinations , urinalyses , and liver function studies ( aspartate aminotransferase , alanine aminotransferase , alkaline phosphatase , and total bilirubin levels ) at study entry , at least once weekly during the study , and within 3 days of completion of prophylaxis with the study drug . Serum cyclosporine levels , measured by using high-pressure liquid chromatography , were also monitored during the study ( 25 ) . In patients receiving itraconazole , trough plasma levels of itraconazole and its active metabolite , hydroxy-itraconazole , were measured by using high-performance liquid chromatography on days 3 and 7 of the study and then once every 1 or 2 weeks thereafter ( 26 ) . We obtained cultures of the blood and other suspected sites of fungal infection whenever a patient 's clinical condition suggested the possibility of infection . Chest radiography , computed tomography , bronchoscopy , and biopsies were also done when clinical ly indicated to diagnose fungal infection . We determined minimum inhibitory concentrations ( MICs ) of itraconazole and fluconazole for yeast and filamentous fungi isolated from patients with documented fungal infections to evaluate the possible emergence of resistant organisms . Antifungal susceptibility testing was performed by a central reference laboratory according to guidelines of the National Committee for Clinical Laboratory St and ards ( 27 , 28 ) . Definitions of Fungal Infection Superficial fungal infections were diagnosed by the isolation of a fungus from the skin , oropharynx , gastrointestinal tract , or vagina in association with signs of inflammation , ulcerations , plaques , exu date s , or other manifestations of infection not explainable by other pathogens . Invasive fungal infections were diagnosed by using criteria published by the National Institutes of Health Mycoses Study Group and the European Organization for Research and Treatment of Cancer ( 29 ) . The diagnosis of invasive fungal |
14,023 | 22,873,682 | While there was no change in control group weight , control groups receiving usual care lost 1 kg more than control groups that received no intervention , beyond measurement .
Conclusions There are several possible explanations why control group changes occur in intervention trials targeting other behaviours , but not for weight loss . | Background Unanticipated control group improvements have been observed in intervention trials targeting various health behaviours .
This phenomenon has not been studied in the context of behavioural weight loss intervention trials .
The purpose of this study is to conduct a systematic review and meta-regression of behavioural weight loss interventions to quantify control group weight change , and relate the size of this effect to specific trial and sample characteristics . | RATIONALE Obesity is the most important risk factor for obstructive sleep apnea ( OSA ) . However , although included in clinical guidelines , no r and omized controlled studies have been performed on the effects of weight reduction on mild OSA . OBJECTIVES The aim of this prospect i ve , r and omized controlled parallel-group 1-year follow-up study was to determine whether a very low calorie diet ( VLCD ) with supervised lifestyle counseling could be an effective treatment for adults with mild OSA . METHODS Seventy-two consecutive overweight patients ( body mass index , 28 - 40 ) with mild OSA were recruited . The intervention group ( n = 35 ) completed the VLCD program with supervised lifestyle modification , and the control group ( n = 37 ) received routine lifestyle counseling . The apnea-hypopnea index ( AHI ) was the main objective ly measured outcome variable . Change in symptoms and the 15D- Quality of Life tool were used as subjective measurements . MEASUREMENTS AND MAIN RESULTS The lifestyle intervention was found to effectively reduce body weight ( -10.7 + /- 6.5 kg ; body mass index , -3.5 + /- 2.1 [ mean + /- SD ] ) . There was a statistically significant difference in the mean change in AHI between the study groups ( P = 0.017 ) . The adjusted odds ratio for having mild OSA was markedly lowered ( odds ratio , 0.24 [ 95 % confidence interval , 0.08 - 0.72 ] ; P = 0.011 ) in the intervention group . All common symptoms related to OSA , and some features of 15D- Quality of Life improved after the lifestyle intervention . Changes in AHI were strongly associated with changes in weight and waist circumference . CONCLUSIONS VLCD combined with active lifestyle counseling result ing in marked weight reduction is a feasible and effective treatment for the majority of patients with mild OSA , and the achieved beneficial outcomes are maintained at 1-year follow-up OBJECTIVE To evaluate the effectiveness of a worksite health promotion program on improving cardiovascular disease risk factors . METHODS In St Louis , Missouri from 2005 to 2006 , 151 employees ( 134 F , 17 M , 81 % overweight/obese ) participated in a cohort-r and omized trial comparing assessment s + intervention ( worksite A ) with assessment s only ( worksite B ) for 1 year . All participants received personal health reports containing their assessment results . The intervention was design ed to promote physical activity and favorable dietary patterns using pedometers , healthy snack cart , WeightWatchers(R ) meetings , group exercise classes , seminars , team competitions , and participation rewards . Outcomes included BMI , body composition , blood pressure , fitness , lipids , and Framingham 10-year coronary heart disease risk . RESULTS 123 participants , aged 45+/-9 yr , with BMI 32.9+/-8.8 kg/m(2 ) completed 1 year . Improvements ( P < or = 0.05 ) were observed at both worksites for fitness , blood pressure , and total- , HDL- , and LDL-cholesterol . Additional improvements occurred at worksite A in BMI , fat mass , Framingham risk score , and prevalence of the metabolic syndrome ; only the changes in BMI and fat mass were different between worksites . CONCLUSION A multi-faceted worksite intervention promoted favorable changes in cardiovascular disease risk factors , but many of the improvements were achieved with worksite health assessment s and personalized health reports in the absence of an intervention BACKGROUND Studies of weight loss and changes in bone mineral density ( BMD ) have primarily been short-term trials in obese subjects . OBJECTIVE We examined the effects of a 5-yr intervention design ed to prevent menopausal weight gain or promote modest weight loss on BMD in premenopausal women participating in the Women 's Healthy Lifestyle Project . DESIGN We enrolled 373 premenopausal women ( age 44 - 50 yr ) and r and omly assigned them to either lifestyle intervention ( 175 women , low-fat dietary modification , weight loss , and physical activity intervention ) or control group ( 198 women ) . BMD and body weight were measured at baseline , annual follow-up visits ( 18 , 30 , 42 , and 54 months ) , and two postintervention follow-ups ( 66 and 78 months ) . BMD was measured by dual x-ray absorptiometry . RESULTS Over the 54 months of intervention , women in the intervention group lost 0.4 kg , whereas control women gained 2.6 kg ( P = 0.011 ) . The intervention group experienced significantly greater hip bone loss ( -0.20%/yr ) than the control group ( -0.03%/yr ) . During the postintervention , differences in rates of bone loss disappeared . When considering both menopausal status and use of hormone therapy ( HT ) , the annualized BMD changes were lower in women reporting HT use ; nevertheless , among women on HT , those who lost more than 3 % body weight experienced greater total hip BMD loss ( -0.25%/yr ) compared with those who gained weight ( -0.02%/yr ) ( P = 0.025 ) . CONCLUSIONS Women r and omized to a lifestyle intervention aim ed at preventing menopausal weight gain or promoting modest weight loss experienced greater rates of hip bone loss than control women OBJECTIVE To evaluate the effectiveness of a lifestyle intervention for male workers in the construction industry at risk of cardiovascular disease ( CVD ) . METHODS In a r and omized controlled trial performed in the Netherl and s between 2007 and 2009 , usual care was compared to 6 months of individual counseling using motivational interviewing techniques , delivered face to face and by telephone . Participants aim ed at improving energy balance-related behavior or smoking cessation . Linear regression analyses were performed to determine the effects . RESULTS Body weight had significantly decreased at 6 ( β=-1.9 , 95 % CI -2.6 ; -1.2 ) and 12 months ( β=-1.8 , 95%CI -2.8 ; -1.1 ) . The intervention effects were also significant for diastolic blood pressure at 6 months ( β=-1.7 , 95 % CI -3.3 ; -0.1 ) . Among participants who had aim ed at energy balance , the intervention had a significant favorable effect on body weight at 6 ( β=-2.1 , 95 % CI -2.9 ; -1.3 ) and 12 months ( β=-2.2 , 95 % CI -3.1 ; -1.3 ) and at HDL cholesterol ( β=0.05 , 95 % CI 0.01 ; 0.10 ) and HbA1c ( β=-0.06 , 95%CI -0.12 ; -0.001 ) at 12 months , although there was no intervention effect on these variables over time . CONCLUSION Individual-based counseling result ed in significant beneficial long-term effects on body weight . This is an important finding for occupational health , considering the rising prevalence of obesity and CVD Obesity is associated with vascular endothelial dysfunction , as indicated by impaired endothelium-dependent dilation . Presently there is no direct evidence that energy intake – restricted weight loss alone improves conduit or resistance artery endothelium-dependent dilation , the mechanisms involved , or whether improvements differ with patient age . A total of 40 overweight or obese ( body mass index : ≥25<40 kg/m2 ) nondiabetic men and women aged 21 to 69 years completed 12 weeks of reduced energy intake ( n=26 ; 15 male ) or attention control ( n=14 ; 9 male ) and 4 weeks of weight maintenance ( r and omized trial ) . Energy intake restriction reduced estimated total energy intake ( 33 % ) , body weight ( 10.5 % ) , total and abdominal body fat , plasma leptin , oxidized low-density lipoprotein , and improved several metabolic risk factors . Brachial artery flow-mediated dilation was increased by 30 % ( 6.0±0.7 % versus 7.9±0.7%&Dgr ; ; P=0.01 ; n=17 ) . Peak forearm blood flow during intrabrachial artery infusion of acetylcholine was increased by 26 % ( 16.8±1.4 versus 21.1±1.9 mL/100 mL per minute ; P<0.05 ; n=15 ) ; this was inversely related to the reduction in the abdominal visceral : subcutaneous fat ratio ( r=−0.46 ; P<0.05 ) and was abolished by inhibition of NO synthesis with NG-monomethyl-l-arginine . Improvements in endothelium-dependent dilation were not related to age : mean increases in subjects > 50 years of age were similar to or greater than those < 50 years of age . Energy intake – restricted weight loss alone is an effective intervention for improving peripheral conduit and resistance artery endothelial function in young and older overweight/obese adults . The improvements in resistance artery function are mediated by an increase in NO bioavailability and are related to reductions in abdominal visceral fat Background The increased prevalence of overweight and obesity warrants preventive actions , particularly among people in transitional stages associated with lifestyle changes , such as occupational retirement . The purpose is to investigate the effect of a one year low-intensity computer-tailored energy balance programme among recent retirees on waist circumference , body weight and body composition , blood pressure , physical activity and dietary intake . Methods A r and omised controlled trial was conducted among recent retirees ( N = 413 ; mean age 59.5 years ) . Outcome measures were assessed using anthropometry , bio-impedance , blood pressure measurement and question naires . Results Waist circumference , body weight and blood pressure decreased significantly in men of the intervention and control group , but no significant between-group-differences were observed at 12 or at 24-months follow-up . A significant effect of the programme was only observed on waist circumference ( -1.56 cm ( 95%CI : -2.91 to -0.21 ) ) at 12 month follow up among men with low education ( n = 85 ) . Physical activity and dietary behaviours improved in both the intervention and control group during the intervention period . Although , these behaviours changed more favourably in the intervention group , these between-group-differences were not statistically significant . Conclusions The multifaceted computer-tailored programme for recent retirees did not appear to be effective . Apparently the transition to occupational retirement and /or participation in the study had a greater impact than the intervention programme . Trial registration Clinical Trials NCT00122213 Background Rising levels of obesity coupled with the limited success of currently available weight control methods highlight the need for investigation of novel approaches to obesity treatment . This study aims to determine the effectiveness and cost-effectiveness of an Internet-based re source for obesity management . Methods A r and omised controlled trial conducted in a community setting , where obese volunteers ( n = 221 ) were r and omly assigned to Internet group ( n = 111 ) or usual care group ( n = 110 ) . Objective measures of weight and height were obtained . Question naires were used to collect dietary , lifestyle , physical activity and quality of life data . Data were collected at baseline , six months and 12 months . Results Data were collected on 54 ( 49 % ) participants in the Internet group and 77 ( 70 % ) participants in the usual care group at 12 months . Based on analysis conducted on all available data , the Internet group lost 1.3 kg , compared with 1.9 kg weight loss in the usual care group at 12 months , a non-significant difference ( difference = 0.6 kg ; 95 % CI : -1.4 to 2.5 , p = 0.56 ) . No significant differences in change in secondary outcome measures between the two groups at six or 12 months were revealed . Total costs per person per year were higher in the Internet group than the usual care group ( £ 992.40 compared to £ 276.12 ) , primarily due to the fixed costs associated with setting up the website , and QALYs were similar ( 0.78 and 0.77 ) for both groups . Conclusion This trial failed to show any additional benefit of this website in terms of weight loss or secondary outcome measures compared with usual care . High attrition and low compliance limits the results of this research . The results suggest that the Internet-based weight control re source was not a cost-effective tool for weight loss in the obese sample studied . Trail Registration IS RCT N CONTEXT Obesity in the United States has increased dramatically during the past several decades . There is debate about optimum calorie balance for prevention of weight gain , and proponents of some low-carbohydrate diet regimens have suggested that the increasing obesity may be attributed , in part , to low-fat , high-carbohydrate diets . OBJECTIVES To report data on body weight in a long-term , low-fat diet trial for which the primary end points were breast and colorectal cancer and to examine the relationships between weight changes and changes in dietary components . DESIGN , SETTING , AND PARTICIPANTS R and omized intervention trial of 48,835 postmenopausal women in the United States who were of diverse background s and ethnicities and participated in the Women 's Health Initiative Dietary Modification Trial ; 40 % ( 19,541 ) were r and omized to the intervention and 60 % ( 29,294 ) to a control group . Study enrollment was between 1993 and 1998 , and this analysis includes a mean follow-up of 7.5 years ( through August 31 , 2004 ) . INTERVENTIONS The intervention included group and individual sessions to promote a decrease in fat intake and increases in vegetable , fruit , and grain consumption and did not include weight loss or caloric restriction goals . The control group received diet-related education material s. MAIN OUTCOME MEASURE Change in body weight from baseline to follow-up . RESULTS Women in the intervention group lost weight in the first year ( mean of 2.2 kg , P<.001 ) and maintained lower weight than control women during an average 7.5 years of follow-up ( difference , 1.9 kg , P<.001 at 1 year and 0.4 kg , P = .01 at 7.5 years ) . No tendency toward weight gain was observed in intervention group women overall or when stratified by age , ethnicity , or body mass index . Weight loss was greatest among women in either group who decreased their percentage of energy from fat . A similar but lesser trend was observed with increases in vegetable and fruit servings , and a nonsignificant trend toward weight loss occurred with increasing intake of fiber . CONCLUSION A low-fat eating pattern does not result in weight gain in postmenopausal women . Clinical Trial Registration Clinical Trials.gov , NCT00000611 OBJECTIVE Our objective was to study the effects of physical training combined with dietary measures in obese adults . In a second step , we sought to compare two training protocol s and establish the additional contribution of strength training . METHODS We performed a r and omized , prospect i ve survey from July 2004 to November 2007 . Included patients were r and omized into three groups : a control group ( G1 ) , a group ( G2 ) performing dietary measures and a programme of treadmill training at 60 % of each individual 's maximum heart rate ( HRmax ) and a group ( G3 ) who followed the G2 programme supplemented with strength training . All patients underwent an initial and final assessment of anthropometric & cardiovascular parameters , muscle strength , dyspnoea during activities of daily living , metabolic disorders , psychological status and quality of life . RESULTS The greatest weight loss ( 7.24 % ) was observed in G3 . Reduction in waistline measurement ( WL ) of 4.3 % and 10.26 % were noted in G2 and G3 , respectively ( p < 0.001 ) . The percentage fat body mass fell by 10.4 % in G3 ( p < 0.001 ) and 8.6 % in G2 ( p = 0.03).We particularly noted an improvement in physical condition in groups 2 and 3 , with lower HR and blood pressure values at rest and at maximum effort . The overall improvement in both arm and leg muscle strength was greater for G3 than for G2 . Likewise , we noted an improvement in the metabolic parameters and depression & anxiety scores for the trained groups ( G2 , G3 ) , relative to the control group ( G1 ) . We also noted improvements in the total impact of weight on quality of life ( IWQOL ) lite score of 15.2 % in G2 and 18 % in G3 . CONCLUSION Our survey demonstrated the beneficial effect of combining dietary measures and physical training in obese patients . In addition to weight loss , the programme enabled a reduction in the patients ' body fat mass and abdominal obesity , a correction of metabolic disorders and an improvement in aerobic capacity . The improvement in all these parameters also enhanced the patients ' psychological status and quality of life . The addition of strength training produced notable improvements in weight loss , arm muscle strength and abdominal obesity The goal of evidence -based medicine is ultimately to improve patient outcomes and quality of care . Systematic review s of the available published evidence are required to identify interventions that lead to improvements in behavior , health , and well-being . Authoritative literature review s depend on the quality of published research and research reports . The Consoli date d St and ards for Reporting Trials ( CONSORT ) Statement ( www.consort-statement.org ) was developed to improve the design and reporting of interventions involving r and omized clinical trials ( RCTs ) in medical journals . We describe the 22 CONSORT guidelines and explain their application to behavioral medicine research and to evidence -based practice . Additional behavioral medicine-specific guidelines ( e.g. , treatment adherence ) are also presented . Use of these guidelines by clinicians , educators , policymakers , and research ers who design , report , and evaluate or review RCTs will strengthen the research itself and accelerate efforts to apply behavioral medicine research to improve the processes and outcomes of behavioral medicine practice Background Current obesity interventions use intensive behavior changes to achieve large initial weight loss . However , weight regain after treatment is common , and drop out rates are relatively high . Smaller behavioral changes could produce initial weight loss and be easier to sustain after active treatment . Purpose We examined the efficacy of an intervention that targeted small but cumulative participant-chosen changes in diet and physical activity ( ASPIRE ) and compared this treatment to st and ard didactic and wait-list control groups . The primary outcome measures were body weight , waist circumference , and intra-abdominal fat . Methods Fifty-nine overweight or obese sedentary adults were r and omized to one of three groups : ( 1 ) the ASPIRE group ( n = 20 ) , ( 2 ) a st and ard educationally-based treatment group ( n = 20 ) , or ( 3 ) a wait list control group ( n = 19 ) for 4 months . Active treatment groups received identical resistance and aerobic training programs . Results Intention-to-treat analyses showed that participants in the ASPIRE group lost significantly more weight than the st and ard and control groups ( −4.4 vs. −1.1 and + 0.1 kg , respectively ) , and the greater initial weight loss in the ASPIRE group was sustained 3 months after active treatment ( 4.1 kg ) . An alternative analytic strategy ( 0.3 kg/month weight gain for those lost to follow-up ) showed continued weight loss ( −0.2 kg after active treatment ; −4.6 kg from baseline ) at follow-up in the ASPIRE group . Similar patterns were observed for the other adiposity measures . Conclusion More modest behavioral changes are capable of promoting weight loss , decreasing adiposity markers and sustaining these changes over 3 months . Longer-term studies comparing this approach with traditional behavioral weight loss treatments are warranted Purpose This study developed and tested a culturally appropriate , church-based intervention to improve diabetes self-management . Research Design and Methods This was a r and omized trial conducted at 24 African American churches in central North Carolina . Churches were r and omized to receive the special intervention ( SI ; 13 churches , 117 participants ) or the minimal intervention ( MI ; 11 churches , 84 participants ) . The SI included an 8-month intensive phase , consisting of 1 individual counseling visit , 12 group sessions , monthly phone contacts , and 3 encouragement postcards , followed by a 4-month reinforcement phase including monthly phone contacts . The MI received st and ard educational pamphlets by mail . Outcomes were assessed at 8 and 12 months ; the primary outcome was comparison of 8-month A1C levels . Results At baseline , the mean age was 59 years , A1C 7.8 % , and body mass index 35.0 kg/m2 ; 64 % of participants were female . For the 174 ( 87 % ) participants returning for 8-month measures , mean A1C ( adjusted for baseline and group r and omization ) was 7.4 % for SI and 7.8 % for MI , with a difference of 0.4 % ( 95 % confidence interval [ CI ] , 0.1 - 0.6 , P = .009 ) . In a larger model adjusting for additional variables , the difference was 0.5 % ( 95 % CI , 0.2 - 0.7 , P < .001 ) . At 12 months , the difference between groups was not significant . Diabetes knowledge and diabetes-related quality of life significantly improved in the SI group compared with the MI group . Among SI participants completing an acceptability question naire , intervention components and material s were rated as highly acceptable . Conclusions The church-based intervention was well received by participants and improved short-term metabolic control BACKGROUND Dietary energy density ( ED ) reductions are associated with energy intake ( EI ) reductions . Little is known about influences on body weight ( BW ) . OBJECTIVES We examined the effects of behavioral interventions on ED values and explored how 6-mo ED changes relate to BW . DESIGN Prehypertensive and hypertensive persons were r and omly assigned to 1 of 3 groups : the established group received an 18-session intervention implementing well-established hypertension recommendations ( eg , weight loss , sodium reduction , and physical activity ) , the established+Dietary Approaches to Stop Hypertension ( DASH ) group received an 18-session intervention also implementing the DASH diet , and the advice group received 1 session on these topics . Two 24-h dietary recalls were collected ( n=658 ) . RESULTS Each group had significant declines in EI , ED , and BW . The established and established+DASH groups had the greatest EI and BW reductions . The established+DASH group had the greatest ED reduction and the greatest increase in the weight of food consumed . When groups were combined and analyzed by ED change tertiles , participants in the highest tertile ( ie , largest ED reduction ) lost more weight ( 5.9 kg ) than did those in the middle ( 4.0 kg ) or lowest ( 2.4 kg ) tertile . Participants in the highest and middle tertiles increased the weight of food they consumed ( 300 and 80 g/d , respectively ) but decreased their EI ( 500 and 250 kcal/d ) . Conversely , those in the lowest tertile decreased the weight of food consumed ( 100 g/d ) , with little change in EI . The highest and middle tertiles had favorable changes in fruit , vegetable , vitamin , and mineral intakes . CONCLUSION Both large and modest ED reductions were associated with weight loss and improved diet quality BACKGROUND Although it is known that abdominal obesity increases the risk of chronic diseases , prospect i ve data examining the relation between lifestyle factors and the accumulation of abdominal adipose tissue are sparse . OBJECTIVE The objective of the study was to determine the associations of changes in diet , physical activity , alcohol consumption , and smoking with 9-y waist gain among US men . DESIGN A prospect i ve cohort comprised 16 587 US men aged 40 - 75 y at baseline in 1986 . Data on lifestyle factors were provided periodically with the use of self-reported question naires , and participants measured and reported their waist circumference in 1987 and 1996 . RESULTS In multivariate analyses , a 2 % increment in energy intake from trans fats that were isocalorically substituted for either polyunsaturated fats or carbohydrates was significantly associated with a 0.77-cm waist gain over 9 y ( P < 0.001 for each comparison ) . An increase of 12 g total fiber/d was associated with a 0.63-cm decrease in waist circumference ( P < 0.001 ) , whereas smoking cessation and a 20-h/wk increase in television watching were associated with a 1.98-cm and 0.59-cm waist gain , respectively ( P < 0.001 ) . Increases of 25 metabolic equivalent tasks ( METs ) * h/wk in vigorous physical activity and of > /= 0.5 h/wk in weight training were associated with 0.38-cm and 0.91-cm decreases in waist circumference , respectively ( P < 0.001 for each comparison ) . These associations remained significant after further adjustment for concurrent change in body mass index . Changes in total fat and alcohol consumption and in walking volume were not significantly related to waist gain . CONCLUSIONS Waist gain may be modulated by changes in trans fat and fiber consumption , smoking cessation , and physical activity OBJECTIVES To examine the long-term effects of a new behavioral weight control program ( Kenkou-tatsujin , KT program ) . The program consisted of twice-interactive letter communications including computer-tailored personal advice on treatment needs and behavioral modification . DESIGN A r and omized controlled trial comparing Group KM : KT program with 6-month weight and targeted behavior 's self-monitoring , Group K : KT program only , Group BM : an untailored self-help booklet with 7-month self-monitoring of weight and walking , and Group B : the self-help booklet only . PARTICIPANTS Two hundreds and five overweight Japanese females were recruited via a local newspaper . MEASUREMENTS Weight loss ( body weight , BMI , reduction quotient , etc . ) and behavioral changes ( daily eating , exercise and sleeping habits ) . FINDINGS A significant weight loss was observed in all groups . At 1 month , Groups KM and K were superior , but at 7 months , the mean weight loss was significantly more in Group KM than the other 3 groups . At 7 months , 8 dietary habits and 4 physical activities were improved in all subjects . Habitual improvement was related to the weight loss in Groups KM and K at 1 month Objective : To compare the effects of aerobic and resistance exercise on weight , muscle strength , cardiovascular fitness , blood pressure and mood in obese women who were not on an energy-restricted diet . Design : R and omized , prospect i ve , controlled trial . Setting : Department of Physical Medicine and Rehabilitation , University Hospital . Subjects : Sixty obese women were assigned to one of three groups : aerobic exercise ( n=20 ) , resistance exercise ( n=20 ) and control group ( n=20 ) . Interventions : The aerobic exercise group performed both walking and leg cycle exercise with increasing duration and frequency . The resistance exercise group performed progressive weight-resistance exercises for the upper and lower body . Main outcome measures : Before and after a 12-week period , all subjects were evaluated by anthropometric measurement , rating of mood , cardiorespiratory capacity and maximum strength of trained muscles . Results : After a 12-week training period , subjects in the resistance group showed significant improvement in one-repetition maximum test of hip abductors ( 7.95±3.58 kg ) , quadriceps ( 14±7.18 kg ) , biceps ( 3.37± 2.84 kg ) and pectorals ( 8.75±5.09 kg ) compared with those in the control group ( P<0.001 ) . VO2 max increased ( 0.51±0.40 ) and Beck Depression Scale scores decreased ( -5.40±4.27 ) in the aerobic exercise group compared with the control group , significantly ( P<0.001 ) . Only in hip abductor muscle strength was there a significant increase in the resistance exercise group compared with the aerobic exercise group ( P < 0.05 ) . Conclusion : Both aerobic exercise and resistance exercise result ed in improved performance and exercise capacity in obese women . While aerobic exercise appeared to be beneficial with regard to improving depressive symptoms and maximum oxygen consumption , resistance exercise was beneficial in increasing muscle strength OBJECTIVE To test the hypothesis that family dietary coaching would improve nutritional intakes and weight control in free-living ( noninstitutionalized ) children and parents . DESIGN R and omized controlled trial . SETTING Fifty-four elementary schools in Paris , France . PARTICIPANTS One thous and thirteen children ( mean age , 7.7 years ) and 1013 parents ( mean age , 40.5 years ) . INTERVENTION Families were r and omly assigned to group A ( advised to reduce fat and to increase complex carbohydrate intake ) , group B ( advised to reduce both fat and sugar and to increase complex carbohydrate intake ) , or a control group ( given no advice ) . Groups A and B received monthly phone counseling and Internet-based monitoring for 8 months . OUTCOME MEASURES Changes in nutritional intake , body mass index ( calculated as weight in kilograms divided by height in meters squared ) , fat mass , physical activity , blood indicators , and quality of life . RESULTS Compared with controls , participants in the intervention groups achieved their nutritional targets for fat intake and to a smaller extent for sugar and complex carbohydrate intake , leading to a decrease in energy intake ( children , P < .001 ; parents , P = .02 ) . Mean changes in body mass index were similar among children ( group A , + 0.05 , 95 % confidence interval [ CI ] , - 0.06 to 0.16 ; group B , + 0.10 , 95 % CI , - 0.03 to 0.23 ; control group , + 0.13 , 95 % CI , 0.04 - 0.22 ; P = .45 ) , but differed in parents ( group A , + 0.13 , 95 % CI , - 0.01 to 0.27 ; group B , - 0.02 , 95 % CI , - 0.14 to 0.11 ; control group , + 0.24 , 95 % CI , 0.13 - 0.34 ; P = .001 ) , with a significant difference between group B and the control group ( P = .01 ) . CONCLUSIONS Family dietary coaching improves nutritional intake in free-living children and parents , with beneficial effects on weight control in parents . Trial Registration clinical trials.gov Identifier : NCT00456911 OBJECTIVES We examined the viability and efficacy of a known quantity of exercise in facilitating weight loss among previously sedentary or irregularly active overweight and obese adult women residing in a slum ( favela ) in Brazil . METHODS In this r and omized controlled trial , 156 women were r and omized to a control or intervention group ( 78 in each group ) . Exercise was supervised , consisting of three 50-minute aerobic sessions each week for 6 months . RESULTS Ninety-one percent ( 71 ) of the participants in the intervention group completed 6 months of the exercise program . At 6 months , women in the treatment group showed significant reduction in weight ( mean=-1.69 kg ; 95 % confidence interval [CI]=-2.36,-1.03 ) and body mass index ( mean=-0.63 kg/m2 ; 95 % CI=-0.97 , -0.30 ) compared with controls ( P for both<.001 ) . CONCLUSIONS A moderately intense , structured exercise program result ed in modest weight loss in women when sustained for 6 months Prevention of type 2 diabetes by intensive lifestyle intervention design ed to achieve and maintain ideal body weight was assessed in subjects with impaired glucose tolerance ( IGT ) . Male subjects with IGT recruited from health-screening examinees were r and omly assigned in a 4:1 ratio to a st and ard intervention group ( control group ) and intensive intervention group ( intervention group ) . The final numbers of subjects were 356 and 102 , respectively . The subjects in the control group and in the intervention group were advised to maintain body mass index ( BMI ) of < 24.0 kg/m2 and of < 22.0 kg/m2 , respectively , by diet and exercise . In the intervention group , detailed instructions on lifestyle were repeated every 3 - 4 months during hospital visits . Diabetes was judged to have developed when two or more consecutive fasting plasma glucose ( FPG ) values exceeded 140 mg/dl . A 100 g oral glucose tolerance test was performed every 6 months to detect improvement of glucose tolerance . The subjects were seen in an ordinary outpatient clinic . The cumulative 4-year incidence of diabetes was 9.3 % in the control group , versus 3.0 % in the intervention group , and the reduction in risk of diabetes was 67.4 % ( P < 0.001 ) . Body weight decreased by 0.39 kg in the control group and by 2.18 kg in the intervention group ( P < 0.001 ) . The control group was subclassified according to increase and decrease in body weight . The incidence of diabetes was positively correlated with the changes in body weight , and the improvement in glucose tolerance was negatively correlated . Subjects with higher FPG at baseline developed diabetes at a higher rate than those with lower FPG . Higher 2h plasma glucose values and higher BMI values at baseline were also associated with a higher incidence of diabetes , but the differences were not significant . Subjects with a low insulinogenic index ( DeltaIRI/DeltaPG 30 min after an oral glucose load ) developed diabetes at a significantly higher rate than those with a normal insulinogenic index . Comparison of the BMI data and incidence of diabetes in five diabetes prevention studies by lifestyle intervention revealed a linear correlation between the incidence of diabetes and the BMI values , with the exception of the DaQing Study . However , the slope of the reduction in incidence of diabetes in the intensive intervention groups was steeper than expected simply on the basis of the reduction of BMI , suggesting that the effect of lifestyle intervention can not be solely ascribed to the body weight reduction . We conclude that lifestyle intervention aim ed at achieving ideal body weight in men with IGT is effective and can be conducted in an outpatient clinic setting OBJECTIVES We tested a community-based intervention design ed to reduce cardiovascular disease risk in sedentary midlife and older women who were overweight or obese . METHODS In a r and omized controlled trial conducted in 8 counties in Arkansas and Kansas , counties were assigned to the intervention ( a 12-week twice-weekly heart health program ) group or to the delayed-intervention control group . Ten to fifteen women were selected from each site , and participants ' weight , waist circumference , diet , physical activity , and self-efficacy were measured before and after the intervention . Data were analyzed with multiple regressions . RESULTS Compared with the control group , participants in the intervention group had a significant decrease in body weight ( -2.1 kg ; 95 % confidence interval [ CI ] = -3.2 , -1.0 ) , waist circumference ( -2.3 in ; 95 % CI = -4.2 , -0.5 ) , and energy intake ( -390 kcal/day ; 95 % CI = -598 , -183 ) ; an increase in activity ( + 1637 steps/day ; 95 % CI = 712 , 2562 ) ; and an increase in self-efficacy for dietary and physical activity behaviors . CONCLUSIONS Our results suggest that a community-based program can improve self-efficacy , increase physical activity , and decrease energy intake , result ing in decreased waist circumference and body weight among at-risk women Objective To assess the effect of weight loss induced by a very low energy diet on moderate and severe obstructive sleep apnoea in obese men . Design Single centre , two arm , parallel , r and omised , controlled , open label trial . Blocked r and omisation procedure used for treatment allocation . Setting Outpatient obesity clinic in a university hospital in Stockholm , Sweden . Participants 63 obese men ( body mass index 30 - 40 , age 30 - 65 years ) with moderate to severe obstructive sleep apnoea ( apnoea-hypopnoea index ( AHI ) ≥15 ) , treated with continuous positive airway pressure . Interventions The intervention group received a liquid very low energy diet ( 2.3 MJ/day ) for seven weeks to promote weight loss , followed by two weeks of gradual introduction of normal food , reaching 6.3 MJ/day at week 9 . The control group adhered to their usual diet during the nine weeks of follow-up . Main outcome measure AHI , the major disease severity index for obstructive sleep apnoea . Data from all r and omised patients were included in an intention to treat analysis ( baseline carried forward for missing data ) . Results Of the 63 eligible patients , 30 were r and omised to intervention and 33 to control . Two patients in the control group were dissatisfied with allocation and immediately discontinued . All other patients completed the trial . Both groups had a mean AHI of 37 events/h ( SD 15 ) at baseline . At week 9 , the intervention group ’s mean body weight was 20 kg ( 95 % confidence interval 18 to 21 ) lower than that of the control group , while its mean AHI was 23 events/h ( 15 to 30 ) lower . In the intervention group , five of 30 ( 17 % ) were disease free after the energy restricted diet ( AHI < 5 ) , with 15 of 30 ( 50 % ) having mild disease ( AHI 5 - 14.9 ) , whereas the AHI of all patients in the control group except one remained at 15 or higher . In a subgroup analysis of the intervention group , baseline AHI significantly modified the effectiveness of treatment , with a greater improvement in AHI in patients with severe obstructive sleep apnoea ( AHI > 30 ) at baseline compared with those with moderate ( AHI 15 - 30 ) sleep apnoea ( AHI −38 v −12 , P<0.001 ) , despite similar weight loss ( −19.2 v −18.2 kg , P=0.55 ) . Conclusion Treatment with a low energy diet improved obstructive sleep apnoea in obese men , with the greatest effect in patients with severe disease . Long term treatment studies are needed to vali date weight loss as a primary treatment strategy for obstructive sleep apnoea . Trial registration Current Controlled Trials IS RCT N70090382 Caloric restriction ( CR ) decreases circulating triiodothyronine ( T(3 ) ) concentration . However , it is not known if this effect is due to body fat mass reductions or due to CR , per se . The purpose of this study was to test the hypothesis that plasma T(3 ) concentration decreases with CR-induced reductions in fat mass but not in response to similar decreases in fat mass that are induced by exercise . Sedentary , nonobese 50- to 60-year-old men and women with no clinical evidence of cardiovascular or metabolic disease and not taking thyroid medications were r and omly assigned to 12 months of caloric restriction ( n = 18 ) or exercise-induced weight loss ( n = 17 ) or to a control group ( n = 9 ) . Body weight and composition and plasma concentrations of the thyroid hormones T(3 ) , thyrotropin ( TSH ) , thyroxine ( T(4 ) ) , and free thyroxine ( FT(4 ) ) were measured at baseline and 12 months . Fat mass changed significantly in the CR ( -6.3 + /- 1.0 kg ) and exercise ( -5.5 + /- 1.0 kg ) groups but not in the control group ( -0.6 + /- 1.4 kg ) . The changes were not significantly different between the CR and exercise groups . Plasma T(3 ) concentration decreased in the CR group ( -9.8 + /- 2.0 ng/dL , p < 0.0001 ) but not in the exercise ( -3.8 + /- 2.1 ng/dL , p = 0.07 ) or control ( -1.3 + /- 2.8 ng/dL , p = 0.65 ) groups . TSH , T(4 ) , and FT(4 ) did not change in any of the study groups . Twelve months of CR decreased circulating T(3 ) concentrations in middle-aged adults . This effect does not appear to be attributable to changes in body fat mass because a comparable decrease in T(3 ) concentration was not observed in response to an exercise-induced fat mass reduction Objective : To describe and evaluate long-term efficacy ( 18 months from the end of treatment ) of a new cognitive short-term weight reducing treatment program for obese patients . Subjects : One hundred and five obese [ Body Mass Index ( BMI ) ≥30 ] patients participated in the study . Of these , 62 took part in the treatment program and 43 served as controls . Method : From an obesity unit ’s waiting list , the patients were r and omly assigned to either a treatment group or remained in the waiting list to serve as a control group . The treatment group participated in a 10-week ( 30 hours ) cognitive group treatment program . All participants were weighed at the outset of the study , directly after treatment and at a 6- , 12- and 18-month post-treatment follow-up without any booster treatment after the 10-week program . Results : Fifty-seven ( 92 % ) patients completed treatment . For the 34 ( 60 % ) patients who participated in the study 18 months after treatment was terminated , the mean weight loss at treatment ’s end was 8.5 kg ( SD=16.1 ) . Eighteen months later their mean weight loss was 10.4 kg ( SD=10.8 ) . The control patients ( n=31 , 72 % ) that participated in the study during the same period increased in weight by 2.3 kg ( SD=7.0 ) . The weight difference between the treatment and control group at the 18-month follow-up was highly significant ( p<0.001 ) . Conclusion : The cognitive group treatment program was highly acceptable among the participants and was completed by nearly all the patients . The 10-week treatment program result ed in satisfactory weight loss . The weight difference between the treatment group and controls was nearly the same at 18 monthts after end of treatment as at six months . The study , therefore , does not provide support for the contention that a lengthy therapy for obesity is necessary if treatment results are lasting We tested the hypothesis that weight loss via a hypocaloric diet would reduce arterial stiffness in overweight and obese middle-aged and older adults . Thirty-six individuals were r and omly assigned to a weight loss ( n=25 ; age : 61.2±0.8 years ; body mass index : 30.0±0.6 kg/m2 ) or a control ( n=11 ; age : 66.1±1.9 years ; body mass index : 31.8±1.4 kg/m2 ) group . Arterial stiffness was measured via carotid artery ultrasonography combined with applanation tonometry and carotid-femoral pulse wave velocity via applanation tonometry at baseline and after the 12-week intervention . Body weight , body fat , abdominal adiposity , blood pressure , & bgr;-stiffness index , and carotid-femoral pulse wave velocity were similar in the 2 groups at baseline ( all P>0.05 ) . Body weight ( −7.1±0.7 versus −0.7±1.1 kg ) , body fat , and abdominal adiposity decreased in the weight loss group but not in the control group ( all P<0.05 ) . Brachial systolic and diastolic blood pressures declined ( P<0.05 ) only in the weight loss group . Central systolic and pulse pressures did not change significantly in either group . & bgr;-Stiffness index ( −1.24±0.22 versus 0.52±0.37 U ) and carotid-femoral pulse wave velocity ( −187±29 versus 15±42 cm/s ) decreased in the weight loss group but not in the control group ( all P<0.05 ) . The reductions in carotid-femoral pulse wave velocity were correlated with reductions in total body and abdominal adiposity ( r=0.357–0.602 ; all P<0.05 ) . However , neither total body nor abdominal adiposity independently predicted reductions in arterial stiffness indices . In summary , our findings indicate that weight loss reduces arterial stiffness in overweight/obese middle-aged and older adults , and the magnitudes of these improvements are related to the loss of total and abdominal adiposity BACKGROUND Caloric restriction ( CR ) increases maximal life span in short-lived organisms , and its effects are being explored in nonhuman primates . The objectives of this study were to determine the feasibility of prolonged CR in nonobese adults and to compare the effects of CR- and exercise-induced weight loss on body composition and abdominal adiposity . METHODS A r and omized , controlled trial was conducted with 48 healthy , nonobese women and men , aged 57 + /- 1 ( mean + /- st and ard error [ SE ] ) years , with body mass index 27.3 + /- 0.3 kg/m2 . Participants were r and omly assigned to a 20 % calorically-restricted diet ( CR , n = 19 ) , exercise design ed to produce a similar energy deficit ( EX , n = 19 ) , or a healthy lifestyle control group ( HL , n = 10 ) for 1 year . Assessment s included weight , body composition by dual-energy x-ray absorptiometry , abdominal adipose tissue by magnetic resonance imaging , and energy intake by doubly labeled water . RESULTS The average level of CR achieved by the CR group was 11.5 + /- 2.1 % , and the EX group completed 59 + /- 6.7 % of their prescribed exercise . Weight changes were greater ( p < or=.0005 ) in the CR ( -8.0 + /- 0.9 kg ) and EX ( -6.4 + /- 0.9 ) groups as compared to the HL group ( -1.3 + /- 0.9 kg ) , corresponding to reductions of 10.7 % , 8.4 % , and 1.7 % of baseline weights , respectively . Whole-body fat mass and visceral and subcutaneous abdominal adipose tissue decreased significantly ( p < .005 ) and comparably in the CR and EX groups , but did not change in the HL group . CONCLUSIONS CR for 1 year was feasible , but the level of CR achieved was less than prescribed . CR and exercise were equally effective in reducing weight and adiposity Aim : The aim of the study was to develop and implement an obesity and weight gain prevention program targeted to a high-risk group . Method : Women , 18–28 years old , with at least one severely obese parent , were r and omized to the intervention or control group of the ‘ Health Hunters ’ program . During 1 year of follow-up , the intervention group received an individualized behavioral program focusing on food choice , physical activity and other lifestyle factors . Anthropometric measures , DXA-based body composition and fitness levels were measured at baseline and after 1 year . Self-reported changes in obesity-related behaviors were also assessed . Results : Baseline examinations were conducted in 40 women , of whom 30 completed follow-up examinations 1 year later . Pregnancy was the most common reason for failure to complete the study . Compared to the control group ( which gained weight ) , the intervention group displayed significant improvements in body weight , body mass index , waist circumference , waist-to-hip ratio and self-reported physical activity . Changes in body composition , although not significant , suggested that the intervention tended to be associated with improved body composition . Further analysis of changes in diet and fitness in relation to concurrent weight changes indicated that the strongest ‘ protective ’ associations were for energy percent protein , fiber density and fitness . Conclusion : Pilot data from the Health Hunters obesity prevention program indicates that it is effective in high-risk young women with familial predisposition for obesity Objective : To evaluate the efficacy of a simple weight loss intervention , based on principles of habit formation . Design : An exploratory trial in which overweight and obese adults were r and omized either to a habit-based intervention condition ( with two subgroups given weekly vs monthly weighing ; n=33 , n=36 ) or to a waiting-list control condition ( n=35 ) over 8 weeks . Intervention participants were followed up for 8 months . Participants : A total of 104 adults ( 35 men , 69 women ) with an average BMI of 30.9 kg m−2.Intervention : Intervention participants were given a leaflet containing advice on habit formation and simple recommendations for eating and activity behaviours promoting negative energy balance , together with a self-monitoring checklist . Main outcome measures : Weight change over 8 weeks in the intervention condition compared with the control condition and weight loss maintenance over 32 weeks in the intervention condition . Results : At 8 weeks , people in the intervention condition had lost significantly more weight ( mean=2.0 kg ) than those in the control condition ( 0.4 kg ) , with no difference between weekly and monthly weighing subgroups . At 32 weeks , those who remained in the study had lost an average of 3.8 kg , with 54 % losing 5 % or more of their body weight . An intention-to-treat analysis ( based on last-observation-carried-forward ) reduced this to 2.6 kg , with 26 % achieving a 5 % weight loss . Conclusions : This easily disseminable , low-cost , simple intervention produced clinical ly significant weight loss . In limited re source setting s it has potential as a tool for obesity management We assessed the major factors regulating adiponectin levels and the influence of exercise training on adiponectin levels in young obese men ( 19.2±1.1 yrs , BMI : 31.1±4.2 , % fat : 27.2±3.9 % ) . Subjects were separated into three groups ( aerobic exercise group [ AE : n=7 ] , aerobic and resistance exercise group [ AE+RE : n=7 ] , control group [ n=7 ] ) . AE underwent an 8-week training program ( three times per week , more than 30 min endurance exercise at ventilatory threshold ( VT ) intensity ) . AE+RE went through resistance exercise two or three times per week together with the above endurance exercise for 5 months . Prior to intervention ( n=21 ) , adiponectin levels were significantly correlated with percentage of fat . Stepwise multiple regression analysis revealed that percent body fat was an independent predictor of basal adiponectin levels ( r2=0.370 ; P<0.01 ) . After intervention , fat mass , and VT were significantly improved in AE . AE+RE exhibited significant reduction in weight , BMI , percent body fat and fat mass , and had significantly increased VT , $ $ \ifmmode\exp and after\dot\else\exp and after\.\fi{V}{\text{O}}_{2 } \max , $ $ cycling power and torque . Insulin was not changed in both groups . The control group exhibited no significant change in any variables . Although adiponectin levels were unchanged in the three groups , a significant negative correlation between delta fat mass and delta adiponectin levels was observed ( n=21 , r=−0.461 , P<0.05 ) . In addition , delta percent body fat was an independent predictor of delta adiponectin levels ( r2=0.327 , P<0.05 ) . These findings indicate that for increasing the adiponectin level , improvement of the body composition of young obese men is more important than the way training is performed Aims : To evaluate the effects of a lifestyle intervention programme in primary healthcare , targeted to patients with moderate to high risk of cardiovascular disease in terms of cardiovascular risk factors , physical activity , and quality of life . Method : R and omized controlled trial with one-year follow-up , carried out in a primary healthcare centre in Northern Sweden . A total of 151 middle-aged men and women , with hypertension , dyslipidemia , type 2 diabetes , or obesity were enrolled . The subjects were r and omized to either the intervention ( n=75 ) or the control group ( n=76 ) . A total of 123 subjects completed the one-year follow-up . Interventions : Exercise : supervised endurance and circuit training in groups three times a week for three months . Diet : five group sessions of diet counselling with a dietitian . Follow- up meetings with a physiotherapist were conducted monthly thereafter . Primary outcomes were changes in anthropometry , maximal oxygen uptake , health-related quality of life , and self-reported physical activity . The secondary outcomes were changes in blood pressure and metabolic variables . Results : After one year the intervention group significantly increased maximal oxygen uptake , physical activity , and quality of life and significantly decreased body weight , waist and hip circumference , body mass index , waist — hip ratio , systolic and diastolic blood pressure , triglycerides , and glycosylated haemoglobin . There were significant differences between groups , mean changes ( and their 95 % confidence intervals , CI ) in waist circumference -1.9 cm ( -2.80 to -0.90 ; p<0.001 ) , in waist — hip ratio -0.01 ( -.02 to -0.004 ; p<0.01 ) and in diastolic blood pressure -2.3 mmHg ( -4.04 to -0.51 ; p<0.05 ) . Conclusion : A prevention programme in primary healthcare with a focus on physical activity and diet counselling followed by structured follow-up meetings can favourably influence several risk factors for cardiovascular diseases and quality of life in high-risk subjects for at least one year Obesity and diabetes have caused problems for individuals with schizophrenia long before atypical antipsychotic agents . The prevalence of obesity , insulin resistance , impaired glucose tolerance , type 2 diabetes mellitus , dyslipidemia , and the Metabolic Syndrome has increased in people with schizophrenia as compared to the general population . Risk reduction studies for persons with obesity , diabetes , and cardiovascular disease indicate that cognitive/behavioral interventions that promote motivation and provide strategies to overcome the barriers in adherence to diet and activity modification are effective interventions for weight management and risk reduction . In the l and mark multi-center r and omized-controlled trial study , the Diabetes Prevention Project ( DPP ) , a cognitive/behavioral intervention , was more successful in producing weight loss and preventing diabetes than the drugs metformin , troglitazone or placebo . This pilot study examined the effectiveness of a cognitive/behavioral group intervention , modified after the DPP program , in individuals with schizophrenia or schizoaffective disorder taking atypical antipsychotics in a large urban public mental health system . Outcome measures included body weight , body mass index , waist-hip ratios , and fasting glucose levels . Both groups demonstrated elevated fasting glucose levels and were obese with a mean BMI of 33 . The group that received the cognitive/behavioral group intervention lost more weight than the treatment as usual group . The CB group participants lost an average of 5.4 lb or 2.9 % of body weight , and those in the control group lost 1.3 lb or 0.6 % body weight . The range of weight loss for the treatment group was from 1 to 20 lb . This pilot study has demonstrated that weight loss is possible with cognitive/behavioral interventions in a population with a psychotic disorder The Women 's Intervention Nutrition Study is a r and omized clinical trial design ed to evaluate if a lifestyle intervention targeting fat intake reduction influences breast cancer recurrence in women with early stage , resected disease receiving conventional cancer management . This report details the concept , content , and implementation of the low-fat eating plan used in the dietary intervention group of this trial . Intervention group participants were given a daily fat gram goal . The intervention was delivered by central ly trained , registered dietitians who applied behavioral , cognitive , and motivational counseling techniques . The low-fat eating plan was implemented in an intensive phase with eight biweekly ( up to Month 4 ) , individual counseling sessions followed by a maintenance phase ( Month 5 up to and including Year 5 ) with registered dietitian visits every 3 months and optional monthly group sessions . Self-monitoring ( daily fat gram counting and recording ) , goal setting , and motivational interviewing strategies were key components . Dietary fat intake was equivalent at baseline and consistently lower in the intervention compared with the control group at all time points ( percent energy from fat at 60 months 23.2%+/-8.4 % vs 31.2%+/-8.9 % , respectively , P<0.0001 ) and was associated with mean 6.1 lb mean weight difference between groups ( P=0.005 ) at 5 years ( baseline and 5 years , respectively : control 160.0+/-35.0 and 161.7+/-32.8 lb ; intervention 160.2+/-35.1 and 155.6+/-32.1 lb ) . Together with previously reported efficacy results , this information suggests that a lifestyle intervention that reduces dietary fat intake and is associated with modest weight loss may favorably influence breast cancer recurrence . The Women 's Intervention Nutrition Study low-fat eating plan can serve as a model for implementing such a long-term dietary intervention in clinical practice The present study sought to assess the impact of an intervention to reduce weight and control risk factors of noncommunicable chronic diseases in overweight or obese adults who are users of primary and secondary healthcare units of the public health system of Pelotas , Brazil . We hypothesized that individuals who received an educational intervention regarding how to lose weight and prevent other noncommunicable chronic disease risk factors through nutrition would lose weight and acquire active habits during leisure time more frequently than individuals under regular care . Two hundred forty-one participants from the Nutrition Outpatient Clinic of the Medical Teaching Hospital of the Federal University of Pelotas , Brazil , aged 20 years or older and classified as overweight or obese were r and omly allocated to either the intervention group ( IG ; n = 120 ) or control group ( CG ; n = 121 ) . The IG received individualized nutritional care for 6 months , and the CG received individualized usual care of the health services . Intention-to-treat analyses showed that at 6 months , mean fasting glycemia and daily consumption of sweet foods and sodium were reduced , and the time spent on physical leisure activity was increased in IG . Analysis of adherence to the protocol of the study revealed that individuals from IG had lost more in body weight , waist circumference , and fasting glucose compared to the CG . Leisure time physical activity increased in IG . Individuals adhered equally to the dietetic recommendations , irrespective of the nutrition approach that was used Introduction The high prevalence of cardiovascular disease ( CVD ) in the Hispanic population of the United States , together with low rates of health insurance coverage , suggest a potential cardiovascular health crisis . The objective of Project HEART ( Health Education Awareness Research Team ) was to promote behavior changes to decrease CVD risk factors in a high-risk Hispanic border population . Methods Project HEART took place from 2005 through 2008 as a r and omized community trial with a community-based participatory research framework using promotores de salud ( community health workers ) . A total of 328 participants with at least 1 CVD risk factor were selected by r and omizing 10 US Census tracts in El Paso , Texas , to either the experimental or the control group . The experimental group ( n = 192 ) was assigned to a series of 8 health classes using the Su Corazón , Su Vida curriculum . After 2 months of educational sessions , the group was followed for 2 months . The control group ( n = 136 ) was given basic educational material s at baseline , and no other intervention was used . Main outcomes of interest included changes in health behaviors and clinical measures . Results Participants in the experimental group showed more awareness of CVD risk factors , more confidence in the control of these factors , and improved dietary habits ( ie , lower salt and cholesterol intake , better weight-control practice s ) compared with the control group . Total cholesterol was 3 % lower in the experimental than in the control participants , and non – high-density lipoprotein cholesterol and low-density lipoprotein cholesterol were both 5 % lower . Conclusion The HEART trial suggests that community health education using promotores de salud is a viable strategy for CVD risk reduction in a Hispanic border community Increased circulating adiponectin and insulin sensitivity are usually observed after body fat loss induced by a weight-loss diet . Progressive resistance training ( PRT ) without a concomitant weight-loss diet significantly decreases visceral fat , thus improving insulin sensitivity . Therefore , the purpose of this study was to ascertain the effects of combined 16-week PRT and weight-loss diet on circulating adiponectin and insulin sensitivity index . Thirty-four obese ( BMI : 30 - 40 kg/m(2 ) ) women , aged 40 - 60 year , were r and omized to three groups : a control group ( C ; n = 9 ) ; a diet group ( WL ; n = 12 ) with a caloric restriction of 500 kcal/d ; and a diet plus resistance training group ( WL+RT ; n = 13 ) with the same caloric restriction as group WL and a 16-week supervised whole body PRT of two sessions/week . Both WL and WL+RT groups showed similar decreases in body mass ( -6.3 % and -7.7 % ) and visceral fat ( -19.9 % and -20.5 % ) . WL result ed in an expected increase in circulating levels of adiponectin ( P = 0.07 ) and insulin sensitivity . However , circulating total adiponectin decreased ( P < 0.05 ) in WL+RT group , whereas an improvement in different cardiovascular risk factors ( insulin sensitivity , low-density lipoprotein cholesterol ( LDL-C ) , etc . ) was observed . In conclusion , in obese women a 16-week combined PRT and weight-loss diet is accompanied by significant improvements in different cardiovascular risk factors in spite of a significant decrease of circulating adiponectin Aim : To determine the effect of whole body vibration ( WBV ) , combined with caloric restriction , on weight , body composition and metabolic risk factors in overweight and obese adults . Methods : A r and omized , controlled study with a 6-month intervention period and a 6-month ‘ no intervention ’ follow-up . 61 of the 79 participants completed the study . Data were collected at baseline and at 3 , 6 and 12 months in the control group ( CONTROL ) , the diet only group ( DIET ) , the diet plus fitness group ( FITNESS ) and the diet plus WBV group ( VIBRATION ) . Results : Weight decreased significantly in all three intervention groups . Only FITNESS and VIBRATION managed to maintain a weight loss of 5 % or more in the long term . Visceral adipose tissue ( VAT ) changed most in VIBRATION : –47.8 ± 41.2 and –47.7 ± 45.7 cm2 after 6 and 12 months respectively compared to CONTROL ( –3.6 ± 20.5 or + 26.3 ± 30.6 cm2 ) , DIET ( –24.3 ± 29.8 or –7.5 ± 28.3 cm2 ) and FITNESS ( –17.6 ± 36.6 or –1.6 ± 33.3 cm2 ) ( p < 0.001 ) . Conclusions : Combining aerobic exercise or WBV training with caloric restriction can help to achieve a sustained long-term weight loss of 5–10 % . These preliminary data show that WBV training may have the potential to reduce VAT more than aerobic exercise in obese adults , possibly making it a meaningful addition to future weight loss programs Background Exercise and high-protein/reduced-carbohydrate and -fat diets have each been shown separately , or in combination with an energy-restricted diet to improve body composition and health in sedentary , overweight ( BMI > 25 ) adults . The current study , instead , examined the physiological response to 10 weeks of combined aerobic and resistance exercise ( EX ) versus exercise + minimal nutrition intervention design ed to alter the macronutrient profile , in the absence of energy restriction , using a commercially available high-protein/low-carbohydrate and low-fat , nutrient-dense food supplement ( EXFS ) ; versus control ( CON ) . Methods Thirty-eight previously sedentary , overweight subjects ( female = 19 ; male = 19 ) were r and omly assigned to either CON ( n = 10 ) , EX ( n = 14 ) or EXFS ( n = 14 ) . EX and EXFS participated in supervised resistance and endurance training ( 2 × and 3 × /wk , respectively ) ; EXFS consumed 1 shake/d ( weeks 1 and 2 ) and 2 shakes/d ( weeks 3–10 ) . Results EXFS significantly decreased total energy , carbohydrate and fat intake ( -14.4 % , -27.2 % and -26.7 % , respectively ; p < 0.017 ) , and increased protein and fiber intake ( + 52.1 % and + 21.2 % , respectively ; p < 0.017 ) . EX and EXFS significantly decreased fat mass ( -4.6 % and -9.3 % , respectively ; p < 0.017 ) , with a greater ( p < 0.05 ) decrease in EXFS than EX and CON . Muscle mass increase only reached significance in EXFS ( + 2.3 % ; p < 0.017 ) , which was greater ( p < 0.05 ) than CON but not EX ( + 1.1 % ) . Relative VO2max improved in both exercise groups ( EX = + 5.0 % and EXFS = + 7.9 % ; p < 0.017 ) ; however , only EXFS significantly improved absolute VO2max ( + 6.2 % ; p = 0.001 ) . Time-to-exhaustion during treadmill testing increased in EX ( + 9.8 % ) but was significantly less ( p < 0.05 ) than in EXFS ( + 21.2 % ) . Total cholesterol and LDL decreased only in the EXFS ( -12.0 % and -13.3 % , respectively ; p < 0.017 ) . Total cholesterol-to-HDL ratio , however , decreased significantly ( p < 0.017 ) in both exercise groups . Conclusion Absent energy restriction or other dietary controls , provision of a high-protein/low-carbohydrate and -fat , nutrient-dense food supplement significantly , 1 ) modified ad libitum macronutrient and energy intake ( behavior effect ) , 2 ) improved physiological adaptations to exercise ( metabolic advantage ) , and 3 ) reduced the variability of individual responses for fat mass , muscle mass and time-to-exhaustion – all three variables improving in 100 % of EXFS subjects OBJECTIVE To investigate the short- and long-term effectiveness and the predictors of weight loss in a mobile phone weight-loss programme among healthy overweight adults . DESIGN One hundred and twenty-five healthy , overweight ( BMI = 26 - 36 kg/m2 ) , 25 - 44-year-old , screened volunteers were r and omized to an experimental group ( n 62 ) to use a mobile phone-operated weight-loss programme or to a control group ( n 63 ) with no intervention . Via text messaging , the programme instructed a staggered reduction of food intake and daily weight reporting with immediate tailored feedback . Assessment s were at 0 , 3 , 6 , 9 and 12 months for the experimental group ; at 0 and 12 months for the control group . Main outcome variables were changes in body weight and waist circumference . RESULTS By 12 months the experimental group had lost significantly more weight than the control group ( 4.5 ( sd 5.0 ) v. 1.1 ( sd 5.8 ) kg ; F(1,80 ) = 8.0 , P = 0.006 ) and had a greater reduction in waist circumference ( 6.3 ( sd 5.3 ) v. 2.4 ( sd 5.4 ) cm ; F(1,80 ) = 55.2 , P = 0.0001 ) . Early weight loss , self-efficacy , contact frequency , attitudes towards the medium , changes in work and family life and changes made in dietary habits were the strongest predictors of weight loss . CONCLUSIONS This mobile phone weight-loss programme was effective in short- and long-term weight loss . As a minimum-advice , maximal-contact programme , it offers ideas for future weight-loss programmes We evaluated 4 approaches to improving the reporting of disease prevention and screening behaviors . The conditions evaluated include ( 1 ) the mode in which data are collected , ( 2 ) asking the interview subject about her intention to obtain the procedure before asking whether the behavior occurred , ( 3 ) asking the interview subject about barriers that might keep respondents from getting the procedure before asking about whether she has received it , and ( 4 ) asking the interview subject about exceptions to the regularity with which she might report getting the examination . Data were collected in 2001 from a sample of women aged 50 and older in Champaign-Urbana , Illinois . After completing a telephone or audio computer-assisted self-interview ( ACASI ) , respondents gave permission to abstract their medical records to vali date self-reports of Papanicolaou tests , mammograms , and clinical –gynecologic examinations received during the past 3 years . Interviews and matching medical records were available for 588 respondents . Results indicated that first asking about future intentions may be an important design feature that warrants additional consideration . In addition , the use of ACASI may lead to lower quality reporting among women with little computer experience . This study represents the only research to date that reports experimental attempts to address the social desirability biases commonly found in the reporting of cancer screening behaviors Objectives : To examine whether a weight loss program delivered to one spouse has beneficial effects on the untreated spouse and the home environment . Methods : We assessed untreated spouses of participants in three sites of Look AHEAD , a multicenter r and omized controlled trial evaluating the impact of intentional weight loss on cardiovascular outcomes in overweight individuals with type 2 diabetes . Participants and spouses ( n=357 pairs ) were weighed and completed measures of diet and physical activity at 0 and 12 months . Spouses completed household food and exercise environment inventories . We examined differences between spouses of participants assigned to the intensive lifestyle intervention ( ILI ) or to the enhanced usual care ( DSE ; diabetes support and education ) . Results : Spouses of ILI participants lost −2.2±4.5 kg vs −0.2±3.3 kg in spouses of DSE participants ( P<0.001 ) . In addition , more ILI spouses lost ⩾5 % of their body weight than DSE spouses ( 26 vs 9 % , P<0.001 ) . Spouses of ILI participants also had greater reductions in reported energy intake ( P=0.007 ) and percent of energy from fat ( P=0.012 ) than DSE spouses . Spouse weight loss was associated with participant weight loss ( P<0.001 ) and decreases in high-fat foods in the home ( P=0.05 ) . Conclusion : The reach of behavioral weight loss treatment can extend to a spouse , suggesting that social networks can be utilized to promote the spread of weight loss , thus creating a ripple effect Obesity is a major problem nationwide and even more prevalent among people with psychiatric disabilities . This study examined the efficacy of a psychiatric rehabilitation weight loss program . Twenty-one individuals participated in the 12-week intervention . Another 15 individuals served as matched controls . Results indicate the intervention group improved more than the control group for weight , body mass index , waist circumference and physical activity . The intervention group lost 2.7 kg ( 6 lbs ) and the control group gained 0.5 kg ( 1 lb ) . A weight loss program incorporating psychiatric rehabilitation principles was effective for people with psychiatric disabilities at a community based program OBJECTIVES To identify whether the Coronary Health Improvement Project ( CHIP ) , an intervention design ed to increase physical activity and improve diet , lowers serum C-reactive protein ( CRP ) . The study will also assess whether changes in CRP over the study period are associated with baseline levels of and changes in selected coronary risk factors . METHODS A r and omized controlled study design assigned 348 individuals to the intervention or control group with measurements taken at baseline , 6 weeks , and 6 months of body weight , physical activity , and serum CRP levels . Participants attended an intensive 40-hour educational course delivered over a 4-week period , beginning March 2003 , in Rockford , IL , USA . RESULTS The intervention significantly increased physical activity and decreased BMI , weight , percent body fat , and saturated fat ( P<0.0001 ) . However , the intervention was not significantly associated with a decrease in CRP . Participants in both the intervention and control groups combined showed a decrease in high CRP ( > 3 mg/L ) , from 46 % at baseline to 38 % at 6 weeks and 41 % at 6 months . Those with higher BMI at baseline showed a greater increase in CRP over time ( P<0.0001 ) , whereas those with higher CRP at baseline showed a greater decrease in CRP over time ( P<0.0001 ) . CONCLUSIONS Over 6 week and 6 month follow-up periods , the intervention failed to discriminate changes in CRP . However , the percentage with high CRP did fall , more so for those with lower BMI and higher CRP at baseline . BMI may mediate the influence of physical activity on CRP Objective : To assess the effect of an increased consumption of vegetables and fruit on body weight , risk factors for cardiovascular disease ( CVD ) and antioxidant defense in obese patients with sleep-related breathing disorders ( SRBD ) . Design : R and omized , controlled trial of an intervention to increase the intake of vegetables to 400 g/day and fruit to 300 g/day . Dietary intake was calculated from a food frequency question naire . Antioxidant status was assessed with the ferric-reducing/antioxidant power ( FRAP ) assay . Plasma carotenoids were biomarkers for the intake of vegetables and fruit . Setting : A hospital clinic preventing risk factors for CVD.Subjects : Subjects were 103 men and 35 women with a body mass index of 36.7±5.8 kg/m2 of which 57 ( 86 % ) in the control and 68 ( 94 % ) in the intervention group completed the study .Intervention : Group-based behavioral program during 3 months . Results : The mean between group differences in body weight was −2.0 % ( 95 % CI −3.6 , −0.5 ) , P<0.0001 . The mean between group difference in systolic and diastolic blood pressure ( BP ) was −7.1 mm Hg ( 95 % CI : −11.6 , −2.6 ) , P=0.0022 and −3.9 mm Hg ( 95 % CI : −7.0 , −0.9 ) , P=0.0120 , respectively . The mean change in daily intake of vegetables and fruit was 12 g ( 95 % CI : −33 , 57 ) and −4 g ( 95 % CI : −79 , 71 ) versus 245 g ( 95 % CI : 194 , 296 ) and 248 g ( 95 % CI : 176 , 320 ) in the control and intervention groups , respectively . This was reflected in higher concentrations of α-carotene and β-carotene . No change in FRAP was seen . In a multiple regression analysis the change in intake of vegetables was a significant contributor ( Radj2=0.073 ( 95 % CI : 0.019 , 0.214 ) ) to the change in weight . Conclusion : Targeted dietary advice to increase the intake of vegetables and fruit among subjects with SRBD contributed to weight reduction and reduced systolic and diastolic BP , but had no effect on antioxidant defense measured with FRAP.Sponsorship : None This study examines the effectiveness of a brief self-management intervention to support patients recently diagnosed with type-2 diabetes to achieve sustained improvements in their self-care behaviours . Based on proactive coping , the intervention emphasizes the crucial role of anticipation and planning in maintaining self-care behaviours . In a r and omised controlled trial among recent screen-detected patients , participants who received the intervention were compared with usual-care controls , examining changes in proximal outcomes ( intentions , self-efficacy and proactive coping ) , self-care behaviour ( diet , physical activity and medication ) and weight over time ( 0 , 3 and 12 months ) . Subsequently , the contribution of proactive coping in predicting maintenance of behavioural change was analysed using stepwise hierarchical regression analyses , controlling for baseline self-care behaviour , patient characteristics , and intentions and self-efficacy as measured after the course . The intervention was effective in improving proximal outcomes and behaviour with regard to diet and physical activity , result ing in significant weight loss at 12 months . Furthermore , proactive coping was a better predictor of long-term self-management than either intentions or self-efficacy . Proactive coping thus offers new insights into behavioural maintenance theory and can be used to develop effective self-management interventions Many people use smoking as a weight control mechanism and are averse to quitting for fear of weight gain . These weight-concerned smokers tend to be women , are significantly less likely to stop smoking or to join smoking cessation programs , and will relapse more often than smokers who are not weight-concerned . Research suggests that a woman 's motivation to quit smoking correlates positively with her confidence in her ability to control her weight after quitting . Likewise , success in smoking cessation has been associated with increased self-efficacy for weight control . This r and omized controlled trial investigated the effects of a weight control program on eating and smoking behaviors in a group of female , weight-concerned smokers from July 2005 to June 2006 . Two hundred sixteen subjects who wanted to lose weight but were not yet ready to quit smoking were recruited to participate in a 12-week , cognitive-behavioral weight control program consisting of 12 1-hour sessions . Subjects were r and omly assigned to either the weight-control program ( intervention group ) or the control group . Differences between the intervention and control groups were evaluated using t tests for continuous variables , Wilcoxon rank-sum tests for ordinal variables and chi(2 ) tests for categorical variables . The intervention group had a 14 % increase ( P<0.001 ) in self-efficacy for weight control ( Weight Efficacy Life-Style Question naire ) , which was associated with improved diet quality ( Healthy Eating Index ) ( r=0.292 , P<0.01 ) , weight loss ( r=0.582 , P<0.001 ) , increased self-efficacy for quitting smoking ( Smoking Self-Efficacy Question naire ) ( r=0.291 , P<0.014 ) , a decrease in number of cigarettes smoked ( r=0.331 , P<0.005 ) , and positive movement in stage of change toward smoking cessation ( r=0.435 , P<0.001 ) . These findings suggest that for this group of weight-concerned smokers ' success in changing eating behavior may trigger a positive change in smoking behavior Overweight or obesity is an established negative prognostic factor in breast cancer . Co-morbidities associated with obesity , including cardiovascular disease ( CVD ) , may negatively impact quality of life and survival in this population . Our purpose was to determine the effect of a cognitive behavioral therapy ( CBT ) intervention for weight loss through exercise and diet modification on risk factors for recurrence of breast cancer , and risks for CVD associated with obesity . Eighty-five overweight or obese breast cancer survivors were r and omly assigned to a once weekly , 16-week intervention or wait-list control group . The intervention incorporated elements of CBT for obesity , addressing a reduction in energy intake , as well exercise , with a goal of an average of 1 h a day of moderate to vigorous activity . Body weight , total and regional body fat ( by dual energy X-ray absorptiometry ) , waist and hip circumference , and blood lipids were assessed at baseline and following 16 weeks of intervention . Results : Seventy six women ( 89.4 % ) completed the intervention . Independent t-test to evaluate group differences at 16 weeks showed significant differences in weight , body mass index , percent fat , trunk fat , leg fat , as well as waist and hip circumference between intervention and control groups ( P ≤ 0.05 ) . Furthermore , levels of triglycerides and total cholesterol/high density lipoprotein cholesterol levels were also significantly reduced following the intervention . These results indicate that 16 weeks of a CBT program for weight management may reduce obesity and CVD risk in overweight breast cancer survivors OBJECTIVE This r and omized controlled trial tested a tailored , telephone-based physical activity coaching intervention for a predominantly African American group of women with severe obesity and mobility disability . METHODS We recruited 92 clinic patients from the University of Illinois at Chicago Medical Center referred by their physicians during 2004 - 2007 and r and omized participants to one of three groups -- awareness(informational brochure , no coaching ) , lower support ( phone coaching only ) and higher support ( phone coaching plus monthly exercise support group)--to determine the efficacy of a tailored coaching intervention on key health outcomes , which included body weight and body mass index , blood pressure , cholesterol , physical activity ( barriers and self-reported activity ) , movement and mobility , general health , and social support . RESULTS The higher support group had the greatest reduction in Body Mass Index ( BMI ) ( 7.4 % ) compared with a 0.2 % and 1.6 % increase in BMI for the lower support and awareness groups , respectively ( pb.01 ) . Both the higher and lower support groups had a greater increase in physical activity scores ( 39 % and 30 % , respectively)compared with a decline of 13 % in the awareness group ( pb.05 ) . CONCLUSION Providing phone-based coaching and monthly in-person exercise support group sessions appear to be an effective approach for reducing body weight and increasing physical activity among severely obese , disabled adults residing in difficult social environments OBJECTIVE Women 25 to 45 years old are at risk for weight gain and future obesity . This trial was design ed to evaluate the efficacy of two interventions relative to a control group in preventing weight gain among normal or overweight women and to identify demographic , behavioral , and psychosocial factors related to weight gain prevention . RESEARCH METHODS AND PROCEDURES Healthy women ( N = 284 ) , ages 25 to 44 , with BMI < 30 were r and omized to one of three intervention conditions : a clinic-based group , a correspondence course , or an information-only control . Intervention was provided over 2 years , with a follow-up at Year 3 . BMI and factors related to eating and weight were assessed yearly . RESULTS Over the 3-year study period , 40 % ( n = 114 ) of the women remained at or below baseline body weight ( + /-2 lbs ) , and 60 % gained weight ( > 2 lbs ) . Intervention had no effect on weight over time . Independently of intervention , women who were older , not actively dieting to lose weight , and who reported less perceived hunger at baseline were more likely to be successful at weight maintenance . Weight maintenance also was associated with increasing dietary restraint ( conscious thoughts and purpose ful behaviors to control calorie intake ) and decreasing dietary disinhibition ( the tendency to lose control over eating ) over time . DISCUSSION This study raises concern about the feasibility and efficacy of weight gain prevention interventions because most women were interested in weight loss , rather than weight gain prevention , and the interventions had no effect on weight stability . Novel approaches to the prevention of weight gain are needed OBJECTIVE The majority of endometrial cancer survivors ( ECS ) are obese and at risk for premature death . The purpose of this study was to assess feasibility of a lifestyle intervention program for promoting weight loss , change in eating behaviors , and increased physical activity in obese ECS . STUDY DESIGN Early stage ECS ( n=45 ) were r and omized to a 6-month lifestyle intervention ( LI ; n=23 ) or usual care ( UC ; n=22 ) . The LI group received group and individual counseling for 6 months . The primary endpoint was weight change . Secondary endpoints were physical activity , [ Leisure score index ( LSI ) ] and nutrient intake ( 3-day food records ) . Quantitative vitamin C and folate intake were used to assess fruit/vegetable intake . RESULTS Recruitment was 29 % , adherence ( LI group ) was 73 % and 84 % of participants completed follow-up assessment s. At 12 months , the intervention group lost 3.5 kg compared to a 1.4 kg gain in the control group [ mean difference=-4.9 kg ; 95 % CI : -9.0 to -0.9 kg ; p=.018 ] and had an increased LSI score of 16.4 versus -1.3 in the control group from baseline [ mean group difference=17.8 ; 95 % CI=7.1 to 28.4 ; p=.002 ] . There were no differences in vitamin C and folate intake . The LI group had lower intake of kilocalories , although differences were not significant . CONCLUSION ( S ) A lifestyle intervention program in obese ECS is feasible and can result in sustained behavior change and weight loss over a 1-year period A pilot study was conducted to determine if a nutritional intervention aim ed at portion control leads to significant weight loss in a community of low-income Mexican American women . Nineteen low-income Mexican American women were r and omized to a st and ard care group or an intervention group in portion control . The trial was 20 weeks in length , and the intervention included four 2-hour classes . Both interventions were administered by a certified nurse-midwife ( CNM ) and a promotora de salud ( i.e. , lay health advisor ) . Women in the intervention group lost more weight than women in the st and ard care group , though this difference was not statistically significant . The mean weight loss in the intervention group was 6.57 pounds ( 2.9 kg ) compared to a mean weight loss of 2.8 pounds ( 1.3 kg ) in the st and ard care group ( P = .47 ) . Mean weight loss , regardless of group , was significantly greater when participants reported self-weighing ( P = .02 ) . This pilot study in portion control for low-income Mexican American women merits further study OBJECTIVE We assessed the effect of weight loss on blood pressure ( BP ) and pulse rate during rest , psychological stress , and recovery after stress . METHODS Two groups of men completed two mental stress tests 12 wk apart . The control group continued their usual diet , whereas the weight-loss group underwent a dietary weight-loss program in which they were r and omized to a high-fruit/vegetable and low-fat dairy diet or a low-fat diet . RESULTS Fifty-five men with a baseline BP of 125.9 + /- 6.9/83.6 + /- 7.1 mmHg ( mean + /- SD ) completed the study ( weight-loss group , n = 28 ; control group , n = 27 ) . The weight-loss group lost weight ( mean + /- SEM , -4.3 + /- 0.3 versus + 0.4 + /- 0.4 kg , P = 0.001 ) compared with controls and had a significant decrease in resting systolic BP ( SBP ; -2.0 + /- 1.1 % versus + 2.0 + /- 1.1 % , P < 0.05 ) . There was a greater decrease in SBP ( P < 0.05 ) and pulse rate ( P < 0.05 ) at all time points during the stress test in the weight loss compared with the control group . At week 12 , SBP in 23 ( 82 % ) subjects in the weight-loss group and 24 ( 89 % ) in the control group returned to resting levels , with recovering levels in the weight-loss group returning to resting levels 6.1 + /- 2.6 min earlier than in the control group ( P < 0.05 ) . There was an overall greater decrease in diastolic BP ( DBP ; P < 0.05 ) and DBP during recovery up to 27 min after stress ( P < 0.05 ) in the high-fruit/vegetable and low-fat dairy diet group ( n = 14 ) compared with the low-fat diet group ( n = 14 ) . CONCLUSION A 5 % loss of weight decreased BP during rest and returned SBP to resting levels faster , thus decreasing the period of increased BP as a result of mental stress , which is likely to lower the risk of cardiovascular disease in the long term Objective To assess effects of multifactorial lifestyle modification on antihypertensive drug needs in treated hypertensive individuals . Design R and omized controlled trial . Setting Research studies unit . Participants Overweight hypertensive patients , receiving one or two antihypertensive drugs , were recruited by advertising , and allocated r and omly to a usual care group ( controls ; n = 118 ) or a lifestyle modification group ( programme group ; n = 123 ) . Intervention A 4-month programme of weight loss , a low-sodium ‘ Dietary Approaches to Stop Hypertension’-type diet with added fish , physical activity and moderation of alcohol intake . After 4 months , if mean 24-h ambulatory blood pressure ( ABP ) was less than 135/85 mmHg , antihypertensive drugs were withdrawn over 4 weeks and long-term home blood pressure monitoring was begun . Main outcome measures Antihypertensive drug requirements , ABP , weight , waist girth at 4 months and 1-year follow-up . Results Ninety control group and 102 programme group participants completed the study . Mean 24-h ABP changed after 4 months by −1.0/−0.3 ± 0.5/0.4 mmHg in controls and −4.1/−2.1 ± 0.7/0.5 mmHg with the lifestyle programme ( P < 0.01 ) . At follow-up , changes in the two groups were not significantly different ( 4.1/1.3 ± 1.1/1.0 mmHg in controls ; 2.5/−0.1 ± 1.1/0.8 mmHg in the programme group ; P = 0.73 ) . At 4 months , drug withdrawal differed significantly between the groups ( P = 0.038 ) in men ( control 44 % ; programme 66 % ) but not in women ( 65 and 64 % , respectively ; P = 0.964 ) . At follow-up , sex-related differences were not significant , and 41 % in the control group and 43 % in the programme group maintained drug-withdrawal status . With the programme , net weight loss was 3.3 kg ( P < 0.001 ) at 4 months and 3.0 kg ( P < 0.001 ) at follow-up ; respective net decreases in waist girth were 3.3 cm ( P < 0.001 ) and 3.5 cm ( P < 0.001 ) . Conclusions A 4-month multifactorial lifestyle modification in patients with treated hypertension reduced blood pressure in the short-term . Decreased central obesity persisted 1 year later and could reduce overall cardiovascular risk The aim of this study was to evaluate the effects of a nutrition education program ( NEP ) on anthropometric , dietetic , and metabolic parameters in high-risk subjects for type 2 diabetes mellitus . Fifty-one participants , both sexes , were r and omly assigned to either the control ( 58.8 % ) or the intervention ( NEP ) group . The intervention group received frequent individual and group nutritional counseling from a team of nutritionists . Participants were assessed at baseline ( M0 ) and after 12 months ( M1 ) for anthropometric , dietetic , and metabolic parameters . The hypothesis was that high-risk subjects for type 2 diabetes mellitus participating in NEP would show an improvement in these parameters . At M1 , the intervention group showed a significant decline in body weight ( -3.4 % ) , body mass index ( -5.7 % ) , cholesterol intake ( -49.5 % ) , fasting glycemia ( -14.0 % ) , fasting insulin ( -9.0 % ) , postpr and ial glycemia ( -21.0 % ) , postpr and ial insulin ( -71.0 % ) , total serum cholesterol ( -23.0 % ) , and glycated hemoglobin ( -24.0 % ) . A decrease in energy intake ( 5 % , P = .06 ) and low-density lipoprotein cholesterol ( 25 % , P = .07 ) was observed in the interventional group , although it did not reach statistical significance . In contrast , the control group presented a significantly higher energy intake ( 19 % , P = .04 ) and a nonsignificant increase in consumption of all macronutrients . The long-term NEP was found to improve anthropometric , dietary , and metabolic parameters in high-risk subjects for type 2 diabetes mellitus PURPOSE We evaluated the effect of weight loss on urinary incontinence ( UI ) in overweight and obese women . MATERIAL S AND METHODS A r and omized , controlled clinical trial was conducted among overweight and obese women experiencing at least 4 UI episodes per week . Women were r and omly assigned to a 3-month liquid diet weight reduction program ( 24 in the immediate intervention group ) or a wait-list delayed intervention group ( 24 in the wait-list control group ) . Participants in the wait-list control group began the weight reduction program in month 3 of the study . All women were followed for 6 months after completing the weight reduction program . Wilcoxon tests were used to compare intergroup differences in change in weekly UI episodes and quality of life scores . RESULTS A total of 48 women were r and omized and 40 were assessed 3 months after r and omization . Median ( with 25 % to 75 % interquartile range [ IQR ] ) baseline age was 52 years ( IQR 47 to 59 ) , weight was 97 kg ( IQR 87 to 106 ) and UI episodes were 21 weekly ( IQR 11 to 33 ) . Women in the immediate intervention group had a 16 kg ( IQR 9 to 20 ) weight reduction compared with 0 kg ( IQR -2 to 2 ) in the wait-list control group ( p < 0.0001 ) . The immediate intervention group experienced a 60 % reduction ( IQR 30 % to 89 % ) in weekly UI episodes compared with 15 % ( IQR -9 % to 25 % ) in the wait-list control group ( p < 0.0005 ) and had greater improvement in quality of life scores . Stress ( p = 0.003 ) and urge ( p = 0.03 ) incontinent episodes decreased in the immediate intervention vs wait-list control group . Following the weight reduction program the wait-list control group experienced a similar median reduction in weekly UI episodes ( 71 % ) . Among all 40 women mean weekly UI episodes decreased 54 % ( 95 % CI 40 % to 69 % ) after weight reduction and the improvement was maintained for 6 months . CONCLUSIONS Weight reduction is an effective treatment for overweight and obese women with UI . Weight loss of 5 % to 10 % has an efficacy similar to that of other nonsurgical treatments and should be considered a first line therapy for incontinence AIM The aim of this study was to examine the effect of a cardiac rehabilitation programme on health behaviours and physiological risk parameters in patients with coronary heart disease in Chengdu , China . BACKGROUND Epidemiological studies indicate a dose- , level- and duration -dependent relationship exists between cardiac behavioural and physiological risks and coronary heart disease incidence as well as subsequent cardiac morbidity and mortality . Cardiac risk factor modification has become the very primary goal of modern cardiac rehabilitation programmes . DESIGN METHODS A r and omized controlled trial was conducted . Coronary heart disease patients ( n = 167 ) who met the sampling criteria in two tertiary medical centres in Chengdu , south-west China , were r and omly assigned to either an intervention group ( the cardiac rehabilitation programme ) or control group ( the routine care ) . The change of health behaviours ( walking performance , step II diet adherence , medication adherence , smoking cessation ) and physiological risk parameters ( serum lipids , blood pressure , body weight ) were assessed to evaluate the programme effect . RESULTS Patients in the intervention group demonstrated a significantly better performance in walking , step II diet adherence , medication adherence ; a significantly greater reduction in serum lipids including triglyceride , total cholesterol , low-density lipoprotein ; and significantly better control of systolic and diastolic blood pressure at three months . The majority of these positive impacts were maintained at six months . The effect of the programme on smoking cessation , body weight , serum high-density lipoprotein , was not confirmed . CONCLUSIONS A cardiac rehabilitation programme led by a nurse can significantly improve the health behaviours and cardiac physiological risk parameters in coronary heart disease patients . Nurses can fill significant treatment gaps in the risk factor management of patients with coronary heart disease . RELEVANCE TO CLINICAL PRACTICE This study raises attention regarding the important roles nurses can play in cardiac rehabilitation and the unique way for nurses to meet the rehabilitative care needs of coronary heart disease patients . Furthermore , the hospital-home bridging nature of the programme also created a model for interfacing the acute care and community rehabilitative care Objective : PHLAME ’s ( Promoting Healthy Lifestyles : Alternative Models ’ Effects ) objective was to assess and compare two means to promote healthy lifestyles . Methods : Prospect i ve trial among 599 firefighters r and omized by station to 1 ) team-centered curriculum , 2 ) one-on-one motivational interviewing ( MI ) , and 3 ) controls . Assessment included dietary behavior , physical activity , weight , and general well-being at baseline and 12 months . Program effects were determined using an analysis of covariance ( ANCOVA ) based approach , and models for relationships were evaluated with path analysis . Results : Both interventions were acceptable and delivered with high fidelity . The team and MI programs increased fruit and vegetable consumption ( P < 0.01 and 0.05 , respectively ) and general well-being ( P < 0.01 ) . Significantly less weight gain occurred in both ( P < 0.05 ) . A cross-sectional model was consistent with mediation differing between interventions . Conclusions : Both a team-centered and individual-oriented intervention promoted healthy behaviors . The scripted team curriculum is innovative , exportable , and may enlist influences not accessed with individual formats BACKGROUND The delivery of effective interventions to assist patients to improve their physical activity and dietary behaviors is a challenge in the busy primary care setting . DESIGN Cluster RCT with practice s r and omized to telephone counseling intervention or usual care . Data collection took place from February 2005 to November 2007 , with analysis from December 2007 to April 2008 . SETTING / PARTICIPANTS Four-hundred thirty-four adult patients with type 2 diabetes or hypertension ( mean age=58.2 [ SD=11.8 ] ; 61 % female ; mean BMI = 31.1 [ SD=6.8 ] ) from a disadvantaged community were recruited from ten primary care practice s. INTERVENTION Twelve-month telephone counseling intervention . MAIN OUTCOME MEASURES Physical activity and dietary intake were assessed by self-report at baseline , 4 , and 12 months . RESULTS At 12 months , patients in both groups increased moderate-to-vigorous physical activity by a mean of 78 minutes per week ( SE=10 ) . Significant intervention effects ( telephone counseling minus usual care ) were observed for : calories from total fat ( decrease of 1.17 % ; p<0.007 ) , energy from saturated fat ( decrease of 0.97 % ; p<0.007 ) , vegetable intake ( increase of 0.71 servings ; p<0.039 ) , fruit intake ( increase of 0.30 servings ; p<0.001 ) , and grams of fiber ( increase of 2.23 g ; p<0.001 ) . CONCLUSIONS The study targeted a challenging primary care patient sample and , using a telephone-delivered intervention , demonstrated modest improvements in diet and in physical activity . Results suggest that telephone counseling is a feasible means of delivering lifestyle intervention to primary care patients with chronic conditions- patients whose need for ongoing support for lifestyle change is often beyond the capacity of primary healthcare practitioners Objective : To investigate the effect of an 8-week group-based cognitive behaviour therapy lifestyle intervention with monthly follow-up to 6 months and further follow up at 12 months on change in weight and other weight-related variables , change in physical activity and change in health and well being compared to individualised dietetic treatment or giving an information booklet only ( BO ) . Design : A r and omised controlled trial of two intervention groups , a group-based cognitive behaviour therapy lifestyle intervention , Fat Booters Incorporated – ( FBI ) and individualised dietetic treatment ( IDT ) and control group receiving an information booklet only ( BO ) . The intervention groups involved weekly contact for 8 weeks with monthly follow-up to 6 months and further follow-up at 12 months , conducted in real practice setting .Subjects : A total of 176 adults with body mass index ( BMI ) > 27 kg/m2 , mean ( ±s.d . ) age 48±13 years , mean BMI 34±5.5 kg/m2.Main outcome measures : Weight , percent body fat , waist circumference , physical activity , health status , self-efficacy and satisfaction with life were measured at baseline , 3 , 6 and 12 months . Results : A statistically significant difference between groups was observed for weight change over time ( P=0.05 ) . The change in weight ( mean±s.e . ) for the FBI group was significantly greater than the BO group at 3 and 12 months ( −2.8±0.7 compared to −1.0±0.6 kg , P<0.05 and −2.9±0.9 compared to + 0.5±0.9 kg , P<0.005 , respectively ) . Change in weight in the IDT group did not differ from the FBI group at any time point . For all groups , waist circumference was significantly less than baseline at all time points ( P<0.001 ) . Significant differences in self-efficacy were observed over time ( P=0.02 ) , with both intervention groups having greater self-efficacy than the BO group . Significant drop-outs occurred over time for all three groups . Conclusions : A cognitive behaviour-based lifestyle intervention was more effective than providing an information booklet alone and as effective as intensive individualised dietetic intervention in weight loss and improvements in self-efficacy Elevated body weight among active duty Air Force ( ADAF ) members is a substantial and growing problem , and typically results from gaining small amounts of weight each year over many years . We design ed a strategy to prevent annual weight gain in ADAF members using self-directed behavior change booklets followed by weekly e-mails about diet and physical activity for a year . The intervention was universally offered to ADAF members meeting selection criteria at five U.S. Air Force bases ( n = 3,502 ) ; members at 60 other U.S. Air Force bases served as controls ( n = 65,089 ) . The intervention was completely effective at preventing weight gain in a subgroup of men ( those above the lowest three ranks , with baseline weight above maximum allowable ) and in women , while controls continued to gain weight . Since the intervention did not require personalized contact , this approach has promise for large-scale population -based efforts aim ed at preventing weight gain in working adults OBJECTIVE The Northern Plains Indians of the Cheyenne River Sioux Tribe have experienced significant lifestyle and dietary changes over the past seven generations that have result ed in increased rates of diabetes and obesity . The objective of this study was to determine if Northern Plains Indians with type 2 diabetes mellitus who are r and omized to receive culturally adapted educational lessons based on the Medicine Wheel Model for Nutrition in addition to their usual dietary education will have better control of their type 2 diabetes than a nonintervention , usual care group who received only the usual dietary education from their personal providers . DESIGN A 6-month , r and omized , controlled trial was conducted January 2005 through December 2005 , with participants r and omized to the education intervention or usual care control group . The education group received six nutrition lessons based on the Medicine Wheel Model for Nutrition . The usual care group received the usual dietary education from their personal providers . PARTICIPANTS One hundred fourteen Northern Plains Indians from Cheyenne River Sioux Tribe aged 18 to 65 years , with type 2 diabetes . METHODS Weight , body mass index ( BMI ) , hemoglobin A1c , fasting serum glucose and lipid parameters , circulating insulin , and blood pressure were measured at the beginning and completion . Diet histories , physical activity , and dietary satiety surveys were measured at baseline and monthly through completion . Differences were determined using Student t tests , chi2 tests , and analysis of variance . RESULTS The education group had a significant weight loss ( 1.4+/-0.4 kg , P < or = 0.05 ) and decrease in BMI ( 1.0+/-0.1 , P < or = 0.05 ) from baseline to completion . The usual care group had no change in weight ( 0.5+/-0.5 kg ) or BMI ( 0.5+/-0.2 ) . There were no between group differences due to intervention in energy , carbohydrate , protein , and fat intake and physical activity . CONCLUSIONS The culturally based nutrition intervention promoted small but positive changes in weight . Greater frequency and longer duration of educational support may be needed to influence blood glucose and lipid parameters Overweight and physical inactivity are risk factors for increased disease burden and health care expenditure . Well- design ed studies are still needed to determine the treatment efficacy of worksite interventions targeting such risk factors . This r and omized controlled trial was conducted at one of Australia 's casinos in 2002 - 2003 , to investigate the effects of a comprehensive exercise and lifestyle intervention on physical fitness . Only 6.4 % of the workforce expressed interest in being study participants . Seventy-three employees ( aged 32 + /- 8 years , 51 % overweight/obese , 73 % shift workers and 52 % women ) were recruited and r and omized to treatment or wait-list control groups for 24 weeks , 44 of whom completed the intervention . Components of the intervention include supervised moderate-to-high intensity exercise including combined aerobic ( at least 20 min duration 3 days/week ) and weight-training ( for an estimated 30 min completed 2 - 3 days/week ) , and dietary/health education ( delivered via group seminars , one-on-one counselling and literature through the provision of a worksite manual ) . ANCOVA , by intention-to-treat and of study completers , found significant between-group differences in the mean waist circumference and predicted maximal oxygen uptake ( VO2max ) , favouring the intervention , but effects were concentrated in one subject . For study completers , between-group differences in the mean waist circumference ( 82.3 + /- 9.2 versus 90.5 + /- 17.8 cm , p = 0.01 ) and predicted VO2max ( 47 versus 41 ml/kg/min , p < 0.001 ) remained significant without the outlier , favouring the intervention . Higher intervention compliance predicted greater improvements in physical fitness . No significant effects on body mass or body mass index were found . This worksite intervention significantly improved waist circumference and aerobic fitness in healthy but sedentary employees , most of whom were shift workers . Worksite interventions have the potential to counter the increasing burden of overweight and obesity , particularly visceral adiposity , as well as physical inactivity ; however , substantial barriers to adoption/adherence need to be overcome for greater feasibility and impact on employee physical health Objective : To determine the potential effectiveness of a behavioural weight control programme including physical exercise in the prevention of antipsychotic-induced weight gain and associated comorbid conditions in out patients with schizophrenia and mood disorders . Methods : A prospect i ve , comparative , open and naturalistic study was carried out for a total of 110 patients with schizophrenia , schizoaffective or bipolar disorders ( DSM-IV ) , on treatment with atypical antipsychotics . Of these , 59 patients participated in an 18 month weight control programme that included an educational activity about dietary and physical activity counselling as well as a structured , supervised , facility-based exercise programme . The control group consisted of 51 patients with the same baseline characteristics who did not receive the clinical programme . Anthropometric measurements , plasma lipid – lipoprotein profile , and fasting plasma glucose concentrations were assessed at 11 time-points over the study . In addition , serum concentrations of prolactin , thyrotropin-stimulating hormone ( TSH ) , and glycated haemoglobin ( HbA1c ) were assessed at four time-points . Finally , the Clinical Global Impression scale ( CGI ) , the Brief Psychiatric Rating Scale ( BPRS ) and the Short Form (SF)-36 Health Survey were used . Results : The adherence rate of patients was 85 % , both in the active and in the control group . Whereas the control group experienced a significant increase in bodyweight ( 4.1 % ) , body mass index ( BMI ; 5.5 % ) and waist circumference ( WC ; 4.2 % ) , the active group significantly reduced their bodyweight ( −3.5 % ) , BMI ( −4.4 % ) , and WC ( −4.6 % ) at the study end-point . In addition , a significant increase in low-density lipoprotein (LDL)-cholesterol ( 14.8 % ) and in triglyceride concentrations ( 12.3 % ) was observed at month 18 in the control group . In contrast , high-density lipoprotein-cholesterol ( HDL ) significantly increased ( 21.4 % ) , and LDL cholesterol ( −13.7 % ) , triglycerides ( −26.2 % ) , total cholesterol ( −12.1 % ) , fasting glucose concentrations ( −12.0 % ) , and HbA1c ( −11.4 % ) significantly decreased compared to baseline in the active group . No significant changes were observed regarding serum concentrations of prolactin and TSH during the study . In regard to the changes observed in psychological measures , no between-group differences were seen in the clinical ratings of CGI and BPRS . However , the SF-36 showed that physical health was improved only for subjects in the active group at months 12 and 18 compared to baseline ( p<0.05 ) , and mental health was significantly improved for both groups at months 12 and 18 compared to baseline . Conclusion : Bodyweight and metabolic risk profile in patients receiving atypical antipsychotic medications can be effectively managed with a weight control programme including physical activity Summary Background Excess adiposity has been shown to be associated with increased risk for breast cancer recurrence , and a plant-based eating pattern has been hypothesized to be protective . Whether a plant-based diet without specific energy goals will result in weight loss or changes in body composition in women who have been diagnosed with breast cancer has not been fully explored . Aim of the study This study was conducted to identify changes in body weight , anthropometric measures , and body composition over a four year period in a sub- sample of breast cancer survivors participating in a dietary intervention targeting increased intake of vegetables , fruit and fiber and decreased dietary fat intake . Methods This r and omized , controlled dietary intervention study compared longitudinal changes in intakes , body weight , waist : hip ratio ( WHR ) , body mass index ( BMI ) and body composition by treatment group among fiftytwo women previously treated for Stage I , II , or IIIA breast cancer from the Arizona site of the Women ’s Healthy Eating and Living Study . The dietary intervention aim ed for eight servings of fruit and vegetables , 30 g fiber , ≤ 20 % total energy from fat per day , as well as daily intake of vegetable juice . The comparison group was advised to follow general dietary guidelines for cancer prevention . Results The dietary intervention result ed in a significant and sustained increase in fiber , fruit , vegetable , and vegetable juice consumption ( p < 0.05 ) among intervention group subjects as compared to comparison group subjects . The first 6 months result ed in a reduction in body weight and body fat among the intervention group subjects while the comparison group subjects remained stable . Subsequent measurements , at 12 , 24 or 36 , and 48 months , showed no significant differences in mean body weight , BMI , WHR , or body composition by study group . Also , no significant changes in these measures were demonstrated for either study group between baseline and 48 months . Conclusions The dietary intervention efforts result ed in significant changes in diet toward an increase in plant foods and a decrease in dietary fat . Changes in weight , WHR , BMI , and body composition were not different over time or by study group assignment . Interventions that promote a plantbased diet without specific energy restriction do not appear to promote changes in body weight or body composition in women who have been diagnosed with breast cancer . To adequately examine the role of energy restriction in reducing obesity-associated breast cancer recurrence , future interventions should include prescribed energy imbalance either through reduced intake and /or increased expenditure PURPOSE To determine the efficacy of asking people to add fiber , exercise , and stress management to their lifestyles to enhance markers of wellness and aging . METHODS A 10-week , r and omized control study conducted in a wellness center in St Petersburg , Florida . Participants were adults aged 21 to 65 years who exercised fewer than 3 days per week . Fifty-six subjects were r and omized to a control or an intervention group . Subjects followed a diet with > 30 g of fiber and < 16 g of saturated fat daily and were taught to reach 70 % to 85 % of their maximum heart rate 5 to 6 days per week and to perform strength training 3 days per week . They were also asked to participate in 10 to 20 minutes of stress management activities daily . The study was design ed to determine changes in body composition , maximal rate of oxygen consumption ( VO2 max ) , total cholesterol : high-density lipoprotein ( TC : HDL ) ratio , and cognition . RESULTS Initial analyses with analysis of variance ( ANOVA ) comparing the intervention group to the control group showed significant improvements in TC : HDL ( 8.9 % average ; P = .02 ) and change in weight ( 2.3 kg average ; P = .016 ) . When the groups were compared , the improvements in cognitive flexibility and VO2 max with ANOVA were not significant ( P = .17 and P = .11 , respectively ) . Additional independent t tests showed decreases in TC : HDL of 8.9 % ( P = .02 ) and TC of 7.3 % ( P = .001 ) for the intervention group compared to the control group . A mean increase of 29 % in VO2 max of intervention subjects who exercised aerobically for at least 30 minutes 5 days/week was significant ( P = .02 ) compared to the control group . Over the 10 weeks , the control group showed no significant change in lipids , body composition , cognition , and fitness , whereas the intervention group showed decreased body mass index ( BMI ) of 0.72 ( P = .02 ) , weight loss of 2.3 kg ( P = .016 ) , and decreased body fat of 1.6 % ( P < .0001 ) . In the intervention group , those with a BMI > 24 who exercised 5 to 6 days/week lost 4.8 kg and 4.1 kg in body fat . Also , in the intervention group , several of the cognitive scores showed statistically significant improvements from baseline : mental speed ( 4.6 % , P = .014 ) , reaction time ( 4.5 % , P = .023 ) , and cognitive flexibility ( 11.7 % , P = .019 ) , but none of these cognitive changes was significant with independent t testing when compared to the control group . CONCLUSIONS A diet high in fiber and low in saturated fat combined with strength training , aerobic activity , and stress management activities improves fitness and several markers of wellness and aging OBJECTIVE To evaluate the impact of a low-cost nutritional intervention in changing the lifestyle of adults . DESIGN R and omised clinical trial . SETTING Primary health-care centre in São José do Rio Preto , São Paulo State , Brazil . SUBJECTS We r and omly assigned 104 adults ( 83 women and 21 men aged 30 - 65 years , body mass index 24 - 35 kg m(-2 ) , non-diabetic ) into two groups : nutrition counselling and control . Each subject in the intervention group received three individualised nutritional counselling sessions during the first 6 months aim ed at increasing intakes of fruits , vegetables and olive oil , reducing saturated fat and improving physical activity . Body composition , biochemical indicators and lifestyle were assessed at baseline and at 6 months and 1 year in both groups . RESULTS After 6 months of follow-up , body weight , waist circumference , diastolic blood pressure , fasting blood glucose , total and low-density lipoprotein cholesterol , total and saturated fat , and dietary energy and cholesterol levels showed a more significant decrease among subjects in the intervention group than in the control group ( P < 0.05 ) . Moreover , the intervention group showed significantly greater improvement in each intervention goal , such as reduced intake of saturated fat and increased intakes of fruits , vegetables , fibre and olive oil ( P < 0.05 ) . After 12 months of follow-up , most of the outcomes were maintained . CONCLUSIONS The low-cost nutritional intervention programme improved serum lipids profile and weight control , and appeared to be feasible for use at a primary health-care centre in a developing country Despite multidisciplinary efforts to control the nation 's obesity epidemic , obesity has persisted as one of the U.S. 's top public health problems , particularly among African Americans . Innovative approaches to address obesity that are sensitive to the unique issues of African Americans are needed . Thus , a faith-based weight-loss intervention using a community-based participatory research approach was developed , implemented , and evaluated with a rural African American faith community . A two-group , quasi-experimental , delayed intervention design was used , with church as the unit of assignment ( treatment n = 2 , control n = 2 ) and individual as the unit of observation ( treatment n = 36 , control n = 37 ) . Weekly small groups led by trained community members met for 8 weeks and emphasized healthy nutrition , physical activity , and faith 's connection with health . The mean weight loss of the treatment group was 3.60 ± 0.64 lbs . compared to the 0.59 ± 0.59-lb loss of the control group OBJECTIVE The aim of the study was to determine if multiple patient-centred lifestyle counselling sessions would be of interest to patients at risk of coronary heart disease ( CHD ) , in a primary care setting , and if such sessions would result in changes in physical activity and diet , and health status . A r and omised trial was conducted to compare the counselling intervention with usual care ( health promotion leaflet ) , among 334 mostly obese patients . METHODS Patients were r and omised into an intervention group that received st and ard exercise and nutrition information plus up to five face-to-face counselling sessions with a Physical Activity Specialist ( PAS ) and Registered Dietitian ( RD ) over a 6-month period or to a control group that only received the st and ard information . RESULTS Of those invited , patients r and omised tended to be more obese , older and female . The mean ( S.D. ) sessions attended was 2.0 ( 1.6 ) with 50 % attending at least 3 . At 6 months , the counselling group were more active , particularly with respect to walking , and had reduced weight , blood pressure and cholesterol , but had not changed their diet , compared with the control group . Furthermore , those who did more sessions had greater increases in activity and reductions in weight , blood pressure and cholesterol . CONCLUSION Attending multiple sessions of client-centred counselling in primary care was of interest to patients , and generally reduced CHD risk factors . PRACTICE IMPLICATION S The primary care setting can be used effectively to promote particularly walking , using physical activity specialists and dietitians trained to use an adapted motivational interviewing ( MI ) counselling style PURPOSE We tested the feasibility and preliminary efficacy of a lifestyle intervention for middle-aged and older patients with schizophrenia and type-2 diabetes mellitus , using a r and omized pre-test , post-test control group design . METHOD Individuals with a diagnosis of schizophrenia or schizoaffective disorder over the age of 40 were r and omly assigned to 24-week Diabetes Awareness and Rehabilitation Training ( DART ; n=32 ) groups or Usual Care plus Information ( UCI ; n=32 ) comparison groups . Participants were recruited from board- and -care facilities and day treatment programs . Fifty-seven patients completed baseline and 6-month assessment s consisting of an interview , measures of body mass index , blood pressure , fasting blood chemistry , and accelerometry . A mixed-model analysis of variance was used to analyze the data . RESULTS A significant group x time interaction was found for body weight , with patients in the DART group losing a mean of 5 lb and those in the UCI gaining a mean 6 lb . Significant group x time interactions were also found for triglycerides , diabetes knowledge , diabetes self-efficacy , and self-reported physical activity , but not for fasting plasma glucose or glycosylated hemoglobin . CONCLUSIONS Group-based lifestyle interventions are feasible and produce positive health changes in middle-aged and older patients with schizophrenia and diabetes mellitus OBJECTIVE The purpose of this study was to evaluate the short-term motivational effect of a technology-based weight reduction program for obese adults . METHODS One hundred and eleven obese ( 37.0+/-5.8 kg/m(2 ) ) middle aged ( 45.5+/-10.8 years ) adults ( 62 % female ) were r and omly assigned to a usual care or experimental ( SMART : self-monitoring and resting metabolic rate technology ) group . The usual care group received a st and ard nutritional program in accordance to national guidelines . All participants received a comprehensive weight management program consisting of motivational interviewing ( MI ) sessions and automated e-mail behavioral newsletters . Bodyweight , arterial blood pressure , and psychobehavioral constructs were assessed over 12 weeks . RESULTS Completer analysis ( n=80 ) indicated a significant improvement in bodyweight ( -3.9 % ) , systolic arterial pressure ( -4 mmHg ) , and all motivational constructs following the 12-week study ( p < or=.05 ) . However , there were no significant differences between groups at any time period . CONCLUSION Based on these data , a 12-week comprehensive weight reduction program consisting of MI and automated e-mail behavioral newsletters with or without SMART is efficacious in treating obese adults . PRACTICE IMPLICATION S Although both treatment programs were equally effective , clinicians should consider a treatment program that meets the need of the patient . This study was registered at Clinical Trials.gov NCT00750022 OBJECTIVE Preventing weight gain in adults and excessive weight gain in children is a high priority . We evaluated the ability of a family-based program aim ed at increasing steps and cereal consumption ( for breakfast and snacks ) to reduce weight gain in children and adults . RESEARCH METHODS AND PROCEDURES Families ( n = 105 ) with at least one 8- to 12-year-old child who was at-risk-for-overweight or overweight ( design ated as the target child ) were recruited for the study . Eighty-two families were r and omly assigned to receive the family-based intervention and 23 families to the control condition . The 13-week intervention consisted of specific increases in daily steps ( an additional 2000 steps/d ) and consumption of 2 servings/d of ready-to-eat cereal . RESULTS The intervention was successful in increasing walking ( steps ) and cereal consumption . The intervention had positive , significant effects on percentage BMI -for-age and percentage body fat for target children and weight , BMI , and percentage body fat for parents . On further analysis , the positive effects of the intervention were seen largely in target girls and moms , rather than in target boys and dads . DISCUSSION This family-based weight gain prevention program based on small changes holds promise for reducing excessive weight gain in families and especially in growing overweight children AIM To evaluate the effectiveness of lifestyle interventions in people with impaired glucose tolerance ( IGT ) . METHODS Participants with IGT ( n=78 ) , diagnosed on two consecutive oral glucose tolerance tests ( OGTTs ) , were r and omly assigned to a 2-year lifestyle intervention or to a control group . Main outcome measures were changes from baseline in : nutrient intake ; physical activity ; anthropometry , glucose tolerance and insulin sensitivity . Measurements were repeated at 6 , 12 and 24 months follow-up . RESULTS After 24 months follow-up , there was a significant fall in total fat consumption ( difference in change between groups ( Delta intervention-Delta control)= -17.9 , 95 % confidence interval ( CI ) -33.6 to -2.1g/day ) as a result of the intervention . Body mass was significantly lower in the intervention group compared with controls after 6 months ( -1.6 , 95 % CI -2.9 to -0.4 kg ) and 24 months ( -3.3 , 95 % CI -5.7 to -0.89 kg ) . Whole body insulin sensitivity , assessed by the short insulin tolerance test ( ITT ) , improved after 12 months in the intervention group ( 0.52 , 95 % CI 0.15 - 0.89%/min ) . CONCLUSIONS These findings complement the findings of the Finnish Diabetes Prevention Study and the American Diabetes Prevention Study , both of which tested intensive interventions , by showing that pragmatic lifestyle interventions result in improvements in obesity and whole body insulin sensitivity in individuals with IGT , without change in other cardiovascular risk factors Aim To determine the effect of dietary advice in conjunction with advice to increase physical activity on the body composition , blood lipid and insulin profiles in overweight women . Design A 12-week r and omized controlled intervention study . Subjects were assigned to one of four groups : ( 1 ) no advice , ( 2 ) low-fat , high-carbohydrate ( including sucrose ) energy-reduced diet , ( 3 ) 60 min/day brisk walking , and ( 4 ) diet and activity advice as previous . Subjects Sixty-nine overweight women ( mean age 41 years ) . Measurements Dietary compliance was assessed by 4-day diet diaries . Activity levels were assessed by Caltrac ™ accelerator monitors . Anthropometric changes were recorded at baseline , 6 and 12 weeks . Fasting blood sample s measuring glucose , insulin , and blood lipids were recorded at baseline and 12 weeks . Results Group 4 achieved greatest weight loss of 4.2 kg and greatest reduction in waist circumference of 6.5 cm . Groups 2 and 4 decreased the percentage energy from fat by 5.2 % . Group 3 increased the percentage energy from fat by 4.0 % . Group 4 significantly reduced total cholesterol by 0.45 mmol/l and low-density lipoprotein-cholesterol by 0.53 mmol/l . Conclusion A low-fat , high-carbohydrate , sucrose-containing diet combined with increased physical exercise result ed in greater health benefits than diet or physical activity advice alone STUDY OBJECTIVE To examine the effects of 30 min of self-paced , non-supervised , brisk walking , 5 days per week on the health and fitness of people aged 50 - 65 years . DESIGN R and omized controlled trial . Members of the intervention group ( n = 21 ) were directed to walk briskly for 30 min , 5 days per week , for 12 weeks . Individuals were given the choice to complete the 30 min of walking in one session or in shorter bouts of no less than 10 min . They were asked to record in a diary the time spent walking and the number of steps taken during a single walk using a pedometer . Participants in the control group ( n = 10 ) were asked to maintain their habitual lifestyle and not change their activity or dietary habits . Measurements of body mass index ( BMI ) , waist/hip ratio ( WHR ) , blood pressure , functional capacity , total cholesterol , triglyceride , and lipoprotein subfractions were taken before and after the program . Changes in 10-year risk estimate for coronary heart disease and stroke were calculated using Framingham risk equations . SETTING Three urban general practice s patients : 31 healthy , sedentary 50- to 65-year-old participants recruited following contact by their general practitioner . MAIN RESULTS The mean time spent walking by the intervention group was 27.72 ( + /-9.79 ) min/day : their adherence to the protocol was 90.3 % . Significant decreases in systolic and diastolic blood pressure , reduction in stroke risk , and increased functional capacity were found within the walking group between baseline and 12-week measurements . No changes were found in these parameters within the control group . Significant reductions in 10-year risk of CHD were observed in both groups . No significant changes were found in lipid levels or anthropometric measurements in either group . CONCLUSIONS The study provides evidence for the benefit to fitness and cardiovascular risk of the " 30-min brisk walking , 5 days a week " message to people aged 50 - 65 years who participated in an unsupervised home-based walking program . Further study to overcome the problem of poor recruitment and determine the minimum effective dose of exercise to improve cardiovascular risk prediction scores is required Background : The Mediterranean Lifestyle Program was evaluated for its effects on multiple behavioral risk factors for coronary heart disease ( CHD ) among postmenopausal women with diabetes . Purpose : Our purpose is to test a comprehensive lifestyle management intervention to reduce CHD risk in postmenopausal women with type 2 diabetes . Methods : Participants ( N = 279 ) were r and omized to usual care ( UC ) or Mediterranean Lifestyle Program , a lifestyle change intervention aim ed at the behavioral risk factors ( eating patterns , physical activity , stress management , and social support ) affecting risk for CHD in postmenopausal women with type 2 diabetes . Results : In original and intent-to-treat analyses , Mediterranean Lifestyle Program participants showed significantly greater improvement in dietary behaviors , physical activity , stress management , perceived support , and weight loss at 6 months compared to UC . Conclusions : This study demonstrated the effectiveness of the Mediterranean Lifestyle Program in improving self-care among women with type 2 diabetes , showed that postmenopausal women could make comprehensive lifestyle changes , and provided evidence that a program using social-cognitive strategies and peer support can be used to modify multiple lifestyle behaviors Objective : To investigate the specific impact of resistance training ( RT ) with or without caloric restriction ( CR ) on physical capacity in obese older women . Design : Forty-eight postmenopausal obese women , physically independent and between the ages of 55 and 75 years were recruited . The women were r and omly assigned to one of four groups ( 1 : RT [ n = 12 ] , 2 : CR [ n = 12 ] , 3 : CR + RT [ n = 12 ] , or 4 : control group [ C ; n = 12 ] ) for 3 months . CR and CR + RT groups participated in a weekly group session on nutrition , and RT and CR + RT groups took part in a resistance training program . Physical capacity was measured with 11 different performance tests . A global physical capacity score ( range , 0 - 44 ) was then computed using quartiles of each test . Body composition was measured by dual-energy x-ray absorptiometry . Results : Body weight , total fat mass , percentage of fat mass , and body mass index ( kg/m2 ) significantly decreased in the CR and CR + RT groups ( P < 0.01 ) , whereas only the CR group showed a significant decrease in lean body mass ( P < 0.05 ) after the 3-month program . The global physical capacity score significantly improved in the RT group ( 10.0 ± 8.8 % ; P < 0.01 ) , compared with the C group after 3 months . Conclusion : Overall , the 3-month RT program alone had a greater effect on physical capacity than CR or CR + RT . Thus , a 3-month RT could help prevent long-term decreases in physical capacity in obese older women |
14,024 | 26,898,239 | Sulphoraphane , lycopene , soy isoflavones , POMx , and Pomi-T are safe and well tolerated .
There is limited evidence that they can affect PSA dynamics . | OBJECTIVE To evaluate the evidence from r and omised trials for the efficacy and safety of phytotherapeutic interventions in the management of biochemically recurrent ( BCR ) prostate cancer , indicated by prostate-specific antigen ( PSA ) progression , numbers progressing to/time to initiation of and rogen-deprivation therapy or salvage therapy . | Our objective was to evaluate the tolerability and effect of a daily soy beverage in prostate cancer patients with biochemical failure after radiotherapy . Patients with rising prostate-specific antigen ( PSA ) after radical radiation for prostate cancer were instructed to consume 500 ml of soy beverage daily for 6 mo . Tolerability of the soy beverage and compliance were assessed . PSA doubling times before and after the consumption of soy were compared . Thirty-four subjects were enrolled ; 5 withdrew before 1 mo of soy for reasons unrelated to soy consumption . All remaining 29 subjects were included in the analysis . Mean consumption of the assigned soy beverage was 93 % . Mild gastrointestinal upset ( 38 % ) not affecting soy consumption was the commonest side effect . PSA showed a declining trend in 4 patients ( 13.8 % ) , and there was a > 100 % prolongation of PSA doubling time in 8 patients ( 27.6 % ) . However , PSA doubling time also showed a 50 % or more shortening in 5 patients ( 17.2 % ) . In our cohort of North American subjects , 6 mo of a daily soy beverage was well tolerated and was associated with a declining trend or more than 2 times prolongation of PSA doubling time in 41 % of subjects . Confirmatory studies are warranted Pomegranate has been shown to prolong PSA doubling time in early prostate cancer , but no data from a placebo controlled trial has been published yet . The objective of this study was to prospect ively evaluate the impact of pomegranate juice in patients with prostate cancer . We conducted a phase IIb , double blinded , r and omized placebo controlled trial in patients with histologically confirmed prostate cancer . Only patients with a PSA value ≥ 5ng/ml were included . The subjects consumed 500 ml of pomegranate juice or 500 ml of placebo beverage every day for a 4 week period . Thereafter , all patients received 250 ml of the pomegranate juice daily for another 4 weeks . PSA values were taken at baseline , day 14 , 28 and on day 56 . The primary endpoint was the detection of a significant difference in PSA serum levels between the groups after one month of treatment . Pain scores and adherence to intervention were recorded using patient diaries . 102 patients were enrolled . The majority of patients had castration resistant prostate cancer ( 68 % ) . 98 received either pomegranate juice or placebo between October 2008 and May 2011 . Adherence to protocol was good , with 94 patients ( 96 % ) completing the first period and 87 patients ( 89 % ) completing both periods . No grade 3 or higher toxicities occurred within the study . No differences were detected between the two groups with regard to PSA kinetics and pain scores . Consumption of pomegranate juice as an adjunct intervention in men with advanced prostate cancer does not result in significant PSA declines compared to placebo OBJECTIVES Epidemiological studies have shown significant relationships between the use of dietary components and prostate cancer incidence and mortality . Large studies of primary prevention , which confirm these findings , are desirable but costly and difficult to design . The present tertiary prevention study reports on the effect of a dietary supplement in comparison with placebo on the rate of increase of prostate-specific antigen ( PSA ) . METHODS 49 patients with a history of prostate cancer and rising PSA levels after radical prostatectomy ( n = 34 ) or radiotherapy ( n = 15 ) participated in a r and omised , double-blind , placebo-controlled crossover study of a dietary supplement . Ethical approval of the protocol was obtained . Treatment periods of 10 weeks were separated by a 4-week washout period . The supplement consisted of soy , isoflavones , lycopene , silymarin and antioxidants as main ingredients . Changes in the rate of increase of PSA ( PSA slope and doubling time ) were the primary parameters of efficacy . Analyses according to intention to treat ( ITT ) and per protocol ( PP ) were carried out . RESULTS Baseline parameters did not differ between r and omised groups . Five participants were lost to follow-up , however 46 could be evaluated in an ITT analysis . PP analysis could be performed in 42 men with at least 5 PSA measurements . Per protocol analysis showed a significant decrease in PSA slope ( p = 0.030 ) and (2)log PSA slope ( p = 0.041 ) . This translates into a 2.6 fold increase in the PSA doubling time from 445 to 1150 days for the supplement and placebo periods . No treatment-based changes in safety parameters were observed during the study . CONCLUSIONS The soy-based dietary supplement utilised in this study was shown to delay PSA progression after potentially curative treatment in a significant fashion . More extensive studies of the supplement may be indicated OBJECTIVES To determine whether supplemental amounts of soy isoflavone ( genistein-rich extract ) would lower prostate-specific antigen ( PSA ) levels more than 50 % in patients with prostate cancer ( CaP ) . METHODS A total of 62 men ( mean age 73.6 years , range 61.4 to 89.3 ) with histologically proven CaP who had two consecutive elevated PSA readings were accrued during a 13-month period . An open-label pilot study was conducted for 6 months in which the patients took capsules containing the genistein-rich extract three times daily by mouth . The subjects were in one of five groups : after radical retropubic prostatectomy ( n = 9 ) , after radiotherapy ( n = 17 ) , after both radical retropubic prostatectomy and radiotherapy ( n = 6 ) , off-cycle during hormonal therapy ( intermittent hormones ; n = 14 ) , or active surveillance ( n = 16 ) . The primary endpoint for the trial was a 50 % reduction in the PSA level at 6 months compared with before treatment . RESULTS Of the 62 men enrolled , 52 were available for evaluation at 6 months . Three patients discontinued because of adverse events ( diarrhea ) and seven because of personal choice . One of 52 patients had a more than 50 % reduction in the PSA level ( 1.9 % response , 95 % confidence interval 0.1 % to 10.3 % ) . An additional 7 patients had PSA reductions that were less than 50 % . All 8 patients with lower PSA levels at 6 months were in the active surveillance ( watchful waiting ) treatment subgroup . Repeated measure regression models allowing for correlation between initial levels and change also indicated a decline in PSA in this group compared with other groups : 0 of 52 had a complete response , 9 ( 17 % ) had a partial response , 8 ( 15 % ) had stable disease , and 35 ( 67 % ) had disease progression . In the 9 patients with a partial response , 6 had pathologic findings that were moderately differentiated , 2 had well-differentiated findings , and 1 had poorly differentiated findings . Therefore , the response in this group of patients did not appear to be driven by the Gleason score . The total testosterone level was lowered in one of the patients responding , but it was higher in five others . CONCLUSIONS A genistein-rich extract as the sole treatment for CaP did not reduce PSA levels by 50 % or more in 51 of 52 subjects . Thus , it does not appear to be an effective treatment for CaP when given alone . However , 8 of 13 evaluated patients in the active surveillance group had either no rise or a decline in PSA levels of less than 50 % . More study is warranted for those choosing active surveillance Purpose : Phytochemicals in plants may have cancer preventive benefits through antioxidation and via gene-nutrient interactions . We sought to determine the effects of pomegranate juice ( a major source of antioxidants ) consumption on prostate-specific antigen ( PSA ) progression in men with a rising PSA following primary therapy . Experimental Design : A phase II , Simon two-stage clinical trial for men with rising PSA after surgery or radiotherapy was conducted . Eligible patients had a detectable PSA > 0.2 and < 5 ng/mL and Gleason score ≤7 . Patients were treated with 8 ounces of pomegranate juice daily ( Wonderful variety , 570 mg total polyphenol gallic acid equivalents ) until disease progression . Clinical end points included safety and effect on serum PSA , serum-induced proliferation and apoptosis of LNCaP cells , serum lipid peroxidation , and serum nitric oxide levels . Results : The study was fully accrued after efficacy criteria were met . There were no serious adverse events reported and the treatment was well tolerated . Mean PSA doubling time significantly increased with treatment from a mean of 15 months at baseline to 54 months posttreatment ( P < 0.001 ) . In vitro assays comparing pretreatment and posttreatment patient serum on the growth of LNCaP showed a 12 % decrease in cell proliferation and a 17 % increase in apoptosis ( P = 0.0048 and 0.0004 , respectively ) , a 23 % increase in serum nitric oxide ( P = 0.0085 ) , and significant ( P < 0.02 ) reductions in oxidative state and sensitivity to oxidation of serum lipids after versus before pomegranate juice consumption . Conclusions : We report the first clinical trial of pomegranate juice in patients with prostate cancer . The statistically significant prolongation of PSA doubling time , coupled with corresponding laboratory effects on prostate cancer in vitro cell proliferation and apoptosis as well as oxidative stress , warrant further testing in a placebo-controlled study Increases in serum levels of prostate-specific antigen ( PSA ) occur commonly in prostate cancer after radical prostatectomy and are design ated “ biochemical recurrence . ” Because the phytochemical sulforaphane has been studied extensively as an anticancer agent , we performed a double-blinded , r and omized , placebo-controlled multicenter trial with sulforaphane in 78 patients ( mean age , 69 ± 6 years ) with increasing PSA levels after radical prostatectomy . Treatment comprised daily oral administration of 60 mg of a stabilized free sulforaphane for 6 months ( M0–M6 ) followed by 2 months without treatment ( M6–M8 ) . The study was design ed to detect a 0.012 log (ng/mL)/month decrease in the log PSA slope in the sulforaphane group from M0 to M6 . The primary endpoint was not reached . For secondary endpoints , median log PSA slopes were consistently lower in sulforaphane-treated men . Mean changes in PSA levels between M6 and M0 were significantly lower in the sulforaphane group ( + 0.099 ± 0.341 ng/mL ) than in placebo ( + 0.620 ± 1.417 ng/mL ; P = 0.0433 ) . PSA doubling time was 86 % longer in the sulforaphane than in the placebo group ( 28.9 and 15.5 months , respectively ) . PSA increases > 20 % at M6 were significantly greater in the placebo group ( 71.8 % ) than in the sulforaphane group ( 44.4 % ) ; P = 0.0163 . Compliance and tolerance were very good . Sulforaphane effects were prominent after 3 months of intervention ( M3–M6 ) . After treatment , PSA slopes from M6 to M8 remained the same in the 2 arms . Daily administration of free sulforaphane shows promise in managing biochemical recurrences in prostate cancer after radical prostatectomy . Cancer Prev Res ; 8(8 ) ; 712–9 . © 2015 AACR PURPOSE To up date eligibility and outcome measures in trials that evaluate systemic treatment for patients with progressive prostate cancer and castrate levels of testosterone . METHODS A committee of investigators experienced in conducting trials for prostate cancer defined new consensus criteria by review ing previous criteria , Response Evaluation Criteria in Solid Tumors ( RECIST ) , and emerging trial data . RESULTS The Prostate Cancer Clinical Trials Working Group ( PCWG2 ) recommends a two- objective paradigm : ( 1 ) controlling , relieving , or eliminating disease manifestations that are present when treatment is initiated and ( 2 ) preventing or delaying disease manifestations expected to occur . Prostate cancers progressing despite castrate levels of testosterone are considered castration resistant and not hormone refractory . Eligibility is defined using st and ard disease assessment s to authenticate disease progression , prior treatment , distinct clinical subtypes , and predictive models . Outcomes are reported independently for prostate-specific antigen ( PSA ) , imaging , and clinical measures , avoiding grouped categorizations such as complete or partial response . In most trials , early changes in PSA and /or pain are not acted on without other evidence of disease progression , and treatment should be continued for at least 12 weeks to ensure adequate drug exposure . Bone scans are reported as " new lesions " or " no new lesions , " changes in soft-tissue disease assessed by RECIST , and pain using vali date d scales . Defining eligibility for prevent/delay end points requires attention to estimated event frequency and /or r and om assignment to a control group . CONCLUSION PCWG2 recommends increasing emphasis on time-to-event end points ( ie , failure to progress ) as decision aids in proceeding from phase II to phase III trials . Recommendations will evolve as data are generated on the utility of intermediate end points to predict clinical benefit OBJECTIVES To report a prospect i ve trial of lycopene supplementation in biochemically relapsed prostate cancer . METHODS A total of 36 men with biochemically relapsed prostate cancer were enrolled in a dose-escalating , Phase I-II trial of lycopene supplementation . Six consecutive cohorts of 6 patients each received daily supplementation with 15 , 30 , 45 , 60 , 90 , and 120 mg/day for 1 year . The serum levels of prostate-specific antigen ( PSA ) and plasma levels of lycopene were measured at baseline and every 3 months . The primary endpoints were PSA response ( defined as a 50 % decrease in serum PSA from baseline ) , pharmacokinetics , and the toxicity/tolerability of this regimen . RESULTS A total of 36 patients were enrolled . The median age was 74 years ( range 56 to 83 ) , with a median serum PSA at entry of 4.4 ng/mL ( range 0.8 to 24.9 ) . No serum PSA responses were observed , and 37 % of patients had PSA progression . The median time to progression was not reached . Toxicity was mild , with 1 patient discontinuing therapy because of diarrhea . Significant elevations of plasma lycopene were noted at 3 months and then appeared to plateau for all six dose levels . The plasma levels for doses between 15 and 90 mg/day were similar , with additional elevation only at 120 mg/day . CONCLUSIONS Lycopene supplementation in men with biochemically relapsed prostate cancer is safe and well tolerated . The plasma levels of lycopene were similar for a wide dose range ( 15 to 90 mg/day ) and plateaued by 3 months . Lycopene supplementation at the doses used in this study did not result in any discernible response in serum PSA Background : PSA doubling time ( PSADT ) is an attractive intermediate end point for assessing novel therapies in biochemically recurrent prostate cancer ( BRPC ) . This study explores whether PSADT calculations are influenced by frequency/ duration of PSA measurements , and whether statistical variability leads investigators to find false significant results . Methods : In retrospective analyses of two BRPC cohorts : Johns Hopkins Hospital ( JHH ) patients who deferred therapy and placebo patients on a r and omized clinical trial ( RCT ) , we calculated changes in PSADT from early measurements to later measurements using subsets of available PSAs for patients with ⩾6 and ⩾9 PSAs . We simulated hypothetical single-arm trials using r and omly selected , 50-patient subsets and simulated two-arm RCTs . Results : JHH cohort ( n=205 ) had median follow-up 58 months , median age 61 years and median Gleason 7 . PSA variability changed with duration of PSA measurement as median within-patient PSADT increases for men with > 6 PSAs ranged from 1.0 to 1.4 months by PSA subset while increases for men with ⩾9 PSAs ranged from 3.9 to 4.1 months . Frequency of measurement did not change PSA variability as PSADT increase was unchanged when odd values were used instead of all values . Approximately 30 % of JHH men experienced > 200 % increases in PSADT . Up to 62 % of 50-patient single-arm simulations detected a significant PSADT change , whereas simulated RCTs did not . Results were supported in the RCT placebo cohort ; 46 % of patients experienced PSADT increases > 200 % . Conclusions : These data suggest that calculated PSADT in BRPC may naturally increase over time in the absence of therapy and may be influenced by duration of PSA follow-up . As a result , single-arm trials could show false significant increases despite the lack of active treatment of these patients . Placebo-controlled RCTs including clinical end points are recommended to screen novel agents in men with BRPC to mitigate bias because of natural PSADT variability PURPOSE Prostate specific antigen is a glycoprotein found almost exclusively in normal and neoplastic prostate cells . Prostate specific antigen doubling time , or the change in prostate specific antigen over time , has emerged as a useful predictive marker for assessing disease outcome in patients with prostate cancer . It is important to agree on definitions and values for the calculation of prostate specific antigen doubling time , and to develop a common approach to outcome analysis and reporting . MATERIAL S AND METHODS In September 2006 a conference was held at the National Cancer Institute in Bethesda , Maryl and to define these parameters and develop guidelines for their use . RESULTS The Prostate Specific Antigen Working Group defined criteria regarding prostate specific antigen doubling time including the calculation of prostate specific antigen doubling time , evidence to support prostate specific antigen doubling time as a predictive factor in the setting of biochemical recurrence and the use of prostate specific antigen doubling time as a stratification factor in clinical trials . CONCLUSIONS We propose that investigators calculate prostate specific antigen doubling time before enrolling patients in clinical studies and calculate it as an additional measurement of therapeutic activity . We believe we have developed practical guidelines for the calculation of prostate specific antigen doubling time and its use as a measurement of prognosis and outcome . Furthermore , the use of common st and ards for prostate specific antigen doubling time in clinical trials is important as we determine which treatments should progress to r and omized trials in which " hard " end points such as survival will be used Abstract Dietary intake of lycopene and soy has been associated with a lower risk of prostate cancer . In vitro studies with lycopene and genistein , a soy isoflavone , have shown induction of apoptosis and inhibition of cell growth in and rogen-sensitive ( LNCaP ) and and rogen – independent ( PC3 and VeCaP ) prostate cancer cell lines . In a previous Phase II clinical trial in prostate cancer patients , we observed prostate-specific antigen ( PSA ) stabilization with soy isoflavone intake . In this Phase II clinical trial , we investigated the efficacy of lycopene alone or in combination with soy isoflavones on serum PSA levels in men with prostate cancer . To be eligible for the study , men with prostate cancer had to have rising serum PSA following local therapy or while on hormone therapy . Study population included 71 eligible patients who had 3 successive rising PSA levels or a minimum PSA of 10 ng/ml at 2 successive evaluations prior to starting therapy . Subjects were r and omly assigned to receive a tomato extract capsule containing 15 mg of lycopene alone ( n = 38 ) or together with a capsule containing 40 mg of a soy isoflavone mixture ( n = 33 ) twice daily orally for a maximum of 6 mo . One patient on the lycopene arm did not receive therapy due to his inability to ingest the study pill . There was no decline in serum PSA in either group qualifying for a partial or complete response . However , 35 of 37 ( 95 % ) evaluable patients in the lycopene group and 22 of 33 ( 67 % ) evaluable patients in the lycopene plus soy isoflavone group achieved stable disease described as stabilization in serum PSA level . The data suggest that lycopene and soy isoflavones have activity in prostate cancer patients with PSA relapse disease and may delay progression of both hormone-refractory and hormone-sensitive prostate cancer . However , there may not be an additive effect between the 2 compounds when taken together . Future studies are warranted to further investigate the efficacy of lycopene and soy isoflavones in prostate cancer as well as the mechanism of potential negative interaction between them Background : Men with biochemical recurrence ( BCR ) of prostate cancer are typically observed or treated with and rogen-deprivation therapy . Non-hormonal , non-toxic treatments to slow the rise of PSA are desirable . We studied a combination herbal supplement , Prostate Health Cocktail ( PHC ) , in prostate cancer cell lines and in a population of men with BCR . Methods : PC3 , LAPC3 and LNCaP cells were incubated with increasing concentrations of PHC suspension . Men previously treated for prostate cancer with surgery , radiation or both with rising PSA but no radiographic metastases were treated with three capsules of PHC daily ; the primary end point was 50 % PSA decline . Circulating tumor cells ( CTCs ) were identified using parylene membrane filters . Results : PHC showed a strong dose-dependent anti-proliferative effect in and rogen-sensitive and independent cell lines in vitro and suppression of and rogen receptor expression . Forty eligible patients were enrolled in the clinical trial . Median baseline PSA was 2.8 ng ml−1 ( 1.1–84.1 ) and 15 men ( 38 % ) had a PSA decline on study ( 1–55 % reduction ) ; 25 ( 62 % ) had rising PSA on study . The median duration of PSA stability was 6.4 months . Two patients had grade 2/3 transaminitis ; the only other grade 2 toxicities were hyperglycemia , hypercalcemia and flatulence . There were no significant changes in testosterone or dihydrotestosterone . CTCs were identified in 19 men ( 47 % ) . Conclusions : Although the primary end point was not met , PHC was well tolerated and was associated with PSA declines and stabilization in a significant number of patients . We believe this is the first report of detecting CTCs in men with BCR prostate cancer . R and omized studies are needed to better define the effect of PHC in men with BCR Background : Polyphenol-rich foods such as pomegranate , green tea , broccoli and turmeric have demonstrated anti-neoplastic effects in laboratory models involving angiogenesis , apoptosis and proliferation . Although some have been investigated in small , phase II studies , this combination has never been evaluated within an adequately powered r and omised controlled trial . Methods : In total , 199 men , average age 74 years , with localised prostate cancer , 60 % managed with primary active surveillance ( AS ) or 40 % with watchful waiting ( WW ) following previous interventions , were r and omised ( 2:1 ) to receive an oral capsule containing a blend of pomegranate , green tea , broccoli and turmeric , or an identical placebo for 6 months . Results : The median rise in PSA in the food supplement group ( FSG ) was 14.7 % ( 95 % confidence intervals ( CIs ) 3.4–36.7 % ) , as opposed to 78.5 % in the placebo group ( PG ) ( 95 % CI 48.1–115.5 % ) , difference 63.8 % ( P=0.0008 ) . In all , 8.2 % of men in the FSG and 27.7 % in the PG opted to leave surveillance at the end of the intervention ( χ2 P=0.014 ) . There were no significant differences within the predetermined subgroups of age , Gleason grade , treatment category or body mass index . There were no differences in cholesterol , blood pressure , blood sugar , C-reactive protein or adverse events . Conclusions : This study found a significant short-term , favourable effect on the percentage rise in PSA in men managed with AS and WW following ingestion of this well-tolerated , specific blend of concentrated foods . Its influence on decision-making suggests that this intervention is clinical ly meaningful , but further trials will evaluate longer term clinical effects , and other makers of disease progression This trial investigated the tolerability and effect of modified citrus pectin ( Pecta-Sol ® ) in 13 men with prostate cancer and biochemical prostate-specific antigen ( PSA ) failure after localized treatment , that is , radical prostatectomy , radiation , or cryosurgery . A total of 13 men were evaluated for tolerability and 10 for efficacy . Changes in the prostate-specific antigen doubling time ( PSADT ) of the 10 men were the primary end point in the study . We found that the PSADT increased ( P-value<0.05 ) in seven ( 70 % ) of 10 men after taking MCP for 12 months compared to before taking MCP . This study suggests that MCP may lengthen the PSADT in men with recurrent prostate cancer Background - Data exist that demonstrate isoflavones ' potent antiproliferative effects on prostate cancer cells . We evaluated the efficacy of isoflavone in patients with PSA recurrent prostate cancer after prior therapy . We postulated that isoflavone therapy would slow the rate of rise of serum PSA . Methods -Twenty patients with rising PSA after prior local therapy were enrolled in this open-labeled , Phase II , nonr and omized trial ( Trial registration # NCT00596895 ) . Patients were treated with soy milk containing 47 mg of isoflavonoid per 8 oz serving three times per day for 12 months . Serum PSA , testosterone , lipids , isoflavone levels ( genistein , daidzein , and equol ) , and quality of life ( QOL ) were measured at various time points from 0 to 12 months . PSA outcome was evaluated . Results -Within the mixed regression model , it was estimated that PSA had increased 56 % per year before study entry and only increased 20 % per year for the 12-month study period ( p = 0.05 ) . Specifically , the slope of PSA after study entry was significantly lower than that before study entry in 6 patients and the slope of PSA after study entry was significantly higher than before study entry in 2 patients . For the remaining 12 patients , the change in slope was statistically insignificant . Nearly two thirds of the patients were noted to have significant levels of free equol in their serum while on therapy . Conclusion -Dietary intervention with isoflavone supplementation may have biologic activity in men with biochemical recurrent prostate cancer as shown by a decline in the slope of PSA . This study may lend support to the literature that nutritional supplements have biologic activity in prostate cancer and therefore , further studies with these agents in r and omized clinical trials should be encouraged OBJECTIVES To determine whether supplemental amounts of a polysaccharide/oligosaccharide complex obtained from a shiitake mushroom extract ( SME ) would lower the prostate-specific antigen ( PSA ) level in patients with prostate cancer . METHODS A total of 62 men ( mean age 73.2 years , range 53.6 to 85.5 ) with histologically proven prostate cancer who had two consecutive elevated PSA readings were accrued to the study during a 3-month period . This was an open-label study in which the patients received oral administration of capsules containing SME given three times daily for 6 months . The endpoint for the trial was the lowering of the PSA levels . RESULTS Of the 62 men enrolled in the study , 61 were assessable . At 4 months , 1 patient withdrew because of unrelated surgery and 7 withdrew because of disease progression ; none had responded with a decrease of greater than 50 % in the PSA level . By 6 months , a total of 23 patients had progression and none had responded . Thirty-eight patients had stable PSA levels after 6 months . Although not the primary endpoint of the study , in other studies these patients could have been included as responders . When the patients ' rates of PSA rise before study entry were analyzed , 4 ( 7 % ) had stabilized disease while taking SME . Thus , the final results for our study patients were 0 with a complete response , 0 with a partial response , 4 ( 7 % ) with stable disease , and 23 of 61 with progression while taking SME . CONCLUSIONS SME alone is ineffective in the treatment of clinical prostate cancer Background : Pomegranate juice has been associated with PSA doubling time ( PSADT ) elongation in a single-arm phase II trial . This study assesses biological activity of two doses of pomegranate extract ( POMx ) in men with recurrent prostate cancer , using changes in PSADT as the primary outcome . Methods : This r and omized , multi-center , double-blind phase II , dose-exploring trial r and omized men with a rising PSA and without metastases to receive 1 or 3 g of POMx , stratified by baseline PSADT and Gleason score . Patients ( 104 ) were enrolled and treated for up to 18 months . The intent-to-treat ( ITT ) population was 96 % white , with median age 74.5 years and median Gleason score 7 . This study was design ed to detect a 6-month on- study increase in PSADT from baseline in each arm . Results : Overall , median PSADT in the ITT population lengthened from 11.9 months at baseline to 18.5 months after treatment ( P<0.001 ) . PSADT lengthened in the low-dose group from 11.9 to 18.8 months and 12.2 to 17.5 months in the high-dose group , with no significant difference between dose groups ( P=0.554 ) . PSADT increases > 100 % of baseline were observed in 43 % of patients . Declining PSA levels were observed in 13 patients ( 13 % ) . In all , 42 % of patients discontinued treatment before meeting the protocol -definition of PSA progression , or 18 months , primarily due to a rising PSA . No significant changes occurred in testosterone . Although no clinical ly significant toxicities were seen , diarrhea was seen in 1.9 % and 13.5 % of patients in the 1- and 3-g dose groups , respectively . CONCLUSIONS : POMx treatment was associated with ⩾6 month increases in PSADT in both treatment arms without adverse effects . The significance of this on- study slowing of PSADT remains unclear , reinforcing the need for placebo-controlled studies in this patient population Summary Silibinin is a polyphenolic flavonoid isolated from milk thistle with anti-neoplastic activity in several in vitro and in vivo models of cancer , including prostate cancer . Silybin-phytosome is a commercially available formulation containing silibinin . This trial was design ed to assess the toxicity of high-dose silybin-phytosome and recommend a phase II dose . Silybin-phytosome was administered orally to prostate cancer patients , giving 2.5–20 g daily , in three divided doses . Each course was 4 weeks in duration . Thirteen patients received a total of 91 courses of silybin-phytosome . Baseline patient characteristics included : median age of 70 years , median baseline prostate specific antigen ( PSA ) of 4.3 ng/ml , and a median ECOG performance status of 0 . The most prominent adverse event was hyperbilirubinemia , with grade 1–2 bilirubin elevations in 9 of the 13 patients . The only grade 3 toxicity observed was elevation of alanine aminotransferase ( ALT ) in one patient ; no grade 4 toxicity was noted . No objective PSA responses were observed . We conclude that 13 g of oral silybin-phytosome daily , in 3 divided doses , appears to be well tolerated in patients with advanced prostate cancer and is the recommended phase II dose . Asymptomatic liver toxicity is the most commonly seen adverse event Tomato and soy products are hypothesized to reduce the risk of prostate cancer or enhance efficacy of therapy . A study was completed to determine if men with active prostate cancer will adhere to a dietary intervention rich in tomato products and a soy protein supplement men ( n = 41 ) with recurrent , asymptomatic prostate cancer were r and omized among 2 groups : Group A ( n = 20 ) consumed tomato products ( no soy ) for Weeks 0 through 4 , targeting a minimum of 25 mg of lycopene/day . Group B ( n = 21 ) consumed soy ( no tomatoes ) for Weeks 0 through 4 , providing 40 g of soy protein/day . For Weeks 4 through 8 , all men consumed a combined tomato-rich diet and soy supplements . No grade II through IV toxicities were observed . During Weeks 0 through 4 , mean daily lycopene intake for Group A was 43 mg ( ± 15 mg ) and mean soy intake for Group B was 39 g ( ± 1 g ) , remaining similar during Weeks 4 through 8 . Serum lycopene increased from 0.72 ± 0.09 μ mol/l to 1.21 ± 0.10 μ mol/l ( P < 0.0001 ) and urinary isoflavone excretion increased from not detectable to 54.1 ± 5.7 μ mol/l ( P < 0.05 ) with 8 wk of diet intervention . Serum prostate-specific antigen decreased between Weeks 0 and 8 for 14 / 41 men ( 34 % ) . Mean serum vascular endothelial growth factor for the entire group was reduced from 87 to 51 ng/ml ( P < 0.05 ) over 8 wk . In conclusion , prostate cancer patients will consume diets rich in tomato products and soy with excellent compliance and bioavailability of phytochemicals . Further studies combining tomato and soy foods to determine efficacy for prostate cancer prevention or management are encouraged Each year in the United States , nearly 50,000 prostate cancer patients exhibit a rise in prostate‐specific antigen ( PSA ) levels , which can indicate disease recurrence . For patients with biochemically recurrent prostate cancer , we evaluated the effects of white button mushroom ( WBM ) powder on serum PSA levels and determined the tolerability and biological activity of WBM BACKGROUND Silymarin , a milk thistle flavonolignan mixture , has anti-proliferative and anti-angiogenic activities in xenografts of human prostate cancer ( PCa ) . Low dietary selenium on the other h and has been associated with increased incidence of PCa . The purpose of the current trial was to determine whether a daily administration of a silymarin and selenium ( SM-Se ) combination for 6 months would alter basic clinical chemistry and oxidative stress markers , and improve the quality of life score ( QoL ) in men after radical prostatectomy ( RP ) . METHODS Thirty seven participants , 2 - 3 months after RP , were r and omly assigned to receive 570 mg of silymarin and 240 µg of selenium as selenomethionine ( n = 19 , SM-Se group ) or placebo ( n = 18 , Placebo group ) daily for six months . Both groups had similar clinical and demographic characteristics . Physical examination , QoL score , haematology , basic clinical chemistry and oxidative stress markers , selenium and testosterone levels , antioxidant status were evaluated at baseline , at 3 and 6 months . RESULTS The six months administration of silymarin and selenium improved the QoL score , decreased low density lipoproteins ( LDL ) and total cholesterol and , increased serum selenium levels . The combination had no effect on blood antioxidant status and no influence on testosterone level . No adverse events were recorded . No improvement was found in the placebo group . CONCLUSIONS The selected combination of silymarin and selenium significantly reduced two markers of lipid metabolism known to be associated with PCa progression , LDL and total cholesterol in the blood of men after RP . This suggests that this combination may be effective in reducing PCa progression R and omized , controlled trials ( RCTs ) of herbal interventions often inadequately describe important aspects of their methods ( 1 - 4 ) . Although the quality of reporting of these trials may be improving with time , many still lack important information , particularly about the composition of the herbal intervention ( 4 , 5 ) . Crude herbal drugs are natural products and their chemical composition varies depending on several factors , such as geographic source of the plant material , climate in which it was grown , and time of harvest . Commercially available herbal medicinal products also vary in their content and concentration of chemical constituents from batch to batch and when products containing the same herbal ingredient are compared among manufacturers ( 6 - 14 ) . Even when herbal products are st and ardized for content of known active or marker compounds to achieve more consistent pharmaceutical quality , there is variation in the concentrations of other constituents . These variations can result in differences in pharmacologic activity in vitro ( 15 ) and in bioavailability in humans ( 16 ) . Mindful of these issues , we elaborated on the 22-item checklist of the Consoli date d St and ards of Reporting Trials ( CONSORT ) statement ( 17 ) to help authors and editors improve reporting of RCTs of herbal interventions . Methods We developed these reporting recommendations in 3 phases that included premeeting item generation , a consensus meeting , and postmeeting feedback . The individuals who participated are listed in the Appendix . To generate items , 1 investigator conducted telephone interviews of 16 participants with expertise in the method and reporting of RCTs ( 5 participants ) , pharmacognosy ( 4 participants ) , herbal medicinal products ( 5 participants ) , medical statistics ( 1 participant ) , and herbal product manufacturing ( 1 participant ) . The investigator asked participants to suggest revisions to existing CONSORT checklist items and also to additional items required for reporting trials of herbal interventions . He asked participants to nominate revisions or new items on the basis of empirical evidence that not reporting the item would bias estimates of treatment effect . When no empirical evidence was available , commonsense reasoning was acceptable . After completing all telephone calls , the investigator thematically grouped items and circulated them by e-mail to each participant for review . Fourteen participants attended the consensus meeting . The meeting began with a review of the premeeting checklist item suggestions . We emphasized minimizing item elaborations and additions and basing elaborations on evidence whenever possible . Each item suggestion was presented and followed by debate for its inclusion , deletion , or modification . This process was repeated until all items were review ed and a consensus emerged . After the consensus meeting , we circulated a draft summary report to all participants to ensure that it accurately represented decisions made during the consensus meeting . We then circulated the report to the wider CONSORT Group for input and revised it on the basis of their suggestions . Ethical approval was obtained from The University of Toronto Health Sciences Ethics Review Committee on 23 January 2004 . Financial support for the consensus meeting was provided by the Canadian Institutes of Health Research . The funding body had no role in the design , conduct , or analysis of this study and did not influence the decision to su bmi t the manuscript for publication . All research ers are independent of the funders . Results The group did not recommend any new CONSORT checklist items or modifications in the CONSORT flow diagram . We did , however , elaborate on 9 of the 22 CONSORT checklist items to enhance their relevance to trials of herbal interventions ( Table , Figure ; Appendix Table ) , including minor recommendations for 8 items ( item 1 [ title and abstract ] , item 2 [ background ] , item 3 [ participants ] , item 6 [ outcomes ] , item 15 [ baseline data ] , item 20 [ interpretation ] , item 21 [ generalizability ] , and item 22 [ overall evidence ] ) and detailed recommendations for 1 item ( item 4 [ interventions ] ) . Table . Proposed Elaboration of CONSORT Checklist Item 4 for Reporting R and omized , Controlled Trials of Herbal Medicine Interventions Figure . The high-pressure liquid chromatography chemical fingerprint for the extract of Ginkgo biloba L Appendix Table . Proposed Elaborations of CONSORT Items for R and omized , Controlled Trials of Herbal Medicine Interventions The Table shows the detailed recommendations for item 4 and an example of good reporting related to each recommendation . These recommendations begin with the words where applicable to indicate that all information suggested may not be applicable to every type of herbal medicine intervention . For example , an herbal medicinal product comprising crude herbal material ( for example , leaves and stems ) simply prepared as a tea or decoction does not require description of the type and concentration of solvent used and the ratio of herbal drug to extract ( item 4B.3 ) . Also , not every herbal medicine intervention will have a finished product or extract name or manufacturer ( item 4A.2 ) , but instead may be made by the investigators specifically for the study . In such circumstances , all methods used in preparing and formulating the product must be reported . Similarly , item 4F is not required for herbal interventions when the practitioner is not a part of the intervention . With these exceptions , we recommend that all information shown in the Table be reported for all herbal interventions . Discussion We developed recommendations to be used in conjunction with the existing CONSORT checklist when reporting RCTs of herbal interventions . In particular , we thought it imperative that reports of RCTs provide clear and complete descriptions of the herbal intervention . We think that our recommendations might also be relevant for reporting herbal interventions in other research design s , whether pre clinical ( for example , in vivo or in vitro ) or clinical ( for example , N of 1 trials ) , and refer interested readers to a detailed explanatory document that further describes each of our recommendations and provides additional examples of good reporting ( 22 ) . We hope that authors find our recommendations instructive and that journals will endorse their use and modify their instructions to authors accordingly The objective of this study was to show or to exclude an effect of dietary supplement on rising prostate‐specific antigen ( PSA ) levels . We have studied the effect of a dietary supplement ( verum , administered for 6 weeks ) containing plant estrogens , antioxidants , including carotenoids , selenium and other putative prostate cancer inhibiting substances in a r and omized placebo‐controlled double‐blind crossover study in 37 hormonally untreated men with prostate cancer and increasing PSA levels . Outcome measures were changes in the rates of change of serum concentrations of total and free PSA and changes in male sex hormone levels . Male sex hormone levels were significantly lower during the verum phase ( DHT : −0.11 nmol/L , p = 0.005 ; testosterone : −1 nmol/L , p = 0.02 ) . Total PSA doubling time was unaffected . Free PSA , which increased during the placebo phase ( average doubling time of 68 weeks ) , decreased during the verum period ( average half‐life of 13 weeks ; p = 0.02 ) . In those men in whom the free and rogen index decreased ( 21 out of 32 ) , a significant decrease in the slopes of both total and free PSA was observed ( p = 0.04 ) . Overall total PSA doubling times did not increase significantly during verum . However , the study demonstrates that this dietary intervention reduces DHT and testosterone levels and increases free PSA doubling time ( and total PSA doubling time in a relevant subgroup ) . If future studies confirm that these observations translate into a slowing of disease progression , a dietary intervention may become an attractive option for prostate cancer treatment and prevention . © 2004 Wiley‐Liss , Interest in lycopene has focused primarily on its use in the chemoprevention of prostate cancer ( CaP ) ; there are few clinical trials involving men with established disease . In addition , most data examining its mechanism of action have been obtained from experiments using immortal cell lines . We report the inhibitory effect(s ) of lycopene in primary prostate epithelial cell ( PEC ) cultures , and the results of a pilot phase II clinical study investigating whole-tomato lycopene supplementation on the behavior of established CaP , demonstrating a significant and maintained effect on prostate-specific antigen velocity over 1 year . These data reinforce the justification for a large , r and omized , placebo-controlled study IMPORTANCE Soy consumption has been suggested to reduce risk or recurrence of prostate cancer , but this has not been tested in a r and omized trial with prostate cancer as the end point . OBJECTIVE To determine whether daily consumption of a soy protein isolate supplement for 2 years reduces the rate of biochemical recurrence of prostate cancer after radical prostatectomy or delays such recurrence . DESIGN , SETTING , AND PARTICIPANTS R and omized , double-blind trial conducted from July 1997 to May 2010 at 7 US centers comparing daily consumption of a soy protein supplement vs placebo in 177 men at high risk of recurrence after radical prostatectomy for prostate cancer . Supplement intervention was started within 4 months after surgery and continued for up to 2 years , with prostate-specific antigen ( PSA ) measurements made at 2-month intervals in the first year and every 3 months thereafter . INTERVENTION Participants were r and omized to receive a daily serving of a beverage powder containing 20 g of protein in the form of either soy protein isolate ( n=87 ) or , as placebo , calcium caseinate ( n=90 ) . MAIN OUTCOMES AND MEASURES Biochemical recurrence rate of prostate cancer ( defined as development of a PSA level of ≥0.07 ng/mL ) over the first 2 years following r and omization and time to recurrence . RESULTS The trial was stopped early for lack of treatment effects at a planned interim analysis with 81 evaluable participants in the intervention group and 78 in the placebo group . Overall , 28.3 % of participants developed biochemical recurrence within 2 years of entering the trial ( close to the a priori predicted recurrence rate of 30 % ) . Among these , 22 ( 27.2 % ) occurred in the intervention group and 23 ( 29.5 % ) in the placebo group . The result ing hazard ratio for active treatment was 0.96 ( 95 % CI , 0.53 - 1.72 ; log-rank P = .89 ) . Adherence was greater than 90 % and there were no apparent adverse events related to supplementation . CONCLUSION AND RELEVANCE Daily consumption of a beverage powder supplement containing soy protein isolate for 2 years following radical prostatectomy did not reduce biochemical recurrence of prostate cancer in men at high risk of PSA failure . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00765479 |
14,025 | 23,235,610 | We found no data on the possible reduction of squamous cell carcinoma .
Based on investigator and participant evaluation , imiquimod treatment and photodynamic therapy result ed in better cosmetic outcomes than cryotherapy and 5-fluorouracil .
AUTHORS ' CONCLUSIONS For individual lesions , photodynamic therapy appears more effective and has a better cosmetic outcome than cryotherapy .
For field-directed treatments , diclofenac , 5-fluorouracil , imiquimod , and ingenol mebutate had similar efficacy , but their associated adverse events and cosmetic outcomes are different . | BACKGROUND Actinic keratoses are a skin disease caused by long-term sun exposure , and their lesions have the potential to develop into squamous cell carcinoma .
Treatments for actinic keratoses are sought for cosmetic reasons , for the relief of associated symptoms , or for the prevention of skin cancer development .
Detectable lesions are often associated with alteration of the surrounding skin ( field ) where sub clinical lesions might be present .
The interventions available for the treatment of actinic keratoses include individual lesion-based ( e.g. cryotherapy ) or field-directed ( e.g. topical ) treatments .
These might vary in terms of efficacy , safety , and cosmetic outcomes .
OBJECTIVES To assess the effects of topical , oral , mechanical , and chemical interventions for actinic keratosis . | OBJECTIVE To assess the safety and efficacy of the long-pulsed pulsed dye laser ( LP PDL ) ( 595 nm ) with photodynamic therapy ( PDT ) for treatment of actinic keratoses ( AKs ) . DESIGN Prospect i ve , controlled study with 10-day and 2- , 4-,6- , and 8-month follow-ups . SETTING Clinical research center . PATIENTS Volunteer sample of 41 patients ( age range , 35 - 91 years ; skin types I-III ) with AKs . INTERVENTION Single treatment with application of topical 20 % 5-aminolevulinic acid for 3 hours or 14 to 18 hours , followed by LP PDL irradiation at 595 nm . Controls received LP PDL irradiation alone . MAIN OUTCOME MEASURES Safety assessment s , treatment and recovery times , and efficacy assessment s , including patient mean percentage of lesions cleared and distribution of patients by percentage of lesions cleared for different anatomic sites . RESULTS We observed no to slight pain ; slight to moderate erythema ; no purpura , crusting , or scarring ; treatment time of 1 lesion per second ; and resolution of erythema by 7 to 14 days . The patient mean ( 95 % confidence interval ) percentage of head lesions ( 2620 lesions ) cleared after 1 treatment was 99.47 % ( 99.44%-99.50 % ) at 10 days , 98.19 % ( 98.15%-98.23 % ) at 2 months , 92.94 % ( 92.73%-93.14 % ) at 4 months , 91.65 % ( 91.15%-92.15 % ) at 6 months , and 90.32 % ( 78.10%-100 % ) at 8 months . For extremities ( 949 lesions ) , these were 83.1 % ( 81.4%-84.9 % ) at 10 days , 75.5 % ( 73.4 - 77.6 ) at 2 months , 70.9 % ( 68.9%-72.8 % ) at 4 months , 92.0 % ( 84.0%-100 % ) at 6 months , and 100 % at 8 months . For trunk ( 53 lesions ) , these were 85 % ( 74%-100 % ) at 10 days , 85 % ( 74%-100 % ) , and 65 % ( 50%-80 % ) at 4 months . No difference in safety or efficacy was found between the 3-hour and 14- to 18-hour incubation times . In the laser-only control group , no decrease in lesions was observed . Among 31 patients with head lesions , 28 ( 90 % ) at 10 days , 19 ( 70 % ) at 2 months , 9 ( 47 % ) at 4 months , 5 ( 42 % ) at 6 months , and 5 ( 56 % ) at 8 months were completely ( 100 % ) clear following a single treatment . Skin biopsy specimens of nonresponding lesions demonstrated a high rate of squamous cell carcinoma and other non-AK neoplasms . CONCLUSIONS Treatment of AKs using LP PDL ( 595 nm ) at nonpurpuric parameters following topical application of 5-aminolevulinic acid is safe and effective . The advantages may include minimal discomfort , rapid incubation treatment and recovery times , excellent posttreatment cosmesis , high efficacy rates with respect to head lesions , and practical applicability to large body surface areas BACKGROUND Actinic keratosis is a common precursor to sun-related squamous-cell carcinoma . Treating actinic keratoses and the surrounding skin area ( i.e. , field therapy ) can eradicate clinical and sub clinical actinic keratoses . Topical field therapy currently requires weeks or months of treatment . We investigated the efficacy and safety of a new topical field therapy for actinic keratosis , ingenol mebutate gel ( 0.015 % for face and scalp and 0.05 % for trunk and extremities ) . METHODS In four multicenter , r and omized , double-blind studies , we r and omly assigned patients with actinic keratoses on the face or scalp or on the trunk or extremities to receive ingenol mebutate or placebo ( vehicle ) , self-applied to a 25-cm(2 ) contiguous field once daily for 3 consecutive days for lesions on the face or scalp or for 2 consecutive days for the trunk or extremities . Complete clearance ( primary outcome ) was assessed at 57 days , and local reactions were quantitatively measured . RESULTS In a pooled analysis of the two trials involving the face and scalp , the rate of complete clearance was higher with ingenol mebutate than with placebo ( 42.2 % vs. 3.7 % , P<0.001 ) . Local reactions peaked at day 4 , with a mean maximum composite score of 9.1 on the local-skin-response scale ( which ranges from 0 to 4 for six types of reaction , yielding a composite score of 0 to 24 , with higher numbers indicating more severe reactions ) , rapidly decreased by day 8 , and continued to decrease , approaching baseline scores by day 29 . In a pooled analysis of the two trials involving the trunk and extremities , the rate of complete clearance was also higher with ingenol mebutate than with placebo ( 34.1 % vs. 4.7 % , P<0.001 ) . Local skin reactions peaked between days 3 and 8 and declined rapidly , approaching baseline by day 29 , with a mean maximum score of 6.8 . Adverse events were generally mild to moderate in intensity and resolved without sequelae . CONCLUSIONS Ingenol mebutate gel applied topically for 2 to 3 days is effective for field treatment of actinic keratoses . ( Funded by LEO Pharma ; Clinical Trials.gov numbers , NCT00742391 , NCT00916006 , NCT00915551 , and NCT00942604 . ) BACKGROUND Actinic keratoses ( AKs ) are epidermal skin lesions with the potential to develop into invasive squamous cell carcinoma ( SCC ) . Treatment at an early stage may prevent development of SCC . Current treatment options are highly destructive and associated with significant side-effects . Early studies with topical diclofenac were encouraging and led to its evaluation for the treatment of actinic keratosis . Previous studies have demonstrated that 3 % diclofenac in 2.5 % hyaluronan gel is effective and well tolerated in the treatment of AK . The present study was design ed to further explore the therapeutic potential of this gel . METHODS This r and omized , double-blind , placebo-controlled trial involved out patients with a diagnosis of five or more AK lesions contained in one to three 5 cm(2 ) blocks . Patients received either active treatment ( 3 % diclofenac gel in 2.5 % hyaluronan gel ) or inactive gel vehicle ( hyaluronan ) as placebo ( 0.5 g b.i.d . in each 5 cm(2 ) treatment area for 90 days ) . Assessment s included the Target Lesion Number Score ( TLNS ) , Cumulative Lesion Number Score ( CLNS ) , and Global Improvement Indices rated separately by both the investigator ( IGII ) and patient ( PGII ) . RESULTS Results obtained from 96 patients at follow up ( 30 days after end of treatment ) indicated that a significantly higher proportion of patients who received active treatment had a TLNS = 0 compared to the placebo group ( 50 % vs. 20 % ; P < 0.001 ) . There was also a significant difference between the two groups in CLNS , with 47 % of patients in the active treatment group having a CLNS = 0 compared with only 19 % in the placebo group ( P < 0.001 ) . The proportion of patients with an IGII score of 4 ( completely improved ) at follow-up was 47 % in the active treatment group compared with only 19 % in the placebo group ( P < 0.001 ) ; for PGII these values were 41 % vs. 17 % , P < 0.001 . Both treatments were well tolerated , with most adverse events related to the skin . CONCLUSIONS Topical 3 % diclofenac in 2.5 % hyaluronan gel was effective and well tolerated for the treatment of AK Background Although photodynamic therapy ( PDT ) is becoming an important treatment method for skin lesions such as actinic keratosis ( AK ) and superficial basal cell carcinoma , there are still discussion s about which fluence rate and light dose are preferable . Recent studies in rodents have shown that a low fluence rate is preferable due to depletion of oxygen at high fluence rates . However , these results have not yet been verified in humans INTRODUCTION After renal transplantation , the incidence of premalignant and malignant skin lesions is high . Treatment with acitretin improves the number and aspect of actinic keratoses and appears to reduce the incidence of squamous cell carcinomas , but treatment is hampered by frequent side effects . No optimal long-term dosing advice is available . METHODS A total of 26 long-term renal transplant recipients were r and omized to 1-year treatment with acitretin , either 0.4 mg/kg/d throughout the whole year or 0.4 mg/kg/d during the first 3 months followed by 0.2 mg/kg/d for the remaining 9 months . At 9 different time points , the number of actinic keratoses and tumors was counted , and erythema and thickness of the lesions , and severity of side effects were scored . Patient 's judgment was recorded using visual analog scores . RESULTS In both groups , the number of actinic keratoses decreased by nearly 50 % , but the number of new malignant tumors during the study year was similar to the number of tumors in the year before the study . Thickness of the keratoses decreased significantly in both groups . Acitretin dose had to be reduced in most patients because of the frequent occurrence of mucocutaneous side effects , such as cheilitis , excessive peeling of the skin , and hair disorders . In the 14 patients r and omized to continuous treatment with a dose of 0.4 mg/kg/d , this dose could be maintained in 3 of 14 patients only . Temporary interruption of acitretin therapy was necessary in 7 of 26 patients . Patients ' contentment about the aspect of their skin increased significantly , with no differences between groups . CONCLUSIONS Acitretin therapy decreased the number of actinic keratoses in renal transplant recipients at a low maintenance dose of 0.2 mg/kg/d and significantly decreased the degree of thickness of the lesions . However , the incidence of new skin malignancies remained unchanged . Despite the high incidence of mucocutaneous side effects , patient 's contentment with the aspect of their skin increased significantly BACKGROUND There is no completely satisfactory treatment for multiple actinic keratoses ( AKs ) . OBJECTIVE To evaluate the efficacy of short incubation , broad-area application of delta-aminolevulinic acid followed by exposure to activating light-photodynamic therapy ( delta-ALA/PDT ) for treatment of AKs and background photodamage . The benefit of pretreatment with 40 % urea cream to enhance penetration and the use of topical 3 % lidocaine hydrochloride to decrease discomfort were also evaluated . METHODS Eighteen patients with at least 4 nonhypertrophic facial AKs and mild to moderate diffuse facial photodamage were enrolled in the study . For 7 days , 40 % urea cream or vehicle was applied to half of the treatment area , and then delta-ALA was applied to the entire area for 1 , 2 , or 3 hours . Lidocaine hydrochloride ( 3 % ) or vehicle cream was also applied to the entire area 45 minutes before exposure to 10 J/cm(2 ) of blue light . Pain , phototoxic reactions , AK counts , and photodamage improvement were evaluated 1 day , 1 week , and 1 month after treatment in all patients and after 5 months in 10 patients . RESULTS All patients experienced mild to moderate discomfort during treatment and moderate phototoxic effects for 1 week . At 1 and 5 months there was significant reduction in AKs in all groups and significant improvement of several photodamage parameters . Different delta-ALA application times and pretreatment with urea cream or lidocaine had no significant effect on the results . CONCLUSIONS This delta-ALA/PDT protocol is safe and effective for AK treatment as well as for improving photodamage . Further studies with a larger cohort , longer follow-up , and histologic confirmation of the clinical data would be of value BACKGROUND A new 0.5 % fluorouracil cream has been developed that provides an alternative to the more highly concentrated topical formulations of fluorouracil that are currently available . OBJECTIVE This was a comparison of the tolerability and efficacy of the 0.5 % and 5 % fluorouracil creams in the treatment of actinic keratosis ( AK ) . METHODS During this single-blind , r and omized study , patients with > or = 6 AK lesions were treated for 4 weeks with the 0.5 % ( once daily ) and 5 % ( twice daily ) fluorouracil creams applied to opposite sides of the face . After the end of treatment , patients were followed for an additional 4 weeks . Efficacy variables included absolute and percent reductions in AK lesions from baseline and total clearance of AK lesions . A question naire was used to evaluate patients ' treatment preferences . Tolerability was evaluated through continuous monitoring of adverse events . RESULTS Treatment with 0.5 % fluorouracil cream reduced the number of AK lesions from 11.3 at baseline to 2.5 at the end of the 4-week follow-up phase , compared with a reduction from 10.3 to 4.2 lesions after treatment with 5 % fluorouracil cream . The reduction was significantly greater with the 0.5 % cream compared with the 5 % cream ( P = 0.044 ) . The 0.5 % cream was as effective as the 5 % cream in terms of the percent reduction in AK lesions from baseline ( 67 % and 47 % , respectively ) and in achieving total clearance of AK lesions ( both treatments , approximately 43 % of patients ) . Both treatments were associated with similar degrees of investigator-rated irritation ; however , patients preferred the 0.5 % cream because they felt it was more tolerable ( P = 0.003 ) , easier to apply , and had a once-daily application schedule . Although all patients experienced facial irritation in association with both creams , fewer patients treated with the 0.5 % cream reported symptoms of facial irritation . CONCLUSIONS In this study , 0.5 % fluorouracil cream once daily was at least as effective as 5 % fluorouracil cream twice daily in terms of the percent reduction in AK lesions and total clearance of AK lesions ; it was more effective than the 5 % cream in reducing the absolute number of AK lesions from baseline . Patients preferred the 0.5 % cream to the 5 % cream BACKGROUND Retinoids have been shown to improve the manifestations of skin photodamage , including actinic keratoses . OBJECTIVE The efficacy and tolerability of isotretinoin 0.1 % cream in the treatment of actinic keratoses were evaluated in a r and omized , double-blind , placebo-controlled , parallel-group study . METHODS One hundred patients were r and omly assigned to treatment with 0.1 % cream or vehicle twice daily for 24 weeks to the face , the scalp , and the upper extremities . Patients were assessed every 4 weeks by the investigators , who counted and recorded the number of lesions in each treatment area . The 93 patients who had at least one postbaseline assessment were included for efficacy analysis . Local tolerability was evaluated at each study visit . RESULTS On the face , the reduction in number of actinic keratoses ( mean + /- SEM ) at the end of treatment was greater for patients treated with isotretinoin ( 3.9 + /- 0.6 , i.e. , 66 % of patients with a reduction > 30 % ) than with placebo ( 1.7 + /- 0.5 , i.e. , 45 % of patients with a reduction > 30 % ) ; this difference was statistically significant ( p = 0.001 ) . No significant drug effect was seen for lesions on the scalp or upper extremities . Mild to moderate local reactions with isotretinoin abated with reduced treatment frequency . CONCLUSION Our results suggest that isotretinoin 0.1 % cream can not compete with more rapid treatments of actinic keratoses . However , its effect on facial lesions may be beneficial during long-term treatment of associated sun-damaged skin In a double-blind , r and omized , within-patient comparative study , the efficacy and tolerability of Ro 14 - 9706 ( an arotinoid methyl sulfone ) in the treatment of actinic keratoses was compared with that of tretinoin ( all-trans-retinoic acid ) . A total of 25 patients with more than three lesions on each side of the face completed the study . All patients applied each agent twice daily for 16 weeks as a 0.05 % cream to opposite sides of the face . The number of actinic keratoses in each treatment area was counted before treatment and at weekly intervals . The mean percent decrease in the number of actinic keratoses was 37.8 % for areas treated with Ro 14 - 9706 and 30.3 % for areas treated with tretinoin . Each of these decreases was significantly different from baseline ( p less than 0.01 ) , but not from each other . Ro 14 - 9706 was better tolerated ; local inflammation was slight or absent in most patients , whereas tretinoin caused severe erythema in 50 % and severe scaling in 23 % of patients This double-blind , vehicle-controlled , multicenter study evaluated the efficacy and safety of a new topical antineoplastic agent , masoprocol , in the treatment of actinic keratoses of the head and neck . Of the 113 patients who applied topical masoprocol twice a day for 14 to 28 days , there was a mean decrease in actinic keratoses from 15.0 to 5.4 and a median percent reduction from baseline actinic keratosis count of 71.4 % at the 1-month follow-up visit . Comparable numbers for the vehicle-treated group were 13.4 to 11.1 actinic keratoses and 4.3 % median percent reduction . Irritation , as manifested by erythema or flaking , occurred in 61.5 % of topical masoprocol-treated patients versus 26.7 % of those treated with vehicle and did not correlate with clinical response . Topical masoprocol appears to be useful in the treatment of actinic keratoses BACKGROUND Photodynamic therapy ( PDT ) is a promising new treatment modality for actinic keratoses . Methyl aminolevulinate ( MAL ) ( Metvix , PhotoCure , Oslo , Norway ) leads to selective accumulation of photoactive porphyrins in premalignant skin lesions and makes the lesions susceptible to phototoxic effects on illumination with red light . OBJECTIVE This multicenter , r and omized , double-blind study compared complete response rates , cosmetic outcome , and patient satisfaction for PDT with cream containing 160 mg/g MAL or placebo cream in the treatment of actinic keratoses . METHODS After application of the cream under occlusion for 3 hours , the lesions were illuminated by noncoherent red light ( 570 - 670 nm , light dose 75 J/cm(2 ) ) . Treatment was repeated after 1 week and response was assessed 3 months later . A total of 80 patients were r and omized into the study , 42 in the active and 38 in the placebo group . RESULTS Complete lesion response rate was higher after MAL PDT than placebo , 89 % versus 38 % per protocol analysis ( P = .001 ) . An excellent or good cosmetic outcome was reported in more than 90 % of patients treated with MAL . CONCLUSION In this small study , PDT using topical MAL was a safe and effective treatment for actinic keratoses with excellent cosmetic outcome . It is a promising treatment that could benefit from further study BACKGROUND / PURPOSE Literature data suggest that lower fluence rates are preferable in terms of clinical response and tolerability for treating patients with actinic keratoses ( AKs ) . We aim ed to clarify the impact of different fluence rates on pain during photodynamic therapy ( PDT ) for AKs , as well as on treatment outcome . METHODS Individuals with at least three discrete AKs were recruited . Each lesion was r and omly allocated to 25 , 50 or 75 mW/cm2 of topical 5-aminolevulinic acid ( 5-ALA ) PDT , using non-coherent light source . Primary end point was pain during illumination , evaluated using a visual analogue scale ( VAS ) . Secondary end points were clinical outcome and adverse events . RESULTS Fifty adults , with 150 AKs lesions were recruited in the study . Mean VAS score did not significantly differ between the groups of 25 and 50 mW/cm2 ( P=0.714 ) . However , mean VAS was significantly higher at the group of 75 mW/cm2 in comparison to the former ones ( P=0.000 ) . With respect to the clinical outcome and adverse events during the first year of follow-up , no differences were observed between the three groups . Comparison between the 25 and the 50 mW/cm2 ( P=0.749 ) , as well as between the former and the 75 mW/cm2 , did not show a dependence of complete response rate on fluence ( P=0.749 and P=1.000 , respectively ) . CONCLUSIONS According to our observations a fluence rate between 25 and 50 mW/cm2 is effective and better tolerated by patients treated with topical 5-ALA PDT for AKs background : Actinic keratosis ( AK ) is a very common condition , which has the potential of progressing to squamous cell carcinoma . The present study is a prospect i ve , r and omized study comparing the lesion response , cosmetic outcome , patient satisfaction and tolerability of a new treatment modality , photodynamic therapy ( PDT ) , using topical methyl aminolevulinate ( Metvix ® ) , with the most commonly used st and ard therapy for AK , cryotherapy . methods : A total of 204 patients with clinical ly diagnosed AK were r and omized to either cryotherapy or PDT . The PDT patients were further assigned to an active or placebo group in a r and om , double‐blind manner . Cryotherapy was performed using liquid nitrogen spray in a single freeze – thaw cycle . PDT was performed using 160 mg/g methyl aminolevulinate cream or placebo , a 3‐hour application time , red light ( 570–670 nm ) and a total light dose of 75 J/cm2 . PDT was repeated after 7 days . Two sessions of PDT were undertaken , as a previous study had shown a single session had similar efficacy to cryotherapy . Lesion response was assessed clinical ly after 3 months ( complete response or non‐complete response ) . results : The lesion response rate was 91 % in the methyl aminolevulinate PDT group , 68 % in the cryotherapy group and 30 % in the placebo PDT group . Methyl aminolevulinate PDT was statistically significantly better than both cryotherapy and placebo PDT in terms of response rates and cosmetic outcome . Most patients preferred PDT to other treatments . conclusions : PDT with methyl aminolevulinate is an excellent treatment option , particularly for patients with widespread damage or AK lesions in cosmetically sensitive areas The efficacy of photodynamic therapy ( PDT ) using broad area treatment with 5-aminolevulinic acid ( ALA ) has not been compared to topical 5-fluorouracil ( 5-FU ) in the treatment of actinic keratoses ( AK ) . The purpose of this study was to compare the efficacy and tolerability of PDT using short incubation time , broad area treatment with ALA plus activation with either blue light or laser light to topical 5-FU in the treatment of AK of the face and scalp . Thirty-six subjects with AK of either the face or scalp were r and omized to receive either application of ALA for 1 hour followed by activation with blue light or pulsed dye laser or topical 5-FU . Efficacy was evaluated by grading AK lesions and photoaging signs . Tolerability was assessed by scoring crusting/erosions , erythema and stinging/burning . Treatment with PDT using ALA plus blue light was as effective as topical 5-FU in clearing AK . PDT using ALA plus laser light was the least effective treatment . All treatments made improvements in the signs of photoaging . Both PDT treatments were better tolerated than 5-FU . In conclusion , broad area PDT treatment with ALA plus activation with blue light appears to be as effective as 5-FU in the treatment of AK . ALA plus laser light is somewhat less effective than the above therapies . Efficacy could likely be improved with further study of laser parameters and incubation times Background Photodynamic therapy ( PDT ) with 5‐aminolaevulinic acid ( ALA ) or its methylester [ methyl‐5‐aminolaevulinate ( MAL ) or 5‐amino‐4‐oxopentanoate ] was recently ranked as first‐line therapy for the treatment of actinic keratosis ( AK ) and is an accepted therapeutic option for the treatment of neoplastic skin diseases . BF‐200 ALA ( Biofrontera Bioscience GmbH , Leverkusen , Germany ) is a gel formulation of ALA with nanoemulsion for the treatment of AK which overcomes previous problems of ALA instability and improves skin penetration BACKGROUND Increasing evidence suggests imiquimod may be a safe therapeutic option for the treatment of actinic keratosis ( AK ) . The diagnosis and assessment of most AK lesions is made clinical ly , without histologic confirmation . OBJECTIVE A phase III , r and omized , double-blind , parallel group , vehicle-controlled study evaluated the efficacy of imiquimod 5 % cream compared with vehicle in the treatment of AK lesions on the face and balding scalp including pretreatment and posttreatment biopsy specimens . METHODS A total of 286 patients at 18 centers in 6 European countries with histologically confirmed AK were r and omized to either imiquimod 5 % cream or vehicle cream . Study cream was applied once per day , 3 days per week , for 16 weeks . Clearance of AK lesions was clinical ly and histologically assessed at an 8-week posttreatment visit . RESULTS The complete clearance rate for the imiquimod group was 57.1 % versus 2.2 % for the vehicle group ( P < .001 ) . The partial clearance rate ( > or = 75 % reduction in baseline lesions ) for the imiquimod group was 72.1 % versus 4.3 % for the vehicle group ( P < .001 ) . The most common side effects were erythema , scabbing/crusting , and erosions/ulceration . For the imiquimod group the incidence of severe erythema , scabbing/crusting , or erosions/ulceration was 30.6 % , 29.9 % , and 10.2 % , respectively . CONCLUSION Imiquimod 5 % cream used 3 times per week for 16 weeks is an effective treatment for AK . Clinical clearance was established by both clinical observation and histologic analysis BACKGROUND Actinic keratoses ( AK ) are squamous cell carcinomas in situ and require treatment . Betulin-based oleogel prepared from a st and ardized triterpene dry extract from birch bark represents a new topical agent with anti-inflammatory and anti-tumor potential . PATIENTS AND METHODS In the prospect i ve , r and omized , monocentric phase 2a study 45 patients with < 10 AK were included and r and omly assigned to one of the three treatment groups . Intervention consisted of topical betulin-based oleogel twice daily versus cryotherapy with liquid nitrogen versus the combination of cryotherapy with topical betulin-based oleogel . Treatment response was assessed clinical ly after three months . The clinical response was grade d into complete clearing ( 100 % ) , therapy responders ( > 75 % clearing of the lesions ) and non-responders ( < 75 % clearing ) . Additionally , punch biopsies were obtained from some patients before and at the end of treatment . RESULTS Therapy with betulin-based oleogel was well tolerated . Three patients discontinued therapy because of personal reasons . After three months , the 100 % ( and > 75 % ) clearing rates of the lesions were as follows : 64 % ( 86 % ) with betulin-based oleogel ( n = 14),79 % ( 93 % ) with cryotherapy ( n = 14 ) , and 71 % ( 71 % ) with the combined therapy ( n = 14 ) . Histological analysis of biopsies taken before and after treatment ( n = 8) showed a reduced degree of dysplasia in the epidermis in all study arms . CONCLUSIONS Betulin-based oleogel seems to be an effective novel approach in the topical treatment of actinic keratoses . However , the clinical and histological findings of the present pilot study have to be verified against placebo with larger case numbers BACKGROUND The immune system plays a critical role in the development and pathogenesis of actinic keratosis ( AK ) . Imiquimod has been shown to stimulate the cutaneous immune response and be effective for the treatment of nonmelanoma skin cancers . OBJECTIVE Two phase III , r and omized , double-blind , vehicle-controlled studies evaluated the efficacy of imiquimod 5 % cream compared with vehicle in the treatment of AK lesions on the face and balding scalp . METHODS A total of 436 participants at 24 centers in the United States and Canada were r and omized to either imiquimod 5 % or vehicle cream . Study cream was applied one time per day , 2 days per week for 16 weeks . Clearance of AK lesions was clinical ly assessed at an 8-week posttreatment visit . RESULTS The complete clearance rate was 45.1 % for the imiquimod group and 3.2 % for the vehicle group . The difference in complete clearance rates ( imiquimod minus vehicle ) was 41.9 % with a 95 % confidence interval of 34.9 % to 49 % . The partial ( > or = 75 % ) clearance rate was 59.1 % for the imiquimod group and 11.8 % for the vehicle group . The difference in partial clearance rates ( imiquimod minus vehicle ) was 47.3 % with a 95 % confidence interval of 39.5 % to 55.1 % . The median percent reduction in AK lesions was 83.3 % for the imiquimod group and 0 % for the vehicle group . Local skin reactions were common . Severe erythema was reported by 17.7 % of participants who received imiquimod and 2.3 % of participants who received vehicle . Overall , imiquimod was very well tolerated . CONCLUSION Imiquimod 5 % cream used 2 times per week for 16 weeks is an effective and well-tolerated treatment for AK Background : The beneficial effect of topical colchicine therapy for actinic keratoses has already been described in 1968 . Objective : To confirm that the application of a 1 % colchicine gel is a safe and effective treatment for actinic keratoses . Methods : Twenty patients were included in a double-blinded protocol . They all had actinic keratoses on the scalp , most of which had been previously treated with 5-fluorouracil or cryotherapy . Ten patients applied twice daily on the forehead a hydrophilic gel ( placebo group ) , while the other 10 where treated with the same gel containing 1 % of colchicine ( colchicine group ) . Erythema and efficacy were evaluated at each control on days 7 , 30 and 60 , with repetitive blood tests to exclude a possible systemic absorption . Results : A complete healing of the solar keratoses was observed in 7 out of the 10 patients treated with 1 % colchicine gel ; these showed no recurrence after 2 months of follow-up . Burning and itching occurred only in the colchicine group after 2 or 3 days of application , with an inflammatory reaction on the areas where the gel was applied , while pustules and crusts were located specifically on the actinic keratoses . Repeated blood controls showed that there was no systemic absorption . Conclusions : This double-blind placebo-controlled study confirms the activity of colchicine for the treatment of actinic keratosis . A comparison with other topical treatments in terms of efficacy and practicability is needed BACKGROUND Topical 5-aminolevulinic acid-based photodynamic therapy ( ALA-PDT ) has been established in recent years as an effective treatment for disseminated actinic keratosis ( AK ) . As yet , however , data are lacking to define the optimal light dose for activation of ALA-induced protoporphyrin IX in AK . OBJECTIVE In the present study our purpose was to compare the efficacy and tolerability of 3 different doses of red light for ALA-PDT of AK . METHODS Twenty-seven patients with at least 3 clearly definable , mild or moderate AKs on the scalp or face entered the study . After occlusion for 4 hours with 20 % ALA , one AK each was irradiated at r and om with a single dose of 70 , 100 , or 140 J/cm2 . PDT-induced pain was assessed by the patients by means of a visual analog scale that grade d pain intensity between 0 and 10 . Follow-up examinations were performed 1 and 3 months after PDT . RESULTS One month after PDT , the rate of complete remission ( CR ) was 89 % for 70 J/cm2 , 92 % for 100 J/cm2 , and 81 % for 140 J/cm2 . The CR rates at 3 months were 81 % for 70 J/cm2 , 77 % for 100 J/cm2 , and 69 % for 140 J/cm2 . No significant difference in therapeutic efficacy was found among the 3 light doses at either 1 month ( P = .36 ) or 3 months ( P = .96 ) after PDT . The degree of PDT-induced pain during irradiation was substantial and not statistically different ( P = .06 ) for all 3 light doses . LIMITATIONS The conclusions from this study are limited by the small sample size and only apply to topical ALA-PDT . CONCLUSION Our results indicate that a red light dose of 70 J/cm2 may be sufficient for effective topical ALA-PDT of disseminated , mild to moderate AK on the face and scalp Background : Cryotherapy is the st and ard of care for clinical ly apparent ( target ) actinic keratoses ( AKs ) . Topical imiquimod may reduce initially inapparent or sub clinical AKs . Objective : We evaluated the potential of topical imiquimod to decrease sub clinical AKs after cryotherapy of target AKs . Methods : A r and omized trial of imiquimod or vehicle twice weekly for 8 weeks following 3- to 5-second cryotherapy of target AKs within a 50 cm2 field at the face or scalp was conducted . Efficacy outcomes included clearance of target , sub clinical , and total AKs and proportions clear of AKs . Subjects with residual AKs were offered cryotherapy and open-label imiquimod twice weekly for 8 weeks . Results : Sixty-three subjects completed the r and omized phase . At 12 weeks , target AK clearance was similar for imiquimod and vehicle ( 79 % vs 76 % ) , but fewer total AKs were noted for imiquimod ( 78 vs 116 ) . This was due to a progressive reduction in sub clinical AKs with imiquimod compared with a progressive increase with vehicle . More subjects treated with imiquimod achieved clearance of sub clinical ( 58 % vs 34 % ; p = .06 ) and total ( 23 % vs 9 % ; p = .21 ) AKs . Conclusion : Imiquimod postcryotherapy may increase clearance of sub clinical and total AKs and proportions of subjects clear at 3 months . These findings require confirmation in larger controlled trials powered for statistical significance Background Clinical studies in cutaneous conditions other than actinic keratosis ( AK ) have revealed that the safety and efficacy profile of imiquimod is influenced by dosing frequency OBJECTIVE To determine the effect of facial skin resurfacing for treatment of actinic keratoses ( AKs ) and prophylaxis against new primary basal and squamous cell carcinomas in individuals with previous nonmelanoma skin cancer ( NMSC ) or severe photodamage . DESIGN R and omized , prospect i ve 5-year trial . SETTING Dermatology and otolaryngology clinics of a Veterans Affairs hospital . PATIENTS Thirty-four patients with a history of facial or scalp AKs or basal or squamous cell carcinoma were enrolled . Five of 7 eligible patients who declined study -related treatment were used as controls . Twenty-seven patients were r and omized to 3 treatment arms ; 3 patients were discontinued from the study . INTERVENTIONS Carbon dioxide laser resurfacing , 30 % trichloroacetic acid peel , or 5 % fluorouracil cream applied twice daily for 3 weeks . MAIN OUTCOME MEASURES Reduction in the number of AKs was measured 3 months after treatment . The incidence of new NMSC in treated areas was assessed between January 1 , 2001 , and June 30 , 2005 . Times from baseline to diagnosis of first skin cancer were compared between the treatment and control groups . RESULTS Treatment with fluorouracil , trichloroacetic acid , or carbon dioxide laser result ed in an 83 % to 92 % reduction in AKs ( P < or = .03 ) , a lower incidence of NMSC compared with the control group ( P<.001 ) , and a trend toward longer time to development of new skin cancer compared with the control group ( P=.07 ) . However , no significant differences were noted among the treatment groups . CONCLUSION All 3 modalities demonstrated benefit for AK reduction and skin cancer prophylaxis compared with controls and warrant further study in a larger trial OBJECTIVE To evaluate the efficacy and safety of 5 % imiquimod cream compared with vehicle in the treatment of actinic keratosis ( AK ) . DESIGN Two phase 3 r and omized , double-blind , parallel-group , vehicle-controlled studies . SETTING Twenty-six ambulatory care offices , including dermatologists in private practice or research centers . PATIENTS Four hundred ninety-two patients , 18 years and older , with 4 to 8 AK lesions in a 25-cm(2 ) treatment area on the face or the balding scalp were r and omized ; an additional 162 patients underwent screening but were ineligible . INTERVENTIONS Patients applied 5 % imiquimod ( Aldara ) or vehicle cream to the treatment area once daily , 3 times per week , for 16 weeks , followed by an 8-week posttreatment period . MAIN OUTCOME MEASUREMENTS Complete clearance rate ( proportion of patients at the 8-week posttreatment visit with no clinical ly visible AK lesions in the treatment area ) , partial clearance rate ( proportion of patients at the 8-week posttreatment visit with a > /=75 % reduction in the number of baseline AK lesions in the treatment area ) , and frequency and severity of adverse events and local skin reactions were measured . RESULTS Complete and partial clearance rates for imiquimod-treated patients ( 48.3 % and 64.0 % , respectively ) were clinical ly and statistically significantly higher than for vehicle-treated patients ( 7.2 % and 13.6 % , respectively ) . The median percentage reduction of baseline lesions was 86.6 % for the imiquimod-treated group and 14.3 % for the vehicle-treated group . CONCLUSION The 5 % imiquimod cream dosed 3 times weekly for 16 weeks is safe and effective for the treatment of AK OBJECTIVE To determine the safety and efficacy of photodynamic therapy ( PDT ) using 20 % wt/vol aminolevulinic acid hydrochloride ( hereinafter " ALA " ) and visible blue light for the treatment of multiple actinic keratoses of the face and scalp . DESIGN R and omized , placebo-controlled , uneven parallel-group study . INTERVENTIONS Patients ( N = 243 ) were r and omized to receive vehicle or ALA followed within 14 to 18 hours by PDT . Follow-up visits occurred 24 hours and 1 , 4 , 8 , and 12 weeks following PDT . Target lesions remaining at week 8 were re-treated . MAIN OUTCOME MEASURE Clinical response based on lesion clearing by week 8 . RESULTS Most patients in both groups had 4 to 7 lesions . Complete response rates for patients with 75 % or more of the treated lesions clearing at weeks 8 and 12 were 77 % ( 128/166 ) and 89 % ( 133/149 ) , respectively , for the drug group and 18 % ( 10/55 ) and 13 % ( 7/52 ) , respectively , for the vehicle group ( P<.001 , Cochran-Mantel-Haenszel general association test ) . The 95 % confidence interval for the difference in response rates at week 8 was 46.9 % to 71.0 % and at week 12 , 65.3 % to 86.3 % . The week 12 response rate includes 30 % of patients who received a second treatment . Most patients experienced erythema and edema at the treated sites , which resolved or improved within 1 to 4 weeks after therapy , and stinging or burning during light treatment , which decreased or resolved by 24 hours after light treatment . CONCLUSION Findings indicate that topical ALA PDT is an effective and safe treatment for multiple actinic keratoses of the face and scalp Purpose : Previously , we reported the results of a Phase III , placebo-controlled trial in 2,297 r and omized participants with moderately severe actinic keratoses wherein 25,000 IU/day vitamin A caused a 32 % risk reduction in squamous cell skin cancers . We hypothesized that dose escalation of vitamin A to 50,000 or 75,000 IU/day would be both safe and more efficacious in skin cancer chemoprevention . Experimental Design : One hundred and twenty-nine participants with severely sun-damaged skin on their lateral forearms were r and omized to receive placebo or 25,000 , 50,000 , or 75,000 IU/day vitamin A for 12 months . The primary study end points were the clinical and laboratory safety of vitamin A , and the secondary end points included quantitative , karyometric image analysis and assessment of retinoid and rexinoid receptors in sun-damaged skin . Results : There were no significant differences in expected clinical and laboratory toxicities between the groups of participants r and omized to placebo , 25,000 IU/day , 50,000 IU/day , and 75,000 IU/day . Karyometric features were computed from the basal cell layer of skin biopsies , and a total of 22,600 nuclei from 113 participants were examined , showing statistically significant , dose-response effects for vitamin A at the 25,000 and 50,000 IU/day doses . These karyometric changes correlated with increases in retinoic acid receptor α , retinoic acid receptor β , and retinoid X receptor α at the 50,000 IU/day vitamin A dose . Conclusions : The vitamin A doses of 50,000 and 75,000 IU/day for 1 year proved safe and equally more efficacious than the 25,000 IU/day dose and can be recommended for future skin cancer chemoprevention studies The sap of the plant Euphorbia peplus is a traditional remedy for skin conditions , including actinic keratosis . The active constituent of the sap is ingenol mebutate ( ingenol‐3‐angelate ) , formerly known as PEP005 . This r and omized , double‐blind , vehicle‐controlled , phase IIa study investigated the safety ( and secondarily the efficacy ) of two applications of ingenol mebutate gel in 58 patients with biopsy‐confirmed actinic keratosis . Five preselected lesions were treated with ingenol mebutate gel , 0.0025 % , 0.01 % or 0.05 % , or vehicle gel , on days 1 and 2 ( Arm A ) or days 1 and 8 ( Arm B ) . There were no significant differences in tolerability or efficacy between Arms A and B. Treatment was well tolerated . The most common local skin responses were dose‐related erythema , flaking/scaling/dryness and scabbing/crusting . Efficacy was greatest with ingenol mebutate gel , 0.05 % , which result ed in complete clinical clearance of 71 % of treated lesions ( P < 0.0001 vs vehicle gel ) . In addition , 67 % of patients treated with ingenol mebutate gel , 0.05 % had clinical clearance of at least four of five treated lesions ( P = 0.0185 vs vehicle gel ) . Ingenol mebutate gel is being developed as a short‐course topical therapy for actinic keratosis and non‐melanoma skin cancer OBJECTIVE To compare the efficacy and tolerability of a single ALA-PDT illumination scheme with that of a fractionated ALA-PDT illumination scheme in face and scalp actinic keratoses ( AKs ) . METHODS Eligible patients received either a single ALA-PDT illumination or a fractionated illumination scheme r and omly allocated to alternate sides of face/scalp . The side allocated to a single illumination received 75 J/cm(2 ) . This side received 2 sessions performed 7 days apart . Lesions on the fractionated illumination scheme side received 20 and 80 J/cm(2 ) , 4 and 6 hours after a single ALA application . Patients were evaluated at baseline , at 3 and 12 months after treatment . Efficacy end point included the individual AK lesion clearance rate . RESULTS Thirty three patients with 266 lesions were enrolled in the study . Three months after treatment the overall lesion complete response rate was 89.05 % for the single scheme and 96.12 % for the fractionation scheme while at the 12-months follow-up response rate decreased to 85.4 % for the single illumination and to 93.79 % for the fractionated illumination group . Looking at lesion response based on lesion grade fractionated photodynamic therapy ( PDT ) result ed in larger rates of cured grade I as well as grade II lesions . Recorded adverse events were transient and did not dem and additional therapy . CONCLUSIONS Our results demonstrate that higher responses are achieved with fractionated PDT compared with single illumination PDT . The study data indicate that fewer treatment sessions may be needed with fractionated PDT increasing that way the comfort of the patient regarding number of visits , treatment cost and treatment-related downtime BACKGROUND Imiquimod 5 % cream is approved as a 16-week regimen for the treatment of actinic keratoses involving a 25-cm(2 ) area of skin . OBJECTIVE We sought to evaluate imiquimod 2.5 % and 3.75 % creams for short-course treatment of the entire face and scalp . METHODS In two identical studies , adults with 5 to 20 lesions were r and omized to placebo , or imiquimod 2.5 % or 3.75 % cream ( 1:1:1 ) . Up to two packets ( 250 mg each ) were applied per dose once daily for two 3-week treatment cycles , with a 3-week , no-treatment interval . Efficacy was assessed at 8 weeks posttreatment . RESULTS In all , 490 subjects were r and omized to placebo , or imiquimod 2.5 % or 3.75 % cream . Median baseline lesion counts for the treatment groups were 9 to 10 . Complete and partial clearance rates were 5.5 % and 12.8 % for placebo , 25.0 % and 42.7 % for imiquimod 2.5 % , and 34.0 % and 53.7 % for imiquimod 3.75 % ( P < .001 , each imiquimod vs placebo ; P = .034 , 3.75 % vs 2.5 % for partial clearance ) . Median reductions from baseline in lesion count were 23.6 % , 66.7 % , and 80.0 % for the placebo , imiquimod 2.5 % , and imiquimod 3.75 % groups , respectively ( P < .001 each imiquimod vs placebo ) . There were few treatment-related discontinuations . Temporary treatment interruption ( rest ) rates were 0 % , 17.1 % , and 27.2 % for the placebo , imiquimod 2.5 % , and imiquimod 3.75 % , respectively . LIMITATIONS Local effects of imiquimod , including erythema , may have led to investigator and subject bias . CONCLUSIONS Both imiquimod 2.5 % and 3.75 % creams were more effective than placebo and had an acceptable safety profile when administered daily as a 3-week on/off/on regimen Background . Organ transplant recipients on long-term immunosuppressive therapy are at increased risk of non-melanoma skin lesions . Repeated field photodynamic therapy using topical methyl aminolevulinate ( MAL ) may have potential as a preventive treatment . Methods . This open r and omized , intrapatient , comparative , multicenter study included 81 transplant recipients with 889 lesions ( 90 % actinic keratoses ( AK ) ] . In each patient , the study treatment was initially administered to one 50 cm2 area on the face , scalp , neck , trunk , or extremities ( n=476 lesions ) twice ( 1 week apart ) , with additional single treatments at 3 , 9 , and 15 months . On each occasion , the area was debrided gently and MAL cream ( 160 mg/g ) applied for 3 hr , before illumination with noncoherent red light ( 630 nm , 37 J/cm2 ) . The control , 50 cm2 area ( n=413 lesions ) received lesion-specific treatment ( 83 % cryotherapy ) at baseline and 3 , 9 , and 15 months . Additionally , all visible lesions were given lesion-specific treatment 21 and 27 months in both treatment and control areas . Results . At 3 months , MAL photodynamic therapy significantly reduced the occurrence of new lesions ( 65 vs. 103 lesions in the control area ; P=0.01 ) , mainly AK ( 46 % reduction ; 43 vs. 80 ; P=0.006 ) . This effect was not significant at 27 months ( 253 vs. 312 ; P=0.06 ) . Hypopigmentation , as assessed by the investigator , was less evident in the treatment than control areas ( 16 % vs. 51 % of patients ; P<0.001 ) at 27 months . Conclusion . Our results suggest that repeated field photodynamic therapy using topical MAL may prevent new AK in transplant recipients although further studies are needed Background Photodynamic therapy ( PDT ) is increasingly used for treatment of actinic keratoses ( AKs ) but is a cumbersome procedure . A thin self‐adhesive patch ( PD P 506 A ) containing 5‐aminolaevulinic acid ( 5‐ALA ) was developed to facilitate PDT Photodynamic therapy ( PDT ) is a noninvasive therapy for non-melanoma skin cancer . The aim of this study was comparison of efficacy between fractioned versus single dose illumination in photodynamic therapy ( PDT ) of actinic keratosis ( AK ) and Bowen 's disease ( BD ) . Fifty-one patients ( 36 AK and 15 BD ) were treated with PDT They were r and omly arranged in two treatment groups . Group one included 26 patients ( 20 AK and 6 BD ) that , after five hours of incubation with 20 % 5-ALA , were treated with a single illumination of 100 Jcm(-2 ) at fluence rate of 30 mWcm(-2 ) . Group two included 25 patients ( 16 AK and 9 BD ) that , after 16 hours of incubation with 20 % 5-ALA , were treated with two light fractions ( 50 plus 50 Jcm(-2 ) ) at same fluence rate with dark interval of two hours between fractions . Twenty-four weeks later , a treated area was incubated for four hours again with 5-ALA in order to detect occult areas of abnormal skin with possible remaining tumor tissue . In case of fluorescence , histological examination was performed . In the group one , fluorescence at the end of the session was absent in 19 ( 73 % ) or very weak in 7 ( 27 % ) . Residual tumor was found in 15 ( 75 % ) AK and in 4 ( 66.6 % ) BD . In the group two , fluorescence at the end of second session was more intense ; in one patient ( 4 % ) was absent , very weak in 5 ( 20 % ) and weak in 19 ( 76 % ) of patients . In this group histology revealed remaining tumor tissue in only 2 ( 12.5 % ) AK and 2 ( 22.2 % ) BD . Among the patients in the first group , the remaining tumor tissue was significantly bigger ( p=0.005 ) . The treatment response with clearing of tumor tissue was significantly higher in fractionated illumination than in a single dose illumination group . Fractionated illumination scheme with 16 hours of incubation separated by two hours dark interval significantly improves the therapeutic outcome in tumor eradication Background : Actinic keratoses ( AK ) are sun-induced epithelial skin lesions , which are at risk to progress to squamous cell carcinoma . One of the treatments of AK is photodynamic therapy ( PDT ) , which often has to be repeated . Another treatment for these lesions is diclofenac 3 % gel . Although both treatments have shown to be effective , they have never been studied together . Objective : To investigate whether a pre-treatment of AK on the dorsum of the h and s with diclofenac 3 % gel improves the efficacy of PDT . Methods : In this placebo-controlled , r and omized , double-blind , pilot study with 10 patients , both h and s were pre-treated – one with diclofenac gel and the other with placebo gel – and then the h and s were treated with ALA-PDT . Total lesion number scores , total thickness scores and global improvement scores were used to assess efficacy . Pain scores were recorded during PDT . Results : In both groups , the number of lesions significantly decreased . At 12 months ' follow-up , significantly fewer AK were seen in the diclofenac group . Total lesion thickness scores decreased significantly in both groups . Pain during PDT was greater in the diclofenac group . Conclusions : Both treatments are effective in treating AK . A pre-treatment with diclofenac gel seems to result in fewer AK at 12 months ' follow-up , compared to placebo . Side effects were worse when using the active drug BACKGROUND . Chemical peels have become an increasingly popular method to treat a myriad of benign skin disorders . Individually , glycolic acid ( GA ) and 5‐fluorouracil ( 5‐FU ) have been proven efficacious in the treatment of actinically damaged skin . However , to our knowledge the literature lacks a study examining the synergistic effects of these two agents in the treatment of actinic keratoses ( AKs ) and solar damage . objective . The aim of the study was to determine if a combination of 5‐FU and 70 % GA , when delivered in pulse doses , would have greater efficacy than using GA alone in destroying precancerous AKs and improving the cosmetic appearance of the skin . METHODS . A prospect i ve r and omized controlled study was design ed with 18 subjects who had clinical ly apparent facial AKs . Each patient was treated with the combination of 5‐FU and GA to one half of the face , while GA alone was applied to the other half , in a r and omized fashion . A before‐treatment count of the number of AKs present on each half of the face was recorded and pretreatment photographs were taken . The solutions were applied weekly to all patients for an 8‐week period . A posttreatment count of AKs on each half of the face along with posttreatment photographs followed at 6 months . RESULTS . The combination of 5‐FU and GA cleared 91.94 % of AKs at a 6‐month follow‐up period as compared with 19.67 % clearing by GA alone . There were no significant side effects reported with the combination peel . CONCLUSION . The fluor‐hydroxy pulse peel applied in a pulse dose regimen not only provides cosmetic improvement , but more importantly , has a therapeutic effect on ablating premalignant AKs . This therapeutic effect occurs without the usual morbidity associated with using 5‐FU alone in a nonpulsed dosage . Additionally , it is evident that the superficial peeling induced by alpha hydroxy acids may improve cosmesis of actinically damaged skin , but the GA alone can not destroy a significant number of AKs Photodynamic therapy ( PDT ) with topical methyl aminolevulinate ( MAL ) administered in two treatment sessions separated by 1 week is an effective treatment for actinic keratoses . This open prospect i ve study compared the efficacy and safety of MAL-PDT given as a single treatment with two treatments of MAL-PDT 1 week apart . Two hundred and eleven patients with 413 thin to moderately thick actinic keratoses were r and omized to either a single treatment with PDT using topical MAL ( regimen I ; n=105 ) or two treatments 1 week apart ( regimen II ; n=106 ) . Each treatment involved surface debridement , application of Metvix cream ( 160 mg/g ) for 3 h , followed by illumination with red light using a light-emitting diode system ( peak wavelength 634+/-3 nm , light dose 37 J/cm2 ) . Thirty-seven lesions ( 19 % ) with a non-complete response 3 months after a single treatment were re-treated . All patients were followed up 3 months after the last treatment . A total of 400 lesions , 198 initially treated once and 202 treated twice , were evaluable . Complete response rate for thin lesions after a single treatment was 93 % ( 95 % CI=87 - 97 % ) , which was similar to 89 % ( 82 - 96 % ) after repeated treatment . Response rates were lower after single treatment of thicker lesions ( 70 % ( 60 - 78 % ) vs 84 % ( 77 - 91 % ) ) , but improved after repeated treatment ( 88 % ( 82 - 94 % ) ) . The conclusion of this study is that single treatment with topical MAL-PDT is effective for thin actinic keratosis lesions ; however , repeated treatment is recommended for thicker or non-responding lesions OBJECTIVE Assess long-term , sustained , complete clearance of actinic keratoses after treatment with imiquimod 3.75 % or 2.5 % cream using two two-week or three-week cycles of daily dosing . METHODS Adults with five to 20 baseline actinic keratoses who achieved complete clearance at the eight-week post-treatment visit in four phase 3 placebo-controlled treatment studies were followed for an additional 12 months . RESULTS For imiquimod 3.75 % and 2.5 % cream , respectively , complete clearance was sustained for 12 months in 17/42 ( 40.5 % ) and 13/39 ( 33.3 % ) subjects from the two-week cycle studies , and in 23/48 ( 47.9 % ) and 16/37 ( 43.2 % ) subjects from the three-week cycle studies . There were no safety concerns during the follow-up . CONCLUSION In subjects with a median of eight to nine baseline actinic keratoses who achieved complete clearance after treatment of the full face or balding scalp with topical imiquimod 3.75 % cream , complete clearance of all lesions ( baseline , recurrent or new ) was sustained in ≥ 40 percent of subjects for at least 14 months after the last dose . Clinical trials.gov identifier NCT00668733 Background Imiquimod 5 % cream is a topically applied immune response modifier that has been shown to give effective treatment of actinic keratosis ( AK ) . The therapeutic effects of imiquimod are likely to involve the provocation of a cutaneous immune response against abnormal cells , an assumption based on a strong correlation between complete clearance rates and the severity of the local skin reactions ( erythema , oedema , erosion/ulceration , weeping/exudation and scabbing/crusting ) ; however , no clinical studies have conclusively proved this mechanism OBJECTIVE To determine whether low-dose topical applications of difluoromethylornithine ( DFMO ) with or without Triamcinolone ( Fougena , Melville , New York , U.S.A. ) to moderately sun-damaged skin with actinic skin keratoses are efficacious . STUDY DESIGN There were 4 topically administered , 6-month treatments , DFMO + Eucerin ( Beiersdorf Inc. , Hamburg , Germany ) , DFMO + Triamcinolone , Triamcinolone + Eucerin and Eucerin + Eucerin ( to serve as double placebo ) . Participant eligibility included evidence of at least 2 actinic keratoses on each posterolateral forearm as well as moderate to severe evidence of sun-damaged skin , as evaluated by a board certified dermatologist . High resolution digitized imagery of nuclei from histologic sections of 4-mm punch biopsies from sun-damaged skin on the posterolateral forearms was recorded , at baseline and at the end of 6 months of study . RESULTS With 102 participants and 185 skin biopsies , a total of 16,395 skin cell nuclei were recorded . The nuclei were analyzed to assess the changes in the pattern of the nuclear chromatin . Two specific measures of end point evaluation were computed , including the percentage of nuclei with high values of nuclear abnormality and the reduction of the percentage of nuclei assigned by a discriminant function to the baseline data set . All 3 active interventions , including low-dose topical DFMO , topical Triamcinolone and topical DFMO + Triamcinolone , led to statistically significant reductions of both the number of nuclei with high nuclear abnormality as well as the number of nuclei assigned to the baseline data set . These reductions were found for all 3 treatments involving DFMO or Triamcinolone . For the placebo data sets only small , statistically insignificant increases or decreases of these percentages were observed . CONCLUSION The low-dose , topical drug interventions were all effective in reducing skin biopsy nuclear abnormality by a statistically significant 15 - 20 % , whereas there was no evidence of a double placebo effect by karyometric assessment . These effects were greater than the case-to-case sampling error Prior research shows that topical application of free , nonfatty acid – conjugated vitamin E ( dl-α-tocopherol ) prevents skin cancer in mice , as well as immunosuppression induced by UVB radiation . This study investigated the chemopreventive potential of dl-α-tocopherol in humans through monitoring surrogate end point biomarkers in sun-damaged skin . Contralateral arms of healthy human volunteers with actinic keratoses ( AK ) were r and omly assigned to receive either 12.5 % dl-α-tocopherol or placebo in a crème base for 6 months . Changes in number of AKs , levels of p53 protein expression , proliferating cell nuclear antigen , and polyamines were assessed along with skin and systemic vitamin E levels . Following treatment , plasma concentration levels of dl-α-tocopherol were unchanged , but skin levels were highly elevated ( P < 0.001 ) . Levels of p53 and proliferating cell nuclear antigen did not change significantly , whereas number of AKs declined insignificantly in both placebo and treatment arms . Regression models showed significant decreases in putrescine , spermidine , spermine , and total polyamine concentrations following treatment . Topically applied dl-α-tocopherol was substantially absorbed in skin , but the 6-month application did not significantly reduce numbers of preexisting AKs on moderately to severely sun-damaged forearms . Increases in polyamine synthesis are expected during tumor initiation and promotion ; conversely , the significant reductions in polyamine levels result ing from the topical dl-α-tocopherol application are consistent with reductions in tumorigenesis potential . Topical tocopherol did not normalize established sun-induced lesions , but dl-α-tocopherol – induced reductions in polyamine metabolism are consistent with the inhibition of skin squamous cell carcinogenesis as seen in previous human trials and animal models Summary Background Actinic keratoses ( AKs ) are premalignant skin lesions , which , if left untreated , can develop into squamous cell carcinoma . Current treatments for AKs are destructive and are often associated with significant adverse events . The development of an effective and well‐tolerated topical treatment for AK is desirable Background : Topical diclofenac and imiquimod have been reported to be effective in the treatment of actinic keratosis , but a study to compare these two drugs has not been reported yet . Objective : To compare the efficacy and safety of topical 3 % diclofenac gel plus hyaluronic acid and 5 % imiquimod cream in the treatment of actinic keratosis . Methods : Forty‐nine patients with actinic keratosis were enrolled in this r and omized comparative open‐label study . Twenty‐four patients applied 3 % diclofenac gel once a daily to their lesions , while the other 25 patients were treated with a 5 % imiquimod cream three times a week for 12 weeks . Patients were examined before treatment and every month of the treatment . Assessment s were made by investigators according to the Investigator and the Patient Global Improvement Indices ( IGII ) and ( PGII ) . Results : According to the IGII results , a complete response was observed in 12 % of the diclofenac group and 22 % of the imiquimod group . For the PGII scores , a complete response was observed in 28 % of the diclofenac group and 23 % of the imiquimod group . There were no significant differences between the two groups ( p>0.05 ) . Both treatments were well tolerated , with most adverse events related to skin . Conclusion : The two drugs were found to be equally effective and safe in the treatment of actinic keratosis but complete remission was very low . Therefore , topical treatments with these two drugs were not seen to be completely effective , and combined therapies and further studies are needed BACKGROUND Photodamaged skin typically displays lentigines , actinic keratoses , wrinkles , and textural alteration . Chemical peeling has been used to treat these , but few controlled studies have been performed to determine its efficacy . OBJECTIVE Our purpose was to compare the efficacy of a medium-depth chemical peel with and without tretinoin before and after treatment . METHODS Sixteen men with actinic damage including actinic keratoses were treated with a 40 % trichloroacetic acid(TCA ) chemical peel . Half were pretreated for 6 weeks with topical tretinoin ; they also used tretinoin after the peel . Photographs were obtained at baseline and at 6 weeks and 6 months after treatment . Changes in specific features were rated by a panel of three examiners . RESULTS Some improvement was noted in all patients . More rapid and even frosting was observed in the patients pretreated with tretinoin . Solar lentigines , actinic keratoses , and skin texture were the features of photoaging most affected ; wrinkles were least affected . No statistically significant difference was found between patients treated with TCA and tretinoin ( before and after peel ) and those with TCA alone . CONCLUSION A medium-depth chemical peel with 40 % TCA alone produced moderate improvement in some manifestations of actinic damage but had little effect on wrinkles . Treatment with tretinoin before and after TCA did not significantly enhance the efficacy of the peel Increasing incidence rates of cutaneous malignancies , paralleling rising survival times of grafts and patients in organ transplant recipients , represents an escalating challenge for dermatologists worldwide . Especially , invasive squamous cell carcinomas ( SCC ) in immuno-compromised patients are characterized by significantly increased morbidity and mortality and characteristically outnumber basal cell carcinoma in this population . Effective management of actinic keratoses ( AK ) could help to prevent the further development of invasive SCC . Diclofenac in hyaluronic acid has previously shown to be an effective and well tolerated option for the treatment of AK in immuno-competent patients . However , its safety and efficacy in organ-transplant patients has not been evaluated in a controlled study so far . 32 organ transplant patients ( kidney ( + /- pancreas ) , liver , heart ) screened at our specialized transplant dermatology outpatient clinic were found eligible and were r and omized to either active treatment ( 24 ) or vehicle ( 8) . Patients who had stable status of the transplanted graft in the 12 months prior to entering the study and > /= 3 AK lesions in a contiguous 50 cm2 area on the face , forehead , h and s or balding scalp were eligible for inclusion in the study . Treatment of AK with 3 % diclofenac in 2.5 % hyaluronic acid or placebo twice daily was conducted over a total of 16 weeks , followed by a final evaluation 4 weeks after last application of the study drug . Biopsies were taken from the treated areas at the final visit to verify clinical clearance . Patients were assessed for safety variables that included adverse events , local skin reactions , laboratory results , dosage of immunosuppressive medication and indication of graft rejection . A 24 months follow up was conducted after the end of treatment . 87 % ( n = 28/32 ) of the patients completed the 16 week treatment phase and presented for final evaluation 4 weeks after end of treatment . In the diclofenac 3 % gel treatment group , a complete clearance of AK lesions was achieved in 41 % ( 9/22 ) compared to 0 % ( 0/6 ) in the vehicle group . Side effects in most of the patients included a mild erythema and a mild to moderate swelling of the areas treated . No graft rejections or trends for a deterioration of graft function were detected . No meaningful trends were observed in laboratory results . In 55 % of the previously cleared patients , new AK developed in the study area after an average of 9.3 months . None of these patients developed invasive SCC in the study area within 24 months of follow-up . This study demonstrated a greater lesion clearance rate of AKs in OTRs treated with diclofenac 3 % gel than with vehicle . Despite recurrent AK in 55 % of the previously cleared patients , the 24 month results showed no invasive SCC in this group . This study suggests that diclofenac 3 % gel is not only an efficient and well tolerated treatment for multiple AKs in OTRs but also may prevent invasive SCC in these high-risk patients BACKGROUND The incidence of and mortality from skin cancer are increasing in many countries . In view of the added concern about ozone depletion , many organizations are promoting the regular use of sunscreens to prevent skin cancer , despite the absence of evidence that these products have this effect . Solar ( actinic ) keratosis is a precursor of squamous-cell carcinoma of the skin . METHODS We conducted a r and omized , controlled trial of the effect on solar keratoses of daily use of a broad-spectrum sunscreen cream with a sun-protection factor of 17 in 588 people 40 years of age or older in Australia during one summer ( September 1991 to March 1992 ) . The subjects applied either a sunscreen cream or the base cream minus the active ingredients of the sunscreen to the head , neck , forearms , and h and s. RESULTS The mean number of solar keratoses increased by 1.0 per subject in the base-cream group and decreased by 0.6 in the sunscreen group ( difference , 1.53 ; 95 percent confidence interval , 0.81 to 2.25 ) . The sunscreen group had fewer new lesions ( rate ratio , 0.62 ; 95 percent confidence interval , 0.54 to 0.71 ) and more remissions ( odds ratio , 1.53 ; 95 percent confidence interval , 1.29 to 1.80 ) than the base-cream group . There was a dose-response relation : the amount of sunscreen cream used was related to both the development of new lesions and the remission of existing ones . CONCLUSIONS Regular use of sunscreens prevents the development of solar keratoses and , by implication , possibly reduces the risk of skin cancer in the long-term It is timely to compare the efficacy and tolerability of 2 actinic keratosis ( AK ) therapies--5 % 5-fluorouracil ( 5-FU ) cream and imiquimod cream . Thirty-six patients with 4 or more AKs were r and omly assigned to receive 5 % 5-FU cream twice daily for 2 to 4 weeks or 5 % imiquimod cream twice weekly for 16 weeks . Five percent 5-FU was more effective than imiquimod in exposing what were presumed to be sub clinical AKs , reducing the final AK count ( total AK count declined during the 24-week study by 94 % vs. 66 % , P < .05 ) , achieving complete clearance ( incidence of 84 % vs. 24 % by week 24 , P < .01 ) , and achieving clearance rapidly . Tolerability was similar except for erythema , which was initially significantly higher with 5-FU than imiquimod but resolved rapidly and was significantly lower than imiquimod by week 16 . Five percent 5-FU remains the gold st and ard field therapy for AKs BACKGROUND Actinic keratoses are the most common actinic lesions on Caucasian skin . Cryosurgery with liquid nitrogen is commonly used to treat actinic keratoses , but there have been few studies examining the true rate of cure in everyday dermatologic practice . AIM To determine prospect ively the true efficacy of cryosurgery as a treatment for actinic keratoses in everyday dermatologic practice . METHODS A prospect i ve , multicentered study ( a subsidiary study of a photodynamic therapy trial ) was performed . Patients with untreated actinic keratoses greater than 5 mm in diameter on the face and scalp were recruited . Eligible lesions received a single freeze-thaw cycle with liquid nitrogen given via a spray device and were review ed 3 months thereafter . Each center used their preferred freeze time . The only treatment criterion was complete freezing of actinic keratoses and a 1-mm rim of normal skin . Treated lesions were assessed as complete response or noncomplete response . The influence of the duration of freeze , cosmetic outcomes , and adverse events were examined . RESULTS Ninety adult patients from the community with 421 eligible actinic keratoses were recruited . The overall individual complete response rate was 67.2%[SEM = + /-3.5 % ; 95 % confidence interval ( CI ) = 60.4 - 74.1 % ] . Complete response was 39 % for freeze times of less than 5 s , 69 % for freeze times greater than 5 s , and 83 % for freeze times greater than 20 s. Cosmetic outcomes were good to excellent in 94 % of complete response lesions . The main adverse events were pain , stinging , and burning during treatment , and hypopigmentation after healing . CONCLUSIONS Cryosurgery is an effective treatment for actinic keratoses . The true complete response rate is significantly lower than that previously reported . The freeze duration influences successful treatment . Adverse events are mild and well tolerated Background Pre clinical studies indicate that the enzyme cyclooxygenase 2 plays an important role in ultraviolet-induced skin cancers . We evaluated the efficacy and safety of celecoxib , a cyclooxygenase 2 inhibitor , as a chemopreventive agent for actinic keratoses , the premalignant precursor of nonmelanoma skin cancers , and for nonmelanoma skin cancers , including cutaneous squamous cell carcinomas ( SCCs ) and basal cell carcinomas ( BCCs ) . Methods A double-blind placebo-controlled r and omized trial involving 240 subjects aged 37–87 years with 10–40 actinic keratoses was conducted at eight US academic medical centers . Patients were r and omly assigned to receive 200 mg of celecoxib or placebo administered orally twice daily for 9 months . Subjects were evaluated at 3 , 6 , 9 ( ie , completion of treatment ) , and 11 months after r and omization . The primary endpoint was the number of new actinic keratoses at the 9-month visit as a percentage of the number at the time of r and omization . In an intent-to-treat analysis , the incidence of actinic keratoses was compared between the two groups using t tests . In exploratory analyses , we evaluated the number of nonmelanoma skin cancers combined and SCCs and BCCs separately per patient at 11 months after r and omization using Poisson regression , after adjustment for patient characteristics and time on study . The numbers of adverse events in the two treatment arms were compared using χ2 or Fisher exact tests . All statistical tests were two-sided . Results There was no difference in the incidence of actinic keratoses between the two groups at 9 months after r and omization . However , at 11 months after r and omization , there were fewer nonmelanoma skin cancers in the celecoxib arm than in the placebo arm ( mean cumulative tumor number per patient 0.14 vs 0.35 ; rate ratio [ RR ] = .43 , 95 % confidence interval [ CI ] = 0.24 to 0.75 ; P = .003 ) . After adjusting for age , sex , Fitzpatrick skin type , history of actinic keratosis at r and omization , nonmelanoma skin cancer history , and patient time on study , the number of nonmelanoma skin cancers was lower in the celecoxib arm than in the placebo arm ( RR = 0.41 , 95 % CI = 0.23 to 0.72 , P = .002 ) as were the numbers of BCCs ( RR = 0.40 , 95 % CI = 0.18 to 0.93 , P = .032 ) and SCCs ( RR = 0.42 , 95 % CI = 0.19 to 0.93 , P = .032 ) . Serious and cardiovascular adverse events were similar in the two groups . Conclusions Celecoxib may be effective for prevention of SCCs and BCCs in individuals who have extensive actinic damage and are at high risk for development of nonmelanoma skin cancers BACKGROUND Actinic keratosis ( AK ) is the earliest clinical manifestation of squamous cell carcinoma . Metastatic SCC causes the majority of the 1300 to 2300 deaths attributed to nonmelanoma skin cancer in the United States each year . Recent studies have shown that intralesional administration of interferon can be used successfully in the treatment of AK . OBJECTIVE Imiquimod is an immune response modifier , currently approved for the treatment of genital warts . The topically applied immune response modifier acts by up-regulating interferon and other cytokines involved in the cell-mediated immune response at the site of application . The aim of this was to determine the efficacy and safety of imiquimod 5 % cream for the treatment of AK . METHODS Twenty-two patients with AK lesions were treated with imiquimod 5 % cream , initially at 3 times per week for 8 weeks , or until total clearance of lesions . Patients applied imiquimod to lesions on one side of the body and vehicle cream to the other side . A total of 17 patients who completed treatment were evaluated for number of lesions and adverse reactions before treatment and at weeks 2 , 4 , 6 , and 8 after initiation of treatment . AK lesions were also assessed 4 and 8 weeks after treatment . RESULTS A significant reduction in the average number of lesions per patient was observed for patients treated with imiquimod . The most frequent reactions to treatment were erythema , itching , and scabbing ; however , all adverse events were mild to moderate . CONCLUSION Imiquimod 5 % cream may be a promising treatment for AK BACKGROUND Photodynamic therapy ( PDT ) using methyl aminolevulinate ( MAL ) is an effective first-line treatment for actinic keratoses . A reduced incubation period may have practical advantages . OBJECTIVE This study aims to evaluate the effect of incubation time ( 1 vs. 3 h ) , MAL concentration ( 160 mg/g vs. 80 mg/g ) and lesion preparation in the setting of MAL-PDT for treatment of actinic keratosis ( AK ) . DESIGN Open , r and omized , parallel-group multicentre study . SETTING Outpatient dermatology clinics . SUBJECTS One hundred and twelve patients with 384 previously untreated AK . Most lesions ( 87 % ) were located on the face and scalp and were thin ( 55 % ) or moderately thick ( 34 % ) . METHODS Lesions were debrided , and MAL cream ( 160 mg/g or 80 mg/g ) was applied before illumination with red light ( 570 - 670 nm ; light dose , 75 J/cm2 ) . Patients were followed up at 2 and 3 months . Sixty patients ( 54 % ) were re-treated and assessed at 6 months . MAIN OUTCOME Complete lesion response rates 3 and 12 months after last treatment . RESULTS For lesions on the face/scalp , lesion complete response rates were 78 % for thin AK and 74 % for moderately thick AK lesions after 1 h vs. 96 % and 87 % after 3 h incubation with MAL 160 mg/g . Lesion recurrence rates at 12 months after two treatments were similar [ 19 % ( 3 of 16 ) with 1 h vs. 17 % ( 3 of 18 ) with 3 h 160 mg/kg MAL-PDT ] and lower than for 80 mg/g MAL-PDT ( 44 - 45 % ) . CONCLUSION MAL-PDT using a 1-h incubation may be sufficient for successful treatment of selected AK lesions BACKGROUND Recent research demonstrated that vitamin D , apart from calcium-related actions , has antiproliferative , prodifferentia-tive and immunomodulatory activities . OBJECTIVE To determine whether actinic keratoses may benefit from the antiproliferative and prodifferentiative effects of topical vitamin D. MATERIAL S AND METHODS The study was an investigator-blinded , half-side comparison trial . Patients applied calcipotriol cream to one side and Ultrabase cream as placebo to the other side of the scalp and /or face for 12 weeks . The total number of actinic keratoses ( AKs ) , diameters and total scores of the target lesions were determined at each visit . RESULTS Nine patients were included , eight of whom completed the treatment . There was a statistically significant difference between the total number of AKs at baseline and at week 12 on calcipotriol applied side whereas no difference was detected on placebo applied side ( p = 0.028 vs p = 1.00 ) . The mean total score of the target lesions reduced significantly at week 12 on calcipotriol side ; however , no significant reduction was found on placebo side ( p = 0.017 vs p = 0.056 ) . Although side effects were more common on calcipotriol side , the difference was not statistically significant . CONCLUSION Topical calcipotriol may show promise in the treatment of actinic keratoses . More studies are needed to confirm its efficacy BACKGROUND The approved imiquimod 5 % cream regimen for treating actinic keratoses requires a long treatment time and is limited to a small area of skin . OBJECTIVE We sought to evaluate imiquimod 2.5 % and 3.75 % for short-course treatment of the full face or balding scalp . METHODS In two identical studies , adults with 5 to 20 lesions were r and omized to placebo , imiquimod 2.5 % , or imiquimod 3.75 % ( 1:1:1 ) . Up to two packets ( 250 mg each ) were applied per dose once daily for two 2-week treatment cycles , with a 2-week , no-treatment interval between cycles . Efficacy was assessed at 8 weeks posttreatment . RESULTS A total of 479 patients were r and omized to placebo , or imiquimod 2.5 % or 3.75 % . Complete and partial clearance ( > or = 75 % lesion reduction ) rates were 6.3 % and 22.6 % for placebo , 30.6 % and 48.1 % for imiquimod 2.5 % , and 35.6 % and 59.4 % for imiquimod 3.75 % , respectively ( P < .001 vs placebo , each ; P = .047 , 3.75 % vs 2.5 % for partial clearance ) . Median reductions from baseline in lesion counts were 25.0 % for placebo , 71.8 % for imiquimod 2.5 % , and 81.8 % for imiquimod 3.75 % ( P < .001 , each active vs placebo ; P = .048 3.75 % vs 2.5 % ) . There were few treatment-related discontinuations . Patient rest period rates were 0 % for placebo , 6.9 % for imiquimod 2.5 % , and 10.6 % for imiquimod 3.75 % . LIMITATIONS Local pharmacologic effects of imiquimod , including erythema , may have limited concealment of treatment assignment in some patients . CONCLUSIONS Both imiquimod 2.5 % and 3.75 % creams were more effective than placebo and were well tolerated when administered daily as a 2-week on/off/on regimen to treat actinic keratoses New therapeutic options would benefit patients with actinic keratosis ( AK ) , a precancerous condition that is a significant health concern . The efficacy and safety of a microsphere-based formulation of 0.5 % fluorouracil cream were evaluated in a r and omized , double-blind , multicenter , parallel-group study . Patients ( N= 177 ) were r and omized to receive 0.5 % fluorouracil or vehicle once daily for 1 , 2 , or 4 weeks . Efficacy was assessed by lesion counts and clearance . Safety was evaluated by monitoring adverse events , including facial irritation . Significant improvements were seen from baseline to posttreatment follow-up in all efficacy variables for all fluorouracil regimens compared with vehicle . Patients treated for one week experienced significant improvements compared with vehicle , although efficacy increased with increasing treatment duration . Most patients experienced mild to moderate facial irritation of predictable onset and duration . Once-daily administration of 0.5 % fluorouracil cream for 1 , 2 , or 4 weeks is safe and effective for the treatment of AKs The presence of solar keratoses on the skin is one of the major risk factors for basal cell and squamous cell carcinomas , which constitute a growing public health problem in today 's white population s. In spite of this , little is known of the natural history of solar keratoses . We conducted follow-up studies to monitor the incidence , regression , and recurrence rates of solar keratoses in a r and om sample ( N = 96 ) of the Nambour community in Queensl and . At baseline , 43 participants ( 46 % ) were diagnosed with at least one solar keratosis [ 26 men ( 55 % ) , 17 women ( 37 % ) ] with a total count of 494 prevalent solar keratoses . The distribution of lesions per person was highly skewed , with 11 individuals ( 12 % ) having 65 % of the total number of solar keratoses . During 12 mo of follow-up , 614 incident solar keratoses were diagnosed ( 549 in men and 65 in women ) ; 526 solar keratoses regressed and 53 prevalent solar keratoses recurred , giving a net 45 % increase in solar keratosis numbers in men ( from 354 to 512 solar keratoses ) and a net 44 % reduction in women ( from 114 to 64 ) . Regression rates were higher in prevalent ( 74 % ) than incident ( 29 % ) solar keratoses . Solar keratosis prevalence increased with age in both sexes , and individuals with solar keratoses at baseline were over seven times more likely to develop additional solar keratoses in the next 12 mo than those without prevalent solar keratoses at baseline . These results show that the natural history of solar keratoses in the community is one of high turnover and that a small percentage of susceptible individuals carry the major burden of solar keratoses in the community BACKGROUND The use of light-emitting diode light offers practical advantages in photodynamic therapy ( PDT ) with topical methyl-aminolevulinate ( MAL ) for management of actinic keratoses ( AK ) . OBJECTIVE We sought to evaluate the efficacy of MAL PDT using red light-emitting diode light . METHODS We conducted a multicenter , double-blind , r and omized study . A total of 49 patients with 363 AK lesions had 16.8 % MAL cream applied under occlusion for 3 hours , and 47 patients with 360 AK lesions had vehicle cream similarly applied . The lesions were then illuminated ( 630 nm , light dose 37 J/cm2 ) with repeated treatment 1 week later . Complete lesion and patient ( all lesions showing complete response ) response rates were evaluated 3 months after last treatment . RESULTS MAL PDT was superior ( P<.0001 ) to vehicle PDT with respect to lesion complete response ( 86.2 % vs 52.2 % , odds ratio 6.9 [ 95 % confidence interval 4.7 - 10.3 ] ) and patient complete response ( 59.2 % vs 14.9 % , odds ratio 13.2 [ 95 % confidence interval 4.1 - 43.1 ] ) . LIMITATIONS The study population may not be representative of all patients with AK . CONCLUSION MAL PDT using red light-emitting diode light is an appropriate treatment alternative for multiple AK lesions BACKGROUND Actinic keratoses ( AKs ) are considered as in situ squamous cell carcinoma . Early and effective treatment is important . Objective To compare the efficacy , cosmetic outcome and patient preference of 5-aminolevulinic acid photodynamic therapy ( ALA-PDT ) with that of 5 % imiquimod ( IMIQ ) cream in patients with AKs on the dorsa of h and s and forearms . METHODS Subjects received two ALA-PDT treatment sessions and one or two courses of imiquimod ( three times per week for 4 weeks each ) . Treatments were r and omly allocated to alternate upper extremities . Assessment s included lesion response one and six months after treatment , cosmetic outcome evaluated by the investigators and patients ' preference 6 months after treatment . Efficacy end point included the individual AK lesion clearance rate . RESULTS Thirty patients with 256 lesions were included in the study . At the first follow-up , treatment with ALA-PDT result ed in significantly larger rate of cured lesions relative to 5 % IMIQ cream ( 70.16 % vs. 18.26 % ) . At the second follow-up both treatments showed a high rate of cured lesions ( 65.32 % for PDT vs. 55.65 % for IMIQ cream ) . Response rates obtained in grade I lesions were higher for both treatments ( 71.64 % for PDT vs. 72.13 % for IMIQ ) , while treatment with PDT result ed in a significant larger rate of cured grade II lesions ( 57.89 % for PDT vs. 37.03 for IMIQ ) . Difference in cosmetic outcome was not statistically significant . Results for subject preference favoured ALA-PDT . CONCLUSIONS Our study shows that ALA-PDT and 5 % IMIQ cream are both attractive treatment options for upper extremities AKs with comparable efficacy and cosmetic outcomes Background Photodynamic therapy ( PDT ) with 5‐aminolaevulinic acid ( ALA ) is an effective and safe treatment option for the treatment of actinic keratosis ( AK ) . Incoherent lamps are often used , matching the absorption maxima of ALA OBJECTIVE Evaluate cryosurgery followed by 3.75 % imiquimod cream to treat actinic keratoses ( AK ) . METHODS Adults with > or = 10 AKs on the face underwent cryosurgery of five to 14 lesions . Subjects with > or = 5 lesions remaining were r and omized to 3.75 % imiquimod or placebo cream applied to the entire face daily for two two-week cycles . Efficacy was assessed through week 26 . RESULTS For the cryosurgery/3.75 % imiquimod ( n=126 ) and cryosurgery/placebo ( n=121 ) groups , respectively , median total AK reductions were 86.5 and 50 percent , and proportions of subjects with complete clearance were 30.2 and 3.3 percent ( P < 0.0001 , both ) . Analyzing cryosurgery-treated lesions only , median reductions were 100 and 80 percent ( P = 0.0008 ) , and subject complete clearance rates were 59.5 % and 29.8 % ( P < 0.001 ) , respectively . Only one subject discontinued for a treatment-related adverse event ( cryosurgery/3.75 % imiquimod group ) . LIMITATIONS Cryosurgery was performed per usual study center practice and not st and ardized . CONCLUSION A short , cyclical treatment course of field-directed daily 3.75 % imiquimod cream following lesion-directed cryosurgery was well tolerated and provided additional therapeutic benefits to cryosurgery alone BACKGROUND AND OBJECTIVE Photodynamic therapy ( PDT ) with 5-aminolevulinic acid ( ALA ) and intense pulsed light ( IPL ) is a relatively new combination for the treatment of actinic keratosis ( AK ) and photodamage . The objective of this study was to determine the effect of increasing the fluence of IPL on the outcome of patients with these skin conditions . METHODS Patients ( N = 24 ) were r and omly assigned to five treatment treatment groups : control ( IPL alone ) and ALA with 20 , 25 , 40 , and 50 J/cm(2 ) fluence of IPL . Each patient received a single treatment . ALA was applied twice and allowed to incubate 2 h before IPL irradiation . Results were evaluated 5 - 7 days and 8 weeks after treatment . Clearance of AK lesions was evaluated by counting lesions before and after treatment , and improvement in photodamage was assessed by comparing pre- and post-treatment photographs . Statistical evaluation was based at nonparametric tests with a cut-off level at p < 0.10 and a confidence interval at 95 % . RESULTS Responses to treatment were greatest in patients who received ALA and IPL fluences of 40 and 50 J/cm(2 ) . Responses were " marked " in 19 % of the patients receiving 50 J and " moderate " in 19 % of the patients receiving 40 J. Compared to the mean pre-treatment AK grade s , the mean post-treatment grade s were 56 % lower in the 50 J treatment group , 32 % lower in the 25 J group , 50 % lower in the 40 J group , 20 % lower in the 20 J group , and 7 % lower in the control group . Erythema , edema , crusts and erosion , and pain did not cause any patient to discontinue the study . CONCLUSION AK clearance , but not photorejuvenation , appears to improve with increasing fluence at the ALA PDT-IPL levels used in this study without serious adverse effects BACKGROUND Photodynamic therapy ( PDT ) with a 5-aminolevulinic acid ( ALA ) photosensitizing agent and a variety of lasers and light sources has been shown to enhance the treatment of photodamaged skin and its associated actinic keratoses ( AKs ) . The efficacy of short-contact , full-face ALA by PDT in photorejuvenation has also been demonstrated . OBJECTIVE To evaluate short-contact ( 30 to 60 min ) ALA-PDT with intense pulsed light ( IPL ) activation by comparing ALA-PDT-IPL with IPL alone . METHODS Sixteen patients were enrolled in a split-face study . One side of each patient 's face received ALA-PDT-IPL and the other side received IPL alone . Three treatments were given at 1-month intervals , and follow-up visits occurred at 1 and 3 months after the final treatment . RESULTS Thirteen patients completed the trial . Three months after the final treatment , improvement was greater in the ALA-PDT-IPL side than in IPL-alone side for all facets of photodamage — crow 's feet appearance ( 55 vs 29.5 % ) , tactile skin roughness ( 55 vs 29.5 % ) , mottled hyperpigmentation ( 60.3 vs 37.2 % ) , and telangectasias ( 84.6 vs 53.8 % ) . The clearance rate of AK lesions was also higher ( 78 vs 53.6 % ) . CONCLUSION Short-contact ALA-PDT-IPL brings about greater improvement in photodamaged skin and greater clearance of AK lesions than IPL alone , further confirming the usefulness of ALA-PDT in photorejuvenation BACKGROUND Actinic keratoses ( AKs ) are frequently diagnosed in dermatological patients . As they represent in situ carcinomas , effective treatment is required . OBJECTIVES We investigated the effect of topical 3.0 % diclofenac in 2.5 % hyaluronic acid gel on AK . METHODS Sixty-five patients with AKs were clinical ly evaluated before and after 3 months ' treatment with topical 3.0 % diclofenac in 2.5 % hyaluronic gel . Biopsy specimens were taken and stained with haematoxylin-eosin and immunohistological markers . Specimens were evaluated for histological type of AKs using the AK classification scheme suggested by Röwert-Huber et al. [ ( early ) in situ squamous cell carcinoma type AK Grade I-III ] , number of mitoses per high-power field and expression of immunohistological markers . RESULTS Complete clinical resolution was observed in 11 patients ( 16.9 % ) . A significant ( P<0.001 ) downgrading of AK grade was observed . Complete histological resolution was achieved in 15 patients ( 23.1 % ) . The number of mitoses per high-power field was reduced significantly ( P<0.001 ) . The expression of anti-p53-antibody decreased significantly ( P=0.009 ) , as did the expression of anti-MiB-1 antibody ( P=0.021 ) . CONCLUSIONS 3.0 % diclofenac in 2.5 % hyaluronic acid gel causes regression of signs of cancerous transformation after 3 months ' therapy BACKGROUND AND DESIGN A controlled trial was undertaken from December 1987 to December 1990 to test the hypothesis that a strong sunscreen can reduce the number of cancerous and precancerous skin lesions . C and i date s were selected from a high-risk population attending either a university- or Veterans Affairs-based dermatology practice in Lubbock , Tex , for a prospect i ve , double-blind , controlled trial of daily application of sunscreen vs placebo over a 2-year period . Participants were asked to volunteer if they had demonstrated premalignant changes ( actinic keratoses ) or nonmelanoma skin cancer ( basal cell carcinoma or squamous cell carcinoma ) , had continuing sun exposure , and were not using sunscreen on a regular basis . Fifty-three volunteers were initially enrolled in the study , and 37 came for the final 24-month visit . RESULTS The rate of appearance of new precancerous skin lesions was less for the treatment group than for control subjects . People with darker skin had fewer actinic keratoses , women had fewer lesions than men , and people with fewer lesions at enrollment had fewer lesions during the study . The numbers of new nonmelanoma skin cancers appearing during the study period were too small for statistical analysis . CONCLUSIONS The regular use of sunscreens can significantly reduce cutaneous neoplasia , as indicated by its suppression of precancerous lesions . A longer and /or larger study would be necessary to demonstrate an effect on malignant lesions A r and omized double‐blind controlled trial of 130 patients was performed to study the efficacy and tolerability of topical 3 % diclofenac in 2.5 % hyaluronic acid ( HA ) gel ( active ) versus gel containing 2.5 % HA alone ( control ) in the treatment of solar keratoses . Patients were asked to apply trial gel to the target lesion twice a day and also sunscreen once a day for 24 weeks . The complete response rates were 29 % for the active gel and 17 % for the control gel . The difference was not statistically significant ( P= 0.14 ) . A high percentage of patients in both groups experienced a partial response to treatment ( 38 % active , 45 % control ) but there was no significant difference in the spectrum of response between the two treatments ( P= 0.18 ) . Local adverse reactions occurred significantly more frequently in patients using the active gel ( 29 % compared to 5 % using control gel , P= 0.0002 ) BACKGROUND Aminolevulinic acid hydrochloride ( ALA , Levulan ) applied topically to actinic keratoses ( AKs ) leads to accumulation of the photosensitizer protoporphyrin IX , which , when activated by exposure to light , eradicates AKs . OBJECTIVE We examined the safety and efficacy of photodynamic therapy using topical 20 % ALA in a solution formulation and varying blue light doses to treat multiple AKs on the face and scalp . METHOD This is a multicenter , investigator-blinded , r and omized , vehicle-controlled study . RESULTS Thirty-six patients with clinical ly typical AKs were treated with 20 % ALA ; 14 to 18 hours later , they were irradiated with a nonlaser fluorescent blue light source . With the optimal light dose of 10 J/cm(2 ) , 88 % of the AKs completely cleared 8 weeks after a single photodynamic treatment , compared with 6 % after treatment with vehicle and light . CONCLUSION Topical ALA PDT using a nonlaser , blue light source is an effective treatment for multiple AKs Sequential topical application of fluorouracil and 0.5 % triamcinolone acetonide cream is as effective in the treatment of actinic keratoses as fluorouracil alone , but the combination obviates the unpleasent irritation caused by fluorouracil . Diluted ( 0.1 % ) triamcinolone acetonide cream preparations are ineffective in the suppression of the associated inflammation . There is no detectable difference in the number of new actinic keratoses between the combination therapy and fluorouracil alone . These findings demonstrate that the degree of success with fluorouracil therapy in actinic keratosis is not related to the degree of inflammation associated with the treatment and are consistent with a chemotherapeutic explanation of fluorouracil 's effect on actinic keratosis Alpha-2-(Difluoromethyl)-dl-ornithine ( DFMO ) , an irreversible inhibitor of ornithine decarboxylase , has been shown to suppress skin carcinogenesis in murine models after oral or topical administration . We design ed a r and omized , placebo-controlled study using a topical hydrophilic ointment formulation with or without 10 % ( w/w ) DFMO . Forty-eight participants with moderate-severe actinic keratoses ( AKs ) on their forearms ( i.e. , at least 10 well-circumscribed lesions on the lateral surface ) completed a 1-month run-in on placebo ointment . Before r and omization , all lateral forearm AKs were circled , counted , photographed , and skin biopsies were obtained for DFMO and polyamine levels . Then participants were r and omized to receive DFMO ointment on the right versus the left forearm and placebo hydrophilic ointment on the contralateral forearm twice daily for 6 months . DFMO was not detected in the blood of any subject , and there were no systemic toxicities . None of a sub sample of 17 placebo forearms had measurable concentrations of DFMO , whereas 13 of the corresponding DFMO-treated forearms had high DFMO skin levels . As compared with placebo , the 6-month DFMO treatment caused a 23.5 % reduction in the number of AKs ( P = 0.001 ) as well as significant suppression of AK biopsy spermidine levels ( 26 % ; P = 0.04 ) . Seven of the 48 ( 14.6 % ) participants experienced severe ( 2 ; 4.2 % ) or moderate ( 5 ; 10.4 % ) inflammatory reactions on their DFMO-treated arms which required dosing modification . Topical DFMO for 6 months can reduce the number of AK lesions and skin spermidine concentrations in high-risk participants and deserves additional study as a skin cancer chemopreventive agent The efficacy and safety of a new 0.5 % fluorouracil topical cream were compared with vehicle control for the treatment of actinic keratosis ( AK ) . Active treatment applied once daily for 1 , 2 , or 4 weeks was more effective than vehicle control in achieving reduction from baseline in lesion counts and lesion clearance . Active treatment also result ed in significantly better global assessment s of overall improvement . Treatment was effective regardless of the number of baseline lesions . Although longer treatment duration correlated with greater efficacy , treatment for 1 , 2 , or 4 weeks was effective . This new microsphere-based fluorouracil formulation was generally well tolerated ; adverse events were primarily limited to facial irritation that resolved quickly after treatment . This new treatment provides a safe alternative to the topical fluorouracil formulations currently available for the 1- , 2- , or 4-week treatment of AK BACKGROUND / OBJECTIVE Photodynamic therapy ( PDT ) with 5-aminolevulinic acid ( ALA ) has been shown to be useful in both spot and field treatments of actinic keratoses ( AK ) . This study evaluates the safety and efficacy of pretreatment of AK lesions on the dorsal h and s and forearms with tazarotene gel ( 0.1 % ) twice a day for one week before broad-area ALA PDT . METHODS Ten subjects aged 75.4 ± 11.6 years ( mean plus minus SD ) with at least four AK lesions on their dorsal forearm or h and were r and omized so that one dorsal h and or forearm was pretreated with tazarotene gel ( 0.1 % ) twice daily for one week before ALA PDT with blue light . The other h and or forearm ( control ) was not pretreated . After seven days , ALA was applied to both sides and incubated 60 minutes before irradiation with blue light . ALA was applied first only to the AK lesions and then to the entire treatment area ( defined as the extensor surface of the h and or forearm between the elbow and the base of the fingers ) before 60-minute incubation . The ALA area on the control side was occluded during the 60-minute incubation . Efficacy and adverse effects were evaluated within 48 hours and eight weeks later . RESULTS For both the pretreated and control group , lesion counts of the target areas decreased significantly from baseline to eight weeks after ALA PDT . Reduction percentages of the target area , however , did not differ significantly between the two groups . When reduction percentages of the entire treatment area for both groups were compared the difference between the two groups was of borderline significance ( P=0.0547 ) . When the entire treatment area was analyzed , lesion counts of the tazarotene group differed significantly from baseline at eight weeks ( P=0.0002 ) , but this was not the case with the control group ( P=0.0365 ) . Adverse events were limited to those expected after ALA PDT . Erythema was significantly more severe ( P=0.0029 ) in the pretreated arm five minutes after ALA PDT . CONCLUSION Pretreatment of AK lesions on the dorsal h and and forearm with tazarotene gel ( 0.1 % ) may enhance the therapeutic effect of ALA PDT without serious side effects β‐1 , 3‐D‐glucans are yeast‐derived carbohydrate polymers which have been shown to be potent immunoresponse modulators which promote the regression of certain tumours . To date there is no published data concerning the efficacy of topical β‐1 , 3‐D‐glucan in the treatment of solar keratoses . This r and omized double‐blind prospect i ve pilot study of 20 patients was performed to investigate the efficacy and skin tolerance of β‐1 , 3‐D‐glucan gel versus placebo in the treatment of solar keratoses . The results of this study showed no significant benefit in using β‐1 , 3‐D‐glucan gel over placebo in reducing counts of solar keratoses . No adverse effects were reported by any patient at any stage of the trial BACKGROUND Actinic keratoses ( AKs ) are precancerous epidermal lesions found most frequently on areas of the skin exposed to the sun . Several case studies published recently have indicated that 5 % imiquimod cream , currently licensed for the treatment of genital warts , may be an effective treatment for AK . OBJECTIVE To assess the efficacy and safety of imiquimod for the treatment of AK . DESIGN Patients in this r and omized , double-blind , vehicle-controlled study applied 5 % imiquimod cream or vehicle to AK lesions 3 times per week for a maximum of 12 weeks or until lesions had resolved . In the event of an adverse reaction , application of imiquimod was reduced to 1 or 2 times per week . Rest periods were also allowed if necessary . SETTING A specialized outpatient dermatology clinic within a state-funded hospital in Germany . PATIENTS The study population was aged 45 to 85 years . Of 52 patients screened , 36 men and women with AK confirmed by histological diagnosis were enrolled . Patients were excluded from the study if they did not have a histological diagnosis for AK , if they were older than 85 years , or if they did not comply with the protocol . All patients had responded to a notice asking for volunteers . MAIN OUTCOME MEASURES The number and appearance of lesions were evaluated before , during , and after treatment . All adverse effects were recorded . RESULTS Lesions treated with 5 % imiquimod cream were clinical ly cleared in 21 ( 84 % ) of 25 patients and partially cleared in 2 ( 8 % ) . Clearance was histologically confirmed 2 weeks after the last application of imiquimod in all patients clinical ly diagnosed as lesion free . Only 10 % of patients treated with imiquimod were clinical ly diagnosed with recurrence 1 year after treatment . No reduction in the size or number of AK lesions was observed in vehicle-treated patients . Adverse effects reported by patients treated with imiquimod included erythema , edema , in duration , vesicles , erosion , ulceration , excoriation , and scabbing . However , imiquimod was well tolerated since all patients completed the 12-week treatment . Only a few , mild adverse reactions to the vehicle cream were reported . CONCLUSION Application of 5 % imiquimod cream for 12 weeks is an effective and well-tolerated treatment for AK More than one million new skin cancers are diagnosed yearly in the United States creating the need for effective primary and chemopreventive strategies to reduce the incidence , morbidity , and mortality associated with skin cancer . Skin chemoprevention trials often focus on subjects at high risk of nonmelanoma skin cancers and include biological endpoints like number of actinic keratoses ( AK ) and measures of cell proliferation , apoptosis , and p53 expression and /or mutation . Difluoromethylornithine ( DFMO ) , an irreversible inhibitor of ornithine decarboxylase , suppresses increased polyamine synthesis and inhibits tumors in models of skin carcinogenesis . Thus , DFMO is a good c and i date chemopreventive agent in humans at increased risk of NMSC . We reported previously results of a r and omized , placebo-controlled trial of topical DFMO in 48 participants with AK . In this study there was a significant reduction in the number of AK ( 23.5 % ; P = 0.001 ) and the polyamine , spermidine ( 26 % , P = 0.04 ; Alberts , D. S. et al. Cancer Epidemiol . Biomark . Prev . , 9 : 1281 - 2186 , 2000 ) . In skin biopsies from the same study , we demonstrate that topical DFMO significantly reduces the percentage of p53-positive cells ( 22 % ; P = 0.04 ) ; however , there were no significant changes in proliferating cell nuclear antigen or apoptotic indices , or in the frequency of p53 mutations ( 25 % at baseline , 21 % after placebo , and 26 % after DFMO ) . We conclude that inhibition of the premalignant AK lesions as well as a reduction in the expression of p53 and in spermidine concentrations may serve as surrogate endpoint biomarkers of DFMO and possibly other topically administered skin cancer chemopreventive agents BACKGROUND Topical colchicine has been reported to be an effective treatment for actinic keratoses , but the optimal concentration has not been fully defined . OBJECTIVE The aim of this study was to further support the beneficial effect of topical colchicine therapy for actinic keratoses , and to compare the efficacy and safety of two different concentrations of colchicine cream , 0.5 % and 1 % . METHODS Sixteen patients with actinic keratoses were enrolled in this comparative r and omized study . Eight patients applied 1 % colchicine cream , twice daily on their lesions while the other eight were treated with a 0.5 % colchicine cream for 10 days . Some patients were applied a second course of 10 days ' therapy . Patients were examined before treatment and at 10 days , and followed up at 1 , 2 and 6 months of treatment . Visible and palpable actinic keratoses lesions in each group were counted . Safety and efficacy were also assessed by clinical examination at each study visit . Routine laboratory tests were performed before and after treatment . RESULTS Actinic keratoses lesions showed significant clinical improvement following treatment with 0.5 % and 1 % colchicine cream . Complete healing of actinic keratoses were observed in six of the eight patients in the 1 % colchicine group , and in seven of the eight patients in the 0.5 % colchicine group . The reduction rate in number of actinic keratoses at the end of treatment in the 1 % colchicine group was 73.9 % ( 48/65 ) ( p < 0.001 ) , and the reduction rate in the 0.5 % colchicine group was 77.7 % ( 52/67 ) in total ( p < 0.001 ) . The reduction in number of actinic keratoses ( mean + /- SD ) at the end of treatment was similar in the 1 % colchicine group ( 0.7 + /- 1.3 ) , and the 0.5 % colchicine group ( mean 0.6 + /- 1.7 ) ( p > 0.05 ) . Systemic side effects were not seen in either concentration . CONCLUSIONS Topical colchicine is an effective and safe alternative agent . Cream containing 0.5 % of colchicine is equally effective as 1 % colchicine cream in the treatment of actinic keratoses This r and omized , double‐blind , placebo‐controlled study assessed the efficacy and safety of a topical gel containing 3 % diclofenac in 2.5 % hyaluronan in 150 patients with solar keratoses ( SK ) . The active treatment was compared with the vehicle only , hyaluronan gel , as placebo over a 12‐week period . Patients in both groups applied the active treatment or placebo to a targeted area of skin ( 0.25 g b.d . ) . At 12 weeks the mean lesion‐count reduction in the targeted area was not significantly different between treatments . However , at post‐termination follow up ( 16 weeks ) , there was a highly significant decrease in the number of lesions , 6.2 ± 7.5 st and ard deviations ( SD ) ( 56.1 % reduction ) in the active treatment group compared with 2.4 ± 4.3 SD ( 23.6 % reduction ) in the placebo group ( P < 0.001 ) . Other efficacy measures ( complete lesion resolution , > 50 % lesion reduction ) were also significantly different ( P < 0.01 ) between treatments at 16 weeks . In conclusion , topical 3 % diclofenac in 2.5 % hyaluronan gel was effective and well tolerated in this study , suggesting a role for this therapy in the treatment of SK BACKGROUND AND OBJECTIVES Many treatment modalities exist for actinic keratoses ( AK ) . Topical 5-fluorouracil ( 5-FU ) has been one of the st and ard treatments . Laser resurfacing is a more recent treatment option . In the literature prospect i ve r and omized studies comparing these treatments are lacking . STUDY DESIGN / PATIENTS AND METHODS Prospect i ve r and omized study to compare topical 5-FU with Er : YAG laser resurfacing . Fifty-five patients with multiple AK on the scalp and or the face were included . Clinical and histopathological evaluation took place at 3 , 6 , and 12 months after treatment . RESULTS At 3 , 6 , and 12 months after treatment , there were significantly less recurrences in the laser group compared to the group of patients treated with 5-FU . Side effects did occur more frequently in the laser group , especially erythema and hypopigmentation . CONCLUSIONS Compared to treatment with topical 5-FU , Er : YAG laser resurfacing is more effective regarding recurrence rates . Although significantly more side effects occur , laser resurfacing is a useful therapeutic option especially in patients with widespread AK BACKGROUND No long-term r and omized controlled clinical trial has compared the efficacy of cryosurgery alone vs cryosurgery following fluorouracil applications for the treatment of actinic keratosis . OBJECTIVE To determine the 6-month outcome of a 1-week course of 0.5 % fluorouracil followed by cryosurgery . DESIGN Prospect i ve , multicenter , r and omized , double-blind , vehicle-controlled clinical trial performed in community and academic outpatient clinics . PATIENTS A total of 144 patients with 5 or more visible or palpable actinic keratoses on the face . INTERVENTIONS Topical 0.5 % fluorouracil or vehicle once daily for 7 days . At the 4-week follow-up visit , residual lesions were treated with cryosurgery . MAIN OUTCOME MEASURE Reduction in facial actinic keratoses from baseline to 4 weeks and 6 months . RESULTS At 4 weeks , mean actinic keratosis lesion count was reduced by 62.4 % in the 0.5 % fluorouracil group vs 28.8 % in the vehicle group ( P<.001 ) , and complete clearance was achieved in 16.7 % of patients in the 0.5 % fluorouracil group vs 0 % of those in the vehicle group ( P<.001 ) . At 6 months , mean lesion count was reduced by 67.0 % in the 0.5 % fluorouracil plus cryosurgery group vs 45.6 % in the vehicle plus cryosurgery group ( P = .01 ) , and significantly more patients in the 0.5 % fluorouracil plus cryosurgery group than in the vehicle plus cryosurgery group had complete clearance ( 30 % vs 7.7 % ; P<.001 ) . CONCLUSIONS A 1-week course of topical 0.5 % fluorouracil before cryosurgery is significantly more effective in reducing patients ' numbers of actinic keratosis lesions 6 months after treatment than cryosurgery alone . The high occurrence rate of actinic keratosis lesions at 6 months suggests a need for follow-up BACKGROUND Photodynamic therapy ( PDT ) and imiquimod are the treatments of choice for actinic keratosis ( AK ) . As they have different mechanisms of action , it seems reasonable to assume that applying both treatments sequentially would be efficacious . OBJECTIVES We sought to determine which of these therapeutic modalities provides a better clinical and histologic response in patients with AK and whether sequential use of both was more efficacious than each separately . METHODS Patients were r and omly assigned to one treatment group : group 1 , PDT only ; group 2 , imiquimod only ; or group 3 , sequential use of PDT and imiquimod . The primary outcome measure was complete clinical response . Partial clinical response was defined as a reduction of more than 75 % in the initial number of lesions . A complete clinicopathologic response was defined as lack of evidence of AK in the biopsy specimen . RESULTS In all , 105 patients completed the study ( group 1 , 40 patients ; group 2 , 33 patients ; group 3 , 32 patients ) . Sequential application of PDT and imiquimod was more efficacious in all the outcome measures . More patients were satisfied with PDT than with the other two modalities ( P = .003 ) . No significant differences were observed among the 3 modalities and tolerance to treatment . LIMITATIONS Only one cycle of imiquimod was administered . The follow-up period was brief . CONCLUSIONS Sequential application of PDT and imiquimod provides a significantly better clinical and histologic response in the treatment of AK than PDT or imiquimod monotherapy . It also produces less intense local reactions and better tolerance and satisfaction than imiquimod monotherapy In a r and omized double‐blind controlled study , 19 patients applied 5 % 5‐fluorouracil ( 5‐FU ) cream to actinic keratoses ( AK ) on each arm twice daily , followed by nightly application of 0.05 % tretinoin cream to one arm , and a control cream to the other arm until discomfort precluded further applications . After 3 months , the number of residual AK was compared to pre‐treatment values . The tretinoin‐treated arms had 15.7 ± 6.1 AK before treatment and 3.4±2.6 AK following therapy . The control arms had 15.3±6.9 AK before therapy and 4.2 ± 2.5 lesions afterwards . Using a one‐tailed paired t‐test , the difference in response was statistically significant ( 0.03 < P < 0.04 ) . It was concluded that daily application of 0.05 % tretinoin cream appeared to enhance the efficacy of topical 5‐FU in destruction of AK of the arms and may represent a useful treatment modality BACKGROUND Adapalene is a synthetic retinoid with an established clinical efficacy against acne and good local tolerability . Its effectiveness in the treatment of photodamaged skin has not been studied . OBJECTIVE We sought to determine the safety and efficacy of adapalene gel in the treatment of actinic keratoses and solar lentigines . METHODS In a prospect i ve , 2-center , r and omized , controlled , investigator-masked , parallel-group study , 90 patients with actinic keratoses and solar lentigines were treated daily with either adapalene gel ( 0.1 % or 0.3 % ) or its vehicle gel for 4 weeks , followed by twice-daily applications , if tolerated , for up to 9 months . RESULTS Of the 90 Caucasian patients ( 69 male , 21 female ; mean age 63.1 years ) who were enrolled into the study , 83 patients completed 9 months of treatment . With adapalene gel 0.1 % and 0.3 % , the mean number of actinic keratoses was reduced by 0.5 + /- 0.9 ( mean + /- SE ) and 2.5 + /- 0.9 , respectively . Whereas , with the vehicle gel , there was an increase of 1.5 + /- 1.3 ( P < .05 ) . After 1 month of treatment , the patients who received adapalene had significant lightening of solar lentigines as compared with the patients who were treated with vehicle gel ( P < .05 ) . After 9 months , 57 % and 59 % of the patients had lighter lesions in the adapalene 0.1 % and 0.3 % groups , respectively , in comparison with only 36 % in the vehicle group ( P < .05 ) . Histologic evaluations revealed improved cellular atypia and reduced epidermal melanin in adapalene- , as compared with vehicle-treated group . The differences , however , were not statistically significant . A retrospective evaluation of paired clinical photographs ( before and after 9-month treatment ) by 2 dermatologists who were treatment-blinded revealed significant improvement in wrinkles and other clinical features of photoaged skin with adapalene as compared with its vehicle . CONCLUSION Adapalene gel 0.1 % and 0.3 % were well tolerated and improved actinic keratoses , solar lentigines , and other features of photodamaged skin Pre clinical data suggest that topical methyl aminolevulinate photodynamic therapy may have potential in preventing new skin lesions in transplant recipients . An open intra-patient r and omized study investigated the prevention potential of this treatment in 27 renal transplant patients with actinic keratoses and other skin lesions in two circular contralateral areas ( 5 cm diameter ) . The treatment area surface was debrided and methyl aminolevulinate cream ( 160 mg/g ) was applied for 3 h prior to illumination by non-coherent red light ( 570 - 670 nm , light dose 75 J/cm2 ) . The control area was not treated . The mean time to occurrence of the first new lesion was significantly longer in treated than control areas ( 9.6 vs 6.8 months , treatment difference 2.9 [ 95 % confidence interval 0.2 to 5.5 ] months , p = 0.034 ) . Over 12 months , 62 % ( 16/26 ) of treated areas were free from new lesions compared with 35 % ( 9/26 ) in control areas . These findings indicate that topical methyl aminolevulinate photodynamic therapy is a promising preventive treatment against new skin lesions in immunosuppressed patients 50 patients with actinic keratosis were studied over four months of treatment with either etretinate ( ' Tigason ' ) or placebo . Each treatment was given for two months and the order of administration was r and omised . The clinical response to treatment was assessed by direct measurement and photographs of the lesions at monthly intervals . Of the 44 patients who completed treatment with etretinate 37 had a complete or partial response . Of the 42 patients who completed treatment on placebo only 2 showed a complete or partial response . The response to treatment occurred within the first month of therapy and was maintained even when the dose was reduced because of toxicity Background Photodynamic therapy ( PDT ) with 5‐aminolaevulinic acid ( ALA ) provides a therapeutic option for the treatment of actinic keratosis ( AK ) . Different strategies are applied to overcome the chemical instability of ALA in solution and to improve skin penetration . A new stable nanoemulsion‐based ALA formulation , BF‐200 ALA , is currently in clinical development for PDT of AK BACKGROUND Field-directed therapies for actinic keratosis include photodynamic therapy and imiquimod . OBJECTIVES The author design ed a r and omized , vehicle-controlled , split-face study to explore the safety and efficacy of photodynamic therapy followed by imiquimod . METHODS The entire face of adults with > or = 10 facial actinic keratoses were treated with photodynamic therapy with aminolevulinic acid 20 % at baseline and at month 1 . At month 2 , imiquimod 5 % cream was applied to one-half of the face and vehicle to the other half , 2-times-per-week for 16 weeks . Lesion counts were performed at baseline and months 1 , 2 , 3 , 4 , 6 , and 12 ; and local skin reactions assessment s at months 2 , 3 , 4 , and 6 . RESULTS Of 25 participants enrolled , 24 completed the study . Baseline median lesions were 23.5 and 21.5 for the imiquimod- and vehicle-treated sides , respectively . At month 12 , median lesion reductions was 89.9 % versus 74.5 % ( P=.0023 ) , respectively . No subject discontinued for an adverse event . Severe local skin reactions occurring in the most participants were erythema ( 17 % ) and flaking/scaling/dryness ( 13 % ) . CONCLUSIONS Photodynamic therapy followed by imiquimod was well tolerated and improved reduction of actinic keratoses BACKGROUND Actinic keratoses ( AKs ) are premalignant skin lesions caused by excessive sun exposure . AIMS To explore the therapeutic efficacy of 3 % diclofenac in 2.5 % hyaluronan gel in the topical treatment of AK . METHODS Sixty-four lesions in 20 patients were evaluated . They were r and omized to receive either the active treatment , 3 % diclofenac in 2.5 % hyaluronan gel or placebo , which consisted of the inactive gel vehicle , hyaluronan for a period of three months . The collected data were analyzed by using Student t- tests . RESULTS There was a reduction in the lesion size in 64.7 % of diclofenac-treated lesions and 34.3 % of control lesions during the three-month course of treatment . Only 9.3 % of the lesions in the diclofenac group were completely cleared during three months of treatment . During the treatment , no significant side-effect was observed in both groups . CONCLUSION Considering the malignant potential of actinic keratoses and the importance of clearing them to prevent their transformation to squamous cell carcinoma , the efficacy of diclofenac gel seen in our study seems to be low . This treatment may be useful for patients who do not tolerate other , more effective kinds of treatment for actinic keratoses Background Transplant recipients have an increased propensity to develop multiple actinic keratoses , which demonstrate an increased transformation rate into invasive squamous cell carcinoma Background The results from four phase III , r and omized , vehicle-controlled studies showed that imiquimod 5 % cream ( imiquimod ) was safe and effective in the treatment of actinic keratosis ( AK ) . Patients applied imiquimod or vehicle cream to AK lesions on the face or balding scalp , dosing three times per week or two times per week for 16 weeks . Objective To obtain long-term safety follow-up data and estimate AK recurrence in patients who completely cleared their AK lesions in the treatment area at the 8-week post-treatment visit in the phase III studies . Methods One hundred forty-six patients from 30 study centers in the United States were evaluated for clinical evidence of AK , and safety data were collected . Results After a median follow-up period of 16 months , 24.7 % ( 19 of 77 ) of the patients administered imiquimod three times per week and 42.6 % ( 23 of 54 ) of the patients administered imiquimod two times per week had a recurrence of AK ( the appearance of at least one AK lesion ) in the original treatment area . The median number of AK lesions present was one lesion for both patients receiving imiquimod three times and those receiving imiquimod two times per week compared with a median of six lesions at baseline in the combined three times per week and two times per week phase III studies . There were no long-term safety issues , and the skin quality seen in the imiquimod-treated patients at the end of the phase III studies was maintained . Conclusion One and a half years following treatment , imiquimod continued to provide a long-term clinical benefit in a majority of patients who experienced complete clearance of their AK lesions BACKGROUND Photodynamic therapy ( PDT ) has not been compared with topical 5-fluorouracil ( 5-FU ) in the treatment of epidermal dysplasia . OBJECTIVE The purpose of this study was to assess the efficacy and tolerability of these two treatment modalities in 17 patients with actinic keratoses on the backs of the h and s. METHODS Each patient 's right and left h and s were r and omized to receive either a 3-week course of topical 5-FU applied twice per day or PDT using topical 5-aminolevulinic acid ( 5-ALA ) and then , after 4 hours , irradiation with an incoherent light source consisting of a 1200 W metal halogen lamp emitting red light ( 580 to 740 nm ) . Each h and r and omized for PDT received 150 J/cm(2 ) . The observed median fluence rate was 86 mW/cm(2 ) ( interquartile range , 53 to 100 mW/cm(2 ) ) . All patients were review ed at 1 , 4 , and 24 weeks after starting treatment . RESULTS Fourteen of 17 patients ( 82 % ) completed the study . The mean lesional area treated with topical 5-FU decreased from 1390 mm(2 ) ( st and ard deviation [ SD ] , 1130 ) to 297 mm(2 ) ( SD , 209 ) . This represents a mean reduction in lesional area of 70 % ( confidence interval [ CI ] , 61%-80 % ) . The mean lesional area treated with topical PDT decreased from 1322 mm(2 ) ( SD , 1280 ) to 291 mm(2 ) ( SD , 274 ) , representing a mean reduction in lesional area of 73 % ( CI , 61%-84 % ) . The reduction in lesional area elicited by the two treatment methods was similar ( CI , -25 % to 17 % ) . There was no statistically significant difference between the treatment methods in overall symptom scores for pain and redness . CONCLUSION One treatment with PDT using topical 5-ALA appears to be as effective and well tolerated as 3 weeks of twice-daily topical 5-FU , a cheap and widely available alternative BACKGROUND Actinic keratoses are increasingly common skin lesions that are evaluated and treated by dermatologists on a daily basis . It is estimated that more than 90 % of actinic keratoses in the US are treated by destructive therapies , such as cryosurgery . The purpose of this study was to evaluate the efficacy of sequential therapy of cryosurgery followed by diclofenac sodium 3 % gel . METHODS This prospect i ve , double-arm , multicenter , open-label , phase 4 study was performed at 82 community dermatology centers in the US . A total of 714 subjects who had a clinical diagnosis of actinic keratosis with between 5 and 15 lesions contained in a target area such as the forehead , scalp , and h and s were enrolled in the study . These subjects were r and omized into 2 arms of the study : cryosurgery alone and cryosurgery followed by diclofenac sodium 3 % gel for a period of 90 days . Lesion counts were assessed at baseline , and 45 , 75 , 105 , and 135 days after cryosurgery . RESULTS Of the 521 patients enrolled in the study who successfully completed all of the visits concluding on day 135 , 277 were in the cryosurgery alone arm and 244 were in the cryosurgery followed by diclofenac sodium 3 % gel arm . At the conclusion of the study , 46 % of the subjects in the cryosurgery followed by the use of diclofenac sodium 3 % gel arm achieved 100 % cumulative ( target plus new lesions ) lesion clearance compared to 21 % in the cryosurgery alone arm ( P < .0001 ) . One hundred percent target lesion clearance was achieved in 64 % of the subjects in the active arm compared to 32 % in the cryosurgery alone arm ( P < .0001 ) . CONCLUSIONS With the increased prevalence of actinic keratoses , it is important to consider and evaluate emerging therapeutic options . The sequential treatment with cryosurgery followed by diclofenac sodium 3 % gel for 90 days is well tolerated and can provide a therapeutic modality that may provide patients with actinic keratoses a more successful outcome than monotherapy with cryosurgery by effectively treating clinical and sub clinical lesions A dual‐centre , r and omized , double‐blind , vehicle‐controlled study was conducted to evaluate the safety and efficacy of short courses of therapy with imiquimod 5 % cream in clearing ≥75 % of baseline solar keratoses ( SK ) within a field of treatment . Subjects with 5–15 baseline SK within one treatment area ( scalp , forehead and temples , or both cheeks ) were r and omized to apply imiquimod or vehicle cream to the entire treatment area three times a week for 3 weeks . Subjects were assessed 4 weeks after completing the first course for clearance of lesions . Subjects with < 75 % clearance were commenced on a second 3‐week course of study cream . Subjects with ≥75 % clearance were followed up until study completion without further therapy . All subjects were evaluated at the study endpoint of 14 weeks after initiating therapy for assessment of the primary outcome ( ≥75 % clearance of baseline solar keratoses ) . Twenty‐one out of 29 ( 72 % ) imiquimod‐treated subjects cleared ≥75 % of baseline lesions compared with 3/10 ( 30 % ) subjects using the vehicle cream ( Fisher 's exact test , P = 0.027 ) . Imiquimod was well tolerated . The present study has a short follow‐up endpoint , but suggests that imiquimod is a potential therapeutic alternative in patients with SK Topical fluorouracil is currently approved for the treatment of actinic keratosis ( AK ) and is often used prior to or following cryosurgery as interval therapy in patients with severe AK lesions . No r and omized , controlled studies are available to confirm anecdotal evidence suggesting pretreatment with fluorouracil is beneficial . This prospect i ve , r and omized , double-blind , vehicle-controlled study evaluated the effect of pretreatment with 0.5 % fluorouracil cream ( FC ; Carac ) or a vehicle cream ( VC ) once daily for 7 days to the face plus scalp , ears , neck , and /or lips in patients with > or = 5 visible or palpable AKs on the face prior to cryosurgery . Efficacy was determined by evaluating AK reduction and clearance ( complete lack of AK lesions in the treatment area ) at 4 weeks follow-up . Statistically significant decreases from baseline number of AKs were observed on all treatment areas in both groups . However , the mean number of facial AKs was significantly lower in the FC group at each treatment cycle ( p = .011 ) . No serious adverse events were considered related to treatment The clinical and histological effects of retinyl propionate cream ( a retinyl ester ) on extrinsic skin ageing ( photoageing ) in man were assessed in a double‐blind r and omized placebo‐controlled study of 80 subjects , individual parameters of this being assessed for each treatment site ( face , dorsal right forearm and h and , dorsal left forearm and h and ) at intervals throughout the study , while skin surface replicas from sites of fine wrinkling around the eye and skin biopsies from the dorsal right forearm were also regularly review ed throughout . Seventy‐five subjects completed an initial 24‐week study period , following which 60 elected to continue for a further 24 weeks . Although minimal trends towards improvement occurred , no statistically significant differences between the effects of the retinyl propionate cream and the placebo preparation were apparent for any of the clinical , histological or profilometric parameters of skin photoageing ; however , in the very few subjects affected , actinic keratoses in the active group were reduced virtually to zero by week 48 Background : Photodynamic therapy ( PDT ) with 5‐amino‐4‐oxo‐pentanoate ( methylaminolevulinate , MAL ) is an effective and safe treatment option for actinic keratoses . Light‐emitting diodes ( LED ) are suitable light sources for topical PDT . To evaluate the efficacy , painfulness , patient satisfaction and cosmesis of LED‐based PDT a prospect i ve , r and omized and controlled split‐face study was performed Background Resiquimod , a toll‐like receptor 7 and 8 agonist , may be effective as a topical treatment of actinic keratosis ( AK ) BACKGROUND Photodynamic therapy ( PDT ) is an effective treatment for actinic keratoses ( AKs ) . Light‐emitting diodes ( LEDs ) offer practical advantages when treating multiple lesions . OBJECTIVE To evaluate the efficacy and tolerability of PDT using a LED and topical methyl aminolevulinate ( MAL ) for treatment of multiple AKs . METHODS AND MATERIAL S One hundred thirty‐one patients with four to 10 non‐pigmented , previously untreated thin or moderately thick AKs on the face or scalp were enrolled in this multicenter , double‐blind , r and omized , placebo‐controlled study . MAL or matching placebo cream was applied to the débrided lesion surface for 3 hours before illumination with noncoherent red light ( 630 nm , light dose 37 J/cm2 ) . Treatment was repeated 1 week later . RESULTS Efficacy was evaluated in 57 patients with 418 lesions treated with MAL PDT and 58 with 414 lesions treated with placebo PDT . Sixteen patients were excluded as protocol violators ( not r and omized ) . MAL PDT was superior ( p<.001 ) to placebo PDT in lesion complete response rates ( 83.3 % , 95 % confidence interval (CI)=79.3–86.7 % , vs 28.7 % , 95 % CI=24.4–33.4 % ) and patient complete response rates ( all lesions showing complete response ; 68.4 % , 95 % CI=54.8–80.1 % vs 6.9 % , 95 % CI=1.9–16.7 % ) . CONCLUSIONS Topical MAL PDT using a LED is an effective treatment for multiple AKs . This study was supported by Photocure , ASA |
14,026 | 23,790,138 | Most of the chewing gums with antimicrobial agents or herbal extracts were shown to have a positive effect with respect to plaque and gingivitis scores .
The most compelling evidence was provided for chewing gum containing chlorhexidine .
Meta- analysis and individual results indicate a beneficial effect of chlorhexidine on plaque inhibition .
However , GRADE evidence profile shows that the recommendation to use CHX-gum to reduce plaque scores in the absence of brushing is considered to be ' weak ' .
Other ingredients with positive outcomes on plaque scores are eucalyptus , acacia , funoran , Pycnogenol and mastic .
Limited data with respect to gingivitis scores were available , and the following agents showed a positive effect : magnolia , eucalyptus and CHX | OBJECTIVE This study aim ed to systematic ally review the present literature to establish the clinical effect of medicated , sugar-free chewing gum on plaque indices and parameters of gingival inflammation . | The purpose of the study was to assess the anti-plaque effect of chlorhexidine ( CHX ) in chewing gum . The 0.80 g pieces of test gum contained 5 mg chlorhexidine acetate with or without a hydrogen peroxide releasing agent . The gum base with flavouring agents but containing neither CHX nor H2O2 was used as a control . 12 dental hygiene students volunteered to participate in the 3 x crossed-over double blind clinical trial . During the 4-day test periods , no other oral hygiene measures were allowed than chewing 2 pieces of gum at the time for approximately 10 min , 5 times daily . Between test periods , meticulous mechanical oral hygiene measures were practised for 3 days . At the beginning and at the end of each test period , the quantity of plaque was assessed using the plaque index , plaque wet weight , and the area of plaque on the tooth surface as criteria . The results indicated that both CHX gums completely inhibited the increase in plaque index and plaque weight . With regard to area of plaque , the difference between the 2 test gums and the control gum was less marked but still present . The test persons subjectively assessed the gum base to have a poor cleansing effect but also the least unpleasant taste . It was concluded that use of both the chlorhexidine gum and the gum-containing chlorhexidine in addition to the hydrogen peroxide releasing agent had an excellent plaque growth inhibiting effect during the 4-day test periods Chewing gums may be suitable vehicles for the delivery of xylitol ( X ) and chlorhexidine acetate ( CHX ) , both of which can aid oral health . The aim of this study was to determine the clinical effectiveness of chewing gums containing X or a combination of X and CHX in a double-blind , r and omised , cross over , 5-day clinical trial , with a 9-day washout period in a group of participants over 40 years old . After professional tooth cleaning , 8 subjects ( mean age 51.3+/-10.4 years ) used in a r and om order 2 pieces of ACHX ( a liquorice flavoured CHX/X ) gum , 2 pieces of BCHX ( a chocolate mint flavoured CHX/X ) , 2 pieces of X ( a liquorice flavoured X gum ) and 1 piece of ACHX . Gums were chewed 2x daily for 15 min and volunteers refrained from all other oral hygiene procedures . Data were analysed using Friedman nonparametric analysis of variance . Plaque indices for chewing 2 pieces of ACHX gum ( 0.78+/-0.15 ) and BCHX gum ( 0.52+/-0.15 ) were significantly lower ( p<0.0006 ) than for X gum ( 1.57+/-0.08 ) . The gingival index was significantly greater ( p<0.05 ) for X containing gum than for the other chewing regimes . The subjects ' attitudes to the gums were also assessed by structured question naires which showed that all gums were easy to chew , did not adhere to dentures , teeth or restorations and that the subjects preferred to chew 2 pellets rather than 1 BACKGROUND Studies in vitro showed that eucalyptus extracts possess antibacterial activity against cariogenic and periodontopathic bacteria ; however , the clinical effects with respect to periodontal health in humans remain unproven . The objective of this study was to evaluate the effect of chewing gum containing eucalyptus extract on periodontal health in a double-masked , r and omized , controlled trial . METHODS Healthy humans with gingivitis but not deep periodontal pockets were r and omly assigned to the following groups : high-concentration group ( n=32 ) : use of 0.6 % eucalyptus extract chewing gum for 12 weeks ( 90 mg/day ) ; low-concentration group ( n=32 ) : use of 0.4 % eucalyptus extract chewing gum for 12 weeks ( 60 mg/day ) ; and placebo group ( n=33 ) : use of chewing gum without eucalyptus extract for 12 weeks . Plaque accumulation ( PLA ) , gingival index ( GI ) , bleeding on probing ( BOP ) , periodontal probing depth ( PD ) , and clinical attachment level ( CAL ) were measured at weeks 0 , 4 , 8 , 12 , and 14 . Significance was analyzed with repeated- measures two-way analysis of variance followed by the Games-Howell pairwise comparison test . RESULTS The interaction between the effects of eucalyptus extract chewing gum and the intake period was statistically significant for PLA , GI , BOP , and PD but not for CAL . The low- and high-concentration groups exhibited statistically significant ( P < 0.05 ) improvements compared to the placebo group for PLA , GI , BOP , and PD . CONCLUSIONS Eucalyptus extract chewing gum had a significant effect on PLA , GI , BOP , and PD . The use of eucalyptus extract chewing gum may promote periodontal health Previous studies showed that Persica extracts have antibacterial activity against cariogenic and periodontopathic bacteria and can develop periodontal health ; however , the clinical effects of gum as a delivery device for Persica to periodontal health in human , have not yet been investigated . The objective of this study was to evaluate the effect of chewing gum containing Persica extract on periodontal health in a double-masked , r and omized trial . From a high school in Babol , 72 cases with plaque induced moderate gingivitis were r and omly assigned to the 2 weeks trial in the following groups : S+/P+ ( n = 18 ) : use of Persica extract chewing gum for 2 weeks and two sessions of scaling ; S+/P- ( n = 18 ) : use of placebo chewing gum two sessions of scaling ; S-/P+ ( n = 18 ) : use of Persica extract chewing gum ; and S-/P- ( n = 18 ) : use of placebo chewing gum . Plaque index ( PI ) , gingival index ( GI ) , and bleeding index ( BI ) , were measured at days 0 , 7 , and 14 . Data was analyzed with t test or Mann-Whitney U test . Seven patients from Persica scaling group and five patients from Persica no scaling ( S-/P+ ) group were excluded for complaining about the taste and irritation . The effects of extract chewing gum was statistically significant in reduction of GI , and BI but not for PI in Persica groups compared with the placebo groups in the days of 7 and 14 after the beginning of trial . Persica extract chewing gum had a considerable effect on GI , and BI . The use of Salvadora persica extract chewing gum may promote periodontal health The purpose of this study was to evaluate the inhibitory effect of funoran containing chewing gum ( FG ) and eucalyptus extract- containing chewing gum ( EG ) on plaque formation . Fifteen dentists or dental students were assigned a r and om order of use of either FG , EG or a control gum . All subjects received professional tooth cleanings before the experiment . During the four-day test periods , no oral hygiene measures were allowed other than chewing three pieces of gum for approximately 10 min daily . Chewing gum was used following each morning , noon and evening meal . Plaque formation was evaluated by the Quigley and Hein index . The FG ( 1.83 + /- 1.1 ) and EG ( 1.97 + /- 1.1 ) significantly reduced plaque compared to the control gum ( 2.57 + /- 1.2 ) . Our results suggest that FG and EG may be useful in inhibiting dental plaque formation UNLABELLED Sugar-free chewing gum has been cl aim ed to be a useful means of reducing dental plaque accumulation . The incorporation of additives , such as enzymes , abrasives and divalent metal ions , into gum formulations might improve their antiplaque activity , particularly at the buccal and lingual surfaces of the teeth . OBJECTIVES The aim of this study was to investigate the plaque inhibitory effects of three sugar-free chewing gums each containing lactoperoxidase ( LP ) , micro granules of silicon dioxide ( SD ) , and zinc gluconate ( ZG ) . METHODS The study was an observer-masked , r and omized cross-over design balanced for carryover effects , involving 12 healthy volunteers in a 4-day plaque regrowth model . An additive-free ( AF ) gum served as positive/negative control for occlusal and smooth surfaces , respectively . On day 1 , subjects received professional prophylaxis , suspended oral hygiene measures , and commenced chewing their allocated product . Gum chewing was one piece chewed for 30min 4 times a day . On day 5 , subjects were scored for disclosed plaque . RESULTS There were no significant differences in antiplaque activity of the gums tested , neither for the smooth nor for the occlusal surfaces ( P=0.447 and P=0.418 , respectively ) . Similar results were obtained for the anterior and posterior sites of smooth surfaces ( P>0.05 ) , and for the lower and upper sites of occlusal surfaces ( P=0.451 and P=0.53 , respectively ) . CONCLUSIONS These findings suggest that the chewing gums containing LP , SD and ZG would provide no plaque inhibitory effects on smooth surfaces . The gums containing these additives , therefore , should not be recommended as adjuncts to mechanical oral hygiene ETHNOPHARMACOLOGICAL RELEVANCE Salvadora persica shrub has been used traditionally in folk medicine for different medical condition treatments . The habitual use of Salvadora persica roots ( chewing sticks ) for dental hygiene is still wildly spread throughout parts of Asia , Africa , and Middle . It is one of the most important species with its reported strong antibacterial , antifungal , and antiviral effects . Mechanical removal of dental plaque is regarded as an effective mean of controlling progression of periodontal disease . AIM OF THE STUDY To evaluate the effect of active and inactive miswak on dental plaque , subgingival microbiota and gingival inflammation in patients with gingivitis . MATERIAL S AND METHODS In this double blinded r and omized controlled trial 68 gingivitis patients were r and omly assigned to either active or inactive miswak group , and were instructed to use only issued miswaks for oral hygiene during 3 weeks experimental period . Registration of plaque , gingival inflammation , and plaque sample s were taken at baseline and on completion of the study . Plaque sample s were analyzed by DNA-DNA hybridization technique . RESULTS Active miswak significantly reduced dental plaque ( p = 0.007 ) . There were no differences between active and inactive miswak in reduction of approximal plaque and composition of subgingival microbiota . CONCLUSIONS Miswak has an overall effect on dental plaque and gingival inflammation scores . Similar results were achieved by active and inactive miswak in difficult to reach areas , indicating miswak has limited chemical effects on this study population . Therefore , miswak can be used as a dental hygiene method in conjunction with interproximal cleaning aides A double-blind 3-treatment crossover design employing a 6-day trial period with out mechanical oral hygiene measures was used to compare dental plaque formation following use of chlorhexidine ( CHX ) acetate- , xylitol- , and sorbitol-containing chewing gum . Fourteen dental students were assigned a r and om ordering of the chewing gum products and received professional tooth cleaning at the start of trial periods . For each trial period , subjects were instructed to use 5 pieces of the unlabeled chewing gum daily ( containing 5.0 mg CHX acetate/piece ; 0.8 xylitol/piece ; or 1.0 g sorbitol/piece ) . Two pieces of chewing gum were used following each morning and evening meal and one piece following the noon meal . The subjects were instructed to use the products for 20 minutes at each occasion . A 7-day washout-period between trial periods was used . The Turesky modification of the Quigley and Hein index was used to assess plaque formation . Differences between treatments were evaluated using a repeated measures ANOVA with Newman-Keuls multiple comparisons . The CHX-containing chewing gum showed significantly reduced plaque values ( 0.7 + /- 0.4 ) compared to the sorbitol-(2.7 + /- 0.4 ; P < 0.01 ) and xylitol-product ( 1.7 + /- 0.3 ; P < 0.01 ) . Furthermore , the CHX-product significantly reduced plaque levels compared to the study subjects ' regular plaque control routines ( 1.3 + /- 0.04 ; P < 0.05 ) . The xylitol-product exhibited significantly lower plaque-values than the sorbitol-product ( P < 0.01 ) . Our results suggest that regular use of CHX-containing chewing gum appears useful to control dental plaque formation AIM A r and omised , controlled , double-blind , clinical trial was conducted to investigate the effect of a chlorhexidine acetate/xylitol gum ( ACHX ) on the plaque and gingival indices of 111 elderly occupants in residential homes . A gum containing xylitol alone ( X ) and a no gum ( N ) group was included . Participants ' opinions about chewing gum were also investigated . METHODS Subjects chewed 2 pellets , for 15 min , 2x daily for 12 months . RESULTS In the ACHX group , the plaque and gingival indices significantly decreased ( p<0.001 ) over the 12 months . In the X group , only the plaque score significantly decreased ( p<0.05 ) and in the N control group , both indices remained high and did not change significantly . The acceptance of both chewing gums was high but more participants in the ACHX group felt that the gum kept their mouth healthy ( p<0.05 ) . The effect of the ACHX gum on plaque and gingival indices was significantly greater than for the X gum . CONCLUSION The long-term use of a chlorhexidine acetate/xylitol chewing gum may therefore support oral hygiene routines for an elderly dependent population Gum chewing has been accepted as an adjunct to oral hygiene , as salivary stimulant and vehicle for various agents , as well as for jaw muscle training . The aim of this study was to investigate the effects of prolonged gum chewing on pain , fatigue and pressure tenderness of the masticatory muscles . Fifteen women without temporom and ibular disorders ( TMD ) were requested to perform one of the following chewing tasks in three separate sessions : chewing a very hard gum , chewing a soft gum , and empty-chewing with no bolus . Unilateral chewing of gum or empty chewing was performed for 40 min at a constant rate of 80 cycles/min . In each session , perceived muscle pain and masticatory fatigue were rated on visual analog scales ( VAS ) before , throughout , and after the chewing task . Pressure pain thresholds ( PPTs ) of masseter and anterior temporalis muscles were assessed before and immediately after the chewing tasks , and again after 24 h. The VAS scores for pain and fatigue significantly increased only during the hard gum chewing , and after 10 min of recovery VAS scores had decreased again , almost to their baseline values . No significant changes were found for PPTs either after hard or soft gum chewing . The findings indicate that the jaw muscles recover quickly from prolonged chewing activity in subjects without TMD Objective . To investigate the effect of a chewing gum containing probiotic bacteria on gingival inflammation and the levels of selected inflammatory mediators in gingival crevicular fluid ( GCF ) . Material and Methods . Forty-two healthy adults with moderate levels of gingival inflammation entered a double-blind placebo-controlled study design . The subjects were r and omly assigned to one of three parallel arms : Group A/P was given one active and one placebo gum daily , Group A/A received two active chewing gums , and Group P/P two placebo gums . The chewing gums contained two strains of Lactobacillus reuteri : ATCC 55730 and ATCC PTA 5289 ( 1 × 108 CFU/gum , respectively ) . The subjects were instructed to chew the gums for 10 min over the course of 2 weeks . Bleeding on probing ( BOP ) and GCF sampling were conducted at baseline and after 1 , 2 and 4 weeks . The levels of IL-1β , TNF-α , IL-6 , IL-8 and IL-10 were determined using luminex technology and multiplex immunoassay kits . Results . BOP improved and GCF volume decreased in all groups during the chewing period , but the results were statistically significant ( p<0.05 ) only in Groups A/P and A/A. The levels of TNF-α and IL-8 decreased significantly ( p<0.05 ) in Group A/A compared with baseline after 1 and 2 weeks , respectively . A non-significant decreasing tendency was also observed concerning IL-1β during the chewing period . The levels of IL-6 and IL-10 were unaffected in all groups after 1 and 2 weeks . Conclusions . The reduction of pro-inflammatory cytokines in GCF may be proof of principle for the probiotic approach combating inflammation in the oral cavity Remineralisation has been shown to be an effective mechanism of preventing the progression of enamel caries . The aim of this double-blind , r and omised , cross-over in situ study was to compare enamel remineralisation by chewing sugar-free gum with or without casein phosphopeptide amorphous calcium phosphate ( CPP-ACP ) where the enamel lesions were exposed to dietary intake and some were covered with gauze to promote plaque formation . Participants wore removable palatal appliances containing 3 recessed enamel half-slabs with subsurface lesions covered with gauze and 3 without gauze . Mineral content was measured by transverse microradiography , and plaque composition was analysed by real-time polymerase chain reaction . For both the gauze-free and gauze-covered lesions , the greatest amount of remineralisation was produced by the CPP-ACP sugar-free gum , followed by the gum without CPP-ACP and then the no-gum control . Recessing the enamel in the appliance allowed plaque accumulation without the need for gauze . There was a trend of less remineralisation and greater variation in mineral content for the gauze-covered lesions . The cell numbers of total bacteria and streptococci were slightly higher in the plaque from the gauze-covered enamel for 2 of the 3 treatment legs ; however , there was no significant difference in Streptococcus mutans cell numbers . In conclusion , chewing sugar-free gum containing CPP-ACP promoted greater levels of remineralisation than a sugar-free gum without CPP-ACP or a no-gum control using an in situ remineralisation model including dietary intake irrespective of whether gauze was used to promote plaque formation or not BACKGROUND Chemical plaque control is a useful aid in mechanical oral hygiene , and various chemical agents have been evaluated as antiplaque agents . It has been shown that mastic chewing gum has antibacterial effects on Helicobacter pylori . In this study , the antiplaque effect of mastic chewing gum was investigated . METHODS Twenty dental students who were both systemically and periodontally healthy participated in this study . The effects of mastic gum were assessed from 2 double-blinded , r and omized studies . In the first trial , after mechanical toothbrushing , the inhibitory effect of mastic gum on bacteria in saliva following its use was compared to a placebo gum . Saliva sample s were collected at the end of 1 , 2 , 3 , and 4 hours ; diluted ; inoculated onto 10 % horse blood chocolate agar plates ; and cultured anaerobically at 37 degrees C for 48 hours . The total number of bacterial colonies on each plate was calculated ( n = 20 ) . In the second trial , the effects of mastic gum on de novo plaque formation on tooth surfaces and gingival inflammation were evaluated over a 7-day period without mechanical oral hygiene following r and om use of either mastic or placebo chewing gum . The degree of plaque accumulation and gingival inflammation were compared between the 2 groups ( n = 10 ) . RESULTS The total number of bacterial colonies was significantly reduced during the 4 hours of chewing mastic gum compared to the placebo gum ( P < 0.05 , Student t test ) . The mastic group showed a significantly reduced plaque index ( 2.69 + /- 0.29 versus 3.15 + /- 0.24 ; P = 0.001 , Student t test ) and gingival index ( 0.44 + /- 0.15 versus 0.66 + /- 0.23 , P = 0.021 , Student t test ) compared to the placebo group . CONCLUSION These results suggest that mastic chewing gum is a useful antiplaque agent in reducing the bacterial growth in saliva and plaque formation on teeth The purpose of the present study was to determine the ability of a chewing gum containing 5 % sodium bicarbonate to remove dental plaque and reduce gingivitis when used as a supplement to daily toothbrushing . The study group consisted of 88 adults with moderate gingivitis . Participants were divided into 4 groups and instructed to chew the study gum 0 ( control ) , 1 , 2 , or 3 times daily for 1 month in addition to regular daily toothbrushing . Chewing sodium bicarbonate-containing gum significantly ( P < .05 ) reduced plaque after 1 week , with progressively greater reductions occurring after 2 and 4 weeks of gum chewing . No correlation was observed between plaque reduction and the number of times per day that the gum was chewed . By week 4 , plaque reduction of approximately 16 % was achieved in all groups using the gum as compared with the control group . Reductions in gingivitis were observed in all participants who chewed the gum , and these reductions achieved statistical significance by week 4 . Slightly greater improvements in gingivitis were achieved in participants who chewed the gum 2 or 3 times daily as compared with the control group and those who chewed the gum once daily . No adverse effects on the oral tissues were observed in any of the participants for the duration of the study . In conclusion , regular use of a chewing gum containing 5 % sodium bicarbonate appears safe and effective for the removal of dental plaque and reduction of gingivitis when used in conjunction with daily toothbrushing Studies on the relationship between gum-chewing and calculus formation have produced contradictory results , and it is not clear whether frequent use of chewing gum promotes or inhibits calculus formation . Also , little is known about whether the addition of a small amount of urea to the chewing gum influences calculus formation . The aim of this investigation was to study the effect of sugar-free chewing gum-with and without urea-on calculus formation and some associated clinical variables . Three three-month periods were studied in a double-blind , crossover design , during which the subjects : ( 1 ) chewed 5 pieces/day of a sugar-free , urea-containing chewing gum ( 20 mg urea/piece ) ; ( 2 ) chewed 5 pieces/day of a sugar-free , non-urea-containing gum ; or ( 3 ) performed no gum-chewing . Twenty-nine persons , all calculus-formers , participated . They were scored for calculus at mesio-lingual , lingual , and disto-lingual sites on the 6 anterior m and ibular teeth according to the Volpe-Manhold index . Plaque and gingival bleeding index , stimulated salivary secretion rate and buffer capacity , resting plaque pH , mutans streptococci in saliva and plaque , and lactobacilli in saliva were also determined . No differences in calculus formation were found among the 3 periods . The resting plaque pH was higher after the period with urea-containing gum than after the period with non-urea-containing gum and the no-gum period ( p < 0.05 ) . A slight increase in stimulated salivary secretion rate was found after the 2 gum periods ( p < 0.05 ) . The plaque and gingival bleeding indices decreased , while resting plaque pH and salivary buffer capacity increased throughout the entire study ( p < 0.05 ) . No significant differences in prevalence of the acidogenic micro-organisms were found among the test periods . The main conclusion from this study is that three months ' frequent use of sugar-free chewing gum-with or without urea-neither promotes nor inhibits calculus formation Chlorhexidine is a well-established agent used for the control of supragingival plaque but is not without disadvantages , such as tooth staining , which limits its clinical applications to short-term use . This clinical trial studied the clinical effectiveness and stain-forming potential of chlorhexidine in a chewing gum base . Subjects ( 151 ) were screened for baseline plaque and gingival indices before receiving a dental prophylaxis and r and omized into 3 treatment groups : group 1 chewed 2 pieces of chlorhexidine diacetate gum for 10 min 2x a day ( total daily chlorhexidine = 20 mg ) , group 2 chewed 2 pieces of placebo gum for 10 min 2x a day and group 3 rinsed with 10 ml of 0.2 % chlorhexidine gluconate mouthwash for 1 min 2x per day ( total daily chlorhexidine = 40 mg ) . Plaque , gingivitis and stain evaluations were made at 4 and 8 weeks . Plaque and bleeding scores were significantly lower at 4 and 8 weeks in the chlorhexidine gum group compared to the placebo gum group and similar at 8 weeks to the rinse group . Stain intensity at week 8 was significantly less for the chlorhexidine gum than rinse . The staining measured by extent was also less with the chlorhexidine gum than the rinse , but the difference was not significant at week 4 . At week 8 , stain extent was significantly lower in the chlorhexidine gum group than chlorhexidine rinse . In conclusion , the results of this study demonstrate that this chlorhexidine chewing gum used with normal tooth cleaning provides similar adjunctive benefits to oral hygiene and gingival health as a 0.2 % chlorhexidine rinse The gum of Acacia Arabica is described in the British pharmacopoeia as a source of useful medicaments . It is believed to be of value for treating gingivitis and for reducing plaque . 2 blind crossover trials were carried out to evaluate the antiplaque potential of Acacia gum compared with sugar free gum . In trial 1 , the mean gingival and plaque scores were lower after 7 days of using Acacia compared with sugar-free gum but the differences were insignificant . In trial 2 , daily photographic assessment of erythrocine-stained plaque showed lower scores after Acacia gum compared with sugar-free gum . The total difference in scores for each day from each individual between the 2 treatments was highly significant ( p less than 0.05 ) . This implies the presence of substances in Acacia gum which , compared with ordinary gum , primarily inhibit the early deposition of plaque The aims of this study were to evaluate ( i ) : whether vitamin C in chewing gum , alone or in combination with carbamide , influences calculus formation , and ( ii ) whether carbamide affects the release , stability and uptake of vitamin C in a chewing gum . In two test series ( Series I and II ) , 30 subjects , all calculus formers , participated . They were instructed to chew on five ( Series I ) or 10 ( Series II ) pieces of gum per day for a period of 3 months . The chewing gums were : vitamin C ( 60 mg , Series I ) , non-vitamin C ( Series I ) and vitamin C + carbamide ( 30 mg + 30 mg , Series II ) . In both series , no gum was used as a negative control . Calculus formation was scored on three lingual sites on the six anterior m and ibular teeth according to the Volpe-Manhold index . The effect on plaque and gingivitis was also determined . A significant reduction in the total calculus score was observed after the use of vitamin C ( 33 % ) and vitamin C + carbamide ( 12 % ) gums compared with no gum use ; this reduction was most pronounced in the heavy calculus formers . A reduced amount of visible plaque was also observed after use of vitamin C and non-vitamin C gum , but only the vitamin C gum reduced the number of bleeding sites ( 37 % ) . In a separate study , the release , stability and uptake of vitamin C were evaluated using the iodine titration method in both saliva and urine after exposure to the following gums : vitamin C + carbamide ( 30 mg + 30 mg ) and vitamin C ( 30 mg ) . There was no indication that carbamide affected the release , stability or uptake of vitamin C when used in a chewing gum This clinical cross-over trial investigated the effects of a chewable preparation containing chorhexidine-fluoride-xylitol , xylitol control tablets , or chlorhexidine mouthwash , twice daily , on plaque and gingival index scores of subjects refraining from mechanical cleaning of their teeth . Both preparations containing chlorhexidine were found to be efficient antiplaque agents when compared with the control . There was no statistically significant difference between the tablet preparation and conventional chlorhexidine rinsings with respect to the recorded parameters . Thus , an efficient antiplaque preparation can be made in tablet form , which may have advantages in instances where use of mouthwash solutions is impracticable OBJECTIVE In previous investigations the chlorhexidine ( CHX ) chewing gums tasted unpleasant . The main problem with different CHX formulations is the high incompatibility of CHX with anionic compounds . The purpose of this study is to introduce a new formulation for CHX gum that gives both anti-plaque effectiveness and an acceptable taste . METHODS DESIGN R and omized , double blind , placebo-controlled crossover trial , employing two 5-day trial periods without mechanical oral hygiene . PARTICIPANTS 18 from 22 volunteer dental students ( 8 males , 10 females , mean age 22 + /- 2.3 years ) . INTERVENTION Active gum , containing 10 mg CHX , and placebo were used for 20 min twice daily . A 7-day washout period between trial periods was used . MAIN OUTCOME MEASURES Turesky modification of the Quigley and Hein index was used to assess plaque formation . Success of blinding was assessed at the second day of each test period . At the end of each test period , subjects were asked to evaluate the taste of the products used . RESULTS CHX gum has a significantly higher anti-plaque effect than placebo ( 95 % confidence interval 2.7865 to 3.5302 , p < 0.0001 ) . Subjects could not determine the study drug assignment by taste or otherwise ( p = 0.6250 ) . The difference between subjective evaluations of the taste of chewing gums was not significant ( p = 0.5879 ) . CONCLUSION CHX can be successfully incorporated in a chewing gum-based delivery system for use as an adjunct to or even short-term replacement for mechanical plaque control . The observation period needs to be extended if this product is anticipated for longer-term use PYCNOGENOL is an antioxidant phytochemical shown to have antiinflammatory activity in both the in vitro and in vivo models . This study compared the effects of chewing gums with and without PYCNOGENOL on gingival bleeding and plaque formation in 40 human subjects . In this double-blind study , subjects were assigned r and omly to receive either control gums without PYCNOGENOL or experimental gums containng 5 mg PYCNOGENOL . Subjects used chewing gums for 14 days . Gingival bleeding and plaque scores were taken before and after the experiment . PYCNOGENOL chewing gums significantly reduced gingival bleeding , while no changes were noted in bleeding indexes in control subjects who used regular chewing gums . Subjects using regular control gums had significant increases of dental plaque accumulation during the two-week period . No increases in plaque accumulation were noted in subjects using PYCNOGENOL chewing gums . The data of this study suggest that the use of Pycnogenol chewing gums can minimize gingival bleeding and plaque accumulation The effect of magnolia bark extract ( MBE ) on different variables related to caries and gingivitis administered daily through a sugar-free chewing gum was evaluated . The study was performed with healthy adult volunteers at high risk for caries as a r and omized double-blind interventional study . 120 subjects with a salivary mutans streptococci ( MS ) concentration ≧105 CFU/ml and presence of bleeding on probing > 25 % were enrolled and divided into three groups : magnolia , xylitol and control . The study design included examinations at baseline , after 7 days , after 30 days of gum use and 7 days after the end of gum use . Plaque pH was assessed using the strip method following a sucrose challenge . Area under the curve ( AUC5.7 and AUC6.2 ) was recorded . Whole saliva was collected and the number of salivary MS ( CFU/ml ) was counted . Bleeding on probing was recorded as a proxy of dental plaque . Data were analyzed using ANOVA repeated measures . Magnolia gum significantly reduced plaque acidogenicity , MS salivary concentration and gingival bleeding compared to xylitol and control gums . Subjects from the magnolia and xylitol groups showed both MS concentration ( p = 0.01 and 0.06 , respectively ) and AUC5.7 ( p = 0.01 and 0.04 , respectively ) to be significantly lower compared to baseline . Thirty-day use of a chewing gum containing MBE showed beneficial effects on oral health , including reduction of salivary MS , plaque acidogenicity and bleeding on probing The plaque-reducing effect of a chewing gum containing hydrogen peroxide was assessed . 12 dental hygienist students participated in a double-blind 3 x r and omly crossed-over study . During the 4-day test periods , from Monday to Friday , no oral hygiene measures were allowed other than chewing 2 pieces of gum for approximately 10 min 5 x daily . The 800 mg pieces of gum were V6+regular ( V6 + ) containing 0.4 g sorbitol and 6.3 mg hydrogen peroxide , V6 placebo gum ( PLAC ) containing 0.45 g sorbitol and no hydrogen peroxide , and only the gum base ( GB ) as a negative control . The quantity of plaque was assessed using the plaque index and the visible plaque index , and by scraping " all " plaque off the teeth in half the mouth during 2.5 min for determination of plaque wet weight . With all 3 measurements , chewing of the hydrogen peroxide-releasing gum ( V6 + ) result ed in significantly lower plaque increments , from Monday to Friday , than chewing of the gum base ( P less than 0.05 ) . Chewing of the V6 placebo gum ( PLAC ) result ed in plaque scores which differed from neither those recorded after use of the hydrogen peroxide releasing ( V6 + ) nor the placebo ( GB ) gums . The observed plaque-growth inhibiting effect of the hydrogen peroxide-releasing chewing gum in the present study was found to be of limited clinical significance In a previous study , 800 mg pieces of sorbitol-flavored gum , each piece containing 5 mg chlorhexidine ( CHX ) acetate , when chewed 2 at the time 5 x daily , were found to have an excellent plaque growth inhibiting effect . The aim of Trial 1 of the present study was to assess whether chewing only 2 x daily , 2 pieces of the same concentration CHX gum for about 10 min would be as effective . 6 dental students participated in the 3 x r and omly crossed over double-blind clinical trial . During the 5-day chewing periods , no other oral hygiene measures were allowed . The Hibitane Dental ( HD ) rinse was used as a positive and the gum base containing neither CHX nor the sweetening agent as a negative control . At the end of each test period , recordings were made for the plaque index ( PII ) , the plaque wet weight ( PWW ) and the relative area of plaque covered tooth surface ( plaque area % ) . Chewing of CHX gum twice daily inhibited plaque growth as effectively as the HD rinse . The aim of Trial 2 was to assess the antiplaque effect of lower concentration CHX gums with , hopefully , a less unpleasant taste . For this trial , 8 dental students were recruited to chew 2 x daily during 6-day periods two 800 mg pieces of sorbitol-flavored gum , each piece now containing either 5 mg , 4 mg or 3 mg CHX acetate . The effect of these dosages did not differ from the effect of the HD rinse . ( ABSTRACT TRUNCATED AT 250 WORDS |
14,027 | 31,990,982 | Late administration of EPO reduces the use of one or more RBC transfusions , the number of RBC transfusions per infant ( < 1 transfusion per infant ) but not the total volume ( mL/kg ) of RBCs transfused per infant .
Any donor exposure is likely not avoided as most studies included infants who had received RBC transfusions prior to trial entry .
Late EPO does not significantly reduce or increase any clinical ly important adverse outcomes except for a trend in increased risk for ROP .
The use of satellite packs ( dividing one unit of donor blood into many smaller aliquots ) may reduce donor exposure | BACKGROUND Preterm infants have low plasma levels of erythropoietin ( EPO ) , providing a rationale for the use of erythropoiesis-stimulating agents ( ESAs ) to prevent or treat anaemia .
Darbepoetin ( Darbe ) and EPO are currently available ESAs .
OBJECTIVES To assess the effectiveness and safety of late initiation of ESAs , between eight and 28 days after birth , in reducing the use of red blood cell ( RBC ) transfusions in preterm or low birth weight infants .
SEARCH METHODS We used the st and ard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials ( CENTRAL 2018 , Issue 5 ) , MEDLINE via PubMed ( 1966 to 5 June 2018 ) , Embase ( 1980 to 5 June 2018 ) , and CINAHL ( 1982 to 5 June 2018 ) . | OBJECTIVE : To compare the neurodevelopmental outcome of premature infants treated with recombinant human erythropoietin with that of control infants . STUDY DESIGN : A total of 20 treated infants and 20 control infants who had completed r and omized , double-blind , placebo-controlled studies of recombinant human erythropoietin as treatment for anemia of prematurity were followed for growth and developmental outcome in an intensive care nursery follow-up program . Infants were assessed by st and ard developmental tests . RESULTS : No differences were found between groups for neurologic outcome , cognitive outcome , or growth patterns . All infants treated with recombinant human erythropoietin were neurologically normal . The rate of cognitive deficits was similar in the two groups . CONCLUSION : In this small sample we did not see differences in neurodevelopmental outcome between infants treated with recombinant human erythropoietin and control infants The effectiveness of recombinant human erythropoietin ( r-HuEpo ) in raising haemoglobin concentrations in very low birthweight infants was examined in a r and omised multicentre study . Twenty nine ' healthy ' appropriate for gestational age infants with birth weights 900 - 1400 g entered the study at 3 weeks of age . All infants received breast milk supplemented with 9 g/l human breast milk protein from 3 to 8 weeks of age . Eighteen mg iron was given daily from week 3 and was doubled if serum iron concentration fell below 16.0 mumol/l . Fourteen infants were r and omised to receive 100 U/kg r-HuEpo subcutaneously three times a week from week 3 to week 7 ; 15 infants served as controls . After one week reticulocyte and haemoglobin concentrations were significantly higher in the r-HuEpo treated group and the haemoglobin values remained significantly higher throughout r-HuEpo treatment and at the concentrations observed in full term infants . No adverse effects were associated with the treatment . In stable very low birthweight infants with optimal iron and protein intakes , moderate dose r-HuEpo can produce significant gains in red cell production that may be clinical ly useful Because critically ill premature infants experience significant iron loss due to phlebotomy and have high iron needs for growth , Fe absorption and incorporation studies are clinical ly important . A prospect i ve , controlled , r and omized , open 21-d study was conducted in infants with birth weight < 1300 g and gestational age < 31 wk to assess the efficacy of combining intravenous ( IV ) sucrose iron ( Fe ) with erythropoietin ( EPO ) for increasing Fe absorption , RBC Fe incorporation , and erythropoiesis . Three clinical ly stable groups were enrolled at 3 - 4 wk of age : Control , EPO [ 2100 U EPO/(kg.wk ) ] ; and IV Fe+EPO [ 2 mg IV sucrose Fe/(kg.d ) plus 2100 U EPO/(kg.wk ) ] . All subjects received 9 mg/(kg.d ) of oral Fe polymaltose . Subjects were not allowed RBC transfusions . Indicators of iron status and erythropoiesis were assessed before and 18 d after treatment . On d 4 , tracer doses of oral polymaltose (57)Fe and IV sucrose (58)Fe were administered , and stool and blood sample s were collected for Fe absorption and incorporation determinations . Compared with the Control group , the EPO group demonstrated greater hemoglobin ( Hb ) concentration and reticulocyte count , but no difference in Fe incorporation . In contrast , the IV Fe+EPO group demonstrated greater total Fe incorporation , Hb concentration , plasma ferritin , and reticulocyte count compared with the Control and EPO groups . Absorption of (57)Fe and nonisotopic polymaltose Fe did not differ among the groups ( range : 48 - 58 % , and 41 - 47 % , respectively ) . We conclude that IV sucrose Fe administered in combination with EPO to very-low-birth weight premature infants significantly increases RBC Fe incorporation and erythropoiesis more than EPO alone , but without increasing iron absorption Anaemia of prematurity , a postnatal fall in haemoglobin concentration and haematocrit , is particularly common in those born at less than 32 weeks of gestation . Experimental and clinical data implicate inadequate erythropoietin production as an important reason . In this study recombinant human erythropoietin ( r-HuEpo ) was used in an attempt to treat or prevent this anaemia and thereby provide an alternative to erythrocyte transfusions . Premature infants ( birth weight ≤ 1250 g and gestational age ≤ 32 weeks ) , who were likely to need transfusions , were r and omly assigned to receive 4 weeks of treatment with either subcutaneously administered r-HuEpo ( 200 U ; n = 12 ) or placebo ( n = 12 ) , three times weekly . All patients had oral supplements of elemental iron at a dose of 3 mg/kg/day . Treatment was started in the third week of life . Reticulocyte counts were significantly raised ( P < 0.05 ) in the group treated with r-HuEpo at the end of treatment . The neonates in the group treated with r-HuEpo needed fewer erythrocyte transfusions than those in the placebo group during treatment . There were no toxic effects attributable to r-HuEpo . The results indicate that treatment of infants with very low birth weights with r-HuEpo will reduce their need for erythrocyte Abstract There is no consensus regarding protein intake and the doses of recombinant human erythropoietin ( r-HuEpo ) and iron in the treatment of anaemia of prematurity ( AOP ) . This open , r and omized study has compared the effectiveness of 50 IU r-HuEpo/kg with that of 100 IU/kg , both given subcutaneously thrice weekly . In addition , two different protein supplements have been compared ; lyophilized human milk protein and a commercial cow ’s milk product . Total protein intake was 3 g/kg per day . Daily iron dose was 18–36 mg . “ Healthy ” preterm infants ( n = 32 , birth weight : 800–1400 g , gestational age ≤ 31 weeks ) were studied from age 3 to 8 weeks . The two protein regimens yielded no differences in body growth , reticulocyte count or Hb concentration . In both r-HuEpo dose groups increased number of reticulocytes followed start of treatment ; higher levels were , however , found in the group receiving 100 IU/kg . Mean Hb concentration plateaued at 12 g/dl for infants receiving 100 IU/kg , at 11 g/dl in the 50 IU/kg group . Even though serum levels of ferritin and transferrin saturation indicated no iron deficiency , soluble transferrin receptor increased in both groups , more rapidly and to higher levels in the 100 IU/kg group . In addition , the number of infants having more than 8 % hypochromic red cells increased in both groups . Conclusions Commercial cow ’s milk protein added to human milk was as good as human milk protein supplementation in supporting growth and erythropoiesis . Fifty IU/kg r-HuEpo thrice weekly during AOP stimulated erythropoiesis significantly , but less so than 100 IU/kg . Even when using high oral doses of iron to preterms receiving r-HuEpo , our data suggested a certain degree of iron deficient erythropoiesis To assess the risks and benefits of erythropoietin versus erythrocyte transfusion in the treatment of the anemia of prematurity , we r and omly assigned 19 anemic preterm infants ( birth weight 988 + /- 227 gm ; gestational age 27.6 + /- 1.2 weeks ; age 41 + /- 15 days ; all values mean + /- SD ) to receive either transfusion or subcutaneously administered erythropoietin ( 200 units/kg every other day for 10 doses ) . In the 10 erythropoietin recipients , corrected reticulocyte counts increased from 2 % + /- 1 % to 7 % + /- 2 % ( p less than 0.001 ) and hematocrits increased from 27 % + /- 2 % to 30 % + /- 4 % ( p less than 0.05 ) . In the nine infants who underwent transfusion , reticulocyte counts did not increase , but hematocrits increased from 28 % + /- 4 % to 41 % + /- 2 % after initial transfusion ( p less than 0.001 ) and had decreased to 34 % + /- 5 % by day 20 . Signs attributed to anemia ( tachycardia , apnea with bradycardia , and poor weight gain ) declined in both the erythropoietin recipients and those who underwent transfusion . However , five of nine infants who underwent transfusion had symptoms within 10 to 14 days and were given further transfusions . Marrow aspiration performed after 7 to 10 days of treatment showed that infants receiving erythropoietin had greater percentages of erythropoietic precursors ( p less than 0.01 ) , greater concentrations of mature erythroid progenitors ( p less than 0.001 ) , and higher cycling rates of erythroid progenitors ( p less than 0.001 ) . The percentage of mature stored neutrophils in marrow was lower in the erythropoietin group than in the transfusion group , result ing in an inverse myeloid/erythroid ratio ( 0.5:1 vs 6.2:1 ; p less than 0.001 ) . After 20 days , absolute blood neutrophil counts were lower in the erythropoietin recipients ( 1.8 + /- 0.9 x 10(3 ) cells/microliters ) than in the infants who underwent transfusion ( 3.9 + /- 1.9 x 10(3 ) cells/microliters ; p less than 0.05 ) . Administration of erythropoietin thus stimulated erythropoiesis and relieved signs attributed to anemia ; the significance of the relative neutropenia remains to be determined . We conclude that erythropoietin administration offers promise as an alternative to erythrocyte transfusion in neonates with symptomatic anemia of prematurity AIM To evaluate the role of recombinant human erythropoietin ( R-HuEpo ) in reducing iron infusion , which may exacerbate free radical damage , leading to chronic lung disease . METHODS A multicentre , r and omised , placebo controlled , double blind study was carried out in four neonatal intensive care units in Yorkshire . Infants were r and omly allocated and received either R-HuEpo ( 480 U/kg/wk ) or placebo by twice weekly subcutaneous injection . The primary outcome measure was the number of days on respiratory support and a secondary outcome the number of blood transfusions required . RESULTS Forty two very low birthweight ( VLBW ) infants were r and omly allocated . There was little difference in the need for respiratory support one month after r and omisation , but subsequently there was a trend towards a reduction in the proportion requiring respiratory support in the R-HuEpo group ( difference at three months −0.50 , 95 % confidence interval −1.00 , 0.17 ) . During stay in hospital , the median number of blood transfusions was lower for infants in the R-HuEpo group ( difference in medians −2 , 95 % CI −4 , 0 ) . The study was stopped early because of failure to recruit babies at the expected rate . CONCLUSIONS R-HuEpo seems to reduce the number of days in oxygen for ill VLBW infants . These data could be used to construct a larger multicentre study to evaluate this effect further OBJECTIVE : To determine the effectiveness of a 10-day subcutaneous erythropoietin ( rHuEpo ) course of 300 units per kg per dose plus oral iron compared to oral iron alone in anemic infants during their convalescent phase of illness . STUDY DESIGN : Prospect i ve , r and omized trial performed at a 40-bed , teaching , referral , level III , neonatal intensive care unit . Infants with a gestational age at birth of less than 32 weeks , hematocrit of less than or equal to 28 % with a corrected reticulocyte count of less than or equal to 5 % , postconceptual age of less than 48 weeks or 5 months chronological age , and a diagnosis of anemia of prematurity were considered for inclusion . Major outcome parameters included hematocrit , corrected reticulocyte count and red cell transfusion requirements . RESULTS : A total of 60 infants were enrolled ( n=30 per group ) . Infants r and omized to rHuEpo had a significantly higher post-treatment hematocrit and corrected reticulocyte count than infants in the iron only group ( p<0.001 ) . There was a trend towards fewer red cell requirements in the rHuEpo group . CONCLUSIONS : The rHuEpo regimen studied here was associated with an acute improvement in hematocrit and corrected reticulocyte counts . This study did not demonstrate a statistically significant decrease in transfusion therapy , in part related to increased subsequent use of rHuEpo in the control group . Taken together , these data demonstrate that this regimen can effectively treat anemia in convalescent premature infants To determine whether recombinant erythropoietin ( r-HuEpo ) administered to very low birth weight infants could increase hemoglobin F synthesis , or delay its developmentally programmed decline , we determined serially the synthesis of hemoglobins A and F in 15 preterm infants receiving either a placebo or r-HuEpo . There was no difference between the two groups in the proportion of hemoglobin F being synthesized in relation to postconceptional age ( TBF ) . Furthermore , effective erythropoiesis could also contribute to increased TBF through an absolute increase in the normally senescing red cell mass . In a center-based ancillary study , we estimated in vivo TBF by determining carboxyhemoglobin in the blood (HbCO).n2 A goal of this study was to gather important safety information about increased TBF , a potential r-HuEPO side effect , since the premature infant has a shorter red cell life span than the full-term infant , limited capacity for eliminating the pigment , and thus a propensity for hyperbilirubinemia OBJECTIVE : Darbepoetin is longer acting and more potent than recombinant erythropoietin ( rEpo ) . In certain situations , preterm neonates might benefit from rEpo , and for such patients darbepoetin would require fewer doses at a lower cost . However , the proper dose and dosing interval have not been established . STUDY DESIGN : We performed a prospect i ve trial in two level III Neonatal Intensive Care Units . Patients < 32 weeks gestation at birth , with a birth weight ( BW ) < 1500 g , were eligible for participation if they were > 21-days-old and had a hemoglobin ( Hgb ) concentration ≤10.5 g/dl . In all , 12 were to receive a single subcutaneous ( s.c . ) dose at either 1 or 4 μg/kg . Once before the dose was given , and at two preset intervals after , blood was obtained for immature reticulocyte fraction ( IRF ) and absolute reticulocyte count ( ARC ) . Once before and at four preset intervals after , blood was obtained for pharmacokinetic studies . RESULTS : The 12 subjects had BWs of 1129±245 g ( mean±SD ) , were 29.2±1.2 weeks gestation at delivery , and were 43±12 days old with an Hgb concentration of 9.6±1.0 g/dl when the darbepoetin was given . Six received 1 μg/kg and six 4 μg/kg . The IRF increased ( p<0.05 ) as did the ARC ( p<0.05 ) . The increases in IRF were somewhat greater among the 4 μg/kg recipients ( P=0.06 ) . The highest recorded concentrations of drug occurred 6 to 12 hours after administration . The combined 6 and 12 hours values were 185±106 mU/ml in the 1 μg/kg group vs 597±238 in the 4 μg/kg group ( p<0.002 ) . The t½ was 26 hours ( range 10 to 50 ) . The biovailability-normalized clearance was 19 ml/hour/kg ( range 5 to 54 ) . CONCLUSIONS : A single s.c . dose of darbepoetin given to preterm neonates accelerated effective erythropoiesis . The pharmacodynamic and pharmacokinetic findings suggest that darbepoetin dosing in neonates would require a higher unit dose/kg and a shorter dosing interval than are generally used for anemic adults Background : In the early weeks of life , very low birth weight ( VLBW ) infants experience intense laboratory blood sampling leading to clinical ly significant anemia and the need for red blood cell transfusion . Although controversial , treatment with recombinant human erythropoietin ( EPO ) and iron has been recommended to stimulate erythropoiesis ; optimal dosing of EPO and iron is still uncertain . Objectives : To assess the validity of a four-quadrant diagnostic plot of iron availability ( ferritin index ) versus iron dem and for erythropoiesis ( reticulocyte hemoglobin content , CHr ) for differentiating iron status in anemic VLBW infants . Methods : Study subjects were enrolled in a previously reported r and omized controlled trial of clinical ly stable VLBW infants < 31 weeks ’ gestation and < 1,300 g at birth to receive 18 days of treatment with : group 1 : oral iron ; group 2 : EPO + oral iron , and group 3 : EPO + intravenous + oral iron . Results : At the end of treatment the ferritin index was significantly higher in both EPO groups compared to the control group . By day 18 , CHr of the control group declined into the quadrant of the diagnostic plot characteristic of functional iron deficiency and anemia of chronic disease . Both EPO groups ended in the quadrants that are characteristic for latent iron deficiency and iron deficiency anemia , respectively . Conclusions : The diagnostic plot for differentiating anemia in VLBW infants may be an informative , clinical ly useful tool for iron status assessment under different physiologic and therapeutic erythropoietic states . Larger additional studies in difficult patient population s are needed before the clinical utility of this diagnostic procedure can be unequivocally confirmed Seventy premature infants ( birthweight 1.75 kg or less , gestational age 33 weeks or less ) with hemoglobin less than 10 g/dL and hematocrit less than 30 % were studied and r and omly divided into three groups . All of them received oral elemental iron 3 mg/kg/day and vitamin E 5 mg/kg/day during the study period . Recombinant human erythropoietin ( rHuEPO ) 150 U/kg was administered intravenously twice a week for 4 weeks in group A ( 26 infants ) . Infants in group A received a total of 4 erythrocyte transfusions because of frequent apnea . Infants in group B ( 25 infants ) received erythrocyte transfusion when their hemoglobin levels was less than 10 g/dL with signs and symptoms ( including tachycardia , tachypnea , poor feeding , apnea , poor weight gain ) attributed to anemia or who had a hemoglobin less than 8 g/dL even if asymptomatic . Infants in group B received a total of 36 erythrocyte transfusions . Infants in group C ( 19 infants ) were assigned to a non-rHuEPO and nontransfusion group . Three of the 19 premature infants in group C received erythrocyte transfusions later because of frequent and prolonged apneic episodes and were excluded from this study . Our data revealed that reticulocyte and serum erythropoietin values were higher ( p < 0.01 ) in rHuEPO-treated group than transfusion group and hemoglobin and hematocrit values were lower in group C than the other two groups during the rHuEPO treatment period . No significant difference ( p > 0.05 ) was found in neutrophil and platelet counts among these three groups . Serum ferritin values were found lower in the rHuEPO-treated group than the other two groups . Lower weight gain was found in infants in group C. We conclude that rHuEPO administration can reduce the need for blood transfusion . Poor weight gain can be found in infants with anemia of prematurity who do not receive rHuEPO or blood transfusion therapy An extensive and growing number of review s of the published literature demonstrate that health research publications have frequent deficiencies . Of particular concern are poor reports of r and omised trials , which make it difficult or impossible for readers to assess how the research was conducted , to evaluate the reliability of the findings , or to place them in the context of existing research evidence . As a result , published reports of trials often can not be used by clinicians to inform patient care or to inform public health policy , and the data can not be included in systematic review s. Reporting guidelines are design ed to identify the key information that research ers should include in a report of their research . We describe the history of reporting guidelines for r and omised trials culminating in the CONSORT Statement in 1996 . We detail the subsequent development and extension of CONSORT and consider related initiatives aim ed at improving the reliability of the medical research literature We hypothesized that treatment of very low birth weight premature infants with r-HuEPO would increase erythrocyte incorporation and gastrointestinal absorption of iron . Infants with birth weights ≤1.25 kg and gestational ages < 31 wk were r and omized to receive 6 wk of 500 U of r-HuEPO/kg/wk ( epo group , n = 7 ) or placebo ( placebo group , n = 7 ) . All infants received daily enteral supplementation with 6 mg of elemental iron per kg . An enteral test dose of a stable iron isotope , 58Fe , was administered after the 1st ( “ early dosing ” ) and 4th ( “ late dosing ” ) wk of treatment . Mean ( ±SD ) erythrocyte incorporation of the dose of 58Fe administered determined 2 wk after early dosing was significantly greater in the epo group compared with the placebo group ( 4.4%± 1.6 versus 2.0 ± 1.4 % , p = 0.013 ) . In contrast , after late 58Fe dosing , there was no difference between groups in incorporation ( 3.8 ± 1.6 % versus 5.5 ± 2.7 % ) . Within the epo group , percentage erythrocyte incorporation of58 Fe did not differ between early and late dosing , whereas in the placebo group it increased 3-fold ( p < 0.01 ) . Percentage absorption of 58Fe was not different between the epo and placebo groups after both early dosing ( 30 ± 22 % versus 34 ± 8 % ) and late dosing ( 32 ± 9 % versus 31 ± 6 % ) . Absorption of nonlabeled elemental iron and 58Fe were significantly correlated with one another . The percentage of the absorbed 58Fe dose incorporated into Hb was not different between groups . We conclude that , although erythropoietin treatment stimulates erythrocyte iron incorporation in premature infants , it has no effect on iron absorption at the r-HuEPO dose studied DESIGN AND METHODS We hypothesized that treatment with recombinant human erythropoietin ( r-HuEPO ) would stimulate erythropoiesis and would thereby reduce the need for erythrocyte transfusions in preterm infants . We treated 157 preterm infants born at 26.9 + /- 1.6 weeks of gestation who weighed 924 + /- 183 g at birth with either subcutaneous r-HuEPO ( 100 U/kg/d , 5 days per week ) or placebo for 6 weeks in a r and omized , double-blind , controlled clinical trial . All patients received oral iron and were managed according to uniform conservative transfusion guidelines . RESULTS Treatment with r-HuEPO was associated with fewer erythrocyte transfusions ( 1.1 + /- 1.5 per infant in the r-HuEPO group versus 1.6 + /- 1.7 per infant in the placebo group ; P = .046 ) and with a reduction in the volume of packed erythrocytes transfused ( 16.5 + /- 23.0 mL versus 23.9 + /- 25.7 mL per infant ; P = .023 ) . Overall , 43 % of the infants in the r-HuEPO group and 31 % of placebo-treated infants were transfusion-free during the study ( P = .18 ) . The volume of blood removed for laboratory tests and the need for respiratory support at the start of treatment had major effects on transfusion requirements independent of r-HuEPO . Reticulocyte counts were higher during treatment in the r-HuEPO group ( P = .0001 ) , and r-HuEPO-treated infants had higher hematocrit values at the end of the study ( 32 % versus 27.3 % in the placebo group ; P = .0001 ) . We found no differences in the incidence of major complications of prematurity between the treatment groups . CONCLUSION We conclude that treatment with r-HuEPO at a weekly dose of 500 U/kg stimulates erythropoiesis , moderates the course of anemia , is associated with a reduction in erythrocyte transfusions , and appears safe in very low birth weight preterm infants who are receiving iron supplements . Conservative transfusion criteria , minimization of phlebotomy losses , and treatment with r-HuEPO are complementary strategies to reduce erythrocyte transfusions in these infants OBJECTIVE : To assess the efficacy of erythropoietin in the prevention and treatment of anemia of prematurity , correlating the use of this drug with weight gain , length , and head circumference and comparing two administration schemes of he same weekly dose : daily use and twice a week . METHODS : The study comprised 42 premature newborns with gestational age up to 33 weeks , birthweight up to 1550 g , and postnatal age between 10 and 35 days . The newborns were r and omized into three groups : patients in group 1 received seven daily doses of 100 U/kg erythropoietin per week ; patients in group 2 received two 350 U/kg erythropoietin doses per week ; and patients in group 3 did not receive the drug . Hematologic measurements , blood transfusion requirements , and growth rates were followed during therapy . RESULTS : Cases and controls did not differ with respect to weight , length , head circumference , and total time of hospital stay . At the end of the study , no significant difference was observed in the platelet count measurement means , white blood cell count , and ferritin levels in the three groups . However , the final hematocrit and hemoglobin values of patients who did not receive erythropoietin were significantly lower than those of patients who received the drug . The absolute reticulocyte count mean was significantly higher in patients who received erythropoietin after two weeks of treatment when compared with those patients who did not receive the drug . Patients in group 1 e 2 received fewer excessive transfusions ( 2 or more ) than patients in group 3 . The administration of 700 U/kg/week erythropoietin significantly reduced the number of excessive blood transfusions . There is no significant difference in blood transfusion volume between patients who received erythropoietin on a daily basis and those who received the drug twice weekly . CONCLUSIONS : the use of erythropoietin did not influence weight gain and growth . The administration of 700 U/kg/week erythropoietin in premature infants with gestational age up to 33 weeks and birthweight up to 1550 g stimulates erythropoiesis and significantly reduces excessive blood transfusion requirements . Erythropoietin showed to be a safe and well tolerated medication , with no short-term side effects in the study population Abstract The aim of this study was to compare two different doses and means of administration of iron in recombinant human erythropoietin (rHuEPO)-treated very low birth-weight ( VLBW ) infants . VLBW infants ( n = 41 ) were r and omized to one of three groups . Fourteen infants were treated with rHuEPO ( 300 IU/kg three times a week s.c . ) and oral iron ( ferrofumarate , 6 mg of iron/kg per day ) . Another 14 infants received the same erythropoietin dose and intramuscular iron ( ferroxypolymaltose , once 12 mg of iron/kg weekly ) . Thirteen infants were treated with the same dose of intramuscular iron but did not receive rHuEPO . After the 3-week study period , haemoglobin concentrations and reticulocyte counts were similar in the rHuEPO-treated groups and both were higher than in the group not receiving rHuEPO ( P < 0.001 ) . In both rHuEPO-treated groups the transferrin receptor concentration increased from 6.8–7.2 mg/l to 10.5–11.3 mg/l . Conclusion In erythropoietin-treated very low birth weight infants the iron need for erythropoiesis can be met by oral administration of iron In an attempt to stimulate erythrocyte production and thereby decrease the requirement for red blood transfusions , recombinant human erythropoietin ( rHuEPO ) was administered to 16 premature infants with birth weights less than 1000 g and to 18 with birth weights of 1000 - 1300 g ; two corresponding groups , who did not receive rHuEPO , were used as control groups . The rHuEPO was administered subcutaneously in a dose of 300 IU/kg three times a week for 6 - 8 weeks . The erythropoietin decreased the red blood requirement in both groups of infants , and the increment of hemoglobin following rHuEPO administration was not statistically significant . No correlation was observed between gestational age , number of transfusions , and reticulocyte percentage . The effect of rHuEPO was higher in the group of infants with birth weights of 1000 - 1300 g than in those of less than 1000 g. No significant side effects were observed during rHuEPO administration Objective : Red blood cell ( RBC ) transfusions can suppress erythropoiesis . On this basis , RBC transfusions administered to very low birth weight ( VLBW ) neonates potentially render them more likely to qualify for a subsequent transfusion . Study Design : We hypothesized that ‘ late ’ ( > 14 days after birth ) RBC transfusions given to VLBW neonates result in a decrease in reticulocyte count persisting for at least 7 to 10 days . We also hypothesized that a single dose of darbepoetin given along with the transfusion would have the opposite effect , increasing the reticulocyte count for at least 7 to 10 days . To test this , we conducted a single-centered r and omized trial with 20 VLBW neonates who , according to our transfusion guidelines , qualified for a late transfusion . Result : VLBW infants about to receive a late RBC transfusion were r and omized ( 1:1 ) to also receive vs not receive ( controls ) a single subcutaneous dose of darbepoetin ( 10 μg kg−1 ) . Reticulocyte counts diminished significantly in the controls ( a drop of 85±62 × 103 μl−1 ( mean±s.d . ) at 7 to 10 days ) , but increased significantly in the darbepoetin recipients ( an increase of 177±120 × 103 μl−1 at 7 to 10 days , P<0.0001 ) . At 7 to 10 days after the transfusion , hematocrits of the controls were 8.1±4.9 points above their pre-transfusion values and of the darbepoetin group were 12.4±2.7 points above their pre-transfusion values ( P=0.033 ) . Conclusion : This was a limited-scope , single-centered , r and omized trial intended to pilot-test a new concept in neonatal transfusion practice . Namely , we tested whether a late RBC transfusion suppressed reticulocytosis and whether a concomitant single dose of darbepoetin counteracted that suppression . Using the pilot data presented in this study , larger trials can now be design ed to address meaningful clinical outcomes such as transfusion avoidance using this approach Experimental and clinical data implicate inadequate erythropoietin production as an important reason that infants acquire this anemia and suggest that recombinant human erythropoietin ( r-HuEPO ) might be used to treat or prevent it . We therefore r and omly assigned 20 small premature infants ( birth weight less than or equal to 1250 gm ) who were highly likely to require erythrocyte transfusions for anemia of prematurity to receive 6 weeks of treatment with either intravenously administered r-HuEPO ( at a dose of 100 units/kg twice each week ) or a placebo . Hematologic measurements , transfusion requirements , and growth were followed during therapy and for 6 months thereafter . Treated ( EPO ) and control babies did not differ with respect to weight , hematocrit , overall mean absolute reticulocyte count , calculated erythrocyte mass , or rate of growth . However , reticulocyte counts increased earlier in patients given r-HuEPO . Six of ten babies in the EPO group , and 8 of 10 assigned to the control group , received at least one erythrocyte transfusion during treatment . For all infants the amount of blood sample d for laboratory tests was strongly predictive of the volume of packed erythrocytes transfused ( r = 0.890 ; p = 0.0001 ) . Of nine infants who had less than 20 ml packed erythrocytes removed for laboratory tests , none of four given r-HuEPO received a transfusion , whereas three of five infants assigned to the placebo group received one . No toxic effects were attributable to r-HuEPO , and no significant changes in leukocyte or platelet counts occurred during treatment . Reticulocyte counts were correlated with simultaneous platelet counts and were inversely related to absolute neutrophil counts in both study groups . We conclude that r-HuEPO administration is safe and feasible at the dose studied . Additional controlled trials utilizing higher doses of r-HuEPO and larger numbers of patients are justified ABSTRACT : In the present study we assess the effect of recombinant human erythropoietin ( r-HuEpo ) upon levels of fetal Hb ( HbF ) and adult Hb ( HbA ) in preterm infants . Twenty-eight " healthy , ‘ ’ appropriate for gestational age infants with birth weights 900–1400 g entered the study at 3 wk of age . Fourteen infants were r and omized to receive r-HuEpo , and 14 infants served as controls . Four controls and six r-HuEpo treated infants had been transfused before study start , whereas four control infants were transfused in the course of the study . The untransfused infants showed a high HbF/Hb ratio during the study with only a weak tendency to decline toward the expected time of delivery . The total Hb mass increased ( p < 0.05 ) more in the r-HuEpo-treated infants than in the untreated , whereas the rise in HbF mass was similar in the two groups . After each transfusion , the HbF/Hb ratio reverted gradually to the ratio expected at the infant 's postconceptional age . There was no difference in the production rate of HbF between r-HuEpo-treated infants and controls . The present data indicate that the HbF/HbA ratio in preterm infants is subject to the same programmed mechanisms which govern intrauterine erythropoiesis until term and that exogenous r-HuEpo does not influence this pattern significantly OBJECTIVE To compare the number and volume of red blood cell transfusions ( RBCTs ) in very low birth weight infants under restrictive red blood cell transfusion guidelines with and without erythropoietin administration . METHODS In a controlled clinical trial conducted at the neonatal intensive care unit of Alzahra Hospital , Isfahan , Iran , between April 2002 to April 2004 , 60 premature infants with gestational age up to 34 weeks , birth weight up to 1500 g , and postnatal age between 8 and 14 days were included . The newborns were r and omized into 2 groups : Group 1 received 3 doses of 400 IU/kg erythropoietin per week for 6 weeks , and Group 2 received no treatment aside from their conventional medications . RESULTS The 2 groups did not differ significantly with respect to their mean gestational age , birth weight and hematocrit at the study entry . Fewer transfusions were administered to those receiving erythropoietin ( 26.7 % versus 50 % , p=0.03 ) , but there was no statistically significant difference between groups with respect to volume of transfusion . Compared with the placebo group , the infants receiving erythropoietin had a higher mean hematocrit ( 34 % + /- 4.3 versus 29 % + /- 5.9 , p<0.001 ) and absolute reticulocyte count ( 57 + /- 19 versus 10 + /- 4.8 x 106 , p<0.001 ) at the end of the study . We found no significant difference in the incidence of thrombocytopenia and leukopenia between the 2 groups . CONCLUSION We conclude that when the restrictive RBCT guidelines were followed , treatment with erythropoietin can be useful in reduction of the number of RBCTs OBJECTIVES Human fetuses and neonates ingest erythropoietin ( Epo ) when they swallow amniotic fluid , colostrum , and human milk . This study was design ed to determine whether enterally dosed recombinant Epo ( rEpo ) stimulates erythropoiesis in preterm neonates . METHODS Preterm infants ( < 1500 g birth weight ) were r and omly assigned to receive feedings supplemented with either rEpo ( 1000 U/kg per day ) or placebo for 14 days ( n=36 ) . Reticulocyte counts , serum Epo concentrations , hematocrit , and zinc protoporphyrin to heme ratios were measured at baseline and after 7 and 14 days of study drug administration . Transfusion guidelines were followed . Transfusion requirements , medications , feeding tolerance , and clinical diagnoses were documented . RESULTS Enteral rEpo was well tolerated . There were no differences in erythropoietic indexes based on treatment group . Serum Epo concentrations were not different in the treatment versus placebo group , nor were transfusion requirements . CONCLUSIONS Enterally dosed rEpo ( 1000 U/kg/day ) does not significantly influence erythropoiesis or iron utilization when given for a 2-week period , nor does it elevate the serum Epo concentration in preterm or term infants . Oral administration of rEpo is not an effective substitute for parenteral administration OBJECTIVE To determine whether intravenously administered iron supplements would improve the hematologic response to recombinant erythropoietin in stable preterm infants . METHODS Forty-two preterm infants ( <33 weeks ' gestation , birth weight < 1500 gm , hematocrit < 38 % ) were treated with recombinant human erythropoietin ( Eprex ) , 600 U/kg per week , and r and omly assigned to receive either an oral preparation of ferrous lactate ( elemental iron , 12 mg/kg per day ) or an intravenous preparation of iron sucrose ( 6 mg/kg per week ) . RESULTS Hematocrits , reticulocyte counts , and transfusions were similar in the oral group ( OG ) and the intravenous group ( IVG ) . However , markedly higher serum ferritin concentrations were noted in the IVG ( p < 0.001 ) , and by completion of the study the arithmetic mean values were 265 + /- 127 microg/L versus 137 + /- 65 microg/L in the IVG and the OG , respectively . The numbers of hypochromic erythrocytes increased in both groups during the study but were significantly higher in the OG ( p = 0.04 ) . Mean daily weight gain in the IVG ( 27 + /- 6.4 gm/day ) was greater than in the OG ( 22.9 + /- 4.78 gm/day ; p = 0.04 ) . CONCLUSIONS High doses of both orally administered iron and intravenously administered iron sucrose appear to supply sufficient iron for erythropoiesis in stable infants . Storage iron may become depleted after oral supplementation . The intravenous preparation appears to be safe and maintains serum ferritin concentrations , and it may be indicated for patients with low ferritin levels and for those not established on enteral feedings Twenty four infants between 27 and 33 weeks ' gestation were recruited into a double blind study to investigate the use of recombinant human erythropoietin ( r-HuEpo ) for the prevention of anaemia of prematurity . Between 50 and 150 U of r-HuEpo ( n = 16 ) or placebo was administered subcutaneously twice a week from 7 days of age until discharge . There was a significant increase in the reticulocyte count in infants receiving r-HuEpo sustained from the second week of treatment until discharge compared with placebo . There was a reduction in the number of transfusions required in the r-HuEpo group with only 47 % requiring a transfusion compared with 87 % in the placebo group . During treatment with r-HuEpo there was a significant rise in the red cell folate concentration , a significant fall in the ferritin concentration , and a significantly higher percentage of haemoglobin F at discharge suggesting active erythropoiesis . The study provides strong evidence for the efficacy of r-HuEpo in stimulating erythropoiesis and reducing the requirement for transfusions for anaemia of prematurity The specific aim of the study was to assess the safety and efficacy of recombinant human erythropoietin ( rHuEpo ) in reducing the need for blood transfusions in preterm infants after the 15th day of life . Between 1 October 1994 and 1 October 1995 , 107 preterm infants , gestational age < or = 34 weeks , were admitted to the Neonatal Intensive Care Unit and received rHuEpo subcutaneously , 900 U/kg week-1 , 3 times weekly , supplemented with iron and vitamin E. Treatment was started at 8 days of life and lasted from a minimum of 6 weeks to a maximum of 3 months . A total of 116 preterm infants of the same gestational age , admitted to the Neonatal Intensive Care Unit from 1 January 1992 to 31 December 1992 , served as controls . Entry criteria were gestational age < or = 34 weeks and no major congenital malformation . There were no differences in routine care between the two groups . Hematological measurements and transfusion requirements were followed during therapy . The infants were divided into two groups according to birth weight ( < 1500 g and > or = 1500 g ) , and for each group the number of patients who received blood transfusions and when blood transfusions occurred , before or after the 15th day of life , was recorded . There was a statistically significant difference only for transfusions carried out after the 15th day of life ( p < 0.002 ) . No adverse effects attributable to rHuEpo during the treatment were noted . The results indicate that early rHuEpo treatment , in combination with iron supplements , is effective in reducing the need for blood transfusions in preterm infants after the 15th day of life In the present investigation , we studied the effect of recombinant human erythropoietin ( r-HuEPO ) on serum malondialdehyde ( MDA ) as an index of lipid peroxidation , related to iron-catalyzed free radical reaction and erythrocyte superoxide dismutase ( SOD ) , catalase ( CAT ) , and glutathione peroxidase ( GPX ) activities in very-low-birth weight ( VLBW ) infants . Forty premature infants , at gestational ages were less than 33 weeks and birthweights were less than 1,500 g , were enrolled in the study . The study population was r and omly divided into 2 groups . Twenty infants in Group 1 ( treatment group ) were given r-HuEPO , and 20 infants in Group 2 served as the control . r-HuEPO treatment ( 750 U/kg a week ) was initiated on the 10th day of life and continued for 6 weeks . Preterm infants given erythrocyte transfusions during the study were excluded from the results . Serum ferritin and MDA levels , and erythrocyte superoxide dismutase ( SOD ) , catalase ( CAT ) , and glutathione peroxidase ( GPX ) activities were analyzed at the end of the first week of life ( at the beginning of the study ) . Subsequently , serum ferritin , and MDA levels were measured at the end of the 3rd and the 6th week . SOD , CAT , and GPX activities in the hemolysate were analyzed at the end of the 4th week . Six infants in the control group and 1 infant in the r-HuEPO group received transfusions through the end of the study , and these infants were excluded from the results . Significantly decreased serum ferritin concentrations were found in the r-HuEPO group compared to those in the control group both at the end of the 3rd and the 6th week ( P < 0.05 , and P < 0.01 , respectively ) . In addition , serum MDA levels were also significantly reduced in Group 1 compared to control both at the end of the 3rd and the 6th week ( P < 0.01 and P < 0.05 , respectively ) . A good correlation was found between serum MDA and ferritin levels in Group 1 . When the 2 groups were compared with respect to activities of SOD , CAT , and GPX at the end of the 4th week , no differences were observed . Our findings in this study show that administration of r-HuEPO significantly decreases lipid peroxidation , but does not affect erythrocyte antioxidant enzyme(s ) activities in preterm infants . The mechanism responsible for the r-HuEPO-induced decrease in lipid peroxidation may concern inhibition to iron-catalyzed free radical reactions OBJECTIVES To determine whether treatment with recombinant human erythropoietin ( r-HuEPO ) reduces transfusion requirements in premature neonates at risk of having bronchopulmonary dysplasia and requiring multiple transfusions . STUDY DESIGN A double-blind , r and omized , controlled trial . SUBJECTS Fifty-five infants appropriate in weight for gestational age ( less than 1250 gm birth weight ) who , at 10 days of age , were predicted to have a greater than 75 % probability of having bronchopulmonary dysplasia . This criterion had previously been shown to identify infants requiring multiple transfusions . Twenty-seven infants were r and omly assigned to receive r-HuEPO therapy and 28 to a control group . r-HuEPO was administered in a dosage of 20 U/kg body weight , subcutaneously , three times a week for 6 weeks . Control infants received sham treatment . RESULTS Infants treated with r-HuEPO required significantly fewer transfusions than control infants during their entire hospital stay ( mean 3.48 + /- 1.58 vs 5.68 + /- 2.30 ; p = 0.0001 ) and had a higher mean reticulocyte count ( p < or = 0.0005 ) and a higher mean hemoglobin concentration ( p < or = 0.005 ) during the treatment period . At follow-up , 4 months after term , there were no significant differences between the groups in mean reticulocyte count ( p = 0.86 ) or mean hemoglobin concentration ( p = 0.56 ) . However , two infants in each group had low serum ferritin values indicative of depleted iron stores . CONCLUSIONS Treatment with r-HuEPO effectively stimulated erythropoiesis in premature infants at high risk of having bronchopulmonary dysplasia and requiring multiple transfusions ; the result was a reduction in transfusion requirements . This treatment , together with other strategies to reduce the need for transfusions , is appropriate in this population . Unrelated to r-HuEPO treatment , these infants may be at risk of having iron deficiency later in infancy Aims : To evaluate the effects of vitamin E supplementation on haemoglobin concentration and the requirement for transfusion in premature infants treated with erythropoietin and iron . Methods : R and omised , double blind , placebo controlled trial . Thirty infants ≤32 weeks gestation and ≤1250 g birth weight , who were defined as stable based on minimal requirements for respiratory support and phlebotomy , and absence of major congenital anomalies were enrolled . All were treated with erythropoietin and iron , and were r and omised to receive , in addition , either vitamin E 50 IU/day or placebo for eight weeks or until discharge , whichever came first . Results : Despite higher vitamin E ( α-tocopherol ) levels in the experimental group in weeks 3 ( 49.0 v 28.1 μmol/l ) and 8 ( 66.2 v 38.5 μmol/l ) , there were no differences in haemoglobin , reticulocyte count , iron concentration , or transfusion requirement . Conclusions : Oral vitamin E supplementation at 50 IU/day does not increase the response of preterm infants to erythropoietin and iron . Vitamin E obtained through st and ard nutrition may have been sufficient or higher doses may be required OBJECTIVE To investigate whether recombinant erythropoietin ( rhEPO ) reduces the need for transfusion in extremely low birth weight ( ELBW ) infants ( birth weight 500 - 999 g ) and to determine the optimal time for treatment . METHODS In a blinded multicenter trial , 219 ELBW infants were r and omized on day 3 to one of 3 groups : early rhEPO group ( rhEPO from the first week for 9 weeks , n = 74 ) , late rhEPO group ( rhEPO from the fourth week for 6 weeks , n = 74 ) , or control group ( no rhEPO , n = 71 ) . All infants received enteral iron ( 3 - 9 mg/kg/day ) from the first week . The rhEPO beta dose was 750 IU/kg/week . Success was defined as no transfusion and hematocrit levels never below 30 % . RESULTS Success rate was 13 % in the early rhEPO group , 11 % in the late rhEPO group , and 4 % in the control group ( P = .026 for early rhEPO versus control group ) . Median transfusion volume was 0.4 versus 0.5 versus 0.7 mL/kg/day ( P = .02 ) and median donor exposure was 1.0 versus 1.0 versus 2.0 ( P = .05 ) in the early rhEPO group , the late rhEPO group , and the control group , respectively . Infection risk was not increased and weight gain was not delayed with rhEPO beta . CONCLUSION Early rhEPO beta treatment effectively reduces the need for transfusion in ELBW infants BACKGROUND Limited erythropoietin ( Epo ) production diminishes neonates ' ability to regenerate blood removed by phlebotomy . Neonates requiring surgery are at risk to receive multiple transfusions . We sought to determine if recombinant Epo administration to neonates requiring surgery would stimulate erythropoiesis . METHODS Infants were r and omized in double-masked fashion to receive Epo ( 200 units kg(-1 ) d(-1 ) ) or placebo for 14 days . Complete blood count , absolute reticulocyte count ( ARC ) , phlebotomy losses , and transfusions were measured during the study period . Infants were transfused using a strict transfusion protocol . RESULTS In the Epo group ( n = 10 , 2034 + /- 308 g , 8 + /- 2 days old ; mean + /- SEM ) , ARC increased significantly , whereas in the placebo group ( n = 10 , 2400 + /- 184 g , 7 + /- 2 days old ) , ARC remained low . Hematocrits in the Epo group trended upward from 34.4 1.7 % to 37.3 1.9 % ( although not statistically significant ) despite phlebotomy losses of 53 + /- 12 mL/kg . Hematocrits in the placebo group were 35.9 1.8 % and 33.2 1.6 % on days 1 and 15 , respectively , with phlebotomy losses of 27 + /- 5 mL/kg . There were no differences in absolute neutrophil counts or platelet counts between groups at the end of the study . No adverse effects were noted . CONCLUSIONS Infants r and omized to Epo increased reticulocyte counts and hematocrits without adverse effects . Erythropoietin administration may provide an adjunct to present care in decreasing or eliminating erythrocyte transfusions in surgical neonates OBJECTIVE To evaluate safety and efficacy of recombinant human erythropoietin (r-HuEPO)in reducing the need for red cell transfusions in anemia of prematurity . METHODS forty -two preterm infants ( gestational age < 32 weeks ) were r and omly assigned to a " treatment " group ( r-HuEPO 400 units/kg every alternate day * 10 doses ) or " no treatment " ( control ) group . All infants on enteral feeds received oral iron 3 mg/kg/day , grade d up to 6 mg/kg/day . RESULTS Higher reticulocyte counts in week 2 and 3 and higher hemoglobin levels in week 4 were noted after treatment with r-HuEPO . Despite stumulated erythropoiesis , the frequency of transfusions could not be reduced with r-HuEPO therapy . Overall , Phlebotomy losses , frequency and volume of redcell transfusions were significantly more in neonates with birthweight < 1000 grams compared with those with birthweight > 1000 grams ( p<0.05 ) . Associated side effects of r-HuEPO such as neutropenia , sepsis , hypertension or increased risk of late death did not occur . CONCLUSION r-HuEPO therapy was safe without any side effects . Inability of r-HuEPO therapy to minimize red cell transfusions for anemia of prematurity may be explained by a relatively strict red-cell transfusion policy and the desired degree of treatment effect OBJECTIVE To evaluate the efficacy and safety of recombinant human erythropoietin ( rHuEPO ) in very low birth weight infants with anemia of prematurity . STUDY DESIGN Thirty infants were r and omly assigned to receive either rHuEPO ( 300 U/kg per dose ) or placebo twice a week . Hematologic parameters , transfusion requirements , caloric intake , and growth were monitored . RESULTS The number and volume of erythrocyte transfusions were significantly lower in infants treated with rHuEPO . Serum ferritin levels , similar in both groups at study entry , fell and were significantly lower in rHuEPO-group infants at the completion of the study . An inverse correlation was observed between reticulocyte count and absolute neutrophil count both at entry and at completion of the study . CONCLUSION Twice-a-week administration of rHuEPO significantly reduces the need for erythrocyte transfusion in very low birth weight infants in stable condition . A significant decrease in serum ferritin levels in infants receiving rHuEPO suggests the need to determine the optimal dose of iron supplementation in these infants Erythropoietin ( rHuEPO ) therapy has been shown to be beneficial in preventing and treating anaemia of prematurity and to decrease the need for blood transfusions . There is , however , only scanty data on the effect of rHuEPO therapy on iron metabolism . We studied 29 preterm infants ( age 34 ± 14 days ) who were r and omly assigned to receive either rHuEPO 900 U kg‐1 week‐1 with 6 mg kg‐1 day‐1 of iron for 4 weeks ( n= 15 ) or no therapy . The following parameters were evaluated and compared between and within groups at the beginning , during and at the end of the study : Haematocrit ( SI ) , reticulocytes ( 109μgl‐1 ) , serum ferritin ( μg1‐1 ) and iron ( μmol 1‐1 ) . The results were as follows . At the baseline , erythropoietin levels were similar in both groups : 7.2 ± 5.6 versus 6.2 ± 3.2 mU ml‐1 ( NS ) . In the treated infants the haematocrit remained stable during the study and was significantly higher than in the control group by the end of the study : 0.34 ± 0.03 versus 0.28 ± 0.05 ( p= O.001 ) . rHuEPO therapy increased the reticulocyte count from 130 ± 70 to 430 ± 200 ( p= 0.0002 ) . However , rHuEPO therapy depleted both serum ferritin and it‐on levels from 321 ± 191 to 76 ± 58 $ uMgl‐1 ( p= 0.04 ) and from 18 ± 5 to 13 ± 4 μmoll‐1 ( p= 0.03 ) , respectively . We conclude that rHuEPO therapy prevented anaemia and its sequelae ; however , serum ferritin and iron levels were depleted . We suggest that the effect of rHuEPO may be further increased by higher iron supplementation OBJECTIVE To evaluate the effects of enteral administration of recombinant human erythropoietin ( rhEPO ) on serum level of erythropoietin and erythropoiesis in preterm infants . STUDY DESIGN R and omized controlled trial . SETTING Level III NICU . SUBJECTS 16 preterm infants less than 34 wk with birth weight less than 1800 g. INTERVENTION Enteral rhEPO 400 U/kg , three times/week , plus FeSO4,3 - 6 mg/Kg/day ( Study group , n = 7 ) or FeSO4 only ( Control group , n = 9 ) . OUTCOME MEASURES Hemoglobin , serum erythropoietin ( EPO ) , reticulocyte count , and serum ferritin levels , measured at baseline , after 10 days and at discharge . RESULTS Mean birth weight and gestational age for the Study and the Control groups were 1328.5 + /- 267.4 vs. 1392.8 + /- 196.7 g and 30.7 + /- 2.5 vs. 30.2 + /- 0.9 weeks , respectively . At discharge , there was no difference in hemoglobin or hematocrit but the reticulocyte counts were significantly higher in the Study group ( 1.4 + /- 0.7 vs. 0.7 + /- 0.4 , P = 0.03 ) . Serum erythropoietin level was significantly higher in the Study group ( 18 + /- 11 vs. 8.6 + /- 3.9 mU/mL , P = 0.006 ) . Conversely , serum ferritin level was lower in the study group but did not achieve statistical significance . CONCLUSIONS Enteral administration of rhEPO in preterm infants result ed in increase in serum erythropoietin and reticulocyte counts at the time of discharge without significantly affecting hemoglobin or hematocrit Objective . To investigate the effect of early erythropoietin treatment on induction of erythropoiesis and the need for transfusion in Very Low Birth Weight ( VLBW ) infants with acute neonatal problems . Methods . The study group consisted of 14 VLBW prematures with gestational ages less than 32 weeks who were given subcutaneous erythropoietin ( 600 U/kg per week ) and oral iron ( 3 mg/kg per day ) during the first 7–8 weeks of their life , while 13 other VLBW prematures that were given placebo constituted the control group . Weekly hemotocrit , ( Hct ) reticulocyte ( Ret ) values and the volume of blood drawn and transfused were recorded in the both groups . Results . The groups were comparable regarding with birth weights and gestational ages . The volume of the blood drawn ( 76.8 ± 42.5 and 37.0 ± 15.2 ) was higher and the volume of the transfusions ( 51.84 ± 49.30 and 68.84 ± 41.2 ) was lower in the study group but the differences between the groups were not significant ( p>0.05 ) . The hemotocrit , the reticulocyte and the ferritin values were similar in both the groups at the end of the therapy . Conclusion . Under the neonatal intensive care circumstances of developing countries where blood volumes needed for laboratory analysis are still very high , phlebotomy losses can not be avoided . Thus early erythropoietin and iron therapy at these doses are not effective in decreasing the need for transfusion and induction of endogenous erythropoiesis Twenty‐four premature infants , < 32 weeks gestational age , were r and omly assigned in a double‐blind , placebo‐controlled trial to 6 weeks of treatment with either recombinant human erythropoietin ( rHuEpo ) 150 U/kg three times per week given sc ( n= 12 ) or placebo ( n = 12 ) . The infants were fed a diet rich in protein ( 3.2 g/kg/ day ) and energy ( 130 kcal/kg/day ) based on their own mother 's milk fortified with bovine protein together with moderate iron supplementation ( 4 mg/kg/day ) . During the treatment ( rHuEpo versus placebo ) significant differences in mean ( ±SD ) reticulocyte count ( 4.8 ±1.2 versus 2.7±1.4 % ; P<0.01 ) , mean packed red cell volume ( PCV ) ( 0.38 ± 0.03 versus 0.34 ± 0.04 , p < 0.05 ) and mean haemoglobin concentration ( 12.6 ± 1.1 versus 11.5± 1.2 g/100 ml ; p < 0.05 ) were found . Within the rHuEpo group , PCV and haemoglobin concentration remained unaltered from entry to 1 week after cessation of treatment whereas a significant decline was observed in the placebo group . No indications of iron deficiency were seen . We conclude that moderate doses of rHuEpo given to infants fed a diet rich in protein and energy are effective in ameliorating anaemia of prematurity . High iron supplementation does not seem to be essential for a significant erythropoietic response . No adverse effect attributable to rHuEpo was observed . Anaemia , erythropoietin , iron , prematurity , In a double-blind placebo-controlled study we showed a 3-fold decrease in blood transfusions ( BTFs ) given to preterm infants with anaemia of prematurity who received recombinant erythropoietin . However , only 50 % of placebo recipients required a BTF . Data from the placebo group indicated that either mean daily weight gain < or = 7.5 g/day before study entry or haematocrit < or = 50 % at birth was associated with BTFs ( P < 0.001 ) . We calculated that giving erythropoietin to patients in the treatment group with either of these variables prevented 24 of 28 BTFs and that it would cost R184 to prevent 1 BTF . The cost of each BTF was R187 ( blood filtered to remove white cells and reduce cytomegalovirus transmission ) . Therefore , the costs of the two treatments were similar , but as the risk of transmitting infection is lower with erythropoietin , we recommend its use in selected preterm infants OBJECTIVES The specific objectives of this study were ( 1 ) to assess the safety and efficacy of recombinant human erythropoietin ( rhEPO ) in reducing postnatal hemoglobin decline in premature infants of less than 33 weeks ' gestation , and thus reducing the need for transfusion ; and ( 2 ) to determine the optimal dosage of rhEPO . MATERIAL S AND METHODS Three groups of premature infants of less than 33 weeks ' gestation were treated with rhEPO : group 1 ( n = 10 ) received 300 U/kg per week ; group 2 ( n = 11 ) , 600 U/kg per week ; and group 3 ( n = 10 ) , 900 U/kg per week . These three groups were compared to a reference group of 20 infants of the same gestational age and birth weight . Treatment started on the 10th day of life and lasted 6 weeks . All infants were given oral iron and vitamin E supplements . RESULTS Treated infants had significantly higher reticulocyte counts , and the effect was dose dependent ( P = .009 ) . Postnatal decline of hemoglobin and hematocrit was lessened in the treated groups ; the percent of decrease of hemoglobin and hematocrit was significantly reduced in the treated infants at 35 days of age ( P = .0025 and P = .0036 , respectively ) . The need for blood transfusion was also reduced in the rhEPO-treated groups : 19 % of treated vs 45 % of reference infants received transfusions , and the treated infants received less blood . Serum iron and transferrin saturation percentage dropped significantly during the study and a dose-dependent relationship in treated infants was displayed , suggesting high iron consumption ( P = .0008 and P = .006 , respectively ) . No dose effect on hemoglobin level and the need for blood transfusion was found , possibly because of the higher degree of illness severity and iron consumption in groups 2 and 3 . No side effects related to rhEPO therapy were observed . CONCLUSIONS It is concluded that rhEPO therapy is safe in premature babies when given in the three dosages used in this study ; in addition , it enhances erythropoiesis and reduces the need for blood transfusions . rhEPO therapy seems more efficient when given in higher dosages ; however , illness severity and iron consumption represent major limiting factors . Controlled , r and omized studies are warranted to confirm these data and to determine precise modalities and indications of rhEPO therapy in premature infants OBJECTIVE To examine the effect of protein intake on the erythropoietic response of very low birth weight infants to treatment with recombinant human erythropoietin ( rHuEPO ) . STUDY DESIGN Twenty very low birth weight infants were enrolled in the study and 19 completed the 6 weeks of study . Weekly absolute reticulocyte counts , protein intakes , and growth , as well as selected markers of protein metabolism -- prealbumin , albumin , and transferrin -- were analyzed . Iron stores were estimated for each infant to exclude iron deficiency as a cause of anemia . The relationship between protein intake and absolute reticulocyte count was evaluated with a linear breakpoint analysis to account for any plateau in the relationship at higher protein intakes . RESULTS Adequate iron stores were present in all infants , and transferrin concentrations correlated with measured total iron-binding capacity ( r = 0.95 , p = 0.0001 ) . In the rHuEPO-treated infants , absolute reticulocyte count was significantly associated with protein intake up to 3.1 gm/kg per day and extending to 3.5 gm/kg per day ( p = 0.041 to 0.032 ) ; beyond this point there was no longer any effect . Moreover , in comparison with the infants who received placebo , the rHuEPO-treated infants had a better daily percent weight gain for a protein intake up to 3.5 gm/kg per day ( p = 0.016 ) . CONCLUSIONS In VLBW infants treated with rHuEPO , higher protein intake up to 3.1 to 3.5 gm/kg per day improved the erythropoietic response , and protein utilization for growth was improved . During treatment with rHuEPO , infants who receive adequate protein to achieve satisfactory growth also receive sufficient protein for erythropoiesis OBJECTIVE To test the efficacy and safety of combining intravenous iron in amounts approximating the in utero iron accretion rate and the postnatal iron loss with erythropoietin ( EPO ) in very low birth weight ( VLBW ) infants . METHODS A prospect i ve , controlled , r and omized , unmasked trial lasting 21 days was performed in 29 clinical ly stable VLBW infants < 31 weeks ' gestation and < 1300 g birth weight not treated with red blood cell transfusions during the study period . Mean ( + /- st and ard error of the mean ) age at study entry was 23 + /- 2.9 days . After a 3-day run-in baseline period in which all participants received oral supplements of 9 mg/kg/day of iron polymaltose complex ( IPC ) , participants were r and omized to receive 18 days of treatment with : 1 ) oral IPC alone ( oral iron group ) ; 2 ) 300 U of recombinant human EPO ( r-HuEPO ) kg/day and daily oral IPC ( EPO + oral iron group ) ; 3 ) 2 mg/kg/day of intravenous iron sucrose , r-HuEPO , and oral iron ( intravenous iron + EPO group ) . To assess efficacy of the 3 treatments , serial blood sample s were analyzed for hemoglobin ( Hb ) , hematocrit ( Hct ) , reticulocyte count , red blood cell indices and plasma levels of transferrin , transferrin receptor ( TfR ) , ferritin , and iron . Oxidant injury was assessed before and after treatment by plasma and urine levels of malondialdehyde ( MDA ) and o-tyrosine . RESULTS At the end of treatment , Hb , Hct , reticulocyte count , and plasma TfR were markedly higher in both of the EPO-treated groups , compared with the oral iron group . At study exit a trend toward increasing Hb and Hct levels and significantly higher reticulocyte counts were observed in the intravenous iron + EPO group , compared with the EPO + oral iron group . During treatment , plasma ferritin levels increased significantly in the intravenous iron + EPO group and decreased significantly in the other 2 groups . By the end of treatment , ferritin levels were significantly higher in the intravenous iron + EPO group compared with the other 2 groups . Although plasma and urine MDA or o-tyrosine did not differ among the 3 groups , plasma MDA was significantly greater in the subgroup of intravenous iron + EPO participants sample d at the end of the 2-hour parenteral iron infusion , compared with values observed immediately before and after parenteral iron-dosing . CONCLUSIONS In stable VLBW infants receiving EPO treatment , parenteral supplementation with 2 mg/kg/day of iron sucrose results in a small , but significant , augmentation of erythropoiesis beyond that of r-HuEPO and enteral iron alone . However , to reduce the potential adverse effects of parenteral iron/kg/day on increasing plasma ferritin levels and on causing oxidative injury , we suggest that the parenteral iron dose used should be reduced and /or the time of infusion extended to maintain a serum iron concentration below the total iron-binding capacity We r and omly assigned eight concurrently symptom-free premature infants ( birth weight less than or equal to 1250 gm ) at high risk of requiring erythrocyte transfusions for anemia of prematurity to 6 weeks of intensive treatment with either subcutaneous recombinant human erythropoietin ( r-HuEPO group ) or a placebo ( control group ) . Treatment with r-HuEPO was initiated at a dose of 100 units/kg per day 5 days a week , and was increased to 200 units/kg per day after 2 or 3 weeks if target reticulocyte counts were not achieved . All patients were given supplemental oral iron therapy at a dose of 6 mg/kg per day , as tolerated . Mean reticulocyte counts in r-HuEPO-treated and control infants were 64,600 versus 67,500 cells/mm3 at entry ; were 245,600 versus 78,000 cells/mm3 after 1 week ; and averaged 262,600 versus 136,400 cells/mm3 during the study . Mean reticulocyte counts in r-HuEPO-treated infants were 251,200 cells/mm3 during the week when r-HuEPO , 100 units/kg per day , was given , and were 269,500 cells/mm3 after the dose was increased to 200 units/kg per day . Mean hematocrit values at entry were 33.4 % in babies who received r-HuEPO versus 33.6 % in the control subjects , and were 31.4 % in r-HuEPO-treated and 25.2 % in the control subjects at the end of treatment . One r-HuEPO-treated and three control babies received transfusions during the study ; the total volume of blood given was 17 ml in the r-HuEPO group and 101 ml in the control subjects . The percentage of hemoglobin F increased in infants not given transfusions . We conclude that r-HuEPO stimulates endogenous erythropoiesis in small premature babies who are receiving supplemental oral iron therapy . A controlled multicenter trial has been undertaken to confirm these promising preliminary observations OBJECTIVE To assess the efficacy of recombinant human erythropoietin ( rHuEpo ) in the treatment of the anemia of prematurity . METHODOLOGY A double-blind , placebo-controlled study was conducted on 80 preterm infants ( < or = 32 weeks ; postnatal age , 2 to 8 weeks ; central hematocrit < or = 35 % ) . Patients were r and omly assigned to receive subcutaneous rHuEpo ( Eprex , 600 U/kg per week ) or an equivalent volume of placebo , for up to 6 weeks . All patients received supplements of vitamin E ( 25 IU ) and iron ( 3 mg/kg per day ) . The iron supplement was increased if declining serum ferritin measurements were noted . RESULTS Treatment and placebo groups did not differ significantly with respect to mean gestational age , birth weight , hematocrit , or reticulocyte count at study entry . Fewer transfusions were administered to those receiving erythropoietin ( 7 compared with 21 ; P = .002 ) . Compared with the placebo group , the infants receiving rHuEpo had a higher mean hematocrit ( 32.3 + /- 4 % vs 29.3 + /- 6.2 % ; P = .014 ) and absolute reticulocyte count ( 223 + /- 73 vs 124.9 + /- 73 x 10(9)/L ; P < .001 ) at the end of the study . The mean neutrophil count was not significantly reduced at study exit ( P = .8 ) , nor at any other period during the trial in the rHuEpo group . Intercurrent events ( mostly infections ) were not increased in the treatment group , although there was one case of sudden infant death syndrome at age 4 months . CONCLUSIONS Using a dose of rHuEpo of 600 U/kg per week , this study has shown a clear reduction in the requirement for blood transfusion in preterm infants OBJECTIVE To compare reticulocyte responses of once-per-week erythropoietin ( EPO ) dosing with 3-times-a-week dosing in preterm infants . STUDY DESIGN Infants weighing ≤ 1500 g and ≥ 7 days of age were r and omized to once-per-week EPO , 1200 U/kg/dose , or 3-times-a-week EPO , 400 U/kg/dose , subcutaneously for 4 weeks , along with iron and vitamin supplementation . Complete blood counts , absolute reticulocyte counts ( ARCs ) , transfusions , phlebotomy losses , and adverse events were recorded . RESULTS Twenty preterm infants ( 962 ± 55 g , 27.9 ± 0.4 weeks , 17 ± 3 days of age ) were enrolled . Groups were similar at baseline . Infants in both groups had increased ARCs , which were similar between treatment groups at the start and end of 4 weeks . Hematocrit remained stable , and similar numbers of transfusions were administered . No adverse effects of either dosing schedule were noted . CONCLUSIONS Preterm infants respond to weekly EPO by increasing ARCs and maintaining hematocrit . We speculate that once-per-week EPO dosing might be beneficial to preterm infants requiring increased erythropoiesis UNLABELLED To study the relationship between blood transfusion , iron load and retinopathy of prematurity ( ROP ) , we performed a prospect i ve observational cohort study in a level III neonatal intensive care unit . During a 24-month period , data on the volume of blood transfused during the first 6 weeks of life and on the incidence of ROP were collected in all surviving very low birth weight infants ( n = 114 ; median birth weight 1130 g. range 520 - 1500 g ) . Associations between these data and values for serum iron , transferrin and ferritin measured at weekly intervals were analysed in a nested case-control design by logistic regression . There was a significant association between the volume of blood transfused and the incidence of ROP . After adjustment for gestational age at birth , duration of oxygen therapy ( FiO2 > 0.3 ) and duration of mechanical ventilation , the relative risk of developing ROP was 6.4 ( 95 % CI 1.2 - 33.4 ) for infants who had received 16 - 45 ml/kg , and 12.3 ( 1.6 - 92.5 ) for those who had received more than 45 ml/kg of blood ( reference , 0 - 15 ml/kg ) . In contrast , there was no independent relationship between ROP and any of the parameters on iron metabolism analysed . CONCLUSION This study confirms the role of blood transfusions as an independent risk factor for ROP . This relationship , however , does not appear to be mediated via an increased iron load |
14,028 | 28,705,244 | Trials suggest few adverse events although safety data were not always reported .
Conclusions Bupropion and varenicline , which have been shown to be effective in the general population , also work for people with severe mental ill health and their use in patients with stable psychiatric conditions .
Despite good evidence for the effectiveness of smoking cessation interventions for people with severe mental ill health , the percentage of people with severe mental ill health who smoke remains higher than that for the general population | Background People with severe mental ill health are more likely to smoke than those in the general population . | INTRODUCTION Smokers with serious mental illness ( SMI ) have a high smoking prevalence and a low quit rate . Motivational interviewing ( MI ) is an empirically supported approach for addressing substance use disorders and may motivate smokers with SMI to quit . METHODS We r and omized smokers ( N = 98 ) with SMI to receive a single 45-minute session of ( 1 ) MI with personalized feedback or ( 2 ) interactive education . We hypothesized that participants receiving the MI intervention would be more likely to follow-up on a referral for tobacco dependence treatment , to make a quit attempt , and to quit smoking than those receiving the interactive educational intervention . RESULTS Smokers receiving an MI intervention were significantly more likely to make a quit attempt by the 1-month follow-up ( 34.7 % vs. 14.3 % ; OR = 4.39 [ 95 % CI = 1.44 to 13.34 ] , P = .009 ) ; however , these quit attempts did not translate into abstinence . In addition , 32.7 % of those receiving MI followed-up on a referral for tobacco dependence treatment ( vs. 20.4 % receiving interactive education ; OR = 2.02 [ 95 % CI = 0.76 to 3.55 ] , P = .157 ) . MI Treatment Integrity Code ratings indicated that the interventions were easily distinguishable from each other and that MI was delivered with proficiency . Despite the intervention 's brevity , participants reported high levels of therapeutic alliance with their therapist . CONCLUSIONS A brief adaptation of MI with personalized feedback appears to be a promising approach for increasing quit attempts in smokers with SMI , but future research is required to determine how to best help smokers with SMI to attain sustained abstinence BACKGROUND Substantial concerns have been raised about the neuropsychiatric safety of the smoking cessation medications varenicline and bupropion . Their efficacy relative to nicotine patch largely relies on indirect comparisons , and there is limited information on safety and efficacy in smokers with psychiatric disorders . We compared the relative neuropsychiatric safety risk and efficacy of varenicline and bupropion with nicotine patch and placebo in smokers with and without psychiatric disorders . METHODS We did a r and omised , double-blind , triple-dummy , placebo-controlled and active-controlled ( nicotine patch ; 21 mg per day with taper ) trial of varenicline ( 1 mg twice a day ) and bupropion ( 150 mg twice a day ) for 12 weeks with 12-week non-treatment follow-up done at 140 centres ( clinical trial centres , academic centres , and outpatient clinics ) in 16 countries between Nov 30 , 2011 , and Jan 13 , 2015 . Participants were motivated-to-quit smokers with and without psychiatric disorders who received brief cessation counselling at each visit . R and omisation was computer generated ( 1:1:1:1 ratio ) . Participants , investigators , and research personnel were masked to treatment assignments . The primary endpoint was the incidence of a composite measure of moderate and severe neuropsychiatric adverse events . The main efficacy endpoint was biochemically confirmed continuous abstinence for weeks 9 - 12 . All participants r and omly assigned were included in the efficacy analysis and those who received treatment were included in the safety analysis . The trial is registered at Clinical Trials.gov ( number NCT01456936 ) and is now closed . FINDINGS 8144 participants were r and omly assigned , 4116 to the psychiatric cohort ( 4074 included in the safety analysis ) and 4028 to the non-psychiatric cohort ( 3984 included in the safety analysis ) . In the non-psychiatric cohort , 13 ( 1·3 % ) of 990 participants reported moderate and severe neuropsychiatric adverse events in the varenicline group , 22 ( 2·2 % ) of 989 in the bupropion group , 25 ( 2·5 % ) of 1006 in the nicotine patch group , and 24 ( 2·4 % ) of 999 in the placebo group . The varenicline-placebo and bupropion-placebo risk differences ( RDs ) for moderate and severe neuropsychiatric adverse events were -1·28 ( 95 % CI -2·40 to -0·15 ) and -0·08 ( -1·37 to 1·21 ) , respectively ; the RDs for comparisons with nicotine patch were -1·07 ( -2·21 to 0·08 ) and 0·13 ( -1·19 to 1·45 ) , respectively . In the psychiatric cohort , moderate and severe neuropsychiatric adverse events were reported in 67 ( 6·5 % ) of 1026 participants in the varenicline group , 68 ( 6·7 % ) of 1017 in the bupropion group , 53 ( 5·2 % ) of 1016 in the nicotine patch group , and 50 ( 4·9 % ) of 1015 in the placebo group . The varenicline-placebo and bupropion-placebo RDs were 1·59 ( 95 % CI -0·42 to 3·59 ) and 1·78 ( -0·24 to 3·81 ) , respectively ; the RDs versus nicotine patch were 1·22 ( -0·81 to 3·25 ) and 1·42 ( -0·63 to 3·46 ) , respectively . Varenicline-treated participants achieved higher abstinence rates than those on placebo ( odds ratio [ OR ] 3·61 , 95 % CI 3·07 to 4·24 ) , nicotine patch ( 1·68 , 1·46 to 1·93 ) , and bupropion ( 1·75 , 1·52 to 2·01 ) . Those on bupropion and nicotine patch achieved higher abstinence rates than those on placebo ( OR 2·07 [ 1·75 to 2·45 ] and 2·15 [ 1·82 to 2·54 ] , respectively ) . Across cohorts , the most frequent adverse events by treatment group were nausea ( varenicline , 25 % [ 511 of 2016 participants ] ) , insomnia ( bupropion , 12 % [ 245 of 2006 participants ] ) , abnormal dreams ( nicotine patch , 12 % [ 251 of 2022 participants ] ) , and headache ( placebo , 10 % [ 199 of 2014 participants ] ) . Efficacy treatment comparison did not differ by cohort . INTERPRETATION The study did not show a significant increase in neuropsychiatric adverse events attributable to varenicline or bupropion relative to nicotine patch or placebo . Varenicline was more effective than placebo , nicotine patch , and bupropion in helping smokers achieve abstinence , whereas bupropion and nicotine patch were more effective than placebo . FUNDING Pfizer and GlaxoSmithKline BACKGROUND People with schizophrenia have significantly raised mortality but we do not know how these mortality patterns in the UK have changed since the 1990s . AIMS To measure the 25-year mortality of people with schizophrenia with particular focus on changes over time . METHOD Prospect i ve record linkage study of the mortality of a community cohort of 370 people with schizophrenia . RESULTS The cohort had an all-cause st and ardised mortality ratio of 289 ( 95 % CI 247 - 337 ) . Most deaths were from the common causes seen in the general population . Unnatural deaths were concentrated in the first 5 years of follow-up . There was an indication that cardiovascular mortality may have increased relative to the general population ( P = 0.053 ) over the course of the study . CONCLUSIONS People with schizophrenia have a mortality risk that is two to three times that of the general population . Most of the extra deaths are from natural causes . The apparent increase in cardiovascular mortality relative to the general population should be of concern to anyone with an interest in mental health BACKGROUND Schizophrenic patients have high rates of cigarette smoking compared with the general population . We compared sustained-release ( SR ) bupropion with placebo for smoking cessation in patients with schizophrenic disorders . We also examined how antipsychotic class predicts smoking cessation outcomes with bupropion . METHODS Thirty-two subjects meeting DSM-IV criteria for schizophrenia or schizoaffective disorder and nicotine dependence were r and omized to bupropion SR ( BUP , 300 mg/day ) or placebo ( PLA ) . Outcomes included treatment retention , smoking abstinence rates , expired breath carbon monoxide ( CO ) levels , psychotic symptoms , and medication side effects . RESULTS Bupropion significantly increased trial endpoint 7-day point prevalence smoking abstinence rates compared with placebo [ BUP , 8/16 ( 50.0 % ) , PLA , 2/16 ( 12.5 % ) ; chi(2 ) = 5.24 , df = 1 , p < .05 ] , and reduced CO levels during the trial [ Medication x Time interaction ; Z = 3.09 , p < .01 ] . Positive schizophrenia symptoms were not altered by BUP , but negative symptoms were significantly reduced . Atypical antipsychotic drug treatment enhanced smoking cessation responses to BUP . Major side effects were dry mouth , gastrointestinal symptoms , headache , and insomnia . CONCLUSIONS Our results suggest that 1 ) BUP enhances smoking abstinence rates compared with PLA in nicotine-dependent schizophrenic smokers ; 2 ) BUP is well-tolerated and safe for use in these patients ; and 3 ) atypical antipsychotics may enhance smoking cessation outcomes with BUP OBJECTIVE Schizophrenic patients have high rates of cigarette smoking . The authors compared the outcomes of two group psychotherapy programs for smoking cessation in patients with schizophrenia or schizoaffective disorder who were also treated with the nicotine transdermal patch and with either atypical or typical antipsychotic medications . METHOD Forty-five subjects were r and omly assigned to 1 ) the group therapy program of the American Lung Association ( N=17 ) or 2 ) a specialized group therapy program for smokers with schizophrenia ( N=28 ) that emphasized motivational enhancement , relapse prevention , social skills training , and psychoeducation . All subjects participated in 10 weeks of treatment with the nicotine transdermal patch ( 21 mg/day ) and 10 weekly group therapy sessions and continued to receive their pre study atypical ( N=18 ) or typical ( N=27 ) antipsychotic medications . Outcome variables included treatment retention , rate of smoking abstinence , and expired-breath carbon monoxide level . RESULTS Smoking abstinence rates did not differ in the two group therapy programs . However , atypical antipsychotic agents , in combination with the nicotine transdermal patch , significantly enhanced the rate of smoking cessation ( 55.6 % in the atypical agent group versus 22.2 % in the typical group ) , which was reflected by a significant effect of atypical versus typical agents on carbon monoxide levels . Risperidone and olanzapine were associated with the highest quit rates . CONCLUSIONS The results suggest that 1 ) smoking cessation rates with the nicotine transdermal patch are modest in schizophrenia , 2 ) specialized group therapy for schizophrenic patients is not significantly different from American Lung Association group therapy in its effect on smoking cessation , and 3 ) atypical agents may be superior to typical agents in combination with the nicotine transdermal patch for smoking cessation in schizophrenia Schizophrenia is characterized by cognitive deficits which persist after acute symptoms have been treated or resolved . Transcranial direct current stimulation ( tDCS ) has been reported to improve cognition and reduce smoking craving in healthy subjects but has not been as carefully evaluated in a r and omized controlled study for these effects in schizophrenia . We conducted a r and omized double-blind , sham-controlled study of the effects of 5 sessions of tDCS ( 2 milliamps for 20minutes ) on cognition , psychiatric symptoms , and smoking and cigarette craving in 37 out patients with schizophrenia or schizoaffective disorder who were current smokers . Thirty subjects provided evaluable data on the MATRICS Consensus Cognitive Battery ( MCCB ) , with the primary outcome measure , the MCCB Composite score . Active compared to sham tDCS subjects showed significant improvements after the fifth tDCS session in MCCB Composite score ( p=0.008 ) and on the MCCB Working Memory ( p=0.002 ) and Attention-Vigilance ( p=0.027 ) domain scores , with large effect sizes . MCCB Composite and Working Memory domain scores remained significant at Benjamini-Hochberg corrected significance levels ( α=0.05 ) . There were no statistically significant effects on secondary outcome measures of psychiatric symptoms ( PANSS scores ) , hallucinations , cigarette craving , or cigarettes smoked . The positive effects of tDCS on cognitive performance suggest a potential efficacious treatment for cognitive deficits in partially recovered chronic schizophrenia out patients that should be further investigated Background People with mental illness have higher rates of smoking than the general population and are at greater risk of smoking-related death and disability . In smokers from the general population , electronic cigarettes ( e-cigarettes ) have been shown to have a similar effect on quit rates as nicotine replacement therapy , but little is known about their effect in smokers with mental illness . Methods Secondary analysis of data from the ASCEND trial involving 657 dependent adult smokers motivated to quit , r and omised to 16 mg nicotine e-cigarette , 21 mg nicotine patch , or 0 mg nicotine e-cigarette , with minimal behavioural support . Using self-reported medication use and the Anatomical Therapeutic Chemical Classification System , we identified 86 participants with mental illness and analysed their cessation and smoking reduction outcomes . Results For e-cigarettes alone , and all interventions pooled , there was no statistically significant difference in biochemically verified quit rates at six months between participants with and without mental illness , nor in smoking reduction , adverse events , treatment compliance , or acceptability . Rates of relapse to smoking were higher in participants with mental illness . Among this group , differences between treatments were not statistically significant for cessation ( patch 14 % [ 5/35 ] , 16 mg e-cigarette 5 % [ 2/39 ] , 0 mg e-cigarette 0 % [ 0/12 ] , p = 0.245 ) , adverse events or relapse rates . However , e-cigarette users had higher levels of smoking reduction , treatment compliance , and acceptability . Conclusions The use of e-cigarettes for quitting appears to be equally effective , safe , and acceptable for people with and without mental illness . For people with mental illness , e-cigarettes may be as effective and safe as patches , yet more acceptable , and associated with greater smoking reduction . Trial registration Australian New Zeal and Clinical trials Registry , number : ACTRN12610000866000 BACKGROUND Electronic cigarettes ( e-cigarettes ) can deliver nicotine and mitigate tobacco withdrawal and are used by many smokers to assist quit attempts . We investigated whether e-cigarettes are more effective than nicotine patches at helping smokers to quit . METHODS We did this pragmatic r and omised-controlled superiority trial in Auckl and , New Zeal and , between Sept 6 , 2011 , and July 5 , 2013 . Adult ( ≥18 years ) smokers wanting to quit were r and omised ( with computerised block r and omisation , block size nine , stratified by ethnicity [ Māori ; Pacific ; or non-Māori , non-Pacific ] , sex [ men or women ] , and level of nicotine dependence [ > 5 or ≤5 Fagerström test for nicotine dependence ] ) in a 4:4:1 ratio to 16 mg nicotine e-cigarettes , nicotine patches ( 21 mg patch , one daily ) , or placebo e-cigarettes ( no nicotine ) , from 1 week before until 12 weeks after quit day , with low intensity behavioural support via voluntary telephone counselling . The primary outcome was biochemically verified continuous abstinence at 6 months ( exhaled breath carbon monoxide measurement < 10 ppm ) . Primary analysis was by intention to treat . This trial is registered with the Australian New Zeal and Clinical Trials Registry , number ACTRN12610000866000 . FINDINGS 657 people were r and omised ( 289 to nicotine e-cigarettes , 295 to patches , and 73 to placebo e-cigarettes ) and were included in the intention-to-treat analysis . At 6 months , verified abstinence was 7·3 % ( 21 of 289 ) with nicotine e-cigarettes , 5·8 % ( 17 of 295 ) with patches , and 4·1 % ( three of 73 ) with placebo e-cigarettes ( risk difference for nicotine e-cigarette vs patches 1·51 [ 95 % CI -2·49 to 5·51 ] ; for nicotine e-cigarettes vs placebo e-cigarettes 3·16 [ 95 % CI -2·29 to 8·61 ] ) . Achievement of abstinence was substantially lower than we anticipated for the power calculation , thus we had insufficient statistical power to conclude superiority of nicotine e-cigarettes to patches or to placebo e-cigarettes . We identified no significant differences in adverse events , with 137 events in the nicotine e-cigarettes group , 119 events in the patches group , and 36 events in the placebo e-cigarettes group . We noted no evidence of an association between adverse events and study product . INTERPRETATION E-cigarettes , with or without nicotine , were modestly effective at helping smokers to quit , with similar achievement of abstinence as with nicotine patches , and few adverse events . Uncertainty exists about the place of e-cigarettes in tobacco control , and more research is urgently needed to clearly establish their overall benefits and harms at both individual and population levels . FUNDING Health Research Council of New Zeal and OBJECTIVE Virtually no clinical trials for smoking cessation have been undertaken in bipolar disorder . Varenicline has shown efficacy for smoking cessation , but warnings about neuropsychiatric adverse events have been issued . We assessed the efficacy and safety of varenicline in euthymic bipolar subjects motivated to quit smoking . METHOD Clinical ly stable adult patients with DSM-IV bipolar disorder ( n = 60 ) who smoked ≥ 10 cigarettes per day were r and omized to a 3-month , double-blind , placebo-controlled varenicline trial and a 3-month follow-up . Study enrollment was completed from February 2010 through March 2013 . Varenicline was dosed using st and ard titration , and smoking cessation counseling was provided to all patients . The primary outcome was defined as a 7-day point prevalence of self-reported no smoking verified by expired carbon monoxide level < 10 ppm at 12 weeks . Psychopathology and side-effects were assessed at each visit . RESULTS At 3 months ( end of treatment ) , significantly more subjects quit smoking with varenicline ( n/n = 15/31 , 48.4 % ) than with placebo ( n/n = 3/29 , 10.3 % ) ( OR = 8.1 ; 95 % CI , 2.03 - 32.5 ; P < .002 ) . At 6 months , 6 of 31 varenicline-treated subjects ( 19.4 % ) remained abstinent compared to 2 of 29 ( 6.90 % ) assigned to placebo ( OR = 3.2 ; 95 % CI , 0.60 - 17.6 ; P = .17 ) . Psychopathology scores remained stable . Ten serious adverse events occurred ( n = 6 , varenicline ; n = 4 , placebo ) . Abnormal dreams occurred significantly more often in varenicline-treated subjects ( n/n = 18/31 , 61.3 % ) than in those receiving placebo ( n/n = 9/29 , 31 % ; Fisher exact test , P = .04 ) . Eight varenicline-treated and 5 placebo-assigned subjects expressed fleeting suicidal ideation , a nonsignificant difference . CONCLUSIONS Varenicline shows efficacy for initiating smoking cessation in bipolar patients , but medication trials of longer duration are warranted for maintaining abstinence . Vigilance for neuropsychiatric adverse events is prudent when initiating varenicline for smoking cessation in this patient population . TRIAL REGISTRATION Clinical Trials.gov identifier : NCT01010204 The purpose of this study was to investigate the effect of adding sustained-release ( SR ) bupropion to cognitive behavioral therapy ( CBT ) on smoking behavior and stability of psychiatric symptoms in patients with schizophrenia . We conducted a 3-month , double-blind , placebo-controlled trial of bupropion SR , 150 mg/day , added to a concurrent CBT program with 3-month follow-up in 19 stable out patients with schizophrenia who wanted to quit smoking . Eighteen subjects completed the trial . Bupropion treatment was associated with significantly greater reduction in smoking , as measured by self-report verified by expired-air carbon monoxide ( 6/9 subjects , 66 % ) , than placebo ( 1/9 subjects , 11 % ) during the 3-month active treatment period and the 3-month follow-up period . One subject in the bupropion group ( 11 % ) and no subjects in the placebo group achieved sustained tobacco abstinence for the 6-month trial . Bupropion treatment was associated with improvement in negative symptoms and greater stability of psychotic and depressive symptoms , compared with placebo , during the quit attempt . Subjects in the bupropion group experienced significant weight loss , compared with those on placebo during the smoking cessation attempt . These data suggest that bupropion SR , 150 mg/day , combined with CBT , may facilitate smoking reduction in patients with schizophrenia while stabilizing psychiatric symptoms during a quit attempt BACKGROUND Long-term success rates of smoking cessation programs for patients with schizophrenia are unknown . This study , conducted between June 2001 and November 2002 , evaluated the rate of smoking cessation and reduction in patients with schizophrenia ( DSM-IV ) 2 years after they had participated in a smoking cessation study in order to determine whether subjects who significantly reduced smoking during the original trial resumed their previous level of smoking at 2 years . METHOD Two years following a double-blind placebo-controlled trial of bupropion sustained release , 150 mg/day , added to cognitive-behavioral therapy for smoking cessation in patients with schizophrenia , subjects were interviewed , medical charts were review ed , and carbon monoxide in expired air was measured . RESULTS Seventeen of 18 subjects completed the follow-up assessment . More subjects were abstinent ( 22 % [ N = 4 ] ) at the 2-year follow-up than were abstinent at the end of the trial ( 6 % [ N = 1 ] ) . Subjects who achieved significant smoking reduction during the trial were more likely to be abstinent at 2 years ( 4/7 ) than those who did not significantly reduce smoking during the trial ( 0/11 ) ( chi(2 ) = 8.1 , p < .005 ) . Most subjects who achieved > or = 50 % reduction in smoking at the end of the trial maintained at least that level of reduction at 2 years . Smoking reduction during the treatment intervention was correlated with smoking reduction at follow-up ( r = 0.60 , p = .01 ) . CONCLUSION The results from this naturalistic study suggest that behavior changes achieved in smoking cessation programs for patients with schizophrenia may be durable and may predict future smoking behavior . We conclude that further investigation into the relationship between smoking reduction and future smoking cessation in special population s is indicated INTRODUCTION People with severe mental disorders typically experience a range of health problems ; consequently , interventions addressing multiple health behaviors may provide an efficient way to tackle this major public health issue . This two-arm r and omized controlled trial among people with psychotic disorders examined the efficacy of nicotine replacement therapy ( NRT ) plus either a face-to-face or predominantly telephone delivered intervention for smoking cessation and cardiovascular disease ( CVD ) risk reduction . METHODS Following baseline assessment and completion of a common , individually delivered 90-minute face-to-face intervention , participants ( n = 235 ) were r and omized to receive NRT plus : ( 1 ) a " Healthy Lifestyles " intervention for smoking cessation and CVD risk behaviors or ( 2 ) a predominantly telephone-based intervention ( design ed to control for NRT provision , session frequency , and other monitoring activities ) . Research assistants blind to treatment allocation performed assessment s at 15 weeks ( mid-intervention ) and 12 months after baseline . RESULTS There were no significant differences between intervention conditions in CVD risk or smoking outcomes at 15 weeks or 12 months , with improvements in both conditions ( eg , 12 months : 6.4 % confirmed point prevalence abstinence rate ; 17 % experiencing a 50 % or greater smoking reduction ; mean reduction of 8.6 cigarettes per day ; mean improvement in functioning of 9.8 points ) . CONCLUSIONS The health disparity experienced by people with psychotic disorders is high . Face-to-face Healthy Lifestyle interventions appear to be feasible and somewhat effective . However , given the accessibility of telephone delivered interventions , potentially combined with lower cost , further studies are needed to evaluate telephone delivered smoking cessation and lifestyle interventions for people with psychotic disorders OBJECTIVE Effective smoking cessation treatments are needed for patients with schizophrenia , who , compared with the general population , have high rates of cigarette smoking and more difficulty quitting . We evaluated the safety and efficacy of varenicline for smoking cessation in out patients with stable schizophrenia or schizoaffective disorder . METHOD In this 12-week , r and omized , double-blind , multicenter trial ( May 8 , 2008 , to April 1 , 2010 ) , 127 smokers ( ≥ 15 cigarettes/d ) with DSM-IV-confirmed schizophrenia or schizoaffective disorder received varenicline or placebo ( 2:1 ratio ) . The primary outcome was safety and tolerability of varenicline assessed by adverse events frequency and changes in ratings on the Positive and Negative Syndrome Scale and other psychiatric scales from baseline to 24 weeks . Abstinence was defined as no smoking 7 days prior to weeks 12 and 24 , verified by carbon monoxide level . RESULTS Eighty-four participants received varenicline ; 43 , placebo . At 12 weeks ( end of treatment ) , 16/84 varenicline-treated patients ( 19.0 % ) met smoking cessation criteria versus 2/43 ( 4.7 % ) for placebo ( P = .046 ) . At 24 weeks , 10/84 ( 11.9 % ) varenicline-treated and 1/43 ( 2.3 % ) placebo-treated patients , respectively , met abstinence criteria ( P = .090 ) . Total adverse event rates were similar between groups , with no significant changes in symptoms of schizophrenia or in mood and anxiety ratings . Rates of suicidal ideation adverse events were 6.0 % ( varenicline ) and 7.0 % ( placebo ) ( P = 1.0 ) . There was 1 suicide attempt by a varenicline patient with a lifetime history of similar attempts and no completed suicides . CONCLUSIONS Varenicline was well tolerated , with no evidence of exacerbation of symptoms , and was associated with significantly higher smoking cessation rates versus placebo at 12 weeks . Our findings suggest varenicline is a suitable smoking cessation therapy for patients with schizophrenia or schizoaffective disorder . TRIAL REGISTRATION Clinical Trials.gov identifier : NCT00644969 Rationale Individuals with schizophrenia have high smoking-related morbidity and mortality rates and need powerful and innovative smoking cessation interventions . Objectives This proof-of-concept study investigated the feasibility and initial efficacy of combining a contingency management intervention with bupropion to reduce smoking in people with schizophrenia . Methods Using a double-blind , placebo-controlled , between-groups design , 57 non-treatment-seeking participants were r and omized to receive 300 mg/day bupropion or placebo . One week later , participants were r and omized to a contingency management ( CM ) intervention in which reductions in urinary cotinine levels were reinforced , or a non-contingent reinforcement ( NR ) condition in which session attendance was reinforced , regardless of cotinine level . Over the 22-day study period , participants visited the laboratory approximately three times per week to provide urine sample s for analysis of cotinine levels , to give breath sample s for analysis of carbon monoxide ( CO ) levels , and to report number of cigarettes smoked per day , nicotine withdrawal symptoms , cigarette craving , and psychiatric symptoms . Results Cotinine and CO levels significantly decreased during the study period in participants r and omized to the CM condition , but not the NR condition . Bupropion did not reduce cotinine levels or increase the efficacy of CM . Cigarette craving and psychiatric symptom levels significantly decreased during the study in all groups . Conclusions The results of this study indicate the efficacy and feasibility of this CM intervention for reducing smoking in individuals with schizophrenia Abstract : The objective of this study was to examine the efficacy of bupropion for smoking cessation in patients with schizophrenia . Adults with schizophrenia who smoked more than 10 cigarettes per day and wished to try to quit smoking were recruited from community mental health centers , enrolled in a 12-week group cognitive behavioral therapy intervention , and r and omly assigned to receive either bupropion sustained-release 300 mg/d or identical placebo . Fifty-three adults , 25 on bupropion and 28 on placebo , were r and omized , completed at least 1 postbaseline assessment and were included in the analysis . The primary outcome measures were 7-day point prevalence abstinence in the week after the quit date ( week 4 ) and at the end of the intervention ( week 12 ) . Subjects in the bupropion group were significantly more likely to be abstinent for the week after the quit date ( 36 % [ 9/25 ] vs. 7 % [ 2/28 ] , P = 0.016 ) and at end of the intervention ( 16 % [ 4/25 ] vs. 0 % , P = 0.043 ) . Subjects in the bupropion group also had a higher rate of 4-week continuous abstinence ( weeks 8 - 12 ) ( 16 % [ 4/25 ] vs. 0 % , P = 0.043 ) and a longer duration of abstinence ( 4.2 [ 3.2 ] weeks vs. 1.8 [ 0.96 ] weeks , t = 2.30 , P = 0.037 ) . The effect of bupropion did not persist after discontinuation of treatment . Subjects in the bupropion group had no worsening of clinical symptoms and had a trend toward improvement in depressive and negative symptoms . We conclude that bupropion does not worsen clinical symptoms of schizophrenia and is modestly effective for smoking cessation in patients with schizophrenia . The relapse rate is high after treatment discontinuation The objective of this study was to examine whether there is a benefit of adding bupropion SR to high-dose combination nicotine replacement therapy ( NRT ) and weekly group cognitive behavioral therapy ( CBT ) for smoking reduction or cessation in schizophrenia . Fifty-one adult smokers with schizophrenia were r and omly assigned to a 12-week trial of bupropion SR 300 mg/d or placebo added to transdermal nicotine patch , nicotine polacrilex gum , and CBT . The treatment goal was smoking cessation . The primary outcome measure was biochemically confirmed 7-day point-prevalence of 50 % to 100 % smoking reduction at week 12 . Secondary outcomes were biochemically confirmed tobacco abstinence and change from baseline in expired air carbon monoxide ( CO ) and psychiatric symptoms . Subjects on bupropion + NRT had a greater rate of 50 % to 100 % smoking reduction at weeks 12 ( 60 % vs. 31 % ; P = 0.036 ) and 24 , a lower expired air CO in the treatment and follow-up periods , ( F = 13.8 ; P < 0.001 ) and a greater continuous abstinence rate at week 8 , before NRT taper , ( 52 % vs. 19 % ; P = 0.014 ) . However , relapse rates in subjects on bupropion + dual NRT were 31 % during NRT taper ( weeks 8 - 12 ) and 77 % at the 12-month follow-up . Abstinence rates did not differ by treatment group at weeks 12 ( 36 % vs. 19 % ) , 24 ( 20 % vs. 8 % ) , or 52 ( 12 % vs. 8 % ) . Because abstinence rates were high during treatment with combination pharmacotherapy and relapse rates were very high during taper and after discontinuation of treatment , study of longer term treatment with combination pharmacotherapy and CBT for sustained abstinence is warranted in those who attain initial abstinence with this intervention Compared to the general population , smokers with schizophrenia ( SCZ ) have reduced success in quitting smoking with usual approaches . This study tested two manualized behavioral counseling approaches-Treatment of Addiction to Nicotine in Schizophrenia ( TANS ) or Medication Management (MM)-for smokers who were motivated to quit . Individual counseling sessions were provided by mental health clinicians in mental health setting s , along with nicotine patch . The two treatments varied in intensity and frequency of sessions . Eighty-seven subjects were r and omized and attended at least one treatment session . Twenty-one percent ( n = 18 ) of participants had continuous abstinence at 12 weeks after the target quit date , which was not significantly different between conditions ( 15.6 % TANS vs. 26.2 % MM , chi(2 ) = 1.50 , p = .221 ) . Smokers in both groups significantly reduced smoking as measured by cigarettes per day and expired carbon monoxide . Findings support that mental health clinicians can be trained to effectively help smokers with SCZ maintain tobacco abstinence There have been many studies of smoking cessation using nicotine replacement therapy ( NRT ) with schizophrenic patients , but none exploring the smoking-reduction effects of varying doses of NRT in long-stay patients with schizophrenia . This study aim ed to examine the effect of different doses of the nicotine transdermal patch on smoking-reduction and cessation outcomes in long-term hospitalized schizophrenic patients . A total of 184 subjects participated in a r and omized , controlled , double-blind 8-week clinical trial . Participants were r and omized into two groups using two different doses of NRT : a high-dose NRT group ( 31.2 mg for the first 4 weeks , then 20.8 mg for 4 weeks , n = 92 ) or a low-dose NRT group ( 20.8 mg for 8 weeks , n = 92 ) . The 7-day point prevalence of abstinence was 2.7 % ( 5/184 ) . Participants in the low-dose NRT group reduced smoking by 3.1 more cigarettes on average than those in the high-dose group ( p = 0.005 ) . However , a repeated measures analysis of variance revealed that the main effect of changes in the number of cigarettes smoked , comparing the two types of treatment across periods , was not significant ( p = 0.35 , partial eta square = 0.018 ) . In summary , among a cohort of chronic institutionalized schizophrenic patients , smoking cessation and reduction outcomes were not correlated with NRT dose , and the cessation rate was much lower than rates in similar studies . It indicates that long-term hospitalized schizophrenic patients have more difficulties with quitting smoking . More effective integrative smoking cessation programs should be addressed for these patients The authors examined whether smoking while wearing a transdermal nicotine patch over 32 h was well-tolerated and led to smoking suppression in heavy smokers with schizophrenia . In a crossover design , 10 male veteran smokers with schizophrenia were admitted for two brief inpatient stays to smoke while wearing a transdermal nicotine or placebo patch . Carbon monoxide in expired air , self-reported cigarettes per day , nicotine plasma levels , and psychiatric ratings were measured . Nicotine levels increased during active patch treatment , without evidence of nicotine toxicity . Psychiatric symptoms , carbon monoxide and cigarettes per day did not change , although eight subjects had a decrease in expired carbon monoxide on the active patch . Dyskinesias showed a small , but significant , increase during smoking plus active patch . The heaviest smokers ( identified by placebo phase nicotine plasma level or CO level above group median ; n = 5 ) had a statistically significant decrease in expired carbon monoxide of at least 20 % . Smoking while wearing the nicotine patch over 32 h was well tolerated . Significant decreases in carbon monoxide smoking indices were seen for the heaviest smokers . These findings suggest further investigation of a smoking reduction intervention in this population Abstract Adults with any DSM-IV diagnosed mental illness smoke nearly half of the cigarettes consumed in the U.S. ( Lasser et al. 2000 ) . This study compared two smoking cessation interventions for persons with schizophrenia or other serious mental illness because national data suggests that : ( 1 ) they smoke at two to three times the rate of the general population ; ( 2 ) cessation interventions for this population are understudied ; ( 3 ) most cessation studies exclude persons with serious mental illness ; and ( 4 ) cessation results in public health care savings and disposable income savings for clients . This study included a large number of persons with serious mental illness ( N = 181 ) who were r and omly assigned to one of three groups : contingent reinforcement ( CR ) , CR plus nicotine patch ( 21 mg , CR+NRT ) for 16 weeks , and a minimal intervention , self-quit control group . These participants were followed for 36 weeks . CR was accomplished with escalating financial compensation for achieving and maintaining abstinence as verified by expired carbon monoxide ( CO ) . Quit rates , as measured by expired CO , were higher and discordant with saliva cotinine quit rates . Cotinine showed lower quit rates and small differences between intervention and control partici pants at weeks 20 and 36 . There was , however , evidence of reduced smoking and importantly , no evidence of psychiatric exacerbation R and omised controlled trials , when appropriately design ed , conducted , and reported , represent the gold st and ard in evaluating healthcare interventions . However , r and omised trials can yield biased results if they lack method ological rigour [ 1 ] . To assess a trial accurately , readers of a published report need complete , clear , and transparent information on its methodology and findings . Unfortunately , attempted assessment s frequently fail because authors of many trial reports neglect to provide lucid and complete descriptions of that critical information [ 2,3,4 ] . That lack of adequate reporting fuelled the development of the original CONSORT ( Consoli date d St and ards of Reporting Trials ) statement in 1996 [ 5 ] and its revision five years later [ 6,7,8 ] . While those statements improved the reporting quality for some r and omised controlled trials [ 9,10 ] , many trial reports still remain inadequate [ 2 ] . Furthermore , new method ological evidence and additional experience has accumulated since the last revision in 2001 . Consequently , we organised a CONSORT Group meeting to up date the 2001 statement [ 6,7,8 ] . We introduce here the result of that process , CONSORT 2010 . OBJECTIVE Despite extremely high rates of smoking among individuals with psychotic disorders and the associated financial and health costs , few studies have investigated the efficacy of smoking cessation interventions among this group . The purpose of this study was to compare an integrated psychological and nicotine replacement therapy intervention for people with a psychotic disorder with routine care alone . METHOD The authors recruited 298 regular smokers with a psychotic disorder residing in the community and r and omly assigned them to a routine care comparison condition ( N=151 ) or an eight-session , individually administered smoking cessation intervention ( N=147 ) , which consisted of nicotine replacement therapy , motivational interviewing , and cognitive behavior therapy . Outcome variables included continuous and point-prevalence abstinence rates , smoking reduction status , and changes in symptoms and functioning . RESULTS While there were no overall differences between the treatment group and comparison group in abstinence rates , a significantly higher proportion of smokers who completed all treatment sessions stopped smoking at each of the follow-up occasions ( point-prevalence rates : 3 months , 30.0 % versus 6.0 % ; 6 months , 18.6 % versus 4.0 % ; and 12 months , 18.6 % versus 6.6 % ) . Smokers who completed all treatment sessions were also more likely to have achieved continuous abstinence at 3 months ( 21.4 % versus 4.0 % ) . There was a strong dose-response relationship between treatment session attendance and smoking reduction status , with one-half of those who completed the intervention program achieving a 50 % or greater reduction in daily cigarette consumption across the follow-ups , relative to less than one-fifth of the comparison subjects . There was no evidence of any associated deterioration in symptoms or functioning . CONCLUSIONS These findings demonstrate the utility of a nicotine replacement therapy plus motivational interviewing/cognitive behavior therapy smoking cessation intervention among individuals with a psychotic disorder . Further development of more efficacious interventions is required for those who do not respond to existing interventions BACKGROUND People with severe mental ill health are three times more likely to smoke but typically do not access conventional smoking cessation services , contributing to widening health inequalities and reduced life expectancy . We aim ed to pilot an intervention targeted at smokers with severe mental ill health and to test methods of recruitment , r and omisation , and follow up before implementing a full trial . METHODS The Smoking Cessation Intervention for Severe Mental Ill Health Trial ( SCIMITAR ) is a pilot r and omised controlled trial of a smoking cessation strategy design ed specifically for people with severe mental ill health , to be delivered by mental health nurses and consisting of behavioural support and drugs , compared with a conventional smoking cessation service ( ie , usual care ) . Adults ( aged 18 years or older ) with bipolar disorder or schizophrenia , who were current smokers , were recruited from NHS primary care and mental health setting s in the UK ( York , Scarborough , Hull , and Manchester ) . Eligible participants were r and omly allocated to either usual care ( control group ) or usual care plus the bespoke smoking cessation strategy ( intervention group ) . R and omisation was done via a central telephone system , with computer-generated r and om numbers . We could not mask participants , family doctors , and research ers to the treatment allocation . Our primary outcome was smoking status at 12 months , verified by carbon monoxide measurements or self-report . Only participants who provided an exhaled CO measurement or self-reported their smoking status at 12 months were included in the primary analysis . The trial is registered at IS RCT N.com , number IS RCT N79497236 . FINDINGS Of 97 people recruited to the pilot study , 51 were r and omly allocated to the control group and 46 were assigned to the intervention group . Participants engaged well with the bespoke smoking cessation strategy , but no individuals assigned to usual care accessed NHS smoking cessation services . At 12 months , 35 ( 69 % ) controls and 33 ( 72 % ) people assigned to the intervention group provided a CO measurement or self-reported their smoking status . Smoking cessation was highest among individuals who received the bespoke intervention ( 12/33 [ 36 % ] vs 8/35 [ 23 % ] ; adjusted odds ratio 2·9 , 95 % CI 0·8 - 10·5 ) . INTERPRETATION We have shown the feasibility of recruiting and r and omising people with severe mental ill health in a trial of this nature . The level of engagement with a bespoke smoking cessation strategy was higher than with a conventional approach . The effectiveness and safety of a smoking cessation programme design ed particularly for people with severe mental ill health should be tested in a fully powered r and omised controlled trial . FUNDING National Institute of Health Research Health Technology Assessment Programme |
14,029 | 21,951,607 | Meta- analysis of the literature confirmed a difference in amputation rate between patients with tissue loss and rest pain . | Background Autologous bone marrow-derived stem cells have been ascribed an important therapeutic role in No-Option Critical limb Ischemia ( NO-CLI ) .
One primary endpoint for evaluating NO-CLI therapy is major amputation ( AMP ) , which is usually combined with mortality for AMP-free survival ( AFS ) .
Only a trial which is double blinded can eliminate physician and patient bias as to the timing and reason for AMP . | OBJECTIVES Cell therapy is a novel experimental treatment modality for patients with critical limb ischemia ( CLI ) of the lower extremities and no other established treatment options . This study was conducted to assess the safety and clinical efficacy of intramuscular injection of autologous tissue repair cells ( TRCs ) . METHODS A prospect i ve , r and omized double-blinded , placebo controlled , multicenter study ( RESTORE-CLI ) was conducted at 18 centers in the United States in patients with CLI and no option for revascularization . Enrollment of 86 patients began in April 2007 and ended in February 2010 . For the prospect ively planned interim analysis , conducted in February 2010 , 33 patients had the opportunity to complete the trial ( 12 months of follow-up ) , and 46 patients had completed at least 6 months of follow-up . The interim analysis included analysis of both patient population s. An independent physician performed the bone marrow or sham control aspiration . The aspirate was processed in a closed , automated cell manufacturing system for approximately 12 days to generate the TRC population of stem and progenitor cells . An average of 136 ± 41 × 10(6 ) total viable cells or electrolyte ( control ) solution were injected into 20 sites in the ischemic lower extremity . The primary end point was safety as evaluated by adverse events , and serious adverse events as assessed at multiple follow-up time points . Clinical efficacy end points included major amputation-free survival and time to first occurrence of treatment failure ( defined as any of the following : major amputation , death , de novo gangrene , or doubling of wound size ) , as well as major amputation rate and measures of wound healing . RESULTS There was no difference in adverse or serious adverse events between the two groups . Statistical analysis revealed a significant increase in time to treatment failure ( log-rank test , P = .0053 ) and amputation-free survival in patients receiving TRC treatment , ( log-rank test , P = .038 ) . Major amputation occurred in 19 % of TRC-treated patients compared to 43 % of controls ( P = .14 , Fisher exact test ) . There was evidence of improved wound healing in the TRC-treated patients when compared with controls at 12 months . CONCLUSIONS Intramuscular injection of autologous bone marrow-derived TRCs is safe and decreases the occurrence of clinical events associated with disease progression when compared to placebo in patients with lower extremity CLI and no revascularization options This study evaluated the efficacy and safety of intramuscular administration of NV1FGF , a plasmid-based angiogenic gene delivery system for local expression of fibroblast growth factor 1 ( FGF-1 ) , versus placebo , in patients with critical limb ischemia ( CLI ) . In a double-blind , r and omized , placebo-controlled , European , multinational study , 125 patients in whom revascularization was not considered to be a suitable option , presenting with nonhealing ulcer(s ) , were r and omized to receive eight intramuscular injections of placebo or 2.5 ml of NV1FGF at 0.2 mg/ml on days 1 , 15 , 30 , and 45 ( total 16 mg : 4 x 4 mg ) . The primary end point was occurrence of complete healing of at least one ulcer in the treated limb at week 25 . Secondary end points included ankle brachial index ( ABI ) , amputation , and death . There were 107 patients eligible for evaluation . Improvements in ulcer healing were similar for use of NV1FGF ( 19.6 % ) and placebo ( 14.3 % ; P = 0.514 ) . However , the use of NV1FGF significantly reduced ( by twofold ) the risk of all amputations [ hazard ratio ( HR ) 0.498 ; P = 0.015 ] and major amputations ( HR 0.371 ; P = 0.015 ) . Furthermore , there was a trend for reduced risk of death with the use of NV1FGF ( HR 0.460 ; P = 0.105 ) . The adverse event incidence was high , and similar between the groups . In patients with CLI , plasmid-based NV1FGF gene transfer was well tolerated , and result ed in a significantly reduced risk of major amputation when compared with placebo OBJECTIVES We have previously reported the results of a dose-finding phase II trial showing that HGF angiogenic gene therapy can increase TcPO2 compared with placebo in patients with critical limb ischemia ( CLI ) . The purpose of this r and omized placebo controlled multi-center trial was to further assess the safety and clinical efficacy of a modified HGF gene delivery technique in patients with CLI and no revascularization options . METHODS Patients with lower extremity ischemic tissue loss ( Rutherford 5 and 6 ) received three sets of eight intramuscular injections every 2 weeks of HGF plasmid under duplex ultrasound guidance . Injection locations were individualized for each patient based on arteriographically defined vascular anatomy . Primary safety end point was incidence of adverse events ( AE ) or serious adverse events ( SAE ) . Clinical end points included change from baseline in toe brachial index ( TBI ) , rest pain assessment by a 10 cm visual analogue scale ( VAS ) as well as wound healing , amputation , and survival at 3 and 6 months . RESULTS R and omization ratio was 3:1 HGF ( n = 21 ) vs placebo ( n = 6 ) . Mean age was 76 ± 2 years , with 56 % male and 59 % diabetic . There was no difference in demographics between groups . There was no difference in AEs or SAEs , which consisted mostly of transient injection site discomfort , worsening of CLI , and intercurrent illnesses . Change in TBI significantly improved from baseline at 6 months in the HGF-treated group compared with placebo ( 0.05 ± 0.05 vs -0.17 ± 0.04 ; P = .047 ) . Change in VAS from baseline at 6 months was also significantly improved in the HGF-treated group compared with placebo ( -1.9 ± 1.3 vs + 0.06 ± 0.2 ; P = .04 ) . Complete ulcer healing at 12 months occurred in 31 % of the HGF group and 0 % of the placebo ( P = .28 ) There was no difference in major amputation of the treated limb ( HGF 29 % vs placebo 33 % ) or mortality at 12 months ( HGF 19 % vs placebo 17 % ) between groups . CONCLUSION HGF gene therapy using a patient vascular anatomy specific delivery technique appears safe , maintained limb perfusion , and decreased rest pain in patients with CLI compared with placebo . A larger study to assess the efficacy of this therapy on more clinical ly relevant end points is warranted Background The aim of the present study was to develop a risk-scoring method for prediction of immediate postoperative outcome after infrainguinal surgical revascularization for critical limb ischemia . Methods The Finnvasc registry included data on 3,925 infrainguinal surgical revascularization procedures . This data base was r and omly divided into a derivation and a validation data set of similar sizes . Results In the overall series , 30-day postoperative mortality and major amputation rates were 3.1 % and 6.3 % , respectively . The 30-day postoperative mortality and /or limb-loss rate was 9.2 % . Diabetes , coronary artery disease , foot gangrene , and urgent operation were independent predictors of 30-day postoperative mortality and /or major lower-limb amputation . A risk score was developed by assigning 1 point each to the latter risk factors . In the derivation data set , the 30-day postoperative mortality/amputation rates in patients with scores of 0 , 1 , 2 , 3 , and 4 were 7.7 % , 6.4 % , 11.1 % , 20.4 % , and 27.3 % , respectively , ( P < 0.0001 ) ; mortality rates were 1.3 % , 2.3 % , 4.1 % , 7.7 % , and 12.1 % , respectively , ( P < 0.0001 ) ; and major amputation rates were 6.4 % , 4.3 % , 7.1 % , 12.7 % , and 18.2 % , respectively , ( P < 0.0001 ) . In the validation data set , the 30-day postoperative mortality/amputation rates in patients with scores of 0 , 1 , 2 , 3 , and 4 were 4.8 % , 7.5 % , 10.1 % , 15.9 % , and 22.2 % , respectively , ( P < 0.0001 ) ; mortality rates were 0.7 % , 2.3 % , 4.2 % , 5.5 % , and 14.8 % , respectively , ( P < 0.0001 ) ; and major amputation rates were 4.6 % , 5.3 % , 6.4 % , 11.0 % , and 14.0 % , respectively ( P = 0.011 ) . Conclusions This simple risk-scoring method can be useful to stratify the immediate postoperative outcome of patients undergoing infrainguinal surgical revascularization for critical lower-limb ischemia BACKGROUND Patients with critical limb ischaemia have a high rate of amputation and mortality . We tested the hypothesis that non-viral 1 fibroblast growth factor ( NV1FGF ) would improve amputation-free survival . METHODS In this phase 3 trial ( EFC6145/TAMARIS ) , 525 patients with critical limb ischaemia unsuitable for revascularisation were enrolled from 171 sites in 30 countries . All had ischaemic ulcer in legs or minor skin gangrene and met haemodynamic criteria ( ankle pressure < 70 mm Hg or a toe pressure < 50 mm Hg , or both , or a transcutaneous oxygen pressure < 30 mm Hg on the treated leg ) . Patients were r and omly assigned to either NV1FGF at 0·2 mg/mL or matching placebo ( visually identical ) in a 1:1 ratio . R and omisation was done with a central interactive voice response system by block size 4 and was stratified by diabetes status and country . Investigators , patients , and study teams were masked to treatment . Patients received eight intramuscular injections of their assigned treatment in the index leg on days 1 , 15 , 29 , and 43 . The primary endpoint was time to major amputation or death at 1 year analysed by intention to treat with a log-rank test using a multivariate Cox proportional hazard model . This trial is registered with Clinical Trials.gov , number NCT00566657 . FINDINGS 259 patients were assigned to NV1FGF and 266 to placebo . All 525 patients were analysed . The mean age was 70 years ( range 50 - 92 ) , 365 ( 70 % ) were men , 280 ( 53 % ) had diabetes , and 248 ( 47 % ) had a history of coronary artery disease . The primary endpoint or components of the primary did not differ between treatment groups , with major amputation or death in 86 patients ( 33 % ) in the placebo group , and 96 ( 36 % ) in the active group ( hazard ratio 1·11 , 95 % CI 0·83 - 1·49 ; p=0·48 ) . No significant safety issues were recorded . INTERPRETATION TAMARIS provided no evidence that NV1FGF is effective in reduction of amputation or death in patients with critical limb ischaemia . Thus , this group of patients remains a major therapeutic challenge for the clinician . FUNDING Sanofi-Aventis , Paris , France Fifty percent of diabetics ( 7 % of general population ) suffer from peripheral arterial occlusive disease , which may lead to amputation due to critical limb ischemia ( CLI ) . The aim of our study was to prevent major limb amputation ( MLA ) in this group of patients using a local application of autologous bone marrow stem cells ( ABMSC ) concentrate . A total of 96 patients with CLI and foot ulcer ( FU ) were r and omized into groups I and II . Patients in group I ( n = 42 , 36 males , 6 females , 66.2 ± 10.6 years ) underwent local treatment with ABMSC while those in group II ( n = 54 , control , 42 males , 12 females , 64.1 ± 8.6 years ) received st and ard medical care . The frequency of major limb amputation in groups I and II was 21 % and 44 % within the 120 days of follow up , respectively ( p < 0.05 ) . Only in salvaged limbs of group I both toe pressure and toe brachial index increased ( from 22.66 ± 5.32 to 25.63 ± 4.75 mmHg and from 0.14 ± 0.03 to 0.17 ± 0.03 , respectively , mean ± SEM ) . The CD34 + cell counts in bone marrow concentrate ( BMC ) decreased ( correlation , p = 0.024 ) with age , even though there was no correlation between age and healing . An unexpected finding was made of relative , bone marrow lymphopenia in the initial bone marrow concentrates in patients who failed ABMSC therapy ( 21 % of MLA ) . This difference was statistically significant ( p < 0.040 ) . We conclude ABMSC therapy results in 79 % limb salvage in patients suffering from CLI and FU . In the remaining 21 % lymphopenia and thrombocytopenia were identified as potential causative factors , suggesting that at least a partial correction with platelet supplementation may be beneficial BACKGROUND The treatment of rest pain , ulceration , and gangrene of the leg ( severe limb ischaemia ) remains controversial . We instigated the BASIL trial to compare the outcome of bypass surgery and balloon angioplasty in such patients . METHODS We r and omly assigned 452 patients , who presented to 27 UK hospitals with severe limb ischaemia due to infra-inguinal disease , to receive a surgery-first ( n=228 ) or an angioplasty-first ( n=224 ) strategy . The primary endpoint was amputation ( of trial leg ) free survival . Analysis was by intention to treat . The BASIL trial is registered with the National Research Register ( NRR ) and as an International St and ard R and omised Controlled Trial , number IS RCT N45398889 . FINDINGS The trial ran for 5.5 years , and follow-up finished when patients reached an endpoint ( amputation of trial leg above the ankle or death ) . Seven individuals were lost to follow-up after r and omisation ( three assigned angioplasty , two surgery ) ; of these , three were lost ( one angioplasty , two surgery ) during the first year of follow-up . 195 ( 86 % ) of 228 patients assigned to bypass surgery and 216 ( 96 % ) of 224 to balloon angioplasty underwent an attempt at their allocated intervention at a median ( IQR ) of 6 ( 3 - 16 ) and 6 ( 2 - 20 ) days after r and omisation , respectively . At the end of follow-up , 248 ( 55 % ) patients were alive without amputation ( of trial leg ) , 38 ( 8 % ) alive with amputation , 36 ( 8 % ) dead after amputation , and 130 ( 29 % ) dead without amputation . After 6 months , the two strategies did not differ significantly in amputation-free survival ( 48 vs 60 patients ; unadjusted hazard ratio 1.07 , 95 % CI 0.72 - 1.6 ; adjusted hazard ratio 0.73 , 0.49 - 1.07 ) . We saw no difference in health-related quality of life between the two strategies , but for the first year the hospital costs associated with a surgery-first strategy were about one third higher than those with an angioplasty-first strategy . INTERPRETATION In patients presenting with severe limb ischaemia due to infra-inguinal disease and who are suitable for surgery and angioplasty , a bypass-surgery-first and a balloon-angioplasty-first strategy are associated with broadly similar outcomes in terms of amputation-free survival , and in the short-term , surgery is more expensive than angioplasty Bone marrow cell transplantation has been shown to induce angiogenesis and thus improve ischemic artery disease . This study evaluates the effects of intramuscular bone marrow cell transplantation in patients with limb-threatening critical limb ischemia with a very high risk for major amputation . After failed or impossible operative and /or interventional revascularization and after unsuccessful maximum conservative therapy , 51 patients with impending major amputation due to severe critical limb ischemia had autologous bone marrow cells ( BMC ) transplanted into the ischemic leg . Patients 1–12 received Ficoll-isolated bone marrow mononuclear cells ( total cell number 1.1 ± 1.1 × 109 ) , patients 13–51 received point of care isolated bone marrow total nucleated cells ( 3.0 ± 1.7 × 109 ) . Limb salvage was 59 % at 6 months and 53 % at last follow-up ( mean 411 ± 261 days , range 175–1186 ) . Perfusion measured with ankle-brachial index ( ABI ) and transcutaneous oxygen tension ( tcpO2 ) at baseline and after 6 months increased in patients with consecutive limb salvage ( ABI 0.33 ± 0.18 to 0.46 ± 0.15 , tcpO2 12 ± 12 to 25 ± 15 mmHg ) and did not change in patients eventually undergoing major amputation . No difference in clinical outcome between the isolation methods were seen . Clinical ly most important , patients with limb salvage improved from a mean Rutherford category of 4.9 at baseline to 3.3 at 6 months ( p = 0.0001 ) . Analgesics consumption was reduced by 62 % . Total walking distance improved in nonamputees from zero to 40 m. Three severe periprocedural adverse events resolved without sequelae , and no unexpected long-term adverse events occurred . In no-option patients with end-stage critical limb ischemia due to peripheral artery disease , bone marrow cell transplantation is a safe procedure that can improve leg perfusion sufficiently to reduce major amputations and permit durable limb salvage Abstract In a ( negative ) multicenter r and omized trial on management for inoperable critical lower limb ischemia , comparing spinal cord stimulation and best medical treatment , a number of pre-defined factors were analyzed for prognostic value . We included a radiological arterial disease score , modified from the SVS/ISCVS runoff score . The purpose of this analysis was to evaluate clinical factors and commonly used circulatory measurements for prognostic modeling in patients with critical lower limb ischemia . We determined the incidence of amputation and its relation to various pre-defined risk factors . A total of 120 patients with critical limb ischemia were included in the study . The integrity of circulation in the affected limb was evaluated on five levels : suprainguinal , infrainguinal , popliteal , infrapopliteal and pedal . A total radiological arterial disease score was calculated from 1 ( full integrity of circulation ) to 20 ( maximally compromised state ) . We used Cox regression analysis to quantify prognostic effects and differential treatment ( predictive ) effects . Major amputation occurred in 33 % of the patients at 6 months and in 51 % at 2 years . The presence of ischemic skin lesions and the radiological arterial disease score were independent prognostic factors for amputation . Patients with ulcerations or gangrene had a higher amputation risk ( hazard ratio 2.38 , p = 0.018 and 2.30 , p = 0.036 respectively ) as well as patients with a higher radiological arterial disease score ( hazard ratio 1.17 per increment , p = 0.003 ) . We did not observe significant interactions between prognostic factors and the effect of spinal cord stimulation . In conclusion , in patients with critical lower limb ischemia , the presence of ischemic skin lesions and the described radiological arterial disease score can be used to estimate amputation risk BACKGROUND For patients with critical limb ischaemia , spinal-cord stimulation has been advocated for the treatment of ischaemic pain and the prevention of amputation . We compared the efficacy of the addition of spinal-cord stimulation to best medical treatment in a r and omised controlled trial . METHODS 120 patients with critical limb ischaemia not suitable for vascular reconstruction were r and omly assigned either spinal-cord stimulation in addition to best medical treatment or best medical treatment alone . Primary outcomes were mortality and amputation . The primary endpoint was limb survival at 2 years . FINDINGS The mean ( SD ) age of the patients was 72.6 years ( 10.3 ) . Median ( IQR ) follow-up was 605 days ( 244 - 1171 ) . 40 ( 67 % ) of 60 patients in the spinal-cord-stimulator group and 41 ( 68 % ) of 60 patients in the st and ard group were alive at the end of the study , ( p=0.96 ) . There were 25 major amputations in the spinal-cord-stimulator group and 29 in the st and ard group , ( p=0.47 ) . The hazard ratio for survival at 2 years without major amputation in the spinal-cord stimulation group compared with the st and ard group was 0.96 ( 95 % CI 0.61 - 1.51 ) . INTERPRETATION Spinal-cord-stimulation in addition to best medical care does not prevent amputation in patients with critical limb ischaemia PURPOSE Eicosanoids with vasodilating and angiogenic properties have been postulated to be effective therapies for critical leg ischemia ( CLI ) secondary to atherosclerotic peripheral arterial disease . The ability to deliver active drug to the site of action at adequate doses for sufficient duration has been a major limitation in the clinical development of such therapies . Lipo-ecraprost is a lipid-encapsulated prostagl and in E1 prodrug with the potential to deliver active prostagl and in to the site of critical arterial ischemia . The current trial was design ed to test the hypothesis that lipo-ecraprost would improve amputation-free survival in patients with CLI who had no revascularization options . METHODS The study was r and omized , multicenter , double blind , and placebo controlled . Patients who met clinical and hemodynamic criteria were r and omized to receive placebo or lipo-ecraprost ( 60 microg ) administered intravenously on each of 5 days per week , for a total of 8 weeks . The study 's primary endpoint was the rate of a composite end point of death or amputation above the level of the ankle at 180 days ( 6 months ) . RESULTS The study was terminated on a recommendation from the Data and Safety Monitoring Board after the completion of a protocol -specified interim analysis for futility . At the time of termination , 383 of the planned 560 patients had been r and omized , of which 379 received at least one dose of study medication and thus were included in the intention-to-treat population . Twenty-three patients were lost to follow-up and were not available for 6-month assessment s. At 6 months of follow-up , there were 23 amputations in the 177 patients who received placebo , and 29 amputations in the 179 patients r and omized to lipo-ecraprost . At 6 months , 10 deaths had occurred in the placebo group and 18 deaths had occurred in the lipo-ecraprost arm . Changes in lower-extremity hemodynamics over the 6-month study period did not differ between the placebo and lipo-ecraprost treatment arms . CONCLUSION Intensive treatment with lipo-ecraprost failed to modify the 6-month amputation rate in patients with CLI who were not c and i date s for revascularization OBJECTIVE to assess the predictivity of clinical variables in patients with chronic critical leg ischaemia ( CLI ) . Design observational prospect i ve cohort study . METHODS the i.c.a.i . ( ischemia critica degli arti inferiori ) trial data base was used to assess the impact of patients ' history , cardiovascular risk , manifestations of the disease and specific invasive and pharmacological interventions on mortality , amputation rate and persistence of CLI . RESULTS of 1560 patients , 298 died within one year ; at six months 187 were amputees and 746 still suffered from CLI . Prior major vascular events doubled the risk of dying within one year . Previous revascularisation was associated with a lower mortality , but also with a higher probability of amputation . Among cardiovascular risk factors , only diabetes affected prognosis , in terms of increased mortality and lower probability of recovery from CLI . Patients with tissue loss had a higher amputation rate and less probability of recovery . Ankle pressure was predictive of mortality and amputation only when unmeasurable . Patients requiring revascularisation had better chances of recovering from CLI , but not of longer-term survival or limb salvage compared to those in whom surgery was deemed unnecessary . Antiplatelet drugs caused resolution of CLI and decreased the amputation rate by about 1/3 , while the advantage of the test treatment ( alprostadil-alpha-cyclodextrine ) was confined to CLI resolution only . CONCLUSIONS this study documents the high mortality and heterogeneity of patients with CLI . It provides stratification criteria for reliably estimating the achievable benefit in routine practice and for clinical trials BACKGROUND Patients with critical limb ischemia ( CLI ) are a heterogeneous population with respect to risk for mortality and limb loss , complicating clinical decision-making . Endovascular options , compared with bypass , offer a tradeoff between reduced procedural risk and inferior durability . Risk stratified data predictive of amputation-free survival ( AFS ) may improve clinical decision making and allow for better assessment of new technology in the CLI population . METHODS This was a retrospective analysis of prospect ively collected data from patients who underwent infrainguinal vein bypass surgery for CLI . Two data sets were used : the PREVENT III r and omized trial ( n = 1404 ) and a multicenter registry ( n = 716 ) from three distinct vascular centers ( two academic , one community-based ) . The PREVENT III cohort was r and omly assigned to a derivation set ( n = 953 ) and to a validation set ( n = 451 ) . The primary endpoint was AFS . Predictors of AFS identified on univariate screen ( inclusion threshold , P < .20 ) were included in a stepwise selection Cox model . The result ing five significant predictors were assigned an integer score to stratify patients into three risk groups . The prediction rule was internally vali date d in the PREVENT III validation set and externally vali date d in the multicenter cohort . RESULTS The estimated 1-year AFS in the derivation , internal validation , and external validation sets were 76.3 % , 72.5 % , and 77.0 % , respectively . In the derivation set , dialysis ( hazard ratio [ HR ] 2.81 , P < .0001 ) , tissue loss ( HR 2.22 , P = .0004 ) , age > or=75 ( HR 1.64 , P = .001 ) , hematocrit < or=30 ( HR 1.61 , P = .012 ) , and advanced CAD ( HR 1.41 , P = .021 ) were significant predictors for AFS in the multivariable model . An integer score , derived from the ss coefficients , was used to generate three risk categories ( low < or= 3 [ 44.4 % of cohort ] , medium 4 - 7 [ 46.7 % of cohort ] , high > or=8 [ 8.8 % of cohort ] ) . Stratification of the patients , in each data set , according to risk category yielded three significantly different Kaplan-Meier estimates for 1-year AFS ( 86 % , 73 % , and 45 % for low , medium , and high risk groups , respectively ) . For a given risk category , the AFS estimate was consistent between the derivation and validation sets . CONCLUSION Among patients selected to undergo surgical bypass for infrainguinal disease , this parsimonious risk stratification model reliably identified a category of CLI patients with a > 50 % chance of death or major amputation at 1 year . Calculation of a " PIII risk score " may be useful for surgical decision making and for clinical trial design s in the CLI population OBJECTIVE To determine the effect of spinal cord stimulation ( SCS ) on limb survival in patients with non-reconstructable critical leg ischaemia , and the value of patient selection on the basis of transcutaneous oxygen pressure ( TcpO2 ) measurements and trial screening . DESIGN A prospect i ve , controlled , European multicentre study . METHODS Non-reconstructable patients with stable critical leg ischaemia were divided into three groups . The SCS-Match group comprised patients with a baseline forefoot TcpO2 of < 30 mmHg and both sufficient pain relief and sufficient paraesthesia coverage ( > 75 % ) after a test stimulation period of at least 72 h. If baseline TcpO2 was < 10 mmHg , the TcpO2 should have exceeded 20 mmHg after test stimulation . The SCS-Match group was compared with patients not meeting these criteria , who were treated either with SCS ( SCS-No-Match ) or without SCS ( No-SCS ) . RESULTS At baseline , the mean ( + /- SD ) supine TcpO2 was 14.9 + /- 8.3 mmHg in the SCS-Match group ( n = 41 ) , 11.3 + /- 13.3 mmHg in the SCS-No-Match group ( n = 32 ) and 15.3 + /- 17.1 mmHg in the No-SCS group ( n = 39 ) . In the SCS-Match group a significant improvement in pain relief ( p < 0.005 ) and TcpO2 ( p < 0.001 ) was seen . After 12 months , cumulative limb survival of patients treated with SCS was significantly better than that of patients not treated with SCS ( p < 0.03 ) , and limb survival in the SCS-Match group was significantly higher ( p < 0.03 ) than that in the SCS-No-Match and No-SCS groups ( 78 , 55 and 45 % , respectively ) . CONCLUSION SCS treatment of non-reconstructable critical leg ischaemia provides a significantly better limb survival rate compared with conservative treatment . Patient selection based on TcpO2 and the results of trial screening further increase the probability of limb survival after SCS therapy |
14,030 | 25,480,391 | The highest potential public health impact was found in multi-level interventions that : 1 ) focused on all levels at the beginning of the planning process , 2 ) guided the implementation process using diffusion theory , and 3 ) used a website to disseminate the intervention .
Conclusions Although most studies underreported results within the RE- AIM dimensions , the reported Reach , Effectiveness , Adoption , Implementation and Maintenance were positively evaluated .
However , more information on external validity and sustainability is needed in order to take informed decisions on the choice of interventions that should be implemented in real-world setting s to accomplish long-term changes in obesity-related behaviours | Background This systematic literature review describes the potential public health impact of evidence -based multi-level interventions to improve obesity-related behaviours in adults , using the Reach , Efficacy , Adoption , Implementation and Maintenance ( RE- AIM ) framework . | OBJECTIVE To assess the effects of a comprehensive , integrated community-based lifestyle intervention on diet , physical activity and smoking in two Iranian communities . METHODS Within the framework of the Isfahan Healthy Heart Program , a community trial was conducted in two intervention counties ( Isfahan and Najaf-Abad ) and a control area ( Arak ) . Lifestyle interventions targeted the urban and rural population s in the intervention counties but were not implemented in Arak . In each community , a r and om sample of adults was selected yearly by multi-stage cluster sampling . Food consumption , physical exercise and smoking behaviours were quantified and scored as 1 ( low-risk ) or 0 ( other ) at baseline ( year 2000 ) and annually for 4 years in the intervention areas and for 3 years in the control area . The scores for all behaviours were then added to derive an overall lifestyle score . FINDINGS After 4 years , changes from baseline in mean dietary score differed significantly between the intervention and control areas ( + 2.1 points versus -1.2 points , respectively ; P < 0.01 ) , as did the change in the percentage of individuals following a healthy diet ( + 14.9 % versus -2.0 % , respectively ; P < 0.001 ) . Daily smoking had decreased by 0.9 % in the intervention areas and by 2.6 % in the control area at the end of the third year , but the difference was not significant . Analysis by gender revealed a significant decreasing trend in smoking among men ( P < 0.05 ) but not among women . Energy expenditure for total daily physical activities showed a decreasing trend in all areas , but the mean drop from baseline was significantly smaller in the intervention areas than in the control area ( -68 metabolic equivalent task ( MET ) minutes per week versus -114 MET minutes per week , respectively ; P < 0.05 ) . Leisure time devoted to physical activities showed an increasing trend in all areas . A significantly different change from baseline was found between the intervention areas and the control area in mean lifestyle score , even after controlling for age , sex and baseline values . CONCLUSION The results suggest that community-based lifestyle intervention programmes can be effective in a developing country setting OBJECTIVE To evaluate the effectiveness of a worksite health promotion program on improving cardiovascular disease risk factors . METHODS In St Louis , Missouri from 2005 to 2006 , 151 employees ( 134 F , 17 M , 81 % overweight/obese ) participated in a cohort-r and omized trial comparing assessment s + intervention ( worksite A ) with assessment s only ( worksite B ) for 1 year . All participants received personal health reports containing their assessment results . The intervention was design ed to promote physical activity and favorable dietary patterns using pedometers , healthy snack cart , WeightWatchers(R ) meetings , group exercise classes , seminars , team competitions , and participation rewards . Outcomes included BMI , body composition , blood pressure , fitness , lipids , and Framingham 10-year coronary heart disease risk . RESULTS 123 participants , aged 45+/-9 yr , with BMI 32.9+/-8.8 kg/m(2 ) completed 1 year . Improvements ( P < or = 0.05 ) were observed at both worksites for fitness , blood pressure , and total- , HDL- , and LDL-cholesterol . Additional improvements occurred at worksite A in BMI , fat mass , Framingham risk score , and prevalence of the metabolic syndrome ; only the changes in BMI and fat mass were different between worksites . CONCLUSION A multi-faceted worksite intervention promoted favorable changes in cardiovascular disease risk factors , but many of the improvements were achieved with worksite health assessment s and personalized health reports in the absence of an intervention The purpose of this paper is to present key points of an intervention programme ( Agita São Paulo Program ) to promote physical activity in a developing country . Agita is a multi-level , community-wide intervention design ed to increase knowledge about the benefits and the level of physical activity in a mega- population of 34 million inhabitants of São Paulo State , Brazil . The main message was taken from the Centers for Disease Control/American College of Sports Medicine ( CDC/ACSM ) recommendation that : ' everyone should accumulate at least 30 minutes of physical activity , on most days of the weeks , of moderate intensity , in one single or in multiple sessions ' . Activities were encouraged in three setting s : home , transport and leisure time . Focus groups were students from elementary schools through to college , white and blue collar workers , and elderly people . Innovative aspects included : ( 1 ) a research centre leading the process , ( 2 ) scientific and institutional partnerships ( over 160 groups ) , ( 3 ) a feasible approach -- the ' one-step-ahead ' model , ( 4 ) empowerment , ( 5 ) inclusion , ( 6 ) non-paid media , ( 7 ) social marketing , and ( 8) culture-linked . Data were obtained from 645 r and om , home-based question naires over four years -- stratified by sex , age , education and socio-economic level . These data show that the Agita message reached 55.7 % of the population , and among these , 23.1 % knew the main message . Recall of Agita and knowledge of its purpose were well distributed among different socioeconomic levels , being known by 67 % of the most educated . The prevalence of people reaching the recommendation was 54.8 % ( men 48.7 % , women 61 % ) ; and risk of being sedentary was quite smaller among those who knew the Agita message ( 7.1 % ) compared with those who did not know ( 13.1 % ) . In conclusion , based upon the Agita São Paulo experience , it appears that a multi-level , community-wide intervention to promote physical activity may obtain good results if the model contains the items listed above Background Research and practice partnerships have the potential to enhance the translation of research findings into practice . Purpose This paper describes such a partnership in the development of Walk Kansas ( WK ) and highlights individual and organizational level outcomes . Method Phase 1 examined : ( a ) the reach of WK , ( b ) physical activity changes , and ( c ) maintenance of physical activity changes 6 months after the program was completed . Phase 2 explored WK adoption and sustainability over 5 years . Results WK attracted a large number of participants who were more likely to be female , more active , and older than the adult population within the counties where they resided . Inactive or insufficiently active participants at baseline experienced significant increases in both moderate ( p < 0.001 ) and vigorous ( p < 0.001 ) physical activity . A r and om selection of participants who were assessed 6 months post-program did not demonstrate a significant decrease in moderate or vigorous activity between program completion and 6-month follow-up . The number of counties adopting the program increased across years , peaking at 97 in 2006 and demonstrated the sustainability of the WK over 5 years . Conclusions WK is effective , has a broad reach , and enables participants to maintain increased activity . It also shows promise for broad adoption and sustainability Background U.S. adults are at unprecedented risk of becoming overweight or obese , and most scientists believe the primary cause is an obesogenic environment . Worksites provide an opportunity to shape the environments of adults to reduce obesity risk . The goal of this group-r and omized trial was to implement a four-component environmental intervention at the worksite level to positively influence weight gain among employees over a two-year period . Environmental components focused on food availability and price , physical activity promotion , scale access , and media enhancements . Methods Six worksites in a U.S. metropolitan area were recruited and r and omized in pairs at the worksite level to either a two-year intervention or a no-contact control . Evaluations at baseline and two years included : 1 ) measured height and weight ; 2 ) online surveys of individual dietary intake and physical activity behaviors ; and 3 ) detailed worksite environment assessment . Results Mean participant age was 42.9 years ( range 18 - 75 ) , 62.6 % were women , 68.5 % were married or cohabiting , 88.6 % were white , 2.1 % Hispanic . Mean baseline BMI was 28.5 kg/m2 ( range 16.9 - 61.2 kg/m2 ) . A majority of intervention components were successfully implemented . However , there were no differences between sites in the key outcome of weight change over the two-year study period ( p = .36 ) . Conclusions Body mass was not significantly affected by environmental changes implemented for the trial . Results raise questions about whether environmental change at worksites is sufficient for population weight gain prevention . Trial Registration Clinical Trials.gov : Background Effectiveness of and engagement with website-delivered physical activity interventions is moderate at best . Increased exposure to Internet interventions is reported to increase their effectiveness ; however , there is a lack of knowledge about which specific intervention elements are able to maintain website engagement . Objective To prospect ively study the associations of website engagement and exposure to intervention components for a publicly available physical activity website ( 10,000 Steps Australia ) . Methods Between June and July 2006 a total of 348 members of 10,000 Steps completed a Web-based survey to collect demographic characteristics . Website engagement was subsequently assessed over a 2-year period and included engagement data on website components ; individual challenges , team challenges , and virtual walking buddies ; and indicators of website engagement ( average steps logged , days logging steps , and active users ) . Results On average participants logged steps on 169 ( SD 228.25 ) days . Over a 2-year period this equated to an average of 1.6 logons per week . Binary logistic regression showed that individuals who participated in individual challenges were more likely to achieve an average of 10,000 steps per day ( odds ratio [ OR ] = 2.80 , 95 % confidence interval [ CI ] 1.45–5.40 ) , log steps on a higher than average number of days ( OR = 6.81 , 95 % CI 2.87–13.31 ) , and remain an active user ( OR = 4.36 , 95 % CI 2.17–8.71 ) . Additionally , those using virtual walking buddies ( OR = 5.83 , 95 % CI 1.27–26.80 ) and of older age logged steps on a higher than average number of days . No significant associations were found for team challenges . Conclusions Overall engagement with the 10,000 Steps website was high , and the results demonstrate the relative effectiveness of interactive components to enhance website engagement . However , only exposure to the interactive individual challenge feature was positively associated with all website engagement indicators . More research is needed to examine the influence of intervention components on website engagement , as well as the relationship between website engagement and physical activity change OBJECTIVES Body and Soul was a collaborative effort among two research universities , a national voluntary agency ( American Cancer Society ) , and the National Institutes of Health to disseminate and evaluate under real-world conditions the impact of previously developed dietary interventions for African Americans . METHODS Body and Soul was constructed from two successful research -based interventions conducted in African-American churches . Components deemed essential from the prior interventions were combined , and then tested in a cluster r and omized-effectiveness trial . The primary outcome was fruit and vegetable intake measured with two types of food frequency question naires at baseline and 6-month follow-up . RESULTS At the 6-month follow-up , intervention participants showed significantly greater fruit and vegetable ( F&V ) intake relative to controls . Post-test differences were 0.7 and 1.4 servings for the 2-item and 17-item F&V frequency measures , respectively . Statistically significant positive changes in fat intake , motivation to eat F&V , social support , and efficacy to eat F&V were also observed . CONCLUSIONS The results suggest that research -based interventions , delivered collaboratively by community volunteers and a health-related voluntary agency , can be effectively implemented under real-world conditions Background The Well London program used community engagement , complemented by changes to the physical and social neighborhood environment , to improve physical activity levels , healthy eating , and mental wellbeing in the most deprived communities in London . The effectiveness of Well London is being evaluated in a pair-matched cluster r and omized trial ( CRT ) . The baseline survey data are reported here . Methods The CRT involved 20 matched pairs of intervention and control communities ( defined as UK census lower super output areas ( LSOAs ) ; ranked in the 11 % most deprived LSOAs in London by the English Indices of Multiple Deprivation ) across 20 London boroughs . The primary trial outcomes , sociodemographic information , and environmental neighbourhood characteristics were assessed in three quantitative components within the Well London CRT at baseline : a cross-sectional , interviewer-administered adult household survey ; a self-completed , school-based adolescent question naire ; a fieldworker completed neighborhood environmental audit . Baseline data collection occurred in 2008 . Physical activity , healthy eating , and mental wellbeing were assessed using st and ardized , vali date d question naire tools . Multiple imputation was used to account for missing data in the outcomes and other variables in the adult and adolescent surveys . Results There were 4,107 adults and 1,214 adolescent respondents in the baseline surveys . The intervention and control areas were broadly comparable with respect to the primary outcomes and key sociodemographic characteristics . The environmental characteristics of the intervention and control neighborhoods were broadly similar . There was greater between-cluster variation in the primary outcomes in the adult population compared to the adolescent population . Levels of healthy eating , smoking , and self-reported anxiety/depression were similar in the Well London adult population and the national Health Survey for Engl and . Levels of physical activity were higher in the Well London adult population but this is likely to be due to the different measurement tools used in the two surveys . Conclusions R and omization of social interventions such as Well London is acceptable and feasible and in this study the intervention and control arms are well-balanced with respect to the primary outcomes and key sociodemographic characteristics . The matched design has improved the statistical efficiency of the study amongst adults but less so amongst adolescents . Follow-up data collection will be completed 2012.Trial registration Current Controlled Trials IS RCT Purpose . This study examined how to improve dietary habits of individuals from the general public . Design . The Eating for a Healthy Life project was a r and omized trial . Setting . The study was conducted among members of religious organizations ( ROs ) . Subjects . Participants were a sample of RO members . Intervention . The intervention was a multilevel package , based on our previous experience , design ed to lower fat and increase fruit and vegetable consumption . Measures . The Eating Behaviors Question naire was administered preintervention and postintervention , together with 24-hour food recalls in a r and omly selected subset . Analysis . Linear mixed models were used to evaluate the study 's intervention , incorporating the design effects of blocking , intraclass correlation within RO , and correlation between the preintervention and postintervention points . Results . Participants ( n = 2175 ) reported significantly healthier dietary behaviors in intervention ROs at the 12-month follow-up period , compared to participants in the comparison ROs , for a fat scale change of .08 summary scale points and an adjusted intervention effect of .06 overall . Conclusion . Dietary intervention through ROs is a positive and successful method of changing dietary habits Background Pedometers have become common place in physical activity promotion , yet little information exists on who is using them . The multi- strategy , community-based 10,000 Steps Rockhampton physical activity intervention trial provided an opportunity to examine correlates of pedometer use at the population level . Methods Pedometer use was promoted across all intervention strategies including : local media , pedometer loan schemes through general practice , other health professionals and libraries , direct mail posted to dog owners , walking trail signage , and workplace competitions . Data on pedometer use were collected during the 2-year follow-up telephone interviews from r and om population sample s in Rockhampton , Australia , and a matched comparison community ( Mackay ) . Logistic regression analyses were used to determine the independent influence of interpersonal characteristics and program exposure variables on pedometer use . Results Data from 2478 participants indicated that 18.1 % of Rockhampton and 5.6 % of Mackay participants used a pedometer in the previous 18-months . Rockhampton pedometer users ( n = 222 ) were more likely to be female ( OR = 1.59 , 95 % CI : 1.11 , 2.23 ) , aged 45 or older ( OR = 1.69 , 95 % CI : 1.16 , 2.46 ) and to have higher levels of education ( university degree OR = 4.23 , 95 % CI : 1.86 , 9.6 ) . Respondents with a BMI > 30 were more likely to report using a pedometer ( OR = 1.68 , 95 % CI : 1.11 , 2.54 ) than those in the healthy weight range . Compared with those in full-time paid work , respondents in ' home duties ' were significantly less likely to report pedometer use ( OR = 0.18 , 95 % CI : 0.06 , 0.53 ) . Exposure to individual program components , in particular seeing 10,000 Steps street signage and walking trails or visiting the website , was also significantly associated with greater pedometer use . Conclusion Pedometer use varies between population subgroups , and alternate strategies need to be investigated to engage men , people with lower levels of education and those in full-time ' home duties ' , when using pedometers in community-based physical activity promotion initiatives UNLABELLED This study examines the change in health-related quality of life ( HRQoL ) among ( > or = 60 years ) elderly persons as a result of health education intervention . A community-based intervention study was performed in eight r and omly selected villages ( INTERVENTION n = 4 ; CONTROL n = 4 ) in rural Bangladesh . A total of 1135 elderly persons was selected for this study . The analyses include 839 participants ( INTERVENTION n = 425 ; CONTROL n = 414 ) who participated in both baseline and post-intervention surveys . Participants in the intervention area were further stratified into compliant ( n = 315 ) and non-compliant ( n = 110 ) groups based on the reported compliance to the intervention activities . The intervention includes , for example , physical activity , advice on healthy food intake and other aspects of management . To create an enabling environment , social awareness was provided by means of information about the contribution of and challenges faced by elderly persons at home and the community , including information about elderly persons ' health and health care . The intervention activities were provided to the elderly persons , caregivers , household members and community people for 15 months . The HRQoL was assessed using a multi-dimensional generic instrument design ed for elderly persons . Multivariate analyses revealed that in the non-compliant group the probabilities of increased scores were less likely in overall HRQoL ( OR 0.52 , 95 % CI 0.32 - 0.82 ) . Among the CONTROL group , increased scores were less likely in the physical ( OR 73 , 95 % CI 0.54 - 0.99 ) , social ( OR 0.37 , 95 % CI 0.27 - 0.50 ) , spiritual ( OR 0.60 , 95 % CI 0.34 - 0.94 ) , environment ( OR 0.36 , 95 % CI 0.26 - 0.49 ) dimensions and overall HRQoL ( OR 0.44 , 95 % CI 0.32 - 0.59 ) ( adjusted for age , sex , literacy , marital status and economic status ) . This study concludes that provision of community-based health education intervention might be a potential public health initiative to enhance the HRQoL in old age OBJECTIVE Many physical activity interventions do not reach those people who would benefit the most from them . The Groningen Active Living Model ( GALM ) was successful in recruiting sedentary and underactive older adults . METHOD In the fall of 2000 older adults in three municipalities in the Netherl and s received written information , were visited at home and , if eligible according to the GALM recruitment criteria , filled in the Stages of Change question naire and the Voorrips physical activity question naire . RESULTS By using the strategy we succeeded in including 12.3 % of the older adults ( 315 of the 2551 qualifying participants ) , 79.4 % of whom could be indeed regarded as sedentary or underactive . These results can be considered in line with results described in the literature . The cost of successfully recruiting an older adult was estimated at $ 84 . CONCLUSIONS The GALM recruitment strategy is a potentially useful and effective method for reaching community-dwelling sedentary and underactive older adults The prevalence of obesity is significantly higher among American Indians ( AIs ) and is associated with increased rates of diabetes , hypertension , and cardiovascular disease . We implemented a 14-mo intervention trial ( Navajo Healthy Stores ) on the Navajo Nation that sought to increase availability of healthier foods in local food stores and to promote these foods at the point of purchase and through community media . We divided the Navajo Nation into 10 store regions , half of which were r and omized to intervention and half to comparison . We evaluated the program by using a pre-post sample of systematic ally sample d adult Navajo consumers ( baseline , n = 276 ; postintervention , n = 145 ) . Intervention impact was examined by analyzing pre-post differences by intervention group and by intervention exposure level . When intervention and comparison groups were compared , only body mass index ( BMI ) showed a trend toward impact of the intervention ( P = 0.06 ) . However , greater exposure to the intervention was associated with significantly reduced BMI ( P ≤ 0.05 ) and improved healthy food intentions ( P ≤ 0.01 ) , healthy cooking methods ( P ≤ 0.05 ) , and healthy food getting ( P ≤ 0.01 ) . With increasing exposure , the odds of improving overweight or obese status was 5.02 ( 95 % CI : 1.48 , 16.99 ; P ≤ 0.01 ) times the odds of maintaining or worsening overweight or obese status . In summary , a food store intervention was associated with reduced overweight/obesity and improved obesity-related psychosocial and behavioral factors among those persons most exposed to the intervention on an AI reservation OBJECTIVE : To promote weight loss in Samoan church communities through an exercise program and nutrition education . METHODS : A quasi-experimental design was used to assess weight change , over 1 y , in cohorts of people aged 20–77 y from three non-r and omised Samoan church communities ( two intervention , n=365 and one control , n=106 ) in Auckl and , New Zeal and . The intervention churches received aerobics sessions and nutrition education about dietary fat . RESULTS : Baseline body mass index for the intervention and control churches was ( mean±s.e . ) 34.8±0.4 and 34.3±0.9 kg/m2 , respectively . The intervention churches lost an average of 0.4±0.3 kg compared to a 1.3±0.6 kg weight gain in the control church ( P=0.039 , adjusted for confounders ) . The number of people who were vigorously active increased by 10 % in the intervention churches compared to a 5 % decline in the control church ( P=0.007 ) . Nutrition education had little apparent impact on knowledge or behaviour . CONCLUSION : Samoan communities in New Zeal and are very obese and have high rates of annual weight gain . A community-based intervention program arrested this weight gain in the short term OBJECTIVE To evaluate whether the evidence -based Body & Soul program , when disseminated and implemented without research er or agency involvement and support , would achieve results similar to those of earlier efficacy and effectiveness trials . DESIGN Prospect i ve group r and omized trial . SETTING Churches with predominantly African American membership . PARTICIPANTS A total of 1,033 members from the 15 churches completed baseline surveys . Of these participants , 562 ( 54.4 % ) completed the follow-up survey 6 months later . INTERVENTION Church-based nutrition program for African Americans that included pastoral involvement , educational activities , church environmental changes , and peer counseling . MAIN OUTCOME MEASURE Daily fruit and vegetable ( FV ) intake was assessed at pre- and posttest . ANALYSIS Mixed-effects linear models . RESULTS At posttest , there was no statistically significant difference in daily servings of FVs between the early intervention group participants compared to control group participants ( 4.7 vs 4.4 , P = .38 ) . Process evaluation suggested that added re sources such as technical assistance could improve program implementation . CONCLUSIONS AND IMPLICATION S The disseminated program may not produce improvements in FV intake equal to those in the earlier efficacy and effectiveness trials , primarily because of a lack of program implementation . Program dissemination may not achieve public health impact unless support systems are strengthened for adequate implementation at the church level OBJECTIVES We used a participatory process to develop an obesity intervention appropriate for elementary school personnel . METHODS A r and omized controlled trial included 16 school worksites ( 8 intervention , 8 control ) . Intervention schools formed committees to develop and implement health promotion activities for employees . Anthropometric and self-report data were collected at baseline and postintervention ( 2 years later ) . The primary outcome measures were body mass index ( BMI ) , waist-hip ratio , physical activity , and fruit and vegetable consumption . RESULTS After adjustment for age , ethnicity , and job classification , employees in intervention schools reduced their BMI by an average of 0.04 kg/m2 , and those in control schools increased their BMI by an average of 0.37 kg/m2 . Comparisons for waist-hip ratio , weekly physical activity minutes , and fruit and vegetable consumption were not significant . CONCLUSIONS The participatory process appeared to be an effective means for stimulating change . The intervention may have slowed and perhaps reversed the tendency of adults to gain weight progressively with age BACKGROUND Currently there is a great deal of interest in multi strategy community-based approaches to changing physical activity or health behaviors . The aim of this article is to describe the effectiveness of the physical activity promotion project " 10,000 Steps Ghent " after 1 year of intervention . METHODS A multi strategy community-based intervention was implemented in 2005 with follow-up measurements in 2006 to promote physical activity to adults . A local media campaign , environmental approaches , the sale and loan of pedometers , and several local physical activity projects were concurrently implemented . In 2005 , 872 r and omly selected subjects ( aged 25 to 75 ) , from the intervention community Ghent and 810 from a comparison community , participated in the baseline measurements . Of these , 660 intervention subjects and 634 comparison subjects completed the follow-up measurements in 2006 . Statistical analyses were performed in 2006 . RESULTS After one year there was an increase of 8 % in the number of people reaching the " 10,000 steps " st and ard in Ghent , compared with no increase in the comparison community . Average daily steps increased by 896 ( 95 % CI=599 - 1192 ) in the intervention community , but there was no increase in the comparison community ( mean change -135 [ 95 % CI= -432 to 162 ] ) ( F time x community=22.8 , p<0.001 ) . Results are supported by self-reported International Physical Activity Question naire ( IPAQ ) data . CONCLUSIONS The " 10,000 steps/day " message reached the Ghent population and the project succeeded in increasing pedometer-determined physical activity levels in Ghent , after 1 year of intervention This study evaluates the effects of the American Heart Association ’s Heart At Work program on cardiovascular disease risk factor awareness , self-efficacy , and health behaviors . A prospect i ve , quasi-experimental research design was used to assess the impact of the program at two factory sites ( one intervention and one control ) . A total of 633 employees participated . Intervention site respondents significantly improved their knowledge of blood pressure management , the relationship between nutrition and cardiovascular disease , and heart attack risk factors . They also were more likely to begin treatment for hypertension , to report fewer sick days , and to have plans to improve their diet and lose weight . These findings suggest that the Heart At Work program had a favorable overall impact This article provides an overview of the development , implementation , and baseline findings from a statewide faith-based physical activity ( PA ) initiative . The 3-year program is training African Method ist Episcopal volunteers across South Carolina to implement programs to increase PA in their congregations . To date , 98 churches have been trained . Interviews done with a r and om sample ( n = 39 ) indicated that 54 % are implementing at least one PA program . The baseline telephone survey ( N = 571 ) estimates that 27.8 % of the population is regularly active , 54.9 % underactive , and 17.3 % sedentary . Baseline rates of regular PA were higher in those who were younger , healthier , and nonsmokers . Challenges to date have included obtaining rosters and implementing a large-scale program with limited re sources . Interest in the program has been strong and supported by church leaders . Current efforts are on training additional churches and working with those already trained to support sustainability ' Hartslag Limburg ' ( Dutch for Heartbeat Limburg ) , a regional cardiovascular diseases ( CVD ) prevention program , integrates a community strategy and a high-risk strategy to reduce CVD risk behaviors . The present paper focuses on the effects of the community intervention on fat intake and physical activity . The project was based on community organization principles and health education theories and methods . In order to implement the intervention , nine local Health Committees were set up , each organizing activities that facilitate and encourage people to adopt a healthier lifestyle . A pre-test-post-test control group design with two post-tests was used to evaluate the intervention . At baseline , representative r and om cohort research sample s were selected in the Maastricht region and in a control region . Data on fat intake and physical activity , and on the psychosocial determinants of these behaviors , were gathered by means of mail surveys . The present study indicates that the intervention had a significant effect on fat reduction , especially among respondents aged < or=48 years ( median age ) . Respondents in the Maastricht region were also more realistic about their fat intake at post-test as compared with the control region . Only a limited effect on intentions to increase physical activity was found Objective : To assess the sustainability and effectiveness of a community‐directed program for primary and secondary prevention of obesity , diabetes and cardiovascular disease in an Aboriginal community in north‐west Western Australia The Isfahan Healthy Heart Programme ( IHHP ) is a five to six year comprehensive integrated community-based programme for cardiovascular diseases ( CVD ) prevention and control via reducing CVD risk factors and improvement of cardiovascular healthy behaviour in a target population . IHHP started late in 1999 and will be finished in 2005 - 2006 . A primary survey was done to collect baseline data from interventional ( Isfahan and Najaf-Abad ) and reference ( Arak ) communities . In a two-stage sampling method , we r and omly selected 5 to 10 percent of households from r and omly selected clusters . Then individuals aged ≥19 years were selected for the survey . This way , data from 12,600 individuals ( 6300 in interventional counties and 6300 in the reference county ) was collected and stratified according to living area ( urban vs. rural ) and different age and sex groups . The sample s underwent a 30-minute interview to complete vali date d question naires containing questions on demography , socioeconomic status , smoking behaviour , physical activity , nutritional habits and other behaviour regarding CVD . Blood pressure and body mass index ( BMI ) measurements were done and fasting blood sample s were taken for two hours post load plasma glucose ( 2 hpp ) , serum ( total , HDL and LDL ) cholesterol and triglyceride levels . A twelve-lead electrocardiogram was recorded in all persons above 35 years of age . Community-wide surveillance of deaths , hospital discharges , myocardial infa rct ion and stroke registry was carried out in the intervention and control areas . Four to five years of interventions based on different categories such as mass media , community partnerships , health system involvement and policy and legislation have started in the intervention area while Arak will be followed without intervention . Considering the results of the baseline surveys . ( assessment s needed , the objectives , existing re sources and the possibility of national implementation ) the interventions were planned . They were set based on specific target groups like school children , women , work-site , health personnel , high-risk persons , and community leaders were actively engaged as decision makers . A series of teams was arranged for planning and implementation of the intervention strategies . Monitoring will be done on small sample s to assess the effect of different interventions in the intervention area . While four periodic surveys will be conducted on independent sample s to assess health behaviours related to CVD risk factors in the intervention and reference areas , the original pre-intervention subjects aged more than 35 years will be followed in both areas to assess the individual effect of interventions and outcomes like sudden death , fatal and nonfatal MI and stroke . The whole baseline survey will be repeated on the original and an independent sample in both communities at the end of the study OBJECTIVE The results of an 18-month worksite intervention to prevent obesity among metropolitan transit workers are reported . METHODS Four garages in a major metropolitan area were r and omized to intervention or control groups . Data were collected during the fall of 2005 prior to the start of the intervention and during the fall of 2007 , after the intervention ended . Intervention program components at the garage included enhancement of the physical activity facilities , increased availability of and lower prices on healthy vending machine choices , and group behavioral programs . Mixed model estimates from cross-sectional and cohort sample s were pooled with weights inverse to the variance of their respective estimates of the intervention effects . RESULTS Measurement participation rates were 78 % at baseline and 74 % at follow-up . The intervention effect on garage mean BMI change was not significant ( -0.14 kg/m(2 ) ) . Energy intake decreased significantly , and fruit and vegetable intake increased significantly in intervention garages compared to control garages . Physical activity change was not significant . CONCLUSION Worksite environmental interventions for nutrition and physical activity behavior change may have limited impact on BMI among transit workers who spend most of their workday outside the worksite OBJECTIVES We evaluated the effects of a community-based intervention , the Academia da Cidade program ( ACP ) , on increasing leisure-time physical activity among residents of Recife , Brazil . METHODS We used the International Physical Activity Question naire to assess leisure-time physical activity and transport physical activity ( i.e. , activities involved in traveling from place to place ) levels in a r and om sample of 2047 Recife residents surveyed in 2007 . We also examined factors related to exposure to ACP ( participation in the intervention , residing near an intervention site , hearing about or seeing intervention activities ) . We estimated prevalence odds ratios ( ORs ) of moderate to high leisure-time and transport physical activity levels via intervention exposures adjusted for sociodemographic , health , and environmental variables . RESULTS Prevalence ORs for moderate to high levels of leisure-time physical activity were higher among former ( prevalence OR=2.0 ; 95 % confidence interval [CI]=1.0 , 3.9 ) and current ( prevalence OR=11.3 ; 95 % CI=3.5 , 35.9 ) intervention participants and those who had heard about or seen an intervention activity ( prevalence OR=1.8 ; 95 % CI=1.3 , 2.5 ) . Transport physical activity levels were inversely associated with residing near an ACP site . CONCLUSIONS The ACP program appears to be an effective public health strategy to increase population -level physical activity in urban developing setting The aim of the study was to evaluate the impact of the state-wide dissemination of a physical activity ( PA ) intervention in Fl and ers . In 2011 , a r and om sample was taken of the entire adult ( 25 - 75 years ) population of Fl and ers . Data of the Flemish sample were compared with baseline data of the intervention and control group of ' 10 000 Steps Ghent ' ( 2005 ) . In total , data of the International Physical Activity Question naire were available of 2556 respondents ( 1675 of the comparison sample and 881 of the Flemish sample ) . Pedometer data were obtained by 269 respondents of the Flemish sample and by 1236 respondents of the comparison sample . Compared with the comparison sample of 2005 , the Flemish sample reported more walking ( P < 0.001 ) , moderate ( P < 0.001 ) , vigorous ( P < 0.001 ) , work-related ( P < 0.001 ) , leisure time ( P = 0.01 ) and household PA ( P = 0.03 ) . Step count analyses revealed that the Flemish sample took more pedometer-based daily step counts ( P < 0.001 ) than the comparison sample . Furthermore , a higher proportion of respondents reaching the 10 000 steps/day goal ( P = 0.005 ) was found in the Flemish sample . A positive effect of ' 10 000 Steps Fl and ers ' was found . Results indicate that a state-wide approach based on socio-ecological models is an effective strategy to promote PA in a large population Objective : Examine the effectiveness of the worksite-based weight gain prevention program Netherl and s Heart Foundation-Netherl and s Research program weight Gain prevention In Balance , with regard to behavioral changes and corresponding cognitive determinants . Methods : A nonr and omized pretest-repeated posttest control group design was applied in 12 worksites . Intervention groups received individual and environmental interventions , directed at physical activity and food intake . Measurements were executed at baseline and after 12 and 24 months . Results : Nearly all behaviors in the intervention group improved more than in the control group , even though improvements in behaviors were often too small to reach statistical significance . No positive intervention effects were observed for the cognitive factors . Conclusion : Differential changes between the intervention and control group were observed for several important dietary and physical activity behaviors . Valuable information is gained regarding the implementation of weight gain prevention programs in worksites |
14,031 | 26,455,855 | Moreover , a wide variety of instruments were used to determine impact and outcomes of the teaching methods .
It was shown that both videotaped interviews and virtual simulations were superior to lectures .
In videotaped teaching , interactions between patients and learners performing mental state examination were shown for the learner ’s discussion while virtual simulations mimicked patient symptoms in computer applications .
Virtual simulation was notably a unique learning opportunity for the learners as it allowed learning to take place without the use of diminishing real life re sources .
However , in view of the high cost and learners ’ difficulty in negotiating the virtual environment , videotaped teaching remained as the more commonly used method of teaching mental state examination .
This systematic review study identified teaching strategies utilized in the teaching of mental state examination and their effectiveness .
Videotapes was the most widely used and effective approach , that is , until the issue of high cost and ease of maneuver in virtual simulation could be overcome .
There were also potential benefits of other teaching , such as reflection and use of st and ardized patients , and educators could consider these in the teaching of mental state examination . | BACKGROUND With the evolution of education , there has been a shift from the use of traditional teaching methods , such as didactic or rote teaching , towards non-traditional teaching methods , such as viewing of role plays , simulation , live interviews and the use of virtual environments .
Mental state examination is an essential competency for all student healthcare professionals .
If mental state examination is not taught in the most effective manner so learners can comprehend its concepts and interpret the findings correctly , it could lead to serious repercussions and subsequently impact on clinical care provided for patients with mental health conditions , such as incorrect assessment of suicidal ideation .
However , the methods for teaching mental state examination vary widely between countries , academic institutions and clinical setting s. OBJECTIVES This systematic review aim ed to identify and synthesize the best available evidence of effective teaching methods used to prepare student health care professionals for the delivery of mental state examination . | The efficacy of video recording in transmitting clinical knowledge and skills to medical students was tested by recording on videotape demonstrations of physical examinations given by five clinicians to a r and omly selected group of 12 students ( personal group ) from the first clinical year and then showing these recordings , under identical conditions , to 13 students from the same year ( video group ) . The efficacy of both the personal and video mediums in terms of whether content was retained was tested by a question naire completed by all students at the end of the sessions and by a structured clinical assessment in which students were asked to demonstrate some of the same clinical tasks three weeks after the demonstration . In answering the question naire the video group obtained a mean ( SD ) score of 20.8 ( 7.0 ) ( maximum possible score 40 ) , which was not significantly different from the score achieved by the personal group ( 17.4 ( 7.7 ) ) . The video group was able to reproduce 44 (10)% of the total clinical steps demonstrated and the personal group 45 (14)% . Videotaped demonstrations can be as effective as personal teaching of clinical methods , and video should be developed as a medium for first line clinical teaching In this study , we compared two teaching strategies : lecture notes combined with structured group discussion versus lecture only . We sought to help nurse educators identify the most effective teaching strategies for nursing students . We compared the examination scores of two groups of students who took a 3-credit medical-surgical nursing course . The control group ( N = 88 ) received lecture only as the teaching method , whereas the experimental group ( N = 81 ) received word-processed lecture notes along with structured group discussion . A one-tailed , independent sample t test was used to compare the mean examination scores of the two groups . The chi-square test was used to determine whether a significant difference existed between the course-passing rates of the two groups . The results showed a statistically significant difference between the means of the experimental and control groups . However , no statistically significant difference existed between the course-passing rate of students in the experimental group and that of students in the control group . These results provide strong support for the use of lecture notes in conjunction with structured group discussion as a teaching strategy . We recommend replicating this study using sample s from other courses , and conducting further studies that include students ' NCLEX-RN results as a third dependent variable Closed-circuit television ( CCTV ) provides medical departments with alternatives in instructional formats . Concern , however , has been voiced about teaching via TV because the medium itself might cause inattention . This study investigated whether TV will lower the test scores of medical students . Sixty-one students were r and omly divided into two groups . The lecture ( control ) group received the information via traditional lectures , including use of 2 " X 2 " transparencies . The video group received concurrently the same information via CCTV . Multiple-choice examinations were given after each of the six sessions . The cumulative mean scores were similar : lecture group=87.56 % , video group=87.99 % , i.e. , no significant difference ( P=0.77 ) . To detect attitudinal differences toward the two formats , the students were surveyed at the end of the series and intragroup agreement on specific questions was calculated . The students rated the lecture format more highly . In response to the question ' Did the audiovisual material s used by the instructor aid your learning ? ' , the mean rating from the lecture group was 7.37 ( scale of 0 - 9 ) compared to a mean rating of 5.93 from the video group ( P < 0.0003 ) Group teaching in problem-based interviewing based on video and audiotape feedback of the doctor 's own consultations significantly improved the ability of experienced general practitioners to teach psychiatric skills to their trainees . When the GPs were r and omly allocated to one of three further training experiences -- video feedback of their tutorial sessions , discussion about how to teach and no further teaching , there were very few differences between the groups . The greatest impact on improving teaching skills was brought about by watching their own consultations in a group feedback setting OBJECTIVE This study evaluated a brief educational video design ed to enhance the informed consent process for people with serious mental and medical illnesses who are considering participating in treatment research . METHOD Individuals with schizophrenia who were being recruited for ongoing clinical trials , medical patients without self-reported psychiatric comorbidity , and university undergraduates were r and omly assigned to view either a highly structured instructional videotape about the consent process in treatment research or a control videotape that presented only general information about bioethical issues in human research . Knowledge about informed consent was measured before and after viewing . RESULTS Viewing the experimental videotape result ed in larger gains in knowledge about informed consent . St and ardized effect sizes were large in all groups . CONCLUSIONS The videotape was thus an effective teaching tool across diverse population s , ranging from individuals with severe chronic mental illness to university undergraduates |
14,032 | 28,376,711 | Conclusions In patients with chronic hepatitis C , antiviral therapy can reduce the development of HCC and mortality , especially when SVR is achieved | Background The long-term clinical outcomes of antiviral therapy for patients with chronic hepatitis C are uncertain in terms of hepatitis C virus (HCV)-related morbidity and mortality according to the response to antiviral therapy .
This study aim ed to assess the impact of antiviral treatment on the development of HCC and mortality in patients with chronic HCV infection . | A prospect i ve study was performed to establish whether infection with specific hepatitis C virus ( HCV ) genotypes was associated with an increased risk of development of hepatocellular carcinoma ( HCC ) in cirrhosis . A cohort of 163 consecutive hepatitis C virus antibody (anti-HCV)-positive cirrhotic patients was prospect ively evaluated for the development of HCC at 6-month intervals by ultrasound ( US ) scan and alpha-fetoprotein ( AFP ) concentration . HCV genotypes were determined according to Okamoto . Risk factors associated with cancer development were analyzed by univariate and multivariate statistics . At enrollment , 101 patients ( 62 % ) were infected with type 1b , 48 ( 29.5 % ) were infected with type 2a/c , 2 ( 1.2 % ) were infected with type 3a , 1 ( 0.6 % ) was infected with type 1a , 3 ( 1.8 % ) had a mixed-type infection , and , in 8 patients ( 4.9 % ) , genotype could not be assigned . After a 5- to 7-year follow-up ( median , 68 months ) , HCC developed in 22 of the patients , 19 infected with type 1b and 3 with type 2a/c ( P < .005 ) . Moreover , HCC developed more frequently in males ( P < .01 ) , patients with excessive alcohol intake ( P < .01 ) , those over 60 years of age ( P < .02 ) , and in patients who did not receive interferon treatment ( P < .02 ) . Multivariate analysis showed that type 1b was the most important risk factor associated with tumor development ( odds ratio 6.14 , 1.77 - 21.37 95 % confidence interval ) . Other independent risk factors were older age and male sex . Cirrhotic patients infected with HCV type 1b carry a significantly higher risk of developing HCC than patients infected by other HCV types . The latter may require a less intensive clinical surveillance for the early detection of neoplasia Objective : The purpose of this study was to eluci date the long-term outcome after interferon ( IFN ) therapy in chronic hepatitis C elderly patients . Methods : We studied the incidence of hepatocellular carcinoma ( HCC ) and survival probability after the initiation of IFN therapy in 500 Japanese chronic hepatitis C patients > 60 years . The mean age of initiation of IFN was 63 years and the mean follow-up period was 7.4 years . Cox proportional hazard regression analysis was used to evaluate the long-term outcome after initiation of IFN therapy . Sustained virological response ( SVR ) was defined as negative HCV-RNA by RT-nested PCR 6 months after the completion of long-term IFN therapy . Non-response ( NR ) was applied to patients who did not show SVR . Hepatic fibrosis was defined as the fibrosis score ( score 0–4 ) according to Knodell et al. Results : 140 patients ( 28 % ) had an SVR and 360 patients ( 72 % ) had an NR . 71 of 500 patients developed HCC during follow-up . The cumulative incidence of HCC was 9.6 % at the 5th year , 17.4 % at the 10th year , and 31.3 % at the 15th year . HCC developed with significance when : ( 1 ) HCV was not cleared after IFN therapy ( p < 0.0001 ) , ( 2 ) sex was male ( p < 0.0001 ) , and ( 3 ) staging of liver fibrosis was > 2 ( p = 0.008 ) . 53 of the patients died . The cumulative survival probability was 95.7 % at the 5th year , 86.4 % at the 10th year , and 78 % at the 15th year . Patients achieved a long survival with significance when : ( 1 ) staging of liver fibrosis was 1 ( p < 0.0001 ) , ( 2 ) HCV was cleared after IFN therapy ( p = 0.034 ) , and ( 3 ) sex was female ( p = 0.015 ) . Conclusion : Chronic hepatitis C patients with clearance of HCV after IFN therapy had a significantly reduced risk of HCC appearance and achieved prolonged survival even if they are ≧60 years Background No study has compared the long-term prognoses of hepatitis C patients with hepatitis C virus ( HCV ) antibody-negative individuals and investigated the effects of interferon ( IFN ) treatment . To clarify the long-term prognosis of HCV-positive residents of an isolated Japanese isl and and prospect ively investigate the effects of IFN treatment in comparison with the HCV-negative general population . Methods HCV antibody was positive in 1,343 ( 7.6 % ) of the 17,712 individuals screened . 792 HCV RNA-positive , HBsAg-negative subjects were enrolled . 1,584 HCV antibody-negative , HBsAg-negative general residents were sex- and age-matched to the 792 subjects . A total of 154 < 70-year-old patients without liver cirrhosis ( LC ) or hepatocellular carcinoma ( HCC ) underwent IFN treatment . The survival rate with all-cause death as the endpoint was determined and causes of death were compared . Results The 10- and 20-year survival rates of the hepatitis C and general resident groups were 65.4 % and 87.8 % , and 40.8 % and 62.5 % , respectively ( p < 0.001 ; hazard risk ratio , 0.444 ; 95 % confidence interval ( CI ) : 0.389–0.507 ) . There were 167 liver disease-related deaths and 223 deaths from other causes in the hepatitis C group , and 7 and 451 , respectively , in the general resident group . Liver disease-related death accounted for 43.8 % and 1.5 % of deaths in the hepatitis C and general resident groups ( p < 0.0001 ) . The cumulative survival rate of the hepatitis C patients without IFN ( n = 328 ) was significantly lower than the gender- and age-matched general resident group ( n = 656 ) ( p < 0.0001 ) but there was no significant difference between the IFN-treated ( n = 154 ) and general resident groups ( n = 308 ) . Conclusions In the hepatitis C group , the proportion of liver disease-related death was markedly higher , and the survival rate lower , than the general resident group . Introduction of IFN treatment in < 70-year-old patients with hepatitis C without LC or HCC improved the survival rate to a level comparable to that of the general residents Recent data suggest that interferon therapy ( IFN ) can reduce the risk of progression to hepatocellular carcinoma ( HCC ) in patients with hepatitis C virus (HCV)‐related cirrhosis AIM To determine the role of interferon ( IFN ) with or without ribavirin in preventing or delaying hepatocellular carcinoma ( HCC ) development in patients with hepatitis C virus ( HCV ) related cirrhosis . Data on the preventive effect of IFN plus ribavirin treatment are lacking . METHODS A total of 101 patients ( 62 males and 39 females , mean age 55.1+/-1.4 years ) with histologically proven HCV related liver cirrhosis plus compatible biochemistry and ultrasonography were enrolled in the study . Biochemistry and ultrasonography were performed every 6 mo . Ultrasound guided liver biopsy was performed on all detected focal lesions . Follow-up lasted for 5 years . Cellular proliferation , evaluated by measuring Ag-NOR proteins in hepatocytes nuclei , was expressed as AgNOR-Proliferative index ( AgNOR-PI ) ( cut-off = 2.5 ) . Forty-one patients ( 27 males , 14 females ) were only followed up after the end of an yearly treatment with IFN-alpha2b ( old treatment control group = OTCG ) . Sixty naive patients were stratified according to sex and AgNOR-PI and then r and omized in two groups : 30 were treated with IFN-alpha2b + ribavirin ( treatment group = TG ) , the remaining were not treated ( control group = CG ) . Nonresponders ( NR ) or relapsers in the TG received further IFN/ribavirin treatments after a 6 mo of withdrawal . RESULTS AgNOR-PI was significantly lowered by IFN ( P<0.001 ) . HCC incidence was higher in patients with AgNOR-PI>2.5 ( 26 % vs 3 % , P<0.01 ) . Two NR in the OTCG , none in the TG and 9 patients in the CG developed HCC during follow-up . The Kaplan-Mayer survival curves showed statistically significant differences both between OTCG and CG ( P<0.004 ) and between TG and CG ( P<0.003 ) . CONCLUSION IFN/ribavirin treatment associated with re-treatment courses of NR seems to produce the best results in terms of HCC prevention . AgNOR-PI is a useful marker of possible HCC development Hepatocellular carcinoma , a major cause of death in patients with cirrhosis , is one of the most prevalent malignant tumors worldwide , and its incidence is increasing [ 1 - 5 ] . After isolation of hepatitis C virus ( HCV ) , most patients with chronic hepatitis and those with cirrhosis of unknown origin were found to be positive for anti-HCV [ 6 - 8 ] . Evidence suggests that HCV-related chronic liver disease plays a role in the development of hepatocellular carcinoma [ 9 - 13 ] . A high proportion of patients with hepatocellular carcinoma have anti-HCV , although the prevalence varies geographically . The highest rate of anti-HCV is in southern Europe and Japan , where about 70 % of patients with hepatocellular carcinoma are positive for anti-HCV [ 5 ] . Interferon has been widely used to treat chronic HCV infection . A series of clinical trials showed that some patients who received interferon had sustained normalization of serum aminotransferase levels and elimination of serum HCV RNA [ 14 - 17 ] . Histologic improvement was also seen in patients who received interferon [ 14 , 18 - 20 ] . It is important to determine whether interferon treatment also lowers the incidence of hepatocellular carcinoma in patients with chronic hepatitis C , but the recognized benefits of interferon make a r and omized , controlled trial to address this question unethical . We did a retrospective study to compare the incidence of hepatocellular carcinoma in interferon-treated patients with HCV infection and histologically proven chronic hepatitis or cirrhosis with that in historical controls who did not receive interferon . We also examined the relation between response to interferon therapy and incidence of hepatocellular carcinoma . Methods Patients The interferon group comprised 419 consecutive patients with chronic hepatitis C who had undergone liver biopsy 1 to 2 weeks before interferon therapy and had started treatment between January 1992 and December 1993 . The control group consisted of 144 consecutive patients with chronic hepatitis or cirrhosis who had undergone liver biopsy between January 1986 and December 1989 . All patients had histologically proven chronic hepatitis or cirrhosis ( Child-Pugh class A ) and were positive for anti-HCV . Interferon Treatment In the interferon group , 176 patients received human lymphoblastoid interferon , 149 received recombinant interferon- 2a , and 94 received recombinant interferon- 2b for 6 months . The median total interferon dose was 480 mU ( range , 282 to 800 mU ) . No patient had received interferon therapy before study entry . Contraindications to interferon treatment included pregnancy , presence of hepatitis B surface antigen , other types of liver disease , autoimmune disease , and any other serious illness . Efficacy of interferon therapy was categorized as follows . Patients with persistent normalization of alanine aminotransferase ( ALT ) levels during interferon therapy and follow-up were considered to have sustained response . Patients whose serum ALT level was normal at the end of the treatment but increased to an abnormal level after cessation of treatment were considered to have relapse . All other patients were classified as nonresponders . Follow-up Abdominal ultrasonography or computed tomography was performed every 4 to 8 months , and serum -fetoprotein was measured every 2 to 6 months . The diagnosis of hepatocellular carcinoma was confirmed by needle biopsy , by surgically resected tumor specimens , or by typical radiologic findings on hepatic angiography . The starting date of follow-up for patients in the interferon and control groups was defined as the date of liver biopsy . For both groups , the end of follow-up was the development of hepatocellular carcinoma or December 1991 in the control group and the time of the latest abdominal imaging in the interferon group . To detect hepatocellular carcinoma , follow-up examinations were done in 85.4 % of controls and 90.7 % of patients in the interferon group . The Osaka Cancer Registry was used [ 21 , 22 ] to determine whether hepatocellular carcinoma had occurred in patients lost to follow-up . This population -based cancer registry has been operating since December 1962 with the cooperation of the Osaka Medical Association , the Department of Health of Osaka Prefecture , and Osaka Medical Center for Cancer and Cardiovascular Diseases . It covers all of Osaka Prefecture , which had a population of 8.6 million in 1995 , and registers cases of cancer by using reports from hospitals and clinics and death certificates collected from health centers . One patient in each group who had been lost to follow-up was listed as having hepatocellular carcinoma in the Osaka Cancer Registry . Determination of the Presence of Hepatitis C Virus Antibody and Hepatitis C Virus RNA Hepatitis C virus antibody was measured by first- , second- , or third-generation enzyme-linked immunosorbent assays ( Ortho Diagnostics , Tokyo , Japan ) . Serum HCV RNA was measured by reverse transcription polymerase chain reaction or complementary DNA assay , as reported elsewhere [ 23 , 24 ] . Assessment of Liver Histologic Findings The histologic findings in liver biopsy specimens were scored by three of the authors in a blinded manner by using two scoring methods . For assessment of histologic staging , fibrosis score ( F1 to F3 for chronic hepatitis and F4 for cirrhosis ) was used ; F1 indicated portal fibrous expansion , F2 indicated portal-portal septa without architectural distortion , F3 indicated porto central septa with architectural distortion , and F4 indicated cirrhosis [ 25 ] . For assessment of histologic grading , a total score of histologic activity ( components 1 to 3 ) of the Knodell histologic activity index was used [ 26 ] . Statistical Analysis Patients who did not complete the treatment protocol were included for analysis on an intention-to-treat basis . The chi-square test was used to compare the baseline characteristics of both groups . The Wilcoxon rank-sum test was used to assess a significant difference between tumor sizes in the two groups . The Kaplan-Meier method was used to calculate the cumulative incidence of hepatocellular carcinoma , and the log-rank test was used to compare the cumulative incidence of hepatocellular carcinoma between the groups . To estimate independent risk factors for the development of hepatocellular carcinoma , Cox proportional-hazards regression analysis was used . For analysis , interferon therapy , age , sex , serum ALT level , serum -fetoprotein level , platelet count , histologic staging , and activity scores were used as variables . A P value less than 0.05 was considered statistically significant . Data are expressed as medians and ranges and as risk ratios and 95 % CIs . Results Table 1 shows the baseline characteristics of the interferon and control groups . The groups did not differ for age , sex , serum ALT level , or platelet count . In the interferon group , 387 patients ( 92 % ) had chronic hepatitis ( 128 had F1 disease , 138 had F2 disease , and 121 had F3 disease ) and 32 ( 8 % ) had cirrhosis . In the control group , 124 patients ( 86 % ) had chronic hepatitis ( 30 had F1 disease , 38 had F2 disease , and 56 had F3 disease ) and 20 ( 14 % ) had cirrhosis ( P = 0.005 ) . The proportion of patients with serum -fetoprotein levels greater than 20 ng/mL was higher in the control group ( 24 % ) than in the interferon group ( 15 % ) ( P = 0.011 ) . Table 1 . Baseline Characteristics of Interferon-Treated Patients and Historical Controls with Chronic Hepatitis C In the interferon group , 151 patients ( 36 % ) had sustained response , 120 ( 29 % ) had relapse , and 148 ( 35 % ) were nonresponders . In the 143 patients with sustained response , serum HCV RNA was measured during follow-up . Sustained absence of serum HCV RNA was noted in 120 ( 84 % ) of these patients . Twenty-one patients could not complete the 6-month treatment protocol because of depression ( 5 patients ) , severe general fatigue ( 4 patients ) , skin eruptions ( 2 patients ) , severe reduction of serum platelet count ( 1 patient ) , pulmonary tuberculosis ( 1 patient ) , interstitial pneumonia ( 1 patient ) , severe nausea ( 1 patient ) , ischemic colitis ( 1 patient ) , cardiomyopathy ( 1 patient ) , hyperthyroidism ( 1 patient ) , and hypermenorrhea ( 1 patient ) . One patient stopped treatment because of his business , and one patient discontinued treatment after 3 months because hepatocellular carcinoma was diagnosed . Only 1 of the 21 patients who did not complete treatment showed sustained response ; all others were nonresponders . Median follow-up was 47.6 months ( range , 3.3 to 65.2 months ) in the interferon group and 46.8 months ( range , 6.9 to 71.6 months ) in the control group . During follow-up , hepatocellular carcinoma was found in 19 controls ( 4 with F2 disease , 8 with F3 disease , and 7 with F4 disease ) . In the interferon group , 28 patients developed hepatocellular carcinoma during follow-up ( 2 patients with F1 disease , 5 with F2 disease , 13 with F3 disease , and 8 with F4 disease ) . A final diagnosis of hepatocellular carcinoma was made histologically in 17 patients in the interferon group ( 61 % ) and 11 controls ( 58 % ) . In 11 patients ( 39 % ) in the interferon group and 8 controls ( 42 % ) , a final diagnosis was made on the basis of typical angiographic findings . The maximum tumor sizes of hepatocellular carcinoma in the interferon and control groups at the time of discovery on ultrasonography or computed tomography were 20 mm ( range , 10 to 52 mm ) and 24 mm ( range , 10 to 50 mm ) , respectively ( P > 0.2 ) . Figure 1 shows the cumulative incidence of hepatocellular carcinoma in the interferon and control groups , estimated by using the Kaplan-Meier method . The 4-year rate of hepatocellular carcinoma incidence was 6.6 % in the interferon group and 12.2 % in the control group ( log-rank test , P = 0.040 ) . Figure 1 . Cumulative incidence of hepatocellular carcinoma ( HCC ) in interferon-treated patients ( dotted line ) and historical controls ( solid line ) with chronic hepatitis C. P Cox proportional-hazards regression analysis was performed to identify factors Context Few studies address long-term outcomes of antiviral therapy for patients with chronic hepatitis C and cirrhosis . Contribution This prospect i ve study of adults with chronic hepatitis C and cirrhosis compares outcomes between 74 patients who declined treatment and 271 patients treated with thrice-weekly interferon injections for 26 to 88 weeks . Median follow-up was 6.8 years . Fewer treated patients developed hepatocellular cancer ( 31 % vs. 47 % of untreated patients ) or died ( 17 % vs. 32 % ) . Caution s Because the study was not a r and omized , controlled trial , prognostic factors other than interferon might have contributed to the differences between groups . The Editors Chronic hepatitis C is a common disease that progresses slowly to cirrhosis and eventually may lead to hepatocellular carcinoma ( 1 - 5 ) . The annual incidence of hepatocellular carcinoma and mortality rate were 1.4 % to 3.3 % and 1.9 % to 5.5 % , respectively , in retrospective series of white patients with hepatitis C virus (HCV)related compensated cirrhosis ( 4 - 9 ) ; in Japan , the annual incidence of hepatocellular carcinoma was 5 % to 7 % ( 10 - 12 ) . Risk factors for hepatocellular carcinoma include age older than 50 to 60 years , male sex , advanced fibrosis stage , high histologic activity score , and high alanine aminotransferase ( ALT ) levels ( 4 - 14 ) . Several retrospective studies have shown inhibition of hepatocellular carcinoma development after interferon therapy ( 11 - 14 ) . This inhibitory effect was seen in patients with moderate fibrosis for whom antiviral therapy was effective ( 11 - 14 ) . However , the inhibitory effect in patients with liver cirrhosis was not statistically significant ( 4 , 7 , 8 , 15 ) , possibly because of the low efficacy of interferon therapy in cirrhotic patients ( 15 - 17 ) . Other retrospective ( 6 , 9 ) and prospect i ve ( 18 ) studies that had small patient sample s indicated that interferon therapy reduced the development of hepatocellular carcinoma . Because cirrhosis is a major risk factor for hepatocellular carcinoma , a prospect i ve study is needed to determine whether interferon therapy benefits cirrhotic patients . We previously performed 2 prospect i ve studies on the efficacy of interferon treatment in cirrhotic patients ( 19 , 20 ) . During enrollment , many cirrhotic patients who fulfilled the inclusion criteria were enrolled as controls to clarify the long-term effect of interferon therapy on development of liver tumors . We conducted a 7-year study on the inhibition of hepatocellular carcinoma development in the previous cohorts of our multicenter , prospect i ve study . Methods Study Sample Enrollment of Patients with Compensated Liver Cirrhosis Design s for the 2 protocol s , Interferon alfa-2a prospect i ve trial for cirrhotic patients modification of treatment duration by monitoring HCV RNA in the serum ( 19 ) and Natural interferon trial for cirrhotic patients modification of interferon treatment duration according to pretreatment viral load ( 20 ) were finalized on 18 December 1992 and 20 April 1993 , respectively . While discussing these 2 protocol s , we decided to extend the prospect i ve studies after the initial trial to examine the effect of antiviral therapy on the inhibition of hepatocellular carcinoma development and patient survival as secondary end points . Inclusion Criteria Our previous reports ( 19 , 20 ) describe in more detail the diagnosis of chronic hepatitis C with cirrhosis and the inclusion criteria for the 2 trials ( 19 , 20 ) . The diagnostic criteria were elevated serum ALT levels for more than 6 months , positivity for anti-HCV antibody by the phytohemagglutinin assay ( Dinabbot , Tokyo , Japan ) or enzyme-linked immunosorbent assay ( Ortho Diagnostic Systems , Tokyo , Japan ) , and abnormal histologic findings on liver biopsy specimens . The presence of HCV RNA was tested by reverse transcriptase polymerase chain reaction ( RT-PCR ) ( detection limit , 102 copies/mL ) , and the serum HCV RNA level was measured by competitive RT-PCR according to the method of Kato and colleagues ( 21 ) . The HCV genotype was established by using the method of Okamoto and colleagues ( 22 ) . Liver biopsy was done in all patients within 12 months before enrollment , and specimens were evaluated according to the criteria of Desmet and colleagues ( 23 ) . Inclusion criteria were based on liver histologic characteristics indicating fibrotic stage F4 , positivity for HCV RNA by RT-PCR , platelet count greater than 50 109 cells/L , leukocyte count greater than 3 109 cells/L , and ChildPugh A classification . We excluded patients who had liver cirrhosis caused by hepatitis B , autoimmune hepatitis , primary biliary cirrhosis , or drug-induced liver disease . Before enrollment , patients had abdominal ultrasonography , dynamic computed tomography ( CT ) , or magnetic resonance imaging ( MRI ) ; we excluded patients who were found to have hepatocellular carcinoma . Antiviral Therapy A total of 157 patients received 9 million units ( MU ) of interferon-2a ( Nippon Roche KK , Tokyo , Japan ) by intramuscular injection 3 times a week for 32 to 88 weeks ; duration of therapy was based on serum HCV RNA status during therapy ( 19 ) . The mean and median duration of therapy were 44 and 48 weeks , respectively , and the mean and median dose of interferon were 1011 and 936 MU ( range , 42 to 2378 MU ) , respectively . A total of 114 patients received 9 or 6 MU of natural interferon- ( Sumitomo Pharmaceutical Co. , Osaka , Japan ) by subcutaneous injection 3 times a week for 6 months ( patients with low viral load ) or 12 months ( patients with high viral load ) ( 20 ) . The mean and median duration of therapy were 33 and 26 weeks , respectively , and the mean and median dose of interferon were 688 MU and 564 MU ( range , 18 to 1404 MU ) , respectively . For the 2 trials combined , the mean duration of treatment was 39 weeks ( range , 1 to 88 weeks ) and the mean dose of interferon was 875 MU ( range , 18 to 2376 MU ) . Eighty-eight percent of the patients took more than 80 % of the drug during 80 % of the scheduled treatment period . Patients negative for HCV RNA more than 24 weeks after the completion of interferon therapy were considered to show a sustained virologic response , while patients positive for HCV RNA more than 24 weeks after the completion of interferon therapy were considered to show a nonsustained response . Study Design This was not a r and omized study . A total of 271 patients received interferon therapy ; 74 patients who fulfilled the inclusion criteria for the trials but declined to receive interferon therapy instead received periodic medical screenings at outpatient clinics in each institute , provided informed consent , and were enrolled in the untreated group ( Figure 1 ) . Thus , the sample size for this study was set at 345 as of April 1996 . We established a 5-year follow-up study to obtain statistical significance with a power of 80 % on the assumption that the efficacy of interferon therapy would be 25 % and the incidence of hepatocellular carcinoma development among responders would be reduced to a risk ratio of 0.3 compared to untreated patients or nonsustained responders based on the preliminary data from the retrospective cohort study ( 11 ) . In April 2001 , we extended the length of the mean follow-up period from 5 years to 7 years because the incidence of hepatocellular carcinoma development in the interferon group was higher than initially anticipated . Figure 1 . Flow diagram of the trial . Approval The ethics committee of each participating institution approved the study . Informed consent was obtained from each patient according to the Helsinki Declaration . Previously participating physicians at 6 institutes had resigned before this follow-up study began , and the new chief physicians did not resu bmi t this protocol to the ethical committee of each institute . Thus , we did not follow the patients enrolled at these institutes ( n= 17 ) . We considered these patients to be censored participants who did not go on to participate in the subsequent follow-up study . Patient Follow-up We followed patients by performing blood tests and measuring biochemical variables every 1 to 2 months . Abdominal ultrasonography was done every 3 to 6 months . Patients did not receive any additional antiviral therapy thereafter because the Japanese National Health Insurance plan did not approve interferon treatment for cirrhotic patients . If a patient relocated during follow-up , data from medical examinations at the nearest outpatient clinic were collected from a private physician or by fax or telephone . Patients without data from a medical consultation were contacted by letter or telephone and advised to receive a medical check-up at the closest outpatient clinic . The median follow-up period from the time of initial enrollment was 6.8 years ( range , 0.04 to 10.4 years ) . Detection of Hepatocellular Carcinoma If a suspicious hepatocellular lesion was detected by ultrasonography , the patient had dynamic CT or MRI , along with arteriography . Board-certificated radiologists at each institute diagnosed hepatocellular carcinoma on the basis of typical patterns , such as early-phase hyperattenuation area and late-phase hypoattenuation on dynamic CT or MRI . At times , board-certified pathologists who were unaware of patients ' clinical data confirmed the diagnosis using ultrasonography-guided tumor biopsy . Treatment of Hepatocellular Carcinoma If the liver tumor consisted of fewer than 3 nodules that were less than 3 cm in diameter , patients received percutaneous ethanol injection therapy , microwave coagulation therapy , radiofrequency ablation therapy , or surgical hepatectomy ( 24 - 28 ) . Patients with stage III and IV hepatocellular carcinomas were treated with transarterial chemoembolization or chemotherapy ( 29 ) . Patient Survival We examined patient survival or the causes of death . Statistical Analysis We used SAS , version 8.2 ( SAS Institute , Inc. , Cary , North Carolina ) , for statistical analysis . A Wilcoxon test or Fisher exact test was used to compare the distribution of variables between the groups . Hepatitis C virus ( HCV ) infection rarely resolves spontaneously once it becomes chronic ( 1 ) . Most patients remain asymptomatic for a long period , with liver cirrhosis developing after approximately 30 years ( 2 , 3 ) . Chronic hepatitis C with cirrhosis is a major risk factor for hepatocellular carcinoma ( 4 - 7 ) . It has been previously shown that the risk increases with the degree of liver fibrosis ( 5 ) . Interferon is the only agent known to be effective against HCV infection ( 8 - 10 ) . It induces a sustained virologic response in 15 % to 30 % of patients ( 11 - 14 ) . Responders usually show biochemical and histologic improvement ( 9 , 11 , 15 ) . Recently , interferon therapy in patients with chronic hepatitis C and cirrhosis was shown to be associated with a reduced incidence of hepatocellular carcinoma ( 16 ) . Because most patients treated with interferon do not have cirrhosis , we included noncirrhotic as well as cirrhotic patients in our analysis of the effect of interferon therapy on the incidence and prevention of hepatocellular carcinoma . A national surveillance program , the Inhibition of Hepatocarcinogenesis by Interferon Therapy ( IHIT ) Study , was begun in 1994 as a multicenter , large-scale , retrospective cohort study supported by the Japan Ministry of Health and Welfare as one of the Comprehensive 10-Year Strategy for Cancer Control Projects ( 17 ) . In this program , patients with chronic hepatitis C who have undergone liver biopsy at one of eight participating institutions are enrolled and followed periodically for development of hepatocellular carcinoma by using several imaging techniques . We analyzed the incidence of hepatocellular carcinoma as of February 1998 by using multivariate proportional hazards regression . Methods Patients The IHIT Study Group approved the design of this study on 21 September 1994 . All patients who were positive by a second-generation HCV antibody assay and who had undergone liver biopsy since 1986 at one of the eight participating institutions were enrolled . Patients who were participants in interferon trials for non-A , non-B chronic hepatitis ( 18 - 21 ) and in whom anti-HCV seropositivity was confirmed by using stored sera were also included ; these patients had undergone liver biopsy in 1986 or later . Patients were excluded if at the time of liver biopsy they presented with hepatocellular carcinoma or other liver diseases , such as chronic hepatitis B , alcoholic liver disease , autoimmune hepatitis , or primary biliary cirrhosis . The minimum follow-up was established as 1 year for two reasons . First , if hepatocellular carcinoma is detected within 1 year after liver biopsy , the possibility that the cancer was present at the time of liver biopsy can not be ruled out . Second , interferon therapy must be started within 1year after liver biopsy according to Japanese health insurance rules . By February 1998 , 3223 patients who fulfilled the inclusion criteria were registered . Of these patients , 333 were excluded from the analysis : 161 patients ( 5.0 % ) transferred to other hospitals without follow-up , and the follow-up period after liver biopsy was less than 1 year for172 patients ( 5.3 % ) . Thus , 2890 patients were included in the present analysis . Figure 1 shows the schema for patient selection . Figure 1 . Schema for patient selection . Interferon therapy was given to 2400 patients ; 490 patients did not receive treatment ( control group ) . Interferon therapy was initiated within 1 year after liver biopsy ( within 6 months in 93 % of patients ) ; 84 % of patients received interferon- , 14 % received interferon- , and 2 % received a combination of interferon- and interferon- . The median total dose was 480 MU ( first quartile , 324 MU ; third quartile , 702 MU ) , and the median duration of administration was 160 days(first quartile , 94 days ; third quartile , 168 days ) . Once interferon therapy was started , a patient was included in the interferon treatment group even if therapy was discontinued because of adverse events or other reasons . The 490 patients who did not receive interferon chose this course of action voluntarily on the basis of concerns about adverse effects ; lack of time for therapy ; or physician recommendation , which took into account depression , severe diabetes mellitus , or other medical conditions . Serum HCV load was quantitatively determined at the timeof liver biopsy by using various commercial and in-house assays . Because it is difficult to correlate the results of different assay methods , only data obtained with two widely used assays , the branched-DNA probe assay ( 22 ) and competitive reverse-transcription polymerase chain reaction ( RT-PCR ) ( 23 ) , were used . HCV RNA genotype was determined by RT-PCR using genotype-specific primers ( 24 ) or by serologic grouping of serum antibody ( 25 ) , assuming that genotypes 1a and 1b correspond to serologic group 1 ( genotype 1 ) and genotypes 2a and 2b correspond to serologic group 2 ( genotype 2 ) ( 11 ) . Histologic Evaluation Liver biopsy specimens were evaluated by a representative pathologist at each institution ( a total of eight pathologists were involved ) and were scored for the stage of liver fibrosis and grade of inflammatory activity according to the classification of Desmet and colleagues ( 26 ) . Stage of fibrosis was assessed from stage F0 ( no fibrosis ) to stage F4 ( cirrhosis ) , and grade of inflammatory activity was scored from grade A1 ( mild ) to grade A3 ( severe ) . To confirm interobserver concordance in scoring , a subsequent blind and independent examination of 350r and omly selected liver biopsy specimens was conducted by two of the eight pathologists . Definition of Interferon Response Virologic and biochemical criteria were used to define response to interferon therapy . Hepatitis C virus RNA was used as a marker of virologic response and was determined by RT-PCR . A virologic sustained response was defined as HCV RNA negativity more than 6 months after termination of interferon therapy ; positivity at the same time point was considered a nonsustained response ( 27 ) . Patients with nonsustained response included those who had temporary disappearance of viremia followed by relapse . In patients treated before the availability of RT-PCR , virologicresponse was determined by using sera stored at 30 C or collected afterward . The serum alanine aminotransferase ( ALT ) level was used as a marker of biochemical response to interferon therapy . Sustained biochemical response was defined as persistently normal serum ALT levels more than 6 months after termination of interferon therapy ; nonsustained response was defined as elevated serum ALT levels at the same time point . Nonsustained response was subdivided into two categories : mildly elevated for a serum ALT level less than two times the upper limit of normal and highly elevated for a serum ALT level two or more times the upper limit of normal . Screening for Hepatocellular Carcinoma Patients were examined for hepatocellular carcinoma by abdominal ultrasonography at least every 6 months . If hepatocellular carcinoma was suspected on the basis of ultrasonographic results , additional procedures , such as computed tomography , magnetic resonance imaging , abdominal angiography , and ultrasonography-guided tumor biopsy , were used to confirm the diagnosis . Statistical Analysis Statistical analysis was performed by using SAS software , version 6.12 ( SAS Institute , Inc. , Cary , North Carolina ) . Interobserver concordance of histologic scoring was evaluated by using the Spearman correlation coefficient . Differences between two groups were evaluated by using the unpaired Student t-test or the Mann-Whitney U-test . Categorical data were compared by using the chi-square test or the Fisher exact probability test . Cumulative incidence curves were determined with the Kaplan-Meier method , and the differences between groups were assessed by using the log-rank test . We used the Cox proportional-hazards regression analysis to examine the effect of interferon therapy on the incidence of hepatocellular carcinoma . Because virologic and biochemical responses were mutually dependent , the risk ratio for hepatocellular carcinoma was calculated separately for these factors . The risk ratio attributable to categorical data , such as stage of liver fibrosis and serum ALT level , was calculated by using dummy variables . A P value less than 0.05 was considered statistically significant . Results Patient Characteristics The demographic and clinical features of patients at the time of their enrollment are summarized in Table 1 . The frequency distribution of the stages of liver fibrosis differed between interferon-treated patients and untreated patients . Most laboratory values also differed between the two groups . However , differences in laboratory values between treated patients and untreated patients were not significant at the same stage of fibrosis . This indicated the need to adjust for stage of liver fibrosis , which was done in the following analyses . Table 1 . Demographic and Clinical Characteristics Histologic Evaluation The concordance in scores for stage of fibrosis and grade of inflammatory activity determined at each institution and by the two representative pathologists was strong , with Spearman coefficients ranging from 0.897 to 0.918 for stage of fibrosis and from 0.878 to 0.849 for grade of inflammatory activity . The original score was sustained by at least one of the two pathologists in 319 of 350 cases for fibrosis staging and in 320 of 350cases for grading inflammatory activity . Response to Interferon Therapy Response to interferon therapy was determined in 2357(98.2 % ) of the 2400 interferon-treated patients . Response was not determined in43 patients because of insufficient follow-up ( < 6 months ) after termination of therapy . A sustained virologic response was achieved in 789 patients ( 33.5 % ) . The response rate was similar regardless of the type of interferon used ( 32.3 % , 34.5 % , and 25.6 % for interferon- , interferon- , and the combination of the two , respectively ) . A sustained BACKGROUND / AIM Hepatocellular carcinoma frequently develops during the advanced stages of chronic hepatitis C. We examined whether interferon prevents the development of hepatocellular carcinoma in chronic hepatitis C patients . METHODS Japanese patients with chronic hepatitis C ( n = 1.148 ; 117 with portal fibrous expansion ( F1 ) , 636 with bridging fibrosis ( F2 ) , 355 with bridging fibrosis and architectural distortion ( F3 ) ) and 40 cirrhotic ( F4 ) patients were treated with interferon . These patients were followed from 1 to 7 years after interferon therapy . Blood tests and image analysis were serially performed to assess response to interferon and to detect hepatocellular carcinoma . Fifty-five cirrhotic type C patients ( control F4 ) not receiving interferon were enrolled in this study . RESULTS Sustained ( SR : 27.5 % ) and transient ( TR : 23.0 % ) responders totaled 50.5 % , while 49.5 % did not respond to interferon . SR showed an improvement in disease stage reflected by increased platelet counts . Fifty-two patients ( 9 F2 , 36 F3 , and 7 F4 ) developed hepatocellular carcinoma in the follow-up period ; 3 SR , 8 TR , and 41 non-responders ( NR ) . The cumulative incidence of hepatocellular carcinoma in F2 was significantly lower ( p = 0.019 ) in SR compared with NR , but not in SR in F3 and F4 patients . However , the cumulative incidence of hepatocellular carcinoma was significantly decreased in all SR ( p = 0.0001 ) and TR ( p = 0.0397 ) compared with all NR . CONCLUSION These results indicate that interferon therapy in chronic hepatitis C patients lowered the rate of progression of hepatocellular carcinoma in sensitive cases but not in patients in an advanced stage Background As the era of interferon-alpha (IFN)-based therapy for hepatitis C ends , long-term treatment outcomes are now being evaluated . Aim To more fully underst and the natural history of hepatitis C infection by following a multisite cohort of patients . Methods Patients with chronic HCV were prospect ively enrolled in 1999–2000 from 11 VA medical centers and followed through retrospective medical record review . Results A total of 2211 patients were followed for an average of 8.5 years after enrollment . Thirty-one percent of patients received HCV antiviral therapy , 15 % with st and ard IFN/ribavirin only , 16 % with pegylated IFN/ribavirin , and 26.7 % of treated patients achieved sustained virologic response ( SVR ) . Cirrhosis developed in 25.8 % of patients . Treatment nonresponders had a greater than twofold increase in the hazard of cirrhosis and hepatocellular carcinoma , compared to untreated patients , whereas SVR patients were only marginally protected from cirrhosis . Nearly 6 % developed hepatocellular carcinoma , and 27.1 % died during the follow-up period . Treated patients , regardless of response , had a significant survival benefit compared to untreated patients ( HR 0.58 , CI 0.46–0.72 ) . Improved survival was also associated with college education , younger age , lower levels of alcohol consumption , and longer duration of medical service follow-up — factors typically associated with treatment eligibility . Conclusions As more hepatitis C patients are now being assessed for all-oral combination therapy , these results highlight that patient compliance and limiting harmful behaviors contribute a significant proportion of the survival benefit in treated patients and that the long-term clinical benefits of SVR may be less profound than previously reported BACKGROUND The long-term benefit for chronic hepatitis C ( CHC ) patients treated with interferon (IFN)/ribavirin ( RBV ) combination therapy remains unclear . We aim ed to evaluate the long-term effects of IFN monotherapy and IFN/RBV combination therapy on reducing hepatocellular carcinoma ( HCC ) and mortality in patients with chronic hepatitis C virus ( HCV ) infection , adjusting for risk factors . METHODS A total of 1,619 patients with biopsy-proven CHC , including 1,057 receiving IFN-based therapy ( 760 on IFN/RBV combination therapy ) and 562 untreated controls from three medical centres and one regional core hospital in Taiwan were enrolled in this retrospective- prospect i ve cohort study . RESULTS The incidence of HCC and survival during a follow-up period of 1.0 - 15.3 ( mean 5.18 ) and 1 - 16 ( mean 5.15 ) years in treated and untreated patients , respectively , was analysed using Cox proportional hazards regression . The cumulative incidence of HCC was 35.2 % and 12.2 % for untreated and treated groups , respectively ( P=0.0013 ) . The cumulative survival rate was 93.1 % and 96.2 % for untreated and treated groups , respectively ( P=0.3928 ) . Significantly lower incidences of HCC and mortality were observed in sustained virological responders ( both for IFN monotherapy and IFN/RBV combination ) but not in nonresponders when compared with untreated patients . HCV genotype 1 patients had significantly higher incidences of HCC than genotype non-1 patients . In multivariate analysis , pre-existing cirrhosis , non-response , HCV genotype-1 and age were associated with HCC ; pre-existing cirrhosis and non-response correlated to mortality . CONCLUSION A sustained virological response secondary to IFN monotherapy or IFN/RBV combination therapy could reduce the risk for HCC and improve survival of CHC patients Background Data on the efficacy of antiviral therapy in patients with HCV-related compensated cirrhosis are generally drawn from analyzing subgroups in larger trials . Aims ( 1 ) To analyze the safety and efficacy of combination therapy in naive patients with HCV-related cirrhosis ; ( 2 ) to evaluate the factors influencing the sustained virologic response ( SVR ) in cirrhotic patients by comparison with a group of noncirrhotic patients ; ( 3 ) to analyze the outcome of cirrhotic patients either acquiring SVR and nonresponders to the antiviral therapy during the posttreatment follow-up . Methods We consecutively enrolled 365 patients with biopsy-proven HCV-related chronic hepatitis meeting the inclusion criteria for pegylated interferon a-2b plus Ribavirin : 87 patients had compensated liver cirrhosis and 278 had histologic stages between 1 and 4 according to Ishak 's classification . Results The 2 groups were comparable for genotype , viral load , and alanine transferase at presentation . Cirrhotic patients were significantly older and had significantly higher body mass index , serum ferritin , and gamma-glutamyl transpeptidase . The rate of side effects was similar in the 2 groups , whereas the rate of SVR was significantly lower in cirrhotic ( 45.9 % ) than in noncirrhotic patients ( 65.8 % ) . Logistic regression analysis showed that genotype 1 to 4 and high viral load were independent variables correlating with nonresponse in the sample as a whole . During follow-up , hepatocellular carcinoma developed in 5/38 ( 13.2 % ) cirrhotic patients not responding or relapsing after treatment . No cases of hepatocellular carcinoma were seen among cirrhotic or noncirrhotic patients with a SVR . Conclusions Cirrhotic patients with compensated disease have a reasonably good chance of virologic response and should be offered treatment , carefully monitoring any side-effects To examine the effects of interferon ( IFN ) therapy on clinical , biochemical , and histological features in patients with compensated hepatitis C virus (HCV)-related cirrhosis , we have conducted a r and omized , controlled trial of IFN therapy versus observation . Eight centers included a total of 99 patients with biopsy-proven cirrhosis . IFN-alpha2b , 3 million units three times per week , or no antiviral therapy was given for 48 weeks . Twenty-three patients dropped out . End-of-treatment biochemical response was not observed in any of the 39 controls but was observed in 6 of the 47 treated patients ( P < .02 ) ; sustained biochemical response was obtained in only 2 treated patients . Controls and treated patients did not significantly differ with regard to the changes in serum level of albumin , bilirubin , alpha-fetoprotein , in plasma prothrombin , in histological activity , or liver collagen content . During trial or follow-up ( 160 + /- 57 weeks ) , hepatocellular carcinoma developed in 9 controls and 5 treated patients ( NS ) ; decompensation of cirrhosis occurred in 5 controls and 7 treated patients . Seven controls and 10 treated patients died . In conclusion , in patients with compensated HCV-related cirrhosis , a 48-week course of IFN therapy is safe and is able to induce end-of-treatment biochemical response in a significant proportion of patients . However , a 48-week course of IFN therapy usually fails to achieve sustained response and , within the limit of this study , did not significantly improve the 3-year outcome . Therefore , a longer course of IFN therapy or combination therapy with ribavirin should be evaluated in patients with HCV-related cirrhosis UNLABELLED Retrospective studies suggest that subjects with chronic hepatitis C and advanced fibrosis who achieve a sustained virological response ( SVR ) have a lower risk of hepatic decompensation and hepatocellular carcinoma ( HCC ) . In this prospect i ve analysis , we compared the rate of death from any cause or liver transplantation , and of liver-related morbidity and mortality , after antiviral therapy among patients who achieved SVR , virologic nonresponders ( NR ) , and those with initial viral clearance but subsequent breakthrough or relapse ( BT/R ) in the HALT-C ( Hepatitis C Antiviral Long-Term Treatment Against Cirrhosis ) Trial . Laboratory and /or clinical outcome data were available for 140 of the 180 patients who achieved SVR . Patients with nonresponse ( NR ; n = 309 ) or who experienced breakthrough or relapse ( BT/R ; n = 77 ) were evaluated every 3 months for 3.5 years and then every 6 months thereafter . Outcomes included death , liver-related death , liver transplantation , decompensated liver disease , and HCC . Median follow-up for the SVR , BT/R , and NR groups of patients was 86 , 85 , and 79 months , respectively . At 7.5 years , the adjusted cumulative rate of death/liver transplantation and of liver-related morbidity/mortality in the SVR group ( 2.2 % and 2.7 % , respectively ) was significantly lower than that of the NR group ( 21.3 % and 27.2 % , P < 0.001 for both ) but not the BT/R group ( 4.4 % and 8.7 % ) . The adjusted hazard ratio ( HR ) for time to death/liver transplantation ( HR = 0.17 , 95 % confidence interval [ CI ] = 0.06 - 0.46 ) or development of liver-related morbidity/mortality ( HR = 0.15 , 95 % CI = 0.06 - 0.38 ) or HCC ( HR = 0.19 , 95 % CI = 0.04 - 0.80 ) was significant for SVR compared to NR . Laboratory tests related to liver disease severity improved following SVR . CONCLUSION Patients with advanced chronic hepatitis C who achieved SVR had a marked reduction in death/liver transplantation , and in liver-related morbidity/mortality , although they remain at risk for HCC BACKGROUND / AIMS Recent experiences suggest that interferon may significantly decrease the incidence of hepatocellular carcinoma . We conducted a r and omized study with interferon versus no therapy in hepatitis C virus Child A cirrhosis with abnormal alanine aminotransferase and HCV-RNA positive serum with the aim to investigate the incidence of hepatocellular carcinoma , worsening of cirrhosis 's stage and death or orthotopic liver transplantation . METHODOLOGY A cohort of 122 patients prospect ively followed was analyzed retrospectively to assess the effect of interferon therapy ( mean follow-up : 96 + /- 18.3 months ) . We only chose patients with hepatitis C virus infection who had undergone blood transfusion before 1980 . Hepatitis C virus serotype was determined by hepatitis C virus serotyping 1 - 6 assay ( Murex Biothec Limited Temple Hill , Dartford , Kent , UK ) . HCV-RNA level was determined by bDNA , Chiron Corporation Emeryville , CA . Diagnosis of hepatocellular carcinoma was made on the basis of the appearance of local lesions at periodic ultrasound examination of the liver and confirmed with spiral computed tomography . Fine needle biopsy under sonographic guidance was effected . Fifty-nine patients ( mean age : 55.3 + /- 7 ) received interferon ( 3MU three times a week for 12 months ) , 8 stopped therapy for side effects , 71 did not receive interferon ( mean age : 56.8 + /- 8) . Baseline characteristics were similar . RESULTS It emerges how interferon does not reduce the risk of hepatocellular carcinoma in compensated cirrhosis . In interferon treated patients an improvement in relation with worsening and death/orthotopic liver transplantation has been noted . CONCLUSIONS The use of the interferon seems to be scarcely useful when structural alterations of the cirrhotic kind show up , as cirrhosis represents by itself a risk factor for hepatocellular carcinoma . Nevertheless , in relation to the worsening of cirrhosis 's stage the interferon therapy can be useful in compensated cirrhosis BACKGROUND / AIMS Around 15 - 25 % of chronic hepatitis C patients treated with Peg-IFN plus ribavirin become HCV-RNA negative by PCR during therapy but relapse after its withdrawal . We investigated whether minimal residual viremia ( MRV ) might be detected in these cases by Transcription-Mediated Amplification ( TMA ) . METHODS Two hundred and ninety-two consecutive patients ( 143 HCV-1 , 82 HCV-2 , 56 HCV-3 and 11 HCV-4 ) were prospect ively treated with a st and ard schedule of Peg-IFNalpha 2b plus ribavirin combination and end-of-therapy response was assessed by conventional PCR using 2 protocol serum sample s obtained 6 - 8h before the last two scheduled weekly injections of Peg-IFN . PCR negative sample s were re-tested by TMA and the results were then correlated with the virological outcome after therapy withdrawal . RESULTS Among 208 patients who were repeatedly HCV-RNA negative by PCR at the end-of-therapy , 26 ( 12.5 % ) were found HCV-RNA positive by TMA . Twenty-two of them , ( 96 % ) were PCR-relapsers after therapy withdrawal , compared to only 14 % of the 182 TMA negative patients ( P<0.0001 ) . This virological profile was more frequent in HCV-1 and HCV-3 infected patients and correlated with a slower virological response during therapy . CONCLUSIONS At the end of Peg-IFN plus ribavirin therapy , TMA is superior to PCR in identifying patients with sustained HCV-RNA clearance BACKGROUND / AIMS The role of interferon alfa treatment in improving morbidity endpoints in patients with chronic hepatitis C infection is currently under debate . The aim of this study was to evaluate the effectiveness of interferon in preventing hepatocellular carcinoma and decompensation in cirrhosis type C. METHODS A retrospective cohort study was carried out on 329 consecutive Caucasian patients with cirrhosis followed for a mean period of 5 years at seven tertiary care university hospitals . Inclusion criteria were biopsy-proven cirrhosis , anti-HCV positivity , abnormal serum aminotransferase levels and absence of complications of cirrhosis . RESULTS The yearly incidence of hepatocellular carcinoma was 2.3 % for 136 untreated patients and 1.0 % for 193 patients treated with interferon alfa . The yearly incidence of hepatic decompensation was 5.7 for untreated and 1.5 for the treated patients . Fourteen ( 7 % ) of 193 treated patients showed sustained aminotransferase normalization and none of them developed complications of cirrhosis . At enrollment , untreated patients were older and had more severe liver disease than patients treated with interferon . After adjustment for clinical and serologic differences at entry between treated and untreated patients , the 5-year estimated probability of the occurrence of hepatocellular carcinoma was 2.1 % and 2.7 % and of decompensation was 7 % and 11 % for treated and untreated cases , respectively . CONCLUSIONS This analysis did not detect any significant benefit of interferon alfa on morbidity in patients with compensated cirrhosis type C , although it suggests a reduction in complications of cirrhosis for those with a sustained response to therapy , and it indicates the need for better therapies BACKGROUND The long-term effect of sustained virologic response ( SVR ) to antiviral therapy on the risk of developing hepatocellular carcinoma ( HCC ) , liver complications , liver-related death , and overall death in hepatitis C virus (HCV)-infected patients with liver cirrhosis is not fully known . METHODS These risks were evaluated during long-term follow-up in 351 patients with HCV-related cirrhosis . One hundred ten patients with SVR , 193 with non-SVR , and 48 who were untreated were included in a multicenter cohort that was initiated in 2001 and prospect ively followed up for a mean of 5.3 ( SD , 2.8 ) years . Complementary follow-up data from national registries were used to minimize the loss of patients during follow-up . RESULTS Six patients with SVR developed HCC at 0.04 , 0.64 , 2.4 , 7.4 , 7.4 , and 7.6 years , respectively , after achieving SVR . The incidences of HCC , any liver complication , liver-related death , and overall death per 100 person-years were significantly lower in SVR time with 1.0 , 0.9 , 0.7 , and 1.9 , compared to 2.3 , 3.2 , 3.0 , and 4.1 in non-SVR and 4.0 , 4.9 , 4.5 , and 5.1 in untreated time . The long-term consequences did not decline significantly after > 3 years versus during the first 3 years of follow-up . CONCLUSIONS The risk for HCC , liver decompensation , and death in patients with liver cirrhosis related to HCV was markedly reduced after SVR , but a long-term risk of developing HCC remains for up to 8 years . Cirrhotic patients with HCV who achieve SVR should therefore maintain long-term surveillance for HCC . Future studies aim ed to better identify those with remaining long-term risk for HCC are needed BACKGROUND & AIMS A sustained virologic response ( SVR ) to therapy for hepatitis C virus ( HCV ) infection is defined as the inability to detect HCV RNA 24 weeks after completion of treatment . Although small studies have reported that the SVR is durable and lasts for long periods , it has not been conclusively shown . METHODS The durability of treatment responses was examined in patients originally enrolled in one of 9 r and omized multicenter trials ( n = 1343 ) . The study included patients who received pegylated interferon ( peginterferon ) alfa-2a alone ( n = 166 ) or in combination with ribavirin ( n = 1077 , including 79 patients with normal alanine aminotransferase levels and 100 patients who were coinfected with human immunodeficiency virus and HCV ) and whose serum sample s were negative for HCV RNA ( < 50 IU/mL ) at their final assessment . Patients were assessed annually , from the date of last treatment , for a mean of 3.9 years ( range , 0.8 - 7.1 years ) . RESULTS Most patients ( 99.1 % ) who achieved an SVR had undetectable levels of HCV RNA in serum sample s throughout the follow-up period . Serum sample s from 0.9 % of the patients contained HCV RNA a mean of 1.8 years ( range , 1.1 - 2.9 years ) after treatment ended . It is not clear if these patients were reinfected or experienced a relapse . CONCLUSIONS In a large cohort of patients monitored for the durability of an SVR , the SVR was maintained for almost 4 years after treatment with peginterferon alfa-2a alone or in combination with ribavirin . In patients with chronic hepatitis C infection , the SVR is durable and these patients should be considered as cured Patients with chronic active hepatitis C and cirrhosis often develop hepatocellular carcinoma . Interferon ( IFN ) seems to be effective in some patients but whether it prevents carcinogenesis is unknown . In a prospect i ve r and omised controlled trial , we evaluated the effects of IFN-alpha in cirrhotic patients with HCV infection because of their high risk of hepatocellular carcinoma . 90 patients with compensated chronic active hepatitis C with cirrhosis were r and omly allocated to receive IFN-alpha ( 6 MU three times weekly for 12 - 24 weeks ) ( 45 patients ) or symptomatic treatment ( 45 controls ) , and were followed up for 2 - 7 years . In nine controls , alanine aminotransferase ( ALT ) decreased to less than 80 IU/L but did not stay in the normal range . In 19 patients given IFN-alpha , ALT decreased to less than 80 IU/L ( in seven patients , it became and stayed normal ; p = 0.011 , Wilcoxon rank-sum test ) . However , the mean change in ALT was not significantly different between the two groups . The mean change in peak alpha-fetoprotein values was smaller in patients given IFN-alpha than in controls ( p = 0.021 ) . The mean change in the serum albumin level was higher in the IFN-alpha group ( p < 0.001 ) . The histological activity index in the 12 IFN-alpha patients undergoing a second biopsy after therapy was improved ( p = 0.031 ) . Hepatitis C viral RNA disappeared in seven ( 16 % ) of the 45 IFN-alpha patients ( 95 % CI , 7 - 29 % ) and in none of the 45 controls ( 0 - 8 % ; p = 0.018 ) . Hepatocellular carcinoma was detected in two ( 4 % , 1 - 15 % ) IFN-alpha patients and 17 ( 38 % , 24 - 54 % ) controls ( p = 0.002 , Wilcoxon signed-rank test ) . The risk ratio of IFN-alpha treatment versus symptomatic treatment was 0.067 ( 0.009 - 0.530 ; p = 0.010 Cox 's proportional hazards ) . IFN-alpha improved liver function in chronic active hepatitis C with cirrhosis , and its use was associated with a decreased incidence of hepatocellular carcinoma BACKGROUND / AIMS The aims of alpha-interferon treatment for chronic viral liver infections are clearance of the virus and healing of the disease . Hepatocellular carcinoma is a complication of viral cirrhosis ; but it is not yet known whether treatment of viral cirrhosis with alpha-interferon prevents this complication . METHODS The incidence and the risk ( Cox regression analysis ) of developing hepatocellular carcinoma were calculated in 347 patients with hepatic cirrhosis ; 227 ( 34 hepatitis B virus and 193 hepatitis C virus related ) were treated with alpha-interferon and 120 ( 28 hepatitis B virus and 92 hepatitis C virus ) did not receive this treatment , in order to evaluate the efficacy of alpha-interferon in the prevention of hepatocellular carcinoma . In all patients , the cirrhosis was well compensated ( Child A ) . RESULTS Over mean follow-up periods of 49 months for hepatitis B virus and 32 months for hepatitis C virus , 20/347 patients ( 6/62 hepatitis B virus and 14/285 hepatitis C virus ) developed hepatocellular carcinoma . The risk of developing this tumor was significantly greater in males ( p < 0.007 ) and in patients not treated with alpha-interferon ( p < 0.01 ) . The Relative Risk of developing hepatocellular carcinoma increased significantly ( p < 0.0002 ) with each passing year . In patients with hepatic cirrhosis secondary to hepatitis B virus infections , the risk did not seem to be modified by alpha-interferon treatment , even though a greater , but not significant risk ( Relative Risk = 4.9 ; p = 0.3 ) was calculated for untreated patients ; in contrast , in hepatitis C virus-related cirrhosis , this risk was reduced by a factor of 4.0 ( p = 0.04 ) . The tumor developed only in non-responder patients regardless of virus type . After adjustment for confounding factors ( sex , age , alcohol consumption , cigarette smoking ) , a statistically significant ( p < 0.025 ) effect of interferon treatment in preventing hepatocellular carcinoma was still demonstrated when responders were matched with controls , but not when responders were compared with non-responders . CONCLUSIONS These results show that , in addition to its ability to halt the progression of viral-induced liver disease , alpha-interferon is also of benefit in patients with hepatitis C virus cirrhosis who respond to this treatment by lowering their risk of developing hepatocellular carcinoma We assessed the efficacy of interferon ( IFN ) alpha-2b plus ribavirin therapy in patients with hepatitis C virus (HCV)-related cirrhosis , and eluci date d the risk factors for the development of hepatocellular carcinoma ( HCC ) to determine whether these therapies might reduce the incidence of HCC . One hundred and thirty-two HCV-cirrhotic patients receiving IFN alpha-2b ( 3 or 5 MU thrice weekly ) and oral ribavirin ( 1,000 - 1,200 mg/day ) for 24 or 48 weeks were analysed . Cumulative incidence of HCC was estimated by the Kaplan-Meier method . The prognostic relevance of clinical variables and HCC occurrence was evaluated by univariate analysis with the log-rank test and by multivariate Cox 's regression analysis . A total of 116 patients completed the treatment and 73 ( 55 % ) achieved a sustained virological response ( SVR ) . Stepwise logistic regression analysis showed that nongenotype 1b ( P < 0.001 ) and low viral load ( P = 0.018 ) were independent variables of SVR . During a median follow-up period of 37 ( 12 - 63 ) months , HCC developed in 11 patients with non-SVR and five with SVR ( P = 0.0178 ) , whereas there was no difference between those with transient biochemical response and nonresponse ( P = 0.5970 ) . The Kaplan-Meier method also showed that old age ( > or=60 years ) ( P = 0.0034 ) and genotype 1b ( P = 0.0104 ) were associated with HCC occurrence . Using Cox 's regression analysis , non-SVR ( odds ratio = 3.521 , P = 0.036 ) , male ( odds ratio = 6.269 , P = 0.011 ) and old age ( odds ratio = 3.076 , P = 0.049 ) were independent significant risk factors contributing to HCC development . Our results suggest that achieving SVR by IFN alpha-2b plus ribavirin therapy may decrease the incidence of HCC in patients with HCV-related cirrhosis BACKGROUND The role of interferon treatment on the natural history of hepatitis C virus related cirrhosis is under debate . AIM To evaluate the effect of interferon on the clinical course of compensated hepatitis C virus related cirrhosis . PATIENTS AND METHODS Seventy two cirrhotic patients treated with interferon and 72 untreated controls matched treated patients with for quinquennia of age , sex , and Child-Pugh 's score were enrolled in a prospect i ve non-r and omised controlled trial . Treated patients received leucocytic interferon alfa , with an escalating schedule for 12 months . The incidence and risk ( Cox regression analysis ) of clinical complications ( hepatocellular carcinoma , ascites , jaundice , variceal bleeding , and encephalopathy ) and death were calculated . RESULTS Over median follow up periods of 55 months for treated and 58 for untreated subjects , seven and nine patients , respectively , died , and 20 and 32 , respectively , developed at least one clinical complication ( ns ) . Hepatocellular carcinoma developed in six treated and 19 untreated patients ( p=0.018 ) . Seven treated patients showed sustained aminotranferase normalisation and none died or developed complications . Clinical complications were significantly associated with low albumin , bilirubin , and prothrombin activity while hepatocellular carcinoma was significantly related to no treatment with interferon , oesophageal varices , and high α fetoprotein levels . By stratified analysis , the beneficial effect of interferon was statistically evident only in patients with baseline α fetoprotein levels ⩾20 ng/ml . CONCLUSIONS Interferon does not seem to affect overall or event free survival of patients with hepatitis C virus related cirrhosis while it seems to prevent the development of hepatocellular carcinoma . Patients who achieved sustained aminotransferase normalisation survived and did not develop any complications during follow up |
14,033 | 28,683,420 | Most available IMU- research regarding the shoulder is clinical ly less relevant , given the widely reported humerothoracic kinematics which do not add to clinical -decision-making , and the absence of protocol s assessing the complete upper limb chain . | This review investigates current protocol s using Inertial Measurement Units ( IMUs ) in shoulder research , and outlines future paths regarding IMU use for shoulder research . | Body-worn inertial sensors have enabled motion capture outside of the laboratory setting . In this work , an inertial measurement unit was attached to the upper arm to track and discriminate between shoulder motion gestures in order to help prevent shoulder over-use injuries in athletics through real-time preventative feedback . We present a detection and classification approach that can be used to count the number of times certain motion gestures occur . The application presented involves tracking baseball throws and volleyball serves , which are common overhead movements that can lead to shoulder and elbow overuse injuries . Eleven subjects are recruited to collect training , testing , and r and omized validation data , which include throws , serves , and seven other exercises that serve as a large null class of similar movements , which is analogous to a realistic usage scenario and requires a robust estimator BACKGROUND Variable definitions of outcome ( Constant score , Simple Shoulder Test [ SST ] ) have been used to assess outcome after shoulder treatment , although none has been accepted as the universal st and ard . Physicians lack an objective method to reliably assess the activity of their patients in dynamic conditions . Our purpose was to clinical ly vali date the shoulder kinematic scores given by a portable movement analysis device , using the activities of daily living described in the SST as a reference . The secondary objective was to determine whether this device could be used to document the effectiveness of shoulder treatments ( for glenohumeral osteoarthritis and rotator cuff disease ) and detect early failures . METHODS A clinical trial including 34 patients and a control group of 31 subjects over an observation period of 1 year was set up . Evaluations were made at baseline and 3 , 6 , and 12 months after surgery by 2 independent observers . Miniature sensors ( 3-dimensional gyroscopes and accelerometers ) allowed kinematic scores to be computed . They were compared with the regular outcome scores : SST ; Disabilities of the Arm , Shoulder and H and ; American Shoulder and Elbow Surgeons ; and Constant . RESULTS Good to excellent correlations ( 0.61 - 0.80 ) were found between kinematics and clinical scores . Significant differences were found at each follow-up in comparison with the baseline status for all the kinematic scores ( P < .015 ) . The kinematic scores were able to point out abnormal patient outcomes at the first postoperative follow-up . CONCLUSION Kinematic scores add information to the regular outcome tools . They offer an effective way to measure the functional performance of patients with shoulder pathology and have the potential to detect early treatment failures Clinical practice involves measuring quantities for a variety of purpose s , such as aiding diagnosis , predicting future patient outcomes , and serving as endpoints in studies or r and omized trials . Measurements are almost always prone to various sorts of errors , which cause the measured value to differ from the true value ; accordingly , studies investigating measurement error frequently appear in this and other journals . The importance of measurement error depends upon the context in which the measurements in question are to be used . For example , a certain degree of measurement error may be acceptable if measurements are to be used as an outcome in a comparative study such as a clinical trial , but the same measurement errors may be unacceptably large to make measurements usable in individual patient management , such as screening or risk prediction . In the past 20 years many papers have been published advocating how studies of measurement error should be analyzed , with a paper by Bl and and Altman1 being one of the most cited and well known examples . There has been much controversy concerning the choice of parameter to be estimated and reported , and consequently confusion surrounding the meaning and interpretation of results from studies investigating measurement error . In this paper we first distinguish between the general concepts of agreement and reliability to aid research ers in considering which are relevant for their particular application . We then review the statistical methods that can be used to investigate and quantify agreement and reliability , dealing separately with the different types of measurement error study , while emphasizing the largely common techniques that should be used for data analysis . We reiterate that the judgment of whether agreement or reliability are acceptable must be related to the clinical application , and can not be proven by a statistical test . We highlight the fact that reliability depends on the population in which measurements are made , and not just on the measurement errors of the measurement method . We discuss the advantages of method comparison studies making at least two measurements with each measurement method on each subject . A key advantage is that the cause of a correlation between paired differences and means in the so-called Bl and –Altman plot can be determined , in contrast to when only a single measurement is made with each method . Throughout the paper , we try to emphasize that calculated values of agreement and reliability from measurement error studies are estimates of parameters , and as such we should report such estimates with CIs to indicate the uncertainty with which they have been estimated . We restrict our attention to measurements of a continuous quantity ; alternative methods are required for categorical data 2 Background The B-B Score is a straightforward kinematic shoulder function score including only two movements ( h and to the Back + lift h and as to change a Bulb ) that demonstrated sound measurement properties for patients for various shoulder pathologies . However , the B-B Score results using a smartphone or a reference system have not yet been compared . Provided that the measurement properties are comparable , the use of a smartphone would offer substantial practical advantages . This study investigated the concurrent validity of a smartphone and a reference inertial system for the measurement of the kinematic shoulder function B-B Score . Methods Sixty-five patients with shoulder conditions ( with rotator cuff conditions , adhesive capsulitis and proximal humerus fracture ) and 20 healthy participants were evaluated using a smartphone and a reference inertial system . Measurements were performed twice , alternating between two evaluators . The B-B Score differences between groups , differences between devices , relationship between devices , intra- and inter-evaluator reproducibility were analysed . Results The smartphone mean scores ( SD ) were 94.1 ( 11.1 ) for controls and 54.1 ( 18.3 ) for patients ( P < 0.01 ) . The difference between devices was non-significant for the control ( P = 0.16 ) and the patient group ( P = 0.81 ) . The analysis of the relationship between devices showed 0.97 ICC , −0.6 bias and −13.2 to 12.0 limits of agreement ( LOA ) . The smartphone intra-evaluator ICC was 0.92 , the bias 1.5 and the LOA −17.4 to 20.3 . The smartphone inter-evaluator ICC was 0.92 , the bias 1.5 and the LOA −16.9 to 20.0 . Conclusions The B-B Score results measured with a smartphone were comparable to those of an inertial system . While single measurements diverged in some cases , the intra- and inter-evaluator reproducibility was excellent and was equivalent between devices . The B-B score measured with a smartphone is straightforward and as efficient as a reference inertial system measurement Magneto-Inertial Measurement Unit sensors ( MIMU ) display high potential for the quantitative evaluation of upper limb kinematics , as they allow monitoring ambulatory measurements . The sensor-to-segment calibration step , consisting of establishing the relation between MIMU sensors and human segments , plays an important role in the global accuracy of joint angles . The aim of this study was to compare sensor-to-segment calibrations for the MIMU-based estimation of wrist , elbow , and shoulder joint angles , by examining trueness ( “ close to the reference ” ) and precision ( reproducibility ) validity criteria . Ten subjects performed five sessions with three different operators . Three classes of calibrations were studied : segment axes equal to technical MIMU axes ( TECH ) , segment axes generated during a static pose ( STATIC ) , and those generated during functional movements ( FUNCT ) . The calibrations were compared during the maximal uniaxial movements of each joint , plus an extra multi-joint movement . Generally , joint angles presented good trueness and very good precision in the range 5 ° –10 ° . Only small discrepancy between calibrations was highlighted , with the exception of a few cases . The very good overall accuracy ( trueness and precision ) of MIMU-based joint angle data seems to be more dependent on the level of rigor of the experimental procedure ( operator training ) than on the choice of calibration itself BACKGROUND The objective measurement of dominant/nondominant arm use proportion in daily life may provide relevant information on healthy and pathologic arm behavior . This prospect i ve case-control study explored the potential of such measurements as indicators of upper limb functional recovery after rotator cuff surgery . METHODS Data on dominant/nondominant arm usage were acquired with body-worn sensors for 7 hours . The postsurgical arm usage of 21 patients was collected at 3 , 6 , and 12 months after rotator cuff surgery in the sitting , walking , and st and ing postures and compared with a reference established with 41 healthy subjects . The results were calculated for the dominant and nondominant surgical side subgroups at all stages . The correlations with clinical scores were calculated . RESULTS Healthy right-h and ed and left-h and ed dominant arm usage was 60.2 % ( ±6.3 % ) and 53.4 % ( ±6.6 % ) , respectively . Differences in use of the dominant side were significant between the right- and left-h and ed subgroups for sitting ( P = .014 ) and st and ing ( P = .009 ) but not for walking ( P = .328 ) . The patient group showed a significant underuse of 10.7 % ( ±8.9 % ) at 3 months after surgery ( P < .001 ) . The patients recovered normal arm usage within 12 months , regardless of surgical side . The arm underuse measurement was weakly related to function and pain scores . CONCLUSION This study provided new information on arm recovery after rotator cuff surgery using an innovative measurement method . It highlighted that objective arm underuse measurement is a valuable indicator of upper limb postsurgical outcome that captures a complementary feature to clinical scores Knowledge of three-dimensional scapular movements is essential to underst and post-stroke shoulder pain . The goal of the present work is to determine the feasibility and the within and between session reliability of a movement protocol for three-dimensional scapular movement analysis in stroke patients with mild to moderate impairment , using an optoelectronic measurement system . Scapular kinematics of 10 stroke patients and 10 healthy controls was recorded on two occasions during active anteflexion and abduction from 0 ° to 60 ° and from 0 ° to 120 ° . All tasks were executed unilaterally and bilaterally . The protocol ’s feasibility was first assessed , followed by within and between session reliability of scapular total range of motion ( ROM ) , joint angles at start position and of angular waveforms . Additionally , measurement errors were calculated for all parameters . Results indicated that the protocol was generally feasible for this group of patients and assessors . Within session reliability was very good for all tasks . Between sessions , scapular angles at start position were measured reliably for most tasks , while scapular ROM was more reliable during the 120 ° tasks . In general , scapular angles showed higher reliability during anteflexion compared to abduction , especially for protraction . Scapular lateral rotations result ed in smallest measurement errors . This study indicates that scapular kinematics can be measured reliably and with precision within one measurement session . In case of multiple test sessions , further method ological optimization is required for this protocol to be suitable for clinical decision-making and evaluation of treatment efficacy The purpose of this study was to examine the psychometric properties of the American Shoulder and Elbow Surgeons St and ardized Shoulder Assessment Form ( ASES ) , patient self-report section . Patients with shoulder dysfunction ( n = 63 ) completed the ASES , The University of Pennsylvania Shoulder Score , and the Short Form-36 during the initial evaluation , 24 to 72 hours after the initial visit , and after 3 to 4 weeks of physical therapy . The test-retest reliability ( intraclass correlation coefficient[1-way r and om-effects ] , 0.84 ; 95 % CI lower limit , 0.75 ) and internal consistency ( Cronbach alpha , 0.86 ) values were acceptable . The st and ard error of the measure was 6.7 ASES points ( 90 % CI , 11.0 ) . Construct and discriminant validity was demonstrated . Responsiveness was demonstrated with a st and ardized response mean of 1.5 and an effect size of 1.4 . The minimal detectable change was 9.7 ASES points ( 90 % CI , 16 ) , and the minimal clinical ly important difference was 6.4 ASES points . The results indicate that the ASES is a reliable , valid , and responsive outcome tool OBJECTIVE : To test the feasibility of creating a valid and reliable checklist with the following features : appropriate for assessing both r and omised and non-r and omised studies ; provision of both an overall score for study quality and a profile of scores not only for the quality of reporting , internal validity ( bias and confounding ) and power , but also for external validity . DESIGN : A pilot version was first developed , based on epidemiological principles , review s , and existing checklists for r and omised studies . Face and content validity were assessed by three experienced review ers and reliability was determined using two raters assessing 10 r and omised and 10 non-r and omised studies . Using different raters , the checklist was revised and tested for internal consistency ( Kuder-Richardson 20 ) , test-retest and inter-rater reliability ( Spearman correlation coefficient and sign rank test ; kappa statistics ) , criterion validity , and respondent burden . MAIN RESULTS : The performance of the checklist improved considerably after revision of a pilot version . The Quality Index had high internal consistency ( KR-20 : 0.89 ) as did the subscales apart from external validity ( KR-20 : 0.54 ) . Test-retest ( r 0.88 ) and inter-rater ( r 0.75 ) reliability of the Quality Index were good . Reliability of the subscales varied from good ( bias ) to poor ( external validity ) . The Quality Index correlated highly with an existing , established instrument for assessing r and omised studies ( r 0.90 ) . There was little difference between its performance with non-r and omised and with r and omised studies . Raters took about 20 minutes to assess each paper ( range 10 to 45 minutes ) . CONCLUSIONS : This study has shown that it is feasible to develop a checklist that can be used to assess the method ological quality not only of r and omised controlled trials but also non-r and omised studies . It has also shown that it is possible to produce a checklist that provides a profile of the paper , alerting review ers to its particular method ological strengths and weaknesses . Further work is required to improve the checklist and the training of raters in the assessment of external validity Shoulder-related dysfunction is the second most common musculoskeletal disorder and is an increasing burden on health-care systems . Commonly used clinical question naires suffer from subjectivity , pain dominance and a ceiling effect . Objective functional measurement has been identified as a relevant issue in clinical rehabilitation . Inertia based motion analysis ( IMA ) is a new generation of objective outcome assessment tool ; it can produce objective movement parameters while being fast , cheap and easy to operate . In this prospect i ve study , an inertial sensor comprising a three-dimensional accelerometer and gyroscope is attached at the humerus to measure shoulder movements during two motion tasks in patients with subacromial impingement syndrome at baseline and at five-year after treatment . One hundred healthy subjects served as healthy reference data base and 15 patients were measured pre- and post-treatment . IMA was better able to detect improvement in shoulder movements compared to the clinical question naires ( Disability of Arm , Shoulder and H and ( DASH ) and Simple Shoulder Test ( SST ) ; p < 0.05 ) and was hardly correlated with the clinical question naires ( Pearson R = 0.39 ) . It may therefore add an objective functional dimension to outcome assessment . The fast assessment ( t < 5 min ) of a simple motion test makes it suitable for routine clinical follow-up The validation of two noninvasive methods for measuring the dynamic three-dimensional kinematics of the human scapula with a magnetic tracking device is presented . One method consists of simply fixing a sensor directly to the acromion and the other consists of mounting a sensor to an adjustable plastic jig that fits over the scapular spine and acromion . The concurrent validity of both methods was assessed separately by comparison with data collected simultaneously from an invasive approach in which pins were drilled directly into the scapula . The differences between bone and skin based measurements represents an estimation of skin motion artifact . The average motion pattern of each surface method was similar to that measured by the invasive technique , especially below 120 degrees of elevation . These results indicate that with careful consideration , both methods may offer reasonably accurate representations of scapular motion that may be used to study shoulder pathologies and help develop computational models |
14,034 | 23,775,113 | Our results show that One-shot dilation is an effective and safe procedure for tract creation in PCNL , with shorter access time and X-ray exposure time and without increased complications . | The aim of this study is to evaluate the efficacy and safety of one-shot versus gradual dilation technique for tract creation in percutaneous nephrolithotomy ( PCNL ) . | BACKGROUND AND PURPOSE Percutaneous nephrolithotomy ( PCNL ) can be done in patients who have previously had open nephrolithotomy . Currently , dilatation of the nephrostomy tract is achieved using an Amplatz renal dilator or telescopic metal dilators in these patients . The aim of this study was to compare the safety and efficacy of the " one-shot " procedure in patients with previous open nephrolithotomy with those of the current telescopic technique . PATIENTS AND METHODS Thirty-one patients with past history of open surgery for kidney stone disease underwent PCNL at our institution from February 2006 to March 2007 . Patients were r and omly divided into two groups according to dilation technique used : group A ( telescopic procedure ) and group B ( one-shot procedure ) . X-ray exposure , blood loss , and complications were evaluated . RESULTS No significant difference in hemoglobin decrease was seen in the two groups . The stone-free and complication rates were the same in the two groups . Fluoroscopy time during the one-shot procedure was significantly shorter than that of the telescopic procedure ( P < 0.000 ) . CONCLUSION Our experience indicated that the one-shot procedure is feasible in patients with previous open nephrolithotomy . It is as safe and effective as the telescopic procedure , with significant reduction in x-ray exposure PURPOSE To assess the feasibility of one-stage acute dilation of the nephrostomy tract with a 30F Amplatz dilator in patients who are c and i date for percutaneous nephrolithotomy ( PCNL ) regardless of whether there is a previous renal scar to make the procedure less time consuming and more cost effective . PATIENTS AND METHODS The outcomes of one-stage tract dilation for PCNL in 100 consecutive patients with and without a history of ipsilateral open stone surgery ( OSS ) , treated by one surgeon , were examined prospect ively . Forty-six patients ( group 1 ) had a history of ipsilateral OSS , and 54 patients ( group 2 ) did not have this history . Demographic data as well as intraoperative information , such as access time and radiation exposure time during access , were recorded . The success of the access technique and its bleeding complications were analyzed between the two groups . RESULTS By applying a " one-stage " technique , the targeted calix could be entered with a success rate of 93 % . There was no difference in the procedural success rate between groups 1 and 2 ( 93.5 % v 92.6 % , respectively ) . All seven failed attempts ( 7 % ; three with previous OSS ) were managed successfully using an Alken dilator to gain access to the proposed calix in the same session . Previous OSS did not impact access time , radiation exposure time during access , postoperative hemoglobin drop , and bleeding complications . There were no visceral and vascular injuries . CONCLUSIONS One-stage tract dilation for PCNL is a safe and effective method in almost every adult patient PURPOSE To compare the effects of one-stage vs gradual dilation techniques during percutaneous nephrolithotomy ( PCNL ) on postoperative renal scar formation and overall renal function . PATIENTS AND METHODS Of 152 adult patients who underwent surgery during the study period , 48 were r and omized into two groups . In group 1 ( n=19 ) , gradual tract dilation with Alken metallic dilators was used , and in group 2 ( n=29 ) , one-stage tract dilation was used . We compared patient demographics , intraoperative and preoperative parameters , postoperative overall renal function , and renal scar formation on the target renal pole . RESULTS Access time ( P=0.001 ; 95 % confidence interval [ CI ] : 3.19 - 6.30 ) and radiation exposure during access ( P=0.03 ; 95 % CI : 0.03 - 0.66 ) were significantly shorter in group 2 . In group 1 , the decrease in mean technetium-99 m dimercaptosuccinic acid ( 99m-Tc DMSA ) uptake from 44.1±20.1 % to 43.4±19.6 % 4 weeks postoperatively ( -0.7%±0.5 % ; P=0.27 ; 95 % CI : -0.56 - 1.93 ) was not significant . In group 2 , however , there was a significant decrease in post-PCNL 99m-Tc DMSA uptake 2 ( -2.4±0.3 % , from 50.1±13.5 % to 47.7±13.8 % ; P=0.001 ; 95 % CI : 1.13 - 3.66 ) . Four weeks after surgery , new scar formation or progression of the preoperative scar at the site of access were seen in 14 of 29 ( 48.3 % ) patients who were treated with one-stage dilation whereas only 2 of 19 ( 11.0 % ) patients who were treated with gradual dilation developed new scarring at the access site ( P=0.007 ) . CONCLUSION Although the one-stage tract dilation technique reduced radiation exposure and access time , in the short term , it may cause more parenchymal damage than the gradual dilation technique |
14,035 | 19,155,910 | The model developed by Sassone was the most evaluated prediction model .
All models has acceptable sensitivity and specificity .
However , the Risk of Malignancy Index I and the Risk of Malignancy Index II , which use the product of the serum CA 125 level , an ultrasound scan result , and the menopausal state , were the best predictors .
: Based on our review , the Risk of Malignancy Index should be the prediction model of choice in the preoperative assessment of the adnexal mass | OBJECTIVE : To perform a systematic review of the literature on the accuracy of prediction models in the preoperative assessment of adnexal masses . | The aim of this work was to test and compare the accuracy of five different morphological scoring systems to identify malignant ovarian masses in a prospect i ve multicenter study . Four of the systems had previously been reported by Granberg , Sassone , De Priest and Lerner and the fifth is newly developed . A total of 330 ovarian neoplasms were collected in three different centers , which adopted the same diagnostic procedures . Of these , 261 masses were benign ( mean diameter 50 + /- 26 mm ) and 69 were malignant ( mean diameter 69 + /- 33 mm ) ( prevalence 21 % ) . The area under the receiver operating characteristic ( ROC ) curve for the multicenter score was 0.84 . This was significantly better than the areas of the other four scores which ranged from 0.72 to 0.75 . The cut-off levels derived from the five ROC curves achieved a sensitivity that ranged from 74 % ( Sassone score ) to 88 % ( De Priest score > or = 5 ) , and a specificity from 40 % ( De Priest ) to 67 % ( multicenter ) ; the highest positive predictive value was 41 % ( multicenter ) . With a cut-off level of 9 , the accuracy of the multicenter score was significantly better than the scores of Granberg and De Priest ( McNemar 's test p < 0.0001 ) . Similar results were obtained in 207 ovarian masses of < or = 5 cm in mean diameter , and when 19 borderline and 11 stage 1 cancers only were considered . For the clinical purpose s of a screening test we also checked a possible cut-off level of > or = 8 , which increased the sensitivity to 93 % with a drop of specificity to 56 % . With the use of the same criteria for the scores of the different authors , the following values were obtained for sensitivity : 96 % , 81 % , 93 % and 90 % ; and for specificity : 23 % , 56 % , 28 % and 49 % . The multicenter score performed well at distinguishing malignant from benign lesions , and was better than the other four traditional scores , for both large and small masses . This was mainly due to the introduction of two criteria that allowed correction for typical dermoids and endohemorrhagic corpora lutea . A completely reliable differentiation of benign from malignant masses can not be obtained by sonographic imaging alone Kobal B , Rakar S , Ribic-Pucelj M , Tomazevie T , Zaletel-Kragelj L. Pretreatment evaluation of adnexal tumors predicting ovarian cancer . The objective of this study was to determine the ability of tumor marker assessment , gray-scale transvaginal with color Doppler ultrasonography to predict ovarian malignancy . One hundred thirty-four subjects with ovarian masses who entered the study prospect ively underwent pelvic examination , tumor marker assessment and gray-scale transvaginal with color flow Doppler ultrasonography preoperatively . Malignancy predictors were statistically evaluated with stepwise multiple logistic regression , and the scores from the model were transformed to probability for having a malignant disease . The presence of neovascularization , intracystic papillary projections , elevated serum CA 125 , and age over 45 years were significant predictors for malignancy . Positive predictive value ( PPV ) for the regression model was 89.0 % , and negative predictive value ( NPV ) was 96.8 % . Probability for malignancy ranged from 0.004 to 0.991 depending on which covariates were included . Logistic regression analysis of pretreatment diagnostic gray-scale and color Doppler ultrasonographic characteristics , together with CA 125 enabled a creation of probability assessment scale for individual estimation of ovarian mass , which may contribute to final clinical decision In this work , we develop and evaluate several least squares support vector machine ( LS-SVM ) classifiers within the Bayesian evidence framework , in order to preoperatively predict malignancy of ovarian tumors . The analysis includes exploratory data analysis , optimal input variable selection , parameter estimation , and performance evaluation via receiver operating characteristic ( ROC ) curve analysis . LS-SVM models with linear and radial basis function ( RBF ) kernels , and logistic regression models have been built on 265 training data , and tested on 160 newly collected patient data . The LS-SVM model with nonlinear RBF kernel achieves the best performance , on the test set with the area under the ROC curve ( AUC ) , sensitivity and specificity equal to 0.92 , 81.5 % and 84.0 % , respectively . The best averaged performance over 30 runs of r and omized cross-validation is also obtained by an LS-SVM RBF model , with AUC , sensitivity and specificity equal to 0.94 , 90.0 % and 80.6 % , respectively . These results show that the LS-SVM models have the potential to obtain a reliable preoperative distinction between benign and malignant ovarian tumors , and to assist the clinicians for making a correct diagnosis Objective : To assess the accuracy of pelvic sonography in distinguishing benign from malignant lesions in postmenopausal women , using morphologic criteria and Doppler flow characteristics . Methods : All postmenopausal patients scanned from March 1992 to April 1993 with sonographically identified and pathologically confirmed adnexal masses formed the study group . The adnexal lesions were morphologically categorized prospect ively as benign or malignant , and pulsed Doppler flow studies were measured using the lowest resistance index obtained from each mass . The sensitivity and specificity were determined for morphologic and Doppler flow assessment s , as well as for a combination of these methods , for predicting the presence of malignancy . Results : Thirty-three postmenopausal patients formed the study group ; 12 lesions were malignant and 21 were benign pathologically . Using morphologic criteria alone , the sensitivity in detecting malignancy was 91 % and specificity was 52 % . Using pulsed Doppler alone with a resistance index limit of 0.6 , the sensitivity in predicting malignancy was 66 % , with a specificity of 81 % . If a resistance index limit of 0.8 were used , the sensitivity and specificity would be the same as those for morphology alone . Combining morphology and resistance index , a single malignancy would still have been missed ( sensitivity 91 % ) . Conclusion : In our experience , Doppler flow studies did not add substantially to the prediction of malignancy using morphologic assessment alone Objective To compare color and pulsed Doppler sonography with gray-scale ultrasound imaging and serum CA 125 levels in establishing accurate preoperative diagnoses of adnexal masses . Methods Medical records of 109 patients referred with preexisting adnexal lesions were review ed retrospectively by comparing preoperative ultrasonic data ( gray-scale imaging and color and pulsed Doppler findings ) with serum CA 125 levels . Results Eighty-three masses were removed surgically , confirming seven malignancies and 76 benign tumors , and 26 masses were followed ; 15 regressed and 11 persisted . Color and pulsed Doppler sonography showed the highest sensitivity , followed by gray-scale imaging , whereas serum CA 125 levels revealed the highest specificity in distinguishing malignant from benign adnexal tumors . All three methods had high negative predictive values ( 96–100 % ) , whereas only serum CA 125 had a positive predictive value greater than 50 % . Conclusion Color and pulsed Doppler sonography , which demonstrate a tumor angiogenic activity , are as accurate as gray-scale imaging in the assessment of adnexal lesions . Together with serum CA 125 marker levels , they produce high negative predictive values , providing reassurance that an adnexal mass is benign OBJECTIVE The aim of this study was to generate and evaluate artificial neural network ( ANN ) models from simple clinical and ultrasound-derived criteria to predict whether or not an adnexal mass will have histological evidence of malignancy . DESIGN The data were collected prospect ively from 173 consecutive patients who were scheduled to undergo surgical investigations at the University Hospitals , Leuven , between August 1994 and August 1996 . The outcome measure was the histological classification of excised tissues as malignant ( including borderline ) or benign . METHODS Age , menopausal status and serum CA 125 levels and sonographic features of the adnexal mass were encoded as variables . The ANNs were trained on a r and omly selected set of 116 patient records and tested on the remainder ( n = 57 ) . The performance of each model was evaluated using receiver operating characteristic ( ROC ) curves and compared with corresponding data from an established risk of malignancy index ( RMI ) and a logistic regression model . RESULTS There were 124 benign masses , five of borderline malignancy and 44 invasive cancers ( of which 29 % were metastatic ) ; 37 % of patients with a malignant or borderline tumor had stage I disease . The best ANN gave an area under the ROC curve of 0.979 for the whole data set , a sensitivity of 95.9 % and specificity of 93.5 % . The corresponding values for the RMI were 0.882 , 67.3 % and 91.1 % , and for the logistic regression model 0.956 , 95.9 % and 85.5 % , respectively . CONCLUSION An ANN can be trained to provide clinical ly accurate information , on whether or not an adnexal mass is malignant , from the patient 's menopausal status , serum CA 125 levels , and some simple ultrasonographic criteria OBJECTIVE To apply logistic regression analysis for several clinical and sonographic data for the construction of a predictive model that could be helpful in the preoperative differentiation of adnexal masses . MATERIAL S AND METHODS Two hundred and eight women with tumors thought to be of adnexal origin were examined preoperatively . Initial analysis included age and menopausal status , ultrasound derived morphological features of adnexal masses ( unilateral/bilateral tumors , papillae , septae , tumor size and volume ) as well as color Doppler criteria such as PI , RI , Peak Systolic Velocity , PSV assessment . In all examinations we used B&K 2002 ADI ( Denmark ) and Kretz Voluson V730 ( Austria ) scanners with transvaginal probes 5 - 9 MHz . Stepwise logistic regression analysis was used to construct a predictive model that would allow probability of malignancy calculation for individual patient . RESULTS There were 159 benign and 49 malignant masses . Seven cancers were in FIGO stage one . Statistical analysis revealed that only 5 of initially tested 14 variables had significant influence on the regression equation . These were : age , bilateral mass , presence of septa > 3 mm , papillary projections > 3 mm in the tumor wall and subjective color scale assessment according to Timmerman et al. ( 1999 ) . Sensitivity and specificity at the 50 % probability level of malignancy in the studied tumor were 77.5 % and 96.8 % , respectively . When 25 % cut-off probability level was used , sensitivity increased to 87.7 % and specificity dropped to 89.9 % . Prospect i ve testing in a new group of 30 patients ( 5 ovarian cancers ) gave sensitivity of 80 % and specificity of 100 % . CONCLUSIONS The use of logistic regression analysis can help in modeling clinical and sonographic data . Our model had better predictive value than individual tests and allowed to calculate true probability figure of ovarian malignancy for any given patient with adnexal mass OBJECTIVE To prospect ively evaluate the accuracy of a multiparameter , ultrasound-based triage and its impact on surgical management of adnexal masses . METHODS Masses evaluated as normal according to Ferrazzi 's sonographic morphological score were considered as being at low risk of malignancy and eligible for laparoscopic treatment without further evaluation . Masses evaluated as abnormal , but without additional risk factors such as ascites , diameter > or = 10 cm , bilaterality , immobility , resistance index < or = 0.6 and serum CA 125 > 35 IU/mL were considered at moderate risk and eligible for laparoscopic evaluation and treatment . Masses with abnormal morphological score and any of these additional risk factors were considered at high risk and treated by laparotomy . The results of pathological examination were obtained for each mass . RESULTS Two hundred and four ( 87 % ) masses were benign and 30 ( 13 % ) were malignant . Among 182 low-risk , 19 moderate-risk and 33 high-risk masses , the odds of malignancy were 1 : 90 , 1 : 18 and 4.5 : 1 , respectively . To calculate the diagnostic accuracy of this algorithm , low- and moderate-risk groups were considered together : the sensitivity was 90 % , specificity 97 % , positive predictive value 82 % and negative predictive value 99 % . The new algorithm was significantly more accurate than was morphological score alone ( P = 0.0002 ) . Ninety-six percent of benign masses were treated by laparoscopy . All three patients with malignant masses that were incorrectly assigned to laparoscopy underwent laparoscopic adnexectomy and frozen section . CONCLUSIONS The accuracy of this new algorithm was higher than that of the sonographic morphological scoring system alone . In the present series , it allowed the treatment by laparoscopy of 96 % of benign adnexal masses without mismanagement of any cases of ovarian cancer BACKGROUND Subjective evaluation of gray-scale and Doppler ultrasound findings ( i.e. , pattern recognition ) by an experienced examiner and preoperative serum levels of CA-125 can both discriminate benign from malignant adnexal ( i.e. , ovarian , paraovarian , or tubal ) masses . We compared the diagnostic performance of these methods in a large multicenter study . METHODS In a prospect i ve multicenter study --the International Ovarian Tumor Analysis --1066 women with a persistent adnexal mass underwent transvaginal gray-scale and color Doppler ultrasound examinations by an experienced examiner within 120 days of surgery . Pattern recognition was used to classify a mass as benign or malignant . Of these women , 809 also had blood collected preoperatively for measurement of serum CA-125 . Various levels of CA-125 were used as cutoffs to classify masses . Results from both assays were then compared with histologic findings after surgery . RESULTS Pattern recognition correctly classified 93 % ( 95 % confidence interval [ CI ] = 90.9 % to 94.6 % ) of the tumors as benign or malignant . Serum CA-125 correctly classified at best 83 % ( 95 % CI = 80.3 % to 85.6 % ) of the masses . Histologic diagnoses that were most often misclassified by CA-125 were fibroma , endometrioma , and abscess ( false-positive results ) and borderline tumor ( false-negative results ) . Pattern recognition correctly classified 86 % ( 95 % CI = 81.1 % to 90.4 % ) of masses of these four histologic types as being benign or malignant , whereas a serum CA-125 at a cutoff of 30 U/mL correctly classified 41 % ( 95 % CI = 34.4 % to 47.5 % ) of them . Pattern recognition assigned a correct specific histologic diagnosis to 333 ( 59 % , 95 % CI = 54.5 % to 62.8 % ) of the 567 benign lesions . CONCLUSION Pattern recognition was superior to serum CA-125 for discrimination between benign and malignant adnexal masses OBJECTIVE To construct and cross-vali date logistic regression models used for the prediction of ovarian malignancies in two groups of women with adnexal tumors . MATERIAL S AND METHODS Preoperative clinical , gray-scale and color Doppler ultrasound data of 307 women treated in the Ist Dept of Gynecology of the Medical University in Lublin ( group I ) and 464 of women treated in the Dept of Surgical Gynecology , Medical University in Poznan ( group II ) were analyzed retrospectively . These data were used to construct predictive models which were developed for both groups separately and then cross-vali date d ( 12 cases in each group , six malignant and 6 benign ) between the groups . Multiple logistic regression analysis was chosen to calculate probability of malignancy in each examined mass . RESULTS There were 228 ( 74.2 % ) benign tumors and 79 ( 25.7 % ) malignant tumors in group I. Group II consisted of 299 ( 64.4 % ) benign tumors and 165 ( 35.6 % ) malignant masses . Only six variables were included in the logistic regression model in group I. These were age , bilaterality , septae , papillary projections , volume and color score . In group II there were also 6 variables included in the regression model ( menopausal status , septae , bilaterality , ascites , blood vessel localization and PI ) . At 50 % probability of malignancy the model constructed for group I had a sensitivity and specificity of 74.6 % i 94.7 % , respectively . At the same probability level in group II sensitivity and specificity were 86.1 % i 93.6 % , respectively . Cross-validation of the predictive model constructed for group I in r and omly selected cases from group II had sensitivity of 66.4 % and specificity of 79.2 % . Sensitivity and specificity of the group II model tested in cases from group I were 64.3 % and 75.2 % , respectively . CONCLUSIONS We conclude that predictive models created with the use of multiple logistic regression analysis may be useful in preoperative discrimination of adnexal tumors . However , much better definition of diagnostic criteria , especially color Doppler score must be achieved before these models could be widely used in clinical practice Characterization of adnexal masses to identify patients with malignant ovarian tumors preoperatively for referral to a cancer center for treatment has been extensively studied . A simple algorithm called “ risk of malignancy index ” ( RMI ) reported by Jacobs incorporated the serum CA125 level , menopausal status , and ultrasound morphologic features . This algorithm has subsequently been tested on retrospective and prospect i ve data with encouraging results . However , these studies did not include cases that had had both their serum CA125 measurements and ultrasound examinations from a diverse range of laboratories and sonographers . The purpose of this study was to determine the effectiveness of the RMI algorithm for identifying cases of ovarian malignancy presenting at cancer units for subsequent referral to a cancer center . All cases of suspected ovarian malignancy referred to the Northern Gynaecological Oncology Centre ( NGOC ) during an 18-month period were identified from the NGOC data base . A case note review was performed , and the following data were extracted : patient demographics , the referring physician and the operating surgeon , ultrasound morphology , serum CA125 levels , and menopausal status . All patients had their ultrasound performed by sonographers at the peripheral unit according to local protocol s. A total of 182 patients with a pelvic mass were referred to the center for surgery . A total of 24 % patients had benign tumors , 6 % had tumors of borderline malignancy , and 70 % had invasive tumors . A total of 145 cases had an RMI > 200 ; 125 of these had ovarian or peritoneal cancers . An RMI > 200 had a sensitivity of 88.5 % for diagnosing invasive lesions . The overall sensitivity of this algorithm for diagnosing all borderline , invasive ovarian , or primary peritoneal lesions was 87.4 % , and the positive predictive value was 86.8 % . Our data confirm the effectiveness of the RMI algorithm in clinical practice for the identification and subsequent referral to cancer centers of cases of potential ovarian malignancy . We therefore recommend its continued use Purpose : Several scoring systems have been developed to distinguish between benign and malignant adnexal tumors . However , few of them have been externally vali date d in new population s. Our aim was to compare their performance on a prospect ively collected large multicenter data set . Experimental Design : In phase I of the International Ovarian Tumor Analysis multicenter study , patients with a persistent adnexal mass were examined with transvaginal ultrasound and color Doppler imaging . More than 50 end point variables were prospect ively recorded for analysis . The outcome measure was the histologic classification of excised tissue as malignant or benign . We used the International Ovarian Tumor Analysis data to test the accuracy of previously published scoring systems . Receiver operating characteristic curves were constructed to compare the performance of the models . Results : Data from 1,066 patients were included ; 800 patients ( 75 % ) had benign tumors and 266 patients ( 25 % ) had malignant tumors . The morphologic scoring system used by Lerner gave an area under the receiver operating characteristic curve ( AUC ) of 0.68 , whereas the multimodal risk of malignancy index used by Jacobs gave an AUC of 0.88 . The corresponding values for logistic regression and artificial neural network models varied between 0.76 and 0.91 and between 0.87 and 0.90 , respectively . Advanced kernel-based classifiers gave an AUC of up to 0.92 . Conclusion : The performance of the risk of malignancy index was similar to that of most logistic regression and artificial neural network models . The best result was obtained with a relevance vector machine with radial basis function kernel . Because the models were tested on a large multicenter data set , results are likely to be generally applicable OBJECTIVE The purpose of this study was to assess the diagnostic accuracy of transvaginal sonographic examination of small adnexal masses by simple descriptive sonographic scoring . METHODS In a prospect i ve multicenter study , 4 teaching hospitals and 2 regional hospitals with homogeneous st and ard sonographic equipment and operator experience recruited 677 consecutive patients with small adnexal masses of less than 5 cm . Morphologic scoring was obtained for each mass and recorded . The management of the mass was based on local protocol s. The minimal requirement was that surgery had to be performed for complex masses scoring 8 or higher , and follow-up of at least 12 months had to be performed and recorded for patients not admitted to surgery . Sonographic results were compared with pathologic reports and follow-up findings . RESULTS Fifty-two malignant tumors ( 19 borderline , 15 stage I-II , 15 stage III-IV , 2 tubal carcinomas , and 1 ovarian lymphoma ) , 243 benign tumors at pathologic examination , and 382 masses defined as benign according to follow-up findings were observed . Malignant tumors had a significantly higher mean + /- SD morphologic score ( 11.2 + /- 2.7 ) than benign masses ( 6.2 + /- 2.5 ) ( P = .001 ) . No difference was observed in the scoring assignment of malignant masses in different centers ( P = .56 ) . With a score of 8 or higher , the likelihood ratio was 3.61 ( 95 % confidence interval , 3.09 - 4.21 ) ; sensitivity , 92 % ; specificity , 76.9 % ; and positive predictive value , 25.6 % . CONCLUSIONS Our results provide evidence that descriptive morphologic scoring may overcome the subjectivity of interpretation of morphologic characteristics in small masses , and , at the same time , it can incorporate criteria to avoid simplistic description of a complex mass The goal of this study was to develop a scoring system using combination of Doppler characterization of pelvic/ovarian lesions and serum CA125 level . Our purpose was to maximize the preoperative discrimination between benign and malignant entities . In a prospect i ve study , a total of 101 patients were evaluated preoperatively using a st and ard transvaginal ultrasound and color Doppler imaging with pulse spectral analysis and serum CA125 level within a week prior to surgery . The variables that were analyzed by the multivariate logistic regression method are as follows : tumor structure , ascites , presence of septum , the peak systolic velocity ( PSV ) , the resistance index ( RI ) , and serum CA125 level . Of the 101 patients qualified for the study , 48 patients were diagnosed with benign ( 47.5 % ) and 53 ( 52.5 % ) with malignant tumors . Each criterion used alone provides statistically significant discrimination between benign and malignant tumors . Four criteria could be combined in a malignancy score which is calculated using the product of the serum CA125 level ( 1 if CA125 ≥40 U/mL and 0 if CA125 < 40 U/mL ) , the result of sonography for presence of septum in tumor ( 1 if there was septum ≥3 mm , 0 if there was no septum or <3 mm ) , result of Doppler flow imaging as RI ( 1 if RI ≤0.5 and 0 if RI > 0.5 ) and the PSV ( 1 if PSV ≥40 cm/s and 0 if PSV < 40 cm/s ) . This scoring system devised was statistically more effective discriminator between cancer and benign lesions than formal methods . Using malignancy score cutoff level of two , the sensitivity was 98 % ( CI 88.62–99.9 . ) , the specificity was 85 % ( CI 71.62–93.45 ) , the positive predictive value was 87.5 % , and the negative predictive value was 97.6 % . Area under curve of receiver operative characteristic curves was 0.987 ( CI 0.971–1.004 ) . These values were statistically more significant than those obtained from the independent use of RI , PSV , or serum CA125 level at their optimum decision values ( P < 0.05 ) . There is a need for a prospect i ve evaluation of this score using a larger sample of patients BACKGROUND All r and omized trials of adjuvant chemotherapy for early-stage ovarian cancer have lacked the statistical power to show a difference in the effect on survival between adjuvant chemotherapy and no adjuvant chemotherapy . They have also not taken into account the adequacy of surgical staging . We performed a prospect i ve unblinded , r and omized phase III trial to test the efficacy of adjuvant chemotherapy in patients with early-stage ovarian cancer , with emphasis on the extent of surgical staging . METHODS Between November 1990 and January 2000 , 448 patients from 40 centers in nine European countries were r and omly assigned to either adjuvant platinum-based chemotherapy ( n = 224 ) or observation ( n = 224 ) following surgery . Endpoints were overall survival and recurrence-free survival , and the analysis was on an intention-to-treat basis . The Kaplan-Meier method was used to perform time-to-event analysis , and the log-rank test was used to compare differences between treatment arms . Statistical tests were two-sided . RESULTS After a median follow-up of 5.5 years , the difference in overall survival between the two trial arms was not statistically significant ( hazard ratio [ HR ] = 0.69 , 95 % confidence interval [ CI ] = 0.44 to 1.08 ; P = .10 ) . Recurrence-free survival , however , was statistically significantly improved in the adjuvant chemotherapy arm ( HR = 0.63 , 95 % CI = 0.43 to 0.92 ; P = .02 ) . Approximately one-third of patients ( n = 151 ) had been optimally staged and two-thirds ( n = 297 ) had not . Among patients in the observation arm , optimal staging was associated with a statistically significant improvement in overall and recurrence-free survival ( HR = 2.31 [ 95 % CI = 1.08 to 4.96 ] ; P = .03 and HR = 1.82 [ 95 % CI = 1.02 to 3.24 ] P = .04 , respectively ) . No such association was observed in the chemotherapy arm . In the non-optimally staged patients , adjuvant chemotherapy was associated with statistically significant improvements in overall and recurrence-free survival ( HR = 1.75 [ 95 % CI = 1.04 to 2.95 ] ; P = .03 and HR = 1.78 [ 95 % CI = 1.15 to 2.77 ] ; P = .009 , respectively ) . In the optimally staged patients , no benefit of adjuvant chemotherapy was seen . CONCLUSION Adjuvant chemotherapy was associated with statistically significantly improved recurrence-free survival in patients with early-stage ovarian cancer . The benefit of adjuvant chemotherapy appeared to be limited to patients with non-optimal staging , i.e. , patients with more risk of unappreciated residual disease Purpose : The goal of this study was to maximize the discrimination between benign and malignant masses in patients with sonographically indeterminate ovarian lesions by means of unenhanced and contrast-enhanced MR imaging , and to develop a computer-assisted diagnosis system . Material and Methods : Findings in precontrast and Gd-DTPA contrast-enhanced MR images of 104 patients with 115 sonographically indeterminate ovarian masses were analyzed , and the results were correlated with histopathological findings . of 115 lesions , 65 were benign ( 23 cystadenomas , 13 complex cysts , 11 teratomas , 6 fibro-thecomas , 12 others ) and 50 were malignant ( 32 ovarian carcinomas , 7 metastatic tumors of the ovary , 4 carcinomas of the fallopian tubes , 7 others ) . A logistic regression analysis was performed to discriminate between benign and malignant lesions , and a model of a computer-assisted diagnosis was developed . This model was pro-spectively tested in 75 cases of ovarian tumors found at other institutions . Results : From the univariate analysis , the following parameters were selected as significant for predicting malignancy ( p<0.05 ) : a solid or cystic mass with a large solid component or wall thickness greater than 3 mm ; complex internal architecture ; ascites ; and bilaterality . Based on these parameters , a model of a computer-assisted diagnosis system was developed with the logistic regression analysis . To distinguish benign from malignant lesions , the maximum cut-off point was obtained between 0.47 and 0.51 . In a prospect i ve application of this model , 87 % of the lesions were accurately identified as benign or malignant . Conclusion : Benign and malignant ovarian lesions can be distinguished in most sonographically indeterminate lesions by means of parameters obtained from contrast-enhanced MR imaging The aim of our study was to generate predictive model , which would allow to estimate the influence of analyzed parameters on predictive accuracy of differential diagnosis of adnexal masses and to evaluate prospect ively diagnostic efficacy of the statistic model in the new set of patients . A total of 686 women diagnosed and surgically treated in the Gynecological and Obstetrical Teaching Hospital of University of Medical Sciences in Poznan , Pol and , were recruited into the study . Preoperative diagnostics included gynecological examination , ultrasonographic evaluation , tumor Doppler blood flow analysis , and serum levels of CA125 and TPS . In order to find the best combination of features and to calculate the individual probability of the malignancy , stepwise logistic regression analysis with quasi-Newton estimation was applied . The essential part of the best prognostic model , described by foregoing variables , is as follows : The highest sensitivity and specificity for the obtained model were 87.84 % and 93.74 % , respectively . Prognostic model , constructed with the use of logistic regression analysis , is characterized by higher sensitivity and specificity than individually applied diagnostic tests . Prospect i ve evaluation of this model application in a larger group of patients with adnexal masses will enable precise assessment of its objective clinical usefulness The aim of the study was to assign a probability of malignancy for any patient with an adnexal tumor by the application of multivariate logistic regression analysis to variables recorded at the time of pelvic sonography . Sixty-seven women with known adnexal masses were examined using transvaginal B-mode and color Doppler imaging . For each patient the variables included : ( 1 ) age , ( 2 ) maximum tumor diameter , ( 3 ) tumor volume , ( 4 ) unilocularity ( presence ( 0 ) or absence(1 ) ) , ( 5 ) papillary projections ( presence ( 1 ) or absence ( 0 ) ) , ( 6 ) r and om echogenicity ( presence ( 1 ) or absence ( 0 ) ) , ( 7 ) highest peak systolic velocity ( PSV ) , ( 8) time-averaged maximum velocity ( TAMXV ) , ( 9 ) pulsatility index ( PI ) and ( 10 ) resistance index ( RI ) . The TAMXV , PI and RI were those associated with the highest PSV . These ten independent variables and the final histological diagnosis for each patient ( the dependent variable ) were used for the regression analysis . Approximately 75 % of the entire data set was r and omly selected for generating the regression model . The remaining 25 % was used as the testing set for cross-validation of the model . In the entire data set there were 52 women with benign , three with borderline and 12 with invasive ovarian tumors . Regression analysis on the ten variables result ed in the retention of only ' age ' , ' papillary projection score ' and ' TAMXV ' as significantly contributing to predicting the presence or absence of malignancy . The probability of malignancy for any patient was given by solving the equation : Probability = 1/(1 + e-z ) where e is the base value for natural logarithms and z = ( 0.1273 x Age ) + ( 0.2794 x TAMXV ) + ( 4.4136 x Papillary projections score ) - 14.2046 . Cross-validation of the model on the test set of data gave a 100 % sensitivity and specificity . However , for the entire data set the best sensitivity and specificity were 93.3 and 90.4 % , respectively , at a cut-off value of 25 % probability of malignancy . In conclusion , multivariate logistic regression analysis enables the calculation of probability of malignancy for any patient with a known adnexal mass . The accuracy of this prediction appears to be better than that of morphological or Doppler criteria when the latter are used independently . The value of this model needs to be tested prospect ively INTRODUCTION There have been several different sonographic scoring systems developed for evaluation of particular characteristics of ovarian tumors in order to classify malignant diseases in the most objective way . The aim of this study was to evaluate diagnostic significance of our own scoring system and possibilities of its application in differentiation of malignant and benign ovarian tumors . MATERIAL AND METHODS A prospect i ve study comprised 177 women with different ovarian tumors . All patients underwent ultrasound examination using a unit with a 5 MHz probe . Certain tumor characteristics ( size , morphology , septa , type of capsule and ascites ) were estimated by scores from 0 to 2 whereas the sum of all scores presented the total score . A final diagnosis was made after histopathologic examination : group A -- malignant ovarian tumors ( n = 71 ) and group B -- benign ovarian tumors ( n = 106 ) . RESULTS The highest value of reliability in differentiation of malignant and benign ovarian tumors was score 6 and more than six ( sensitivity 87.3 % , specificity 91.5 % , positive predictive value 87.3 % , negative predictive value 91.5 % and test accuracy 90.9 % ) . DISCUSSION A separate diagnostic problem during application of mentioned sonographic scoring system were solid malignant tumors with a low total score ( 4 and 5 scores ) and benign tumors of complex consistence of high total score ( 7 and 8 scores ) . The total score 1 - 3 eliminates malignant tumors and the score from 9 - 10 eliminates benign type of tumors . CONCLUSION High sensitivity ( 95.7 % ) is present at the total score of 5 and more than five , but low specificity ( 81.1 % ) and test accuracy ( 87 % ) gives advantage to the score 6 and more , where differences between separate statistical parameters are least present OBJECTIVE Transvaginal sonography is limited in its ability to assess early stage cancers of the ovary as well as in distinguishing benign processes . As a method for characterization of tumor vascularization , color-coded Doppler sonography may be able to improve the diagnostic accuracy of B-mode sonography . METHODS Preoperative transvaginal B-mode and Doppler sonography was performed in 63 patients with unclear adnexal lesions prior to operation . Using multiple logistic regression , the independent variables of each procedure were selected and combined to yield a diagnostic flow chart . The diagnostic accuracy of this decision matrix was tested on 257 patients with unclear adnexal tumors . RESULTS In the 63 adnexal tumors investigated , the diagnostic impact of isolated sonomorphological assessment with evidence of a " solid area " was 78 % . Using Doppler sonography , the best discrimination was achieved by displaying the vascular distribution ( " central vascularization " ) . Combining these independent significant variables of the two procedures raised the diagnostic accuracy to 90 % ( sensitivity 86 % , specificity 93 % ) . The validity achieved by this combination was confirmed by the independent application of this method to the 257 adnexal tumors with unclear malignancy status ( diagnostic accuracy 93 % , sensitivity 92 % , specificity 94 % ) . CONCLUSIONS The combination of sonography and Doppler sonography achieves high and reproducible diagnostic accuracy in preoperative malignancy status assessment of adnexal tumors . The additional use of Doppler sonography can thus provide significant aid both for differential diagnostics of adnexal lesions and for the choice of surgical route in the case of an existing indication for operative therapy In the present study we aim ed to develop a formula for predicting adnexal malignancy based on menopausal status , ultrasound morphology , and color Doppler findings . Logistic regression analysis was performed retrospectively in 79 adnexal masses ( 59 benign and 20 malignant ) in 73 unselected and consecutive patients . All these masses had been preoperatively evaluated using transvaginal color Doppler ultrasonography . In logistic analysis menopausal status ( premenopausal vs postmenopausal ) , color Doppler findings ( no flow or lowest resistance index > 0.45 vs lowest resistance index < /=0.45 ) and ultrasound morphology ( nonsuspicious vs suspicious ) were entered as categorical variables . Morphology and color Doppler were found to be independent predictors , whereas menopausal status was not . To assess the validity of the developed mathematical formula , this was applied prospect ively in a second series of 58 consecutive and unselected patients diagnosed of adnexal mass and scheduled for surgery . The probability of malignancy was estimated in each case . Overall , 56 of 58 ( 96.5 % ) adnexal masses were correctly classified . We conclude that the formula developed in this study is easy to apply and could be useful to predict malignancy or benignity of adnexal masses Objective To create a strategy for sonographic differentiation of benign and malignant adnexal tumors in premenopausal and postmenopausal patients . Methods Multiple sonomorphologic criteria were analyzed prospect ively in 754 tumors . Four hundred were found in premenopausal and 354 in postmenopausal women . In a logistic regression model , relevant criteria were selected , and a diagnostic formula for tumor differentiation was derived . Results There were 165 malignant tumors , of which 37 ( 9.2 % ) were found in premenopausal and 128 ( 36.2 % ) in postmenopausal women . In both groups , the criteria of solid phase and ascites were the most significant . Further important diagnostic criteria were structure and tumor size in premenopausal women and cyst architecture and tumor surface in postmenopausal women . These results allowed an estimation of the probability of malignancy . Using a cutoff point of 10 % for the probability to classify tumors as malignant , the sensitivity and specificity in premenopausal patients were 86.5 % and 92.6 % , respectively , with an accuracy of 92 % . In postmenopausal women , the sensitivity , specificity , and accuracy were 93 % , 82.7 % , and 86.6 % , respectively . Assuming a prevalence as given in the study , the positive and negative predictive values were 54.4 % and 98.5 % in premenopausal and 75.3 % and 95.4 % in postmenopausal women . Conclusions With four binary criteria , a useful diagnostic formula for tumor differentiation was obtained . However , estimates for sensitivity , specificity , and accuracy may be too optimistic because they were derived from the same data that were already used for model selection OBJECTIVE To analyze the usefulness of transvaginal color Doppler assessment of venous flow in the differential diagnosis of adnexal masses . MATERIAL AND METHODS Ninety-one consecutive patients ( mean age : 46.6 years , range : 16 - 81 years ) diagnosed as having an adnexal mass were evaluated by transvaginal color Doppler sonography prior to surgery . Color Doppler was used to detect and analyze the flow velocity waveform from arterial and venous blood flow within the tumor . For arterial signals the resistance index and peak systolic velocity , and for veins the maximum venous flow velocity , were calculated . Receiver operator characteristic curves were plotted to determine the best venous flow velocity cut-off . According to our previous study using arterial Doppler , a tumor was considered as malignant when flow was detected and the lowest resistance index was < or = 0.45 . Using venous Doppler a mass was considered as malignant when flow was detected and the venous flow velocity was > or = the best cut-off found on the receiver operator characteristic curve . Definitive histopathological diagnosis was obtained in all cases . Sensitivity , specificity , positive predictive value and negative predictive value for B-mode morphology ( evaluation performed according to Sassone 's scoring system ) , arterial Doppler , venous Doppler , and a combination of both arterial and venous Doppler were calculated . RESULTS Twenty-five masses ( 27.5 % ) were malignant and 66 ( 72.5 % ) benign . Arterial and venous flow was found more frequently in malignant than in benign masses ( 92 % vs. 41 % ( P < 0.001 ) and 72 % vs. 21 % ( P < 0.001 ) , respectively ) . The resistance index was significantly lower in malignant tumors ( 0.42 vs. 0.60 , P = 0.0003 ) . No differences were found in peak systolic velocity . Venous flow velocity was significantly higher in malignant masses ( 18.1 cm/s vs. 8.9 cm/s , P = 0.0006 ) . The best cut-off of venous flow velocity was 10 cm/s . Sensitivity , specificity , positive predictive value and negative predictive value for morphology , arterial Doppler , venous Doppler , and the combination of both arterial and venous Doppler were 92 % , 71 % , 45 % , 96 % ; 76 % , 95 % , 87 % , 91 % ; 68 % , 94 % , 81 % , 89 % ; and 88 % , 91 % , 79 % , 95 % , respectively . CONCLUSIONS Our results indicate that preoperative evaluation by venous flow assessment of adnexal masses may be useful to discriminate between malignant and benign tumors OBJECTIVES To test prospect ively the diagnostic performance of two logistic regression models for calculation of individual risk of malignancy in adnexal tumors ( the ' Tailor model ' and the ' Timmerman model ' ) , and to compare them to that of ' pattern recognition ' ( subjective evaluation of the gray-scale ultrasound image and color Doppler ultrasound examination ) . DESIGN Consecutive women with a pelvic mass judged clinical ly to be of adnexal origin underwent preoperative ultrasound examination including color and spectral Doppler examination . The same examination techniques and definitions as those used in the studies in which the logistic regression models had been created were used . The Tailor model was tested in 133 women ( 35 of whom hada malignancy ) and the Timmerman model in 82 women ( 29 of whom had a malignancy ) . A subset of 79 women ( 28 of whom had a malignancy ) was used to compare the performance of the Tailor model and the Timmerman model by calculating and comparing the areas under the receiver operating characteristics curves of the two models . Sensitivity and specificity with regard to malignancy were calculated for all three methods . RESULTS Pattern recognition performed better than the two logistic regression models ( sensitivity around 85 % , specificity around 90 % ) . Using a risk of malignancy of > 50 % to indicate malignancy ( as suggested in the original publications ) , the sensitivity of the Tailor model was 69 % and the specificity 88 % ( n = 133 ) . The corresponding values for the Timmerman model were 62 % and 79 % ( n = 82 ) . The receiver operating characteristics curves showed the two logistic regression models to have similar diagnostic properties ( area under the curve , 0.87 vs. 0.84 ; P = 0.25 ; n = 79 ) . The diagnostic performance of the mathematical models was much poorer in this study than in those in which the models had been created . CONCLUSION The poor diagnostic performance of the mathematical models can probably be explained by subtle differences in definitions and examination technique and by differences between the original tumor population s and the study population . For mathematical models to be generally useful , they probably need to be created on the basis of a very large number of tumors , and the variables in the model must be unequivocally defined and the examination technique meticulously st and ardized OBJECTIVES To evaluate the efficacy of color Doppler ultrasonography as the predictor of malignant ovarian tumors and to compare the results with CA 125 levels and ultrasonographic morphological patterns . METHODS We compared color Doppler ultrasound with sonographic findings and serum CA 125 levels for predicting ovarian malignancy in 16 patients with malignant and 12 patients with benign ovarian tumors . RESULTS There was a significant difference in pulsatility index ( PI ) value of ovarian vessel between benign and malignant tumors ( 2.42 + /- 0.67 for benign and 1.35 + /- 0.78 for malignant , respectively , P < 0.01 ) . The specificity of morphological findings and CA 125 was lower than that of PI measurements , but sensitivity was not different between the three methods . In addition , the combination of color Doppler and CA 125 or morphological assessment s result ed in a sensitivity of 100 % and a negative predictive value of 100 % , respectively . CONCLUSION PI measurements by transvaginal color Doppler ultrasound combined with CA 125 levels or morphological findings could be an accurate and appropriate screening method for ovarian tumors Objective To test the accuracy of three logistic regression models in diagnosing malignancy in women with adnexal masses . Methods This was a prospect i ve collaborative study . Women were recruited from three hospitals and all assessment s were performed at the Gynaecology Ultrasound Unit , King 's College Hospital . One hundred women with known adnexal masses were examined preoperatively . The demographic , biochemical , and sonographic data recorded for each patient included age , menopausal status , CA 125 levels , ultrasound morphology , and Doppler blood flow analysis . The diagnosis of malignancy was made for each woman using three logistic regression models previously described by Alcazar et al , Tailor et al , and Timmerman et al. Variables used in these models were then combined to form a new model . The results were compared with the final histopathologic diagnosis . Results Sixty-seven women had benign tumors and 33 had ovarian cancer . Women with malignant tumors were older than those with benign masses . There were significant differences in CA 125 levels , presence of papillary proliferations , and ascites between the two groups . The sensitivities and specificities achieved respectively by the models were as follows : 45 % and 93 % with Tailor et al 's model , 9 % and 99 % with Alcazar et al 's model , and 73 % and 91 % with Timmer-man et al 's model . There was no significant improvement over the performance of Timmerman et al 's model and the new combined model . Conclusion All models performed less well than originally reported . Combining the models did not lead to a significant improvement in performance . Larger sample sizes that incorporate all types of ovarian tumors are necessary to design more accurate diagnostic models OBJECTIVE The aim of the study was to test the hypothesis that a combination of a previously devised morphologic scoring system and color flow-directed Doppler measurements would afford better discrimination between benign and malignant ovarian masses . STUDY DESIGN The scoring system and color flow-directed Doppler measurements for 115 masses were prospect ively analyzed and correlated with histopathologic surgical findings . RESULTS In 21 masses ( 18 patients ) no flow was obtained . Seventy-eight masses in 70 patients were benign , and 16 masses in 12 patients were malignant . The mean total score for the benign masses was 6.7 and for the malignant masses 11.7 . The resistance index was 0.64 for the benign lesions and 0.39 for the malignant masses ( range 0.2 to 0.98 ) . The mean pulsatility index of the benign masses was 1.17 and 0.52 for the malignancies ( range 0.2 to 2.6 ) . There were no malignancies in the group with no flow obtained . The sensitivity and specificity of score alone was 94 % and 87 % , respectively , with a 60 % positive predictive value . By means of resistance index or pulsatility index the sensitivity was 94 % , the specificity 99 % , and the positive predictive value 94 % . CONCLUSION These results suggest that Doppler flow measurements alone and in conjunction with a scoring system help differentiate benign from malignant masses OBJECTIVES This prospect i ve study investigated the clinical evaluation of transvaginal color Doppler ultrasonography in the diagnosis of ovarian tumors . METHODS Transvaginal ultrasonography ( morphological assessment , DePriest 's index ) and color Doppler analysis were performed for 31 malignant and 64 benign tumors ovarian tumors . Serum tumor markers such as CA125 , CA72 - 4 , and STN were measured . RESULTS Sensitivity , specificity , positive predictive value , negative predictive value , and accuracy were as follows : DePriest 's index , 90.3 % , 73.4 % , 62.2 % , 94.0 % , 78.9 % ; CA125 , 70.4 % , 87.7 % , 73.1 % , 86.2 % , 82.1 % ; minimum pulsatile index combined with detection of location of arterial blood flow , 83.9 % , 98.4 % , 96.3 % , 92.6 % , 93.7 % , respectively . In cases where arterial blood flow was recognized , malignant tumors had significantly fewer diastolic notches , while benign tumors had many diastolic notches . The difference in the presence of diastolic notch between malignant and benign tumors was significant ( P<0.0004 ) . CONCLUSIONS For diagnosis of ovarian tumors , transvaginal color Doppler analysis combined with detection of arterial location is more useful than other procedures OBJECTIVE To assess a new logistic regression model developed to predict malignancy in adnexal masses . METHODS In the first part of this study , we developed a logistic model by applying logistic regression analysis in a series of 268 adnexal masses ( 203 benign and 65 malignant lesions ) in 248 patients ( mean age , 43.6 years ; SD , 14.2 years ) evaluated and treated at our institution . Eleven parameters were entered in the logistic regression analysis in a forward stepwise way . In the second part of the study , we evaluated the model 's diagnostic performance in a further set of 135 adnexal masses ( 103 benign and 32 malignant tumors ) in 129 patients ( mean age , 44.4 years ; SD , 14.6 years ) . This diagnostic performance was compared with that of age , tumor volume , Sassone 's and Ferrazzi 's B-mode ultrasonographic morphologic scoring systems , serum cancer antigen 125 level , and the tumor 's lowest resistive index . Comparison was done by calculating the area under the receiver operating characteristic curve . RESULTS In logistic analysis , only menopausal status , the presence of papillary projections , the logarithm of the cancer antigen 125 value , tumor blood flow location , and the lowest resistive index were retained in the model . The model had the best area under the curve ( 0.97 ) , significantly higher than patient age ( area under the curve , 0.78 ; P = .001 ) , tumor volume ( area under the curve , 0.68 ; P < .0001 ) , cancer antigen 125 ( area under the curve , 0.88 ; P = .008 ) , lowest resistive index ( area under the curve , 0.85 ; P = .011 ) , Ferrazzi 's scoring system ( area under the curve , 0.89 ; P = .01 ) , and maximal peak systolic velocity ( area under the curve , 0.71 ; P < .0001 ) . Comparison with Sassone 's scoring system ( area under the curve , 0.91 ) did not reach statistical significance , but a clear trend was found ( P = .116 ) . CONCLUSIONS The model had the best diagnostic performance for discriminating between benign and malignant adnexal masses . A clinical prospect i ve evaluation is needed to confirm its actual value OBJECTIVES To determine which extrauterine pelvic masses are difficult to correctly classify as benign or malignant on the basis of ultrasound findings , and to determine if the use of logistic regression models for calculation of individual risk of malignancy would improve the diagnostic accuracy in difficult tumors . METHODS In a prospect i ve , international , European multicenter study involving nine centers , 1066 women with a pelvic mass judged to be of extrauterine origin underwent transvaginal ultrasound examination by an experienced ultrasound examiner before surgery . A st and ardized examination technique and predefined definitions of ultrasound characteristics were used . On the basis of subjective evaluation of ultrasound findings , the examiner classified each mass as being certainly benign , probably benign , unclassifiable , probably malignant or certainly malignant . Even when the examiner found the mass unclassifiable ( i.e. difficult mass ) he or she was obliged to state whether the mass was more likely to be benign or malignant . Borderline tumors were classified as malignant . RESULTS There were 90 ( 8 % ) unclassifiable masses . Multiple logistic regression analysis showed papillary projections , > 10 locules in a cyst without solid components , low-level echogenicity of cyst fluid , and moderate vascularization as assessed subjectively at color Doppler examination to be ultrasound variables independently associated with unclassifiable mass . Borderline malignant tumors ( n = 55 ) proved to be most difficult to assess with only 47 % being correctly classified ( i.e. classified as malignant ) , 29 % being incorrectly classified ( i.e. classified as benign ) and 24 % being unclassifiable vs. 90 % of non-borderline tumors being correctly classified , 3 % being incorrectly classified and 8 % being unclassifiable ( P < 0.0001 ) . Papillary cystadeno(fibro)mas , myomas and cases of struma ovarii were also more common among the unclassifiable masses than among the classifiable ones ( 5.6 % vs. 1.1 % , P = 0.008 ; 4.4 % vs. 0.9 % , P = 0.02 ; 4.4 % vs. 0.2 % , P = 0.0006 ) . No ultrasound variable or clinical variable ( including CA 125 ) entered a logistic regression model to predict malignancy in difficult masses . A model could be constructed for difficult masses containing papillary projections but this model performed no better than subjective evaluation of the ultrasound image . Sensitivity and specificity of subjective evaluation with regard to malignancy in the group of unclassifiable masses were 56 % ( 14/25 ) and 77 % ( 50/65 ) vs. 91 % ( 220/241 ) and 97 % ( 712/735 ) in the classifiable masses . CONCLUSIONS Borderline tumors cause great diagnostic difficulties , but so do papillary cystadeno(fibro)mas , struma ovarii and some myomas . Logistic regression models do not solve the diagnostic problem in difficult pelvic masses OBJECTIVE The purpose of this study was to assess the value of conventional gray-scale ultrasonography , based on a morphologic scoring system , in the differential diagnosis of malignant and benign adnexal tumors . MATERIAL AND METHODS A total of 58 adnexal masses in 51 patients were classified prospect ively as suggestive of malignant or benign , on the basis of gray-scale ultrasonographic morphology . The results were correlated with histopathological diagnosis . RESULTS Histopathology of 42 masses was found to be benign and 16 masses were found to be malignant . On gray-scale analysis 15 of 16 malignant masses were classified as suggestive of malignant and 37 of 42 benign masses were classified as suggestive of benign . The sensitivity , specificity , positive predictive value and negative predictive value are calculated as 93 % , 88 % , 75 % , and 97 % , respectively . CONCLUSION Prediction of malignancy using gray scale ultrasonograhy based on a morphological scoring system was reliable ( NPV = 97 % , PPV = 93 % ) . However further investigations about the assessment of adnexal masses with ultrasonography are BACKGROUND The study analyses the diagnostic possibilities regarding ovarian neoplasms offered by different clinical approaches : B-mode morphological ultrasonographic examination , colour Doppler and Doppler pulsed ultrasonography , and lastly the assay of a number of tumour markers . METHODS A prospect i ve study was carried out in 125 selected patients attending the Ultrasonography unit of the Obstetrics and Gynecology Clinic at Parma University between June 1997 and June 1999 who presented an adnexal mass . All patients underwent transvaginal ultrasonography ( multifrequency vaginal probe 5.0 - 6.5 MHz , Esaote Idea , Genova ) to characterise the mass , applying 5 different ultrasonographic scores : Granberg , Sassone , Di Priest , Lerner , Ferrazzi . Colour Doppler imaging was then performed to analyse the vascularisation of the mass , also using pulsed Doppler to study a number of velocimetric parameters : pulsatility index , index of resistance , systolic and diastolic peak velocity , mean velocity . All the patients underwent surgery using laparotomy or video laparoscopy , accompanied by histological analysis . A number of different tumour markers were assayed prior to surgery : Cal25 , CA19 - 9 , CEA , beta-HCG , alpha-fetoprotein . RESULTS Out of 127 pelvic masses examined , histological analysis showed that 19 were malignant and 108 benign . The diagnostic accuracy of malignancy was comparable for the 5 scores studied , with a minimum of 57.48 % for Lerner and a maximum of 77.16 % for Di Priest . The central importance of vascularisation was the only significant parameter among those analysed using colour Doppler which was useful for the diagnosis of a malignant neoplasm , with a diagnostic accuracy of 82.95 % . No indicator obtained using pulsed Doppler was useful for diagnostic purpose s. CA125 was the only tumour marker that revealed a statistically significant difference emerged between the benign ( 21.6 U/ml ) and malignant ( 220.8 U/ml ) masses . Its diagnostic accuracy was 75.58 % . CONCLUSIONS This study confirmed that the three methods analysed do not differentiate substantially in their overall diagnostic capacity of malignant ovarian neoplasms . The best performances for ecographic scores ( Di Priest ) did not exceed a sensitivity of 89.47 % with a 21.25 % incidence of false positives ; this was comparable to CA125 with a sensitivity of 85.71 % and false positives in 22.09 % . In relation to the central importance of vascularisation , colour Doppler achieved a lower sensitivity ( 55.55 % ) , but this was confirmed by a low incidence of false positives ( 7.95 % ) . This revealed its importance as a useful method , especially for excluding the presence of malignant tumours PURPOSE To collect data for the development of a more universally useful logistic regression model to distinguish between a malignant and benign adnexal tumor before surgery . PATIENTS AND METHODS Patients had at least one persistent mass . More than 50 clinical and sonographic end points were defined and recorded for analysis . The outcome measure was the histologic classification of excised tissues as malignant or benign . RESULTS Data from 1,066 patients recruited from nine European centers were included in the analysis ; 800 patients ( 75 % ) had benign tumors and 266 ( 25 % ) had malignant tumors . The most useful independent prognostic variables for the logistic regression model were as follows : ( 1 ) personal history of ovarian cancer , ( 2 ) hormonal therapy , ( 3 ) age , ( 4 ) maximum diameter of lesion , ( 5 ) pain , ( 6 ) ascites , ( 7 ) blood flow within a solid papillary projection , ( 8) presence of an entirely solid tumor , ( 9 ) maximal diameter of solid component , ( 10 ) irregular internal cyst walls , ( 11 ) acoustic shadows , and ( 12 ) a color score of intratumoral blood flow . The model containing all 12 variables ( M1 ) gave an area under the receiver operating characteristic curve of 0.95 for the development data set ( n = 754 patients ) . The corresponding value for the test data set ( n = 312 patients ) was 0.94 ; and a probability cutoff value of .10 gave a sensitivity of 93 % and a specificity of 76 % . CONCLUSION Because the model was constructed from multicenter data , it is more likely to be generally applicable . The effectiveness of the model will be tested prospect ively at different centers Transvaginal sonography ( TVS ) has been shown to be the most effective means to screen for ovarian cancer . TVS is associated with a high sensitivity and specificity . However , the positive predictive value associated with TVS in the diagnosis of malignancy is low . A morphologic scoring index for use with TVS has been used at the University of Kentucky since 1991 . The current study was performed to more fully evaluate the efficacy and interobserver variation in ultrasonographic morphology index scores attributed to ovarian tumors . Ultrasound records of 213 patients from five participating centers were review ed by three independent observers . Morphology index scores were assigned to each tumor in a blinded fashion . The morphology index scores were then compared with the final histopathologic findings . One hundred sixty-nine patients had benign tumors and 44 patients had ovarian malignancies . The mean morphology index scores were significantly higher in malignant ovarian tumors ( MI 7.3 + /- 1.9 ) than in benign ovarian tumors ( MI 3.3 + /- 1.8 ) . Statistical evaluation of the morphology index scores revealed a sensitivity of 89 % and a positive predictive value of 46 % . Interobserver variation was lowest in assessing ovarian volume and higher in the evaluation of wall structure and septal structure . A multilogistic regression model was used to evaluate the predictive power of each component of the morphology index . The use of a morphology index is an effective and cost-efficient method of increasing the positive predictive value of TVS screening for ovarian cancer . Use of this index in large numbers of patients will generate data which should help refine appropriate structural scoring categories and reduce interobserver variation To assess prospect ively a logistic model based on sonographic morphologic and color Doppler findings , which had been developed to predict adnexal malignancy , 167 consecutive and unselected patients ( mean age , 45.7 yr ; range , 17 to 81 yr ; 113 [ 67.7 % ] premenopausal and 54 [ 32.3 % ] postmenopausal ) diagnosed as having an adnexal mass and scheduled for surgery were prospect ively included in this study . All patients were evaluated by transvaginal color Doppler ultrasonography . The probability of adnexal malignancy was estimated prior to surgery , applying a logistic model developed previously . A probability of malignancy greater than 75 % was considered to assess model performance . Sensitivity , specificity , positive predictive value , negative predictive value , and accuracy were calculated for the model . In all cases definitive histopathologic diagnosis was obtained . One hundred and twenty-five ( 74.9 % ) benign and 42 ( 25.1 % ) malignant tumors were found . The sensitivity , specificity , positive predictive value , and negative predictive value of the model were 85.7 % ( 95 % confidence intervals , 71.4 % to 94.6 % ) , 100 % ( 95 % confidence intervals , 97.1 % to 100 % ) , 100 % ( 95 % confidence intervals , 90.3 % to 100 % ) , and 95.4 % ( 95 % confidence intervals , 90.3 % to 98.3 % ) , respectively . Overall accuracy was 96.4 % ( 95 % confidence intervals , 91.3 % to 98.7 % ) . Our results confirm the validity of the proposed logistic model in predicting adnexal malignancy OBJECTIVE : To evaluate referral guidelines published by American College of Obstetricians and Gynecologists ( ACOG ) and Society of Gynecologic Oncologists ( SGO ) , which provide guidance about when to refer a patient with a pelvic mass to a gynecologic oncologist . METHODS : Data from consecutive patients evaluated for pelvic mass were collected prospect ively over a 5-year period . The performance characteristics of the ACOG/SGO referral guidelines for detection of primary and metastatic ovarian cancer were calculated by using menopausal status , CA 125 level , imaging results , physical findings , and family history . RESULTS : Eight hundred thirty-seven patients met inclusion criteria . Forty-four percent ( 263/597 ) of postmenopausal women were diagnosed with ovarian cancer , whereas 20 % ( 48/240 ) of premenopausal women had ovarian cancer . Seventy-four percent of primary cancers were stage III or IV . The referral guidelines were 79.2 % sensitive and 69.8 % specific for premenopausal women , with a positive predictive value of 39.6 % . For postmenopausal women , the guidelines were 93.2 % sensitive and 59.9 % specific , and positive predictive value was 64.6 % . The referral guidelines performed better for late-stage than early-stage cancers in both sensitivity and positive predictive value , especially in postmenopausal women . Although only 28 patients would not have been referred by the guidelines , the majority of these had early stage ( I or II ) disease . Lowering the CA 125 cutoff level required for referral of premenopausal patients increased the sensitivity of the guidelines in this group . CONCLUSION : The ACOG/SGO guidelines perform well in predicting advanced-stage ovarian cancer , probably owing to the nature of advanced-stage disease . The guidelines perform poorly in identifying early-stage disease , especially in premenopausal women , primarily due to lack of early markers and signs of ovarian cancer . LEVEL OF EVIDENCE : OBJECTIVE To determine whether the combined use of Lerner 's morphologic score and color Doppler ultrasound examination results in better discrimination of benign and malignant adnexal masses than the use of Lerner 's score alone or Doppler variables alone . DESIGN One hundred and seventy-three consecutive women with a pelvic mass judged clinical ly to be of adnexal origin underwent preoperative ultrasound examination including color and spectral Doppler techniques . One hundred and forty-nine tumors were benign and 24 malignant . The sensitivity and false-positive rate with regard to malignancy were calculated for Lerner 's score , six Doppler variables and combinations of Lerner 's score and Doppler variables . Previously defined gray scale and Doppler criteria of malignancy were used and tested prospect ively . The best method was defined as that detecting most malignancies with the lowest false-positive rate . RESULTS Lerner 's score had a sensitivity of 92 % and a false-positive rate of 36 % . The best Doppler variable -- time-averaged maximum velocity -- had similar diagnostic properties with a sensitivity of 100 % and a false-positive rate of 41 % . Combining Lerner 's score with Doppler measurement of time-averaged maximum velocity -- i.e . requiring both Lerner 's score and time-averaged maximum velocity to indicate malignancy for a malignant diagnosis to be made -- had a sensitivity of 92 % and a false-positive rate of 19 % . CONCLUSIONS The combined use of Lerner 's score and measurement of time-averaged maximum velocity is a better method for discrimination of benign and malignant adnexal masses than the use of Lerner 's score alone or Doppler ultrasound examination alone . The clinical value of the combined method needs to be cross-vali date d prospect ively in a new series of tumors PURPOSE Conflicting results on prognostic factors for advanced epithelial ovarian cancer ( EOC ) have been reported because of small sample size and heterogeneity of study population . The purpose of this study was to identify factors predictive of poor prognosis in a similarly treated population of women with advanced EOC . PATIENTS AND METHODS A retrospective review of demographic , pathologic , treatment , and outcome data from 1,895 patients with International Federation of Gynecology and Obstetrics stage III EOC who had undergone primary surgery followed by six cycles of intravenous platinum/paclitaxel was conducted . A proportional hazards model was used to assess the association of prognostic factors with progression-free survival ( PFS ) and overall survival ( OS ) . RESULTS Increasing age was associated with increased risks for disease progression ( HR = 1.06 ; 95 % CI , 1.02 to 1.11 for an increase every 10 years ) and death ( HR = 1.12 ; 95 % CI , 1.06 to 1.18 ) . Mucinous or clear-cell histology was associated with a worse PFS and OS compared with serous carcinomas . Patients with performance status ( PS ) 1 or 2 were at an increased risk for recurrence compared with PS 0 ( HR = 1.12 ; 95 % CI , 1.01 to 1.24 ) . Compared with patients with microscopic residual disease , patients with 0.1 to 1.0 cm and > 1.0 cm residual disease had an increased risk of recurrence ( HR = 1.96 ; 95 % CI , 1.70 to 2.26 ; and HR = 2.36 ; 95 % CI , 2.04 to 2.73 , respectively ) and death ( HR = 2.11 ; 95 % CI , 1.78 to 2.49 ; P < .001 ; and HR = 2.47 ; 95 % CI , 2.09 to 2.92 , respectively ) . CONCLUSION Age , PS , tumor histology , and residual tumor volume were independent predictors of prognosis in patients with stage III EOC . These data can be used to identify patients with poor prognosis and to design future tailored r and omized clinical trials OBJECTIVE To compare the value of the risk of malignancy index ( RMI ) and the ovarian crescent sign ( OCS ) in the diagnosis of ovarian malignancy . METHODS This was a prospect i ve observational study of women with ultrasonographic diagnosis of an ovarian cyst . The RMI was calculated in all cases using a previously published formula ( RMI = U ( ultrasound score ) x M ( menopausal status ) x serum CA125 ( kU/L ) ) . A value > 200 was considered to be diagnostic of ovarian cancer . The OCS was defined as a rim of visible healthy ovarian tissue in the ipsilateral ovary . Its absence was taken as being diagnostic of invasive cancer . RESULTS A total of 106 consecutive women were included in the study , of whom 92 ( 86.8 % ) had a benign ovarian tumor , five ( 4.7 % ) had borderline lesions and nine ( 8.5 % ) had an invasive ovarian cancer . The absence of an OCS diagnosed invasive ovarian cancer with a sensitivity of 100 % ( 95 % CI , 70 - 100 % ) , specificity of 93 % ( 95 % CI , 86 - 96 % ) , positive predictive value ( PPV ) of 56 % , negative predictive value ( NPV ) of 100 % and positive likelihood ratio ( LR+ ) of 13.86 ( 95 % CI , 6.79 - 28.29 ) . This compared favorably with a sensitivity of 89 % ( 95 % CI , 57 - 98 % ) , specificity of 92 % ( 95 % CI , 85 - 96 % ) , PPV of 50 % , NPV of 99 % and LR+ of 10.78 ( 95 % CI , 5.34 - 21.77 ) , which were achieved using RMI > 200 ( P < 0.01 ) . CONCLUSIONS The RMI and the OCS are useful tests for discriminating between invasive and non-invasive ovarian tumors . The application of these tests in a sequential manner might improve the overall accuracy of ovarian cancer diagnosis OBJECTIVE To cross-vali date , prospect ively , the diagnostic performance of established ultrasound methods for discrimination of benign and malignant pelvic masses . METHODS A total of 173 consecutive women with a pelvic mass judged clinical ly to be of adnexal origin underwent preoperative ultrasound examination including color and spectral Doppler techniques . A total of 149 tumors were benign , and 24 were malignant . The sensitivity and false-positive rate with regard to malignancy were calculated for the following methods , using cut-off values recommended in previous publications : Lerner score ; ultrasound morphology , i.e. tumors without solid components being classified as benign and tumors with solid components as malignant ; tumor color score ; pulsatility index ; resistance index ; time-averaged maximum velocity ; peak systolic velocity ; the combined use of ultrasound morphology and tumor color score and the combined use of ultrasound morphology and peak systolic velocity . Sensitivity and false-positive rate were also calculated for subjective evaluation of the gray-scale ultrasound image and for subjective evaluation of the gray-scale ultrasound image supplemented with subjective evaluation of color Doppler ultrasound examination . The confidence with which the diagnosis was made , based on subjective evaluation , was rated on a visual analog scale . RESULTS Subjective evaluation of the gray-scale ultrasound image was by far the best method for distinguishing benign from malignant tumors ( sensitivity 88 % , false-positive rate 4 % ) , followed in descending order by subjective evaluation of the gray-scale ultrasound image supplemented with color Doppler examination , the Lerner score and the time-averaged maximum velocity . Adding Doppler examination to subjective evaluation of the gray-scale image did not increase the number of correct diagnoses , but it increased the confidence with which a correct diagnosis was made in 14 % of tumors . In 11 tumors ( 6 % of the series as a whole ) , the addition of Doppler examination changed the diagnosis based on subjective evaluation of the gray-scale ultrasound image from an incorrect ( n = 1 ) or uncertain ( n = 10 ) diagnosis to a correct and confident diagnosis . CONCLUSION In experienced h and s , subjective evaluation of the gray-scale ultrasound image is the best ultrasound method for discriminating between benign and malignant adnexal masses . The main advantage of adding Doppler examination to subjective evaluation of the gray-scale image is an increase in the confidence with which a correct diagnosis is made OBJECTIVE Because external validation of the present models has not been reported , the purpose of the present study was to assess existing diagnostic models that are used to distinguish malignant from benign masses . METHODS We tested the performance of existing models in a prospect ively assembled data set of 170 patients with an adnexal mass . Twenty-one models that have been reported previously were assessed . The models were based on combinations of ultrasound findings , color Doppler tests , CA-125 measurement , age , and /or menopausal status . For each model , we constructed ROC curves and calculated an area under the ROC curve . RESULTS Of the 170 adnexal masses that were operated on , 30 ( 18 % ) were malignant . The area under the ROC curve of 21 models that were externally vali date d varied between 0.69 and 0.90 . We found the performance of the existing models to be inferior to the performance reported in the initial studies . Even models that incorporated multiple diagnostic tools and that were developed using logistic regression models or neural networks had an area under the ROC curve of 0.86 at maximum . In the case where we focused on almost perfect sensitivity , the highest specificities varied between 0.45 and 0.60 . CONCLUSION Although diagnostic models might be of value in the preoperative assessment of the adnexal mass , their diagnostic performance is not as good as that reported in the original publications Endoscopic surgery is the treatment of choice for adnexal masses in premenopausal women . A prospect i ve observational study was conducted with 100 consecutive premenopausal women with adnexal masses who had been referred for endoscopic management to the University Hospital of Larissa , Larissa , Greece . The aim of the study was to compare the ability of the risk malignancy index ( RMI ) [ 1,2 ] and the Ferrazzi score [ 3 ] ( Table 1 ) to discriminate preoperatively between benign and malignant masses . Histopathologic diagnosis was regarded as the final arbiter . Patients with a RMI of 150 or greater or a Ferrazzi score of 8 or greater were referred to the oncology team and explorative laparotomy was performed . All other patients were treated endoscopically and a frozen-section biopsy was performed . The sensitivity , specificity , positive predictive value ( PPV ) , and negative predictive value ( NPV ) of the Ferrazzi score and RMI were calculated at various cut-off points , separately or in combination , for different age groups . Of the 89 patients who had benign disease , 76 were treated endoscopically . The 10 patients found to have malignant disease underwent explorative laparotomy . The remaining patient ( who also had ovarian torsion ) underwent staging laparotomy after the results of her frozen-section biopsy indicated that she had a borderline tumor . Her serum concentration of cancer antigen (CA)-125 was 192 U/ mL , but the value had not been available preoperatively . Mean age was significantly higher for cancer patients ( 45.4 years ) than for patients with benign disease ( 30.8 years ) ( P<0.001 ) . Ferrazzi score , RMI , and CA-125 levels were significantly associated with cancer diagnosis , but the Ferrazzi score proved the more accurate predictor of malignancy ( Fig. 1 ) . Specificity was 86.5 % and NPV was 93.9 for a RMI of 150 or greater whereas specificity was 100 % and NPV was 92.7 for a Ferrazzi score of 8 or greater . These results suggest that the Ferrazzi score can be strongly recommended . Moreover , specificity was 100 % and NPV was 98 among patients aged 40 years or older who had both a RMI of 150 or greater and a Ferrazzi score of 8 or greater . A possible explanation is that the primary purpose of introducing RMI was to improve the referral of older patients with advanced ovarian cancer to oncology centers [ 1,2,4 ] . In this study 36 % of the patients younger than 40 years had endometriosis , a disease associated with higher CA-125 values , and this high proportion decreased the predictive performance of the RMI . The Ferrazzi score is a detailed morphometric ultrasonographic score that excludes dermoid cysts , which may explain its superior performance [ 3 ] ( Table 1 ) . Preoperative risk scoring for adnexal masses with both Ferrazzi score and RMI can be reliably performed by a generalist gynecologist and would allow for a more effective referral to experienced subspecialists |
14,036 | 26,156,097 | Conclusion Stent retrievers have the potential to achieve a high rate of recanalization and functional independence whilst being relatively safe . | Background and purpose Intra-arterial therapy for acute ischaemic stroke has evolved rapidly in the last few years .
Stent retrievers have now replaced ‘ first-generation ’ devices , which have been the principle devices tested in stroke trials .
Our aims were to determine the rates of successful recanalization and functional independence in acute stroke patients treated with stent retrievers .
We also sought to assess the safety outcomes of stent retrievers by assessing the rates of mortality and intra-cranial haemorrhage .
Material s and methods We conducted a systematic review and meta- analysis of studies which utilized stent retrievers as sole treatment or as part of a multi-modal approach in acute ischaemic stroke . | BACKGROUND In patients with ischemic stroke , endovascular treatment results in a higher rate of recanalization of the affected cerebral artery than systemic intravenous thrombolytic therapy . However , comparison of the clinical efficacy of the two approaches is needed . METHODS We r and omly assigned 362 patients with acute ischemic stroke , within 4.5 hours after onset , to endovascular therapy ( intraarterial thrombolysis with recombinant tissue plasminogen activator [ t-PA ] , mechanical clot disruption or retrieval , or a combination of these approaches ) or intravenous t-PA . Treatments were to be given as soon as possible after r and omization . The primary outcome was survival free of disability ( defined as a modified Rankin score of 0 or 1 on a scale of 0 to 6 , with 0 indicating no symptoms , 1 no clinical ly significant disability despite symptoms , and 6 death ) at 3 months . RESULTS A total of 181 patients were assigned to receive endovascular therapy , and 181 intravenous t-PA . The median time from stroke onset to the start of treatment was 3.75 hours for endovascular therapy and 2.75 hours for intravenous t-PA ( P<0.001 ) . At 3 months , 55 patients in the endovascular-therapy group ( 30.4 % ) and 63 in the intravenous t-PA group ( 34.8 % ) were alive without disability ( odds ratio adjusted for age , sex , stroke severity , and atrial fibrillation status at baseline , 0.71 ; 95 % confidence interval , 0.44 to 1.14 ; P=0.16 ) . Fatal or nonfatal symptomatic intracranial hemorrhage within 7 days occurred in 6 % of the patients in each group , and there were no significant differences between groups in the rates of other serious adverse events or the case fatality rate . CONCLUSIONS The results of this trial in patients with acute ischemic stroke indicate that endovascular therapy is not superior to st and ard treatment with intravenous t-PA . ( Funded by the Italian Medicines Agency , Clinical Trials.gov number , NCT00640367 . ) Background and Purpose — The only Food and Drug Administration ( FDA ) -approved treatment for acute ischemic stroke is tissue plasminogen activator ( tPA ) given intravenously within 3 hours of symptom onset . An alternative strategy for opening intracranial vessels during stroke is mechanical embolectomy , especially for patients ineligible for intravenous tPA . Methods — We investigated the safety and efficacy of a novel embolectomy device ( Merci Retriever ) to open occluded intracranial large vessels within 8 hours of the onset of stroke symptoms in a prospect i ve , nonr and omized , multicenter trial . All patients were ineligible for intravenous tPA . Primary outcomes were recanalization and safety , and secondary outcomes were neurological outcome at 90 days in recanalized versus nonrecanalized patients . Results — Recanalization was achieved in 46 % ( 69/151 ) of patients on intention to treat analysis , and in 48 % ( 68/141 ) of patients in whom the device was deployed . This rate is significantly higher than that expected using an historical control of 18 % ( P<0.0001 ) . Clinical ly significant procedural complications occurred in 10 of 141 ( 7.1 % ) patients . Symptomatic intracranial hemorrhages was observed in 11 of 141 ( 7.8 % ) patients . Good neurological outcomes ( modified Rankin score ≤2 ) were more frequent at 90 days in patients with successful recanalization compared with patients with unsuccessful recanalization ( 46 % versus 10 % ; relative risk [ RR ] , 4.4 ; 95 % CI , 2.1 to 9.3 ; P<0.0001 ) , and mortality was less ( 32 % versus 54 % ; RR , 0.59 ; 95 % CI , 0.39 to 0.89 ; P=0.01 ) . Conclusions — A novel endovascular embolectomy device can significantly restore vascular patency during acute ischemic stroke within 8 hours of stroke symptom onset and provides an alternative intervention for patients who are otherwise ineligible for thrombolytics Background and Purpose — Endovascular mechanical thrombectomy may be used during acute ischemic stroke due to large vessel intracranial occlusion . First-generation MERCI devices achieved recanalization rates of 48 % and , when coupled with intraarterial thrombolytic drugs , recanalization rates of 60 % have been reported . Enhancements in embolectomy device design may improve recanalization rates . Methods — Multi MERCI was an international , multicenter , prospect i ve , single-arm trial of thrombectomy in patients with large vessel stroke treated within 8 hours of symptom onset . Patients with persistent large vessel occlusion after IV tissue plasminogen activator treatment were included . Once the newer generation ( L5 Retriever ) device became available , investigators were instructed to use the L5 Retriever to open vessels and could subsequently use older generation devices and /or intraarterial tissue plasminogen activator . Primary outcome was recanalization of the target vessel . Results — One hundred sixty-four patients received thrombectomy and 131 were initially treated with the L5 Retriever . Mean age±SD was 68±16 years , and baseline median ( interquartile range ) National Institutes of Health Stroke Scale score was 19 ( 15 to 23 ) . Treatment with the L5 Retriever result ed in successful recanalization in 75 of 131 ( 57.3 % ) treatable vessels and in 91 of 131 ( 69.5 % ) after adjunctive therapy ( intraarterial tissue plasminogen activator , mechanical ) . Overall , favorable clinical outcomes ( modified Rankin Scale 0 to 2 ) occurred in 36 % and mortality was 34 % ; both outcomes were significantly related to vascular recanalization . Symptomatic intracerebral hemorrhage occurred in 16 patients ( 9.8 % ) ; 4 ( 2.4 % ) of these were parenchymal hematoma type II . Clinical ly significant procedural complications occurred in 9 ( 5.5 % ) patients . Conclusions — Higher rates of recanalization were associated with a newer generation thrombectomy device compared with first-generation devices , but these differences did not achieve statistical significance . Mortality trended lower and the proportion of good clinical outcomes trended higher , consistent with better recanalization Background Supporting 21st century health care and the practice of evidence -based medicine ( EBM ) requires ubiquitous access to clinical information and to knowledge-based re sources to answer clinical questions . Many questions go unanswered , however , due to lack of skills in formulating questions , crafting effective search strategies , and accessing data bases to identify best levels of evidence . Methods This r and omized trial was design ed as a pilot study to measure the relevancy of search results using three different interfaces for the PubMed search system . Two of the search interfaces utilized a specific framework called PICO , which was design ed to focus clinical questions and to prompt for publication type or type of question asked . The third interface was the st and ard PubMed interface readily available on the Web . Study subjects were recruited from interns and residents on an inpatient general medicine rotation at an academic medical center in the US . Thirty-one subjects were r and omized to one of the three interfaces , given 3 clinical questions , and asked to search PubMed for a set of relevant articles that would provide an answer for each question . The success of the search results was determined by a precision score , which compared the number of relevant or gold st and ard articles retrieved in a result set to the total number of articles retrieved in that set . Results Participants using the PICO templates ( Protocol A or Protocol B ) had higher precision scores for each question than the participants who used Protocol C , the st and ard PubMed Web interface . ( Question 1 : A = 35 % , B = 28 % , C = 20 % ; Question 2 : A = 5 % , B = 6 % , C = 4 % ; Question 3 : A = 1 % , B = 0 % , C = 0 % ) 95 % confidence intervals were calculated for the precision for each question using a lower boundary of zero . However , the 95 % confidence limits were overlapping , suggesting no statistical difference between the groups . Conclusion Due to the small number of search es for each arm , this pilot study could not demonstrate a statistically significant difference between the search protocol s. However there was a trend towards higher precision that needs to be investigated in a larger study to determine if PICO can improve the relevancy of search results Background and Purpose — Little is known in regard to cerebral arterial reocclusion after successful thrombolysis . In the absence of arteriographic information , the National Institute of Neurological Disorders and Stroke ( NINDS ) rt-PA Stroke Trial investigators prospect ively identified clinical deterioration following improvement ( DFI ) as a possible surrogate marker of cerebral arterial reocclusion after rt-PA – induced recanalization . Also , we identified any significant clinical deterioration ( CD ) even if not preceded by improvement . This observational analysis was design ed to determine the incidence of DFI and CD in each treatment group , to identify baseline or posttreatment variables predictive of DFI or CD , and to determine any relationship between DFI , CD , and clinical outcome . Methods — DFI was defined as any 2-point deterioration on the NIH Stroke Scale after an initial 2-point improvement after treatment . CD was defined as any 4-point worsening after treatment compared with baseline . All data were collected prospect ively by investigators blinded to treatment allocation . A noncontrast brain CT was m and ated when a 2-point deterioration occurred . All cases were vali date d by a central review committee . Results — DFI was identified in 81 of the 624 patients ( 13 % ) ; 44 were treated with rt-PA and 37 were treated with placebo ( P = 0.48 ) . DFI occurred more often in patients with a higher baseline NIH Stroke Scale score . CD within the first 24 hours occurred in 98 patients ( 16 % of all patients ) ; 43 were given rt-PA and 55 were given placebo ( P = 0.19 ) . Baseline variables associated with CD included a less frequent use of prestroke aspirin and a higher incidence of early CT changes of edema or mass effect or dense middle cerebral artery sign . Patients with CD had higher rates of increased serum glucose and fibrin degradation products , and they also had higher rates of symptomatic intracranial hemorrhage and death . Patients who experienced either DFI or CD were less likely to have a 3-month favorable outcome . Conclusions — We found no association between DFI , CD , and rt-PA treatment , and no clinical evidence to suggest reocclusion . Deterioration was strongly associated with stroke severity and poor outcome and was less frequent in patients whose stroke occurred while they were on aspirin CONTEXT Intravenous tissue-type plasminogen activator can be beneficial to some patients when given within 3 hours of stroke onset , but many patients present later after stroke onset and alternative treatments are needed . OBJECTIVE To determine the clinical efficacy and safety of intra-arterial ( IA ) recombinant prourokinase ( r-proUK ) in patients with acute stroke of less than 6 hours ' duration caused by middle cerebral artery ( MCA ) occlusion . DESIGN PROACT II ( Prolyse in Acute Cerebral Thromboembolism II ) , a r and omized , controlled , multicenter , open-label clinical trial with blinded follow-up conducted between February 1996 and August 1998 . SETTING Fifty-four centers in the United States and Canada . PATIENTS A total of 180 patients with acute ischemic stroke of less than 6 hours ' duration caused by angiographically proven occlusion of the MCA and without hemorrhage or major early infa rct ion signs on computed tomographic scan . INTERVENTION Patients were r and omized to receive 9 mg of IA r-proUK plus heparin ( n = 121 ) or heparin only ( n = 59 ) . MAIN OUTCOME MEASURES The primary outcome , analyzed by intention-to-treat , was based on the proportion of patients with slight or no neurological disability at 90 days as defined by a modified Rankin score of 2 or less . Secondary outcomes included MCA recanalization , the frequency of intracranial hemorrhage with neurological deterioration , and mortality . RESULTS For the primary analysis , 40 % of r-proUK patients and 25 % of control patients had a modified Rankin score of 2 or less ( P = .04 ) . Mortality was 25 % for the r-proUK group and 27 % for the control group . The recanalization rate was 66 % for the r-proUK group and 18 % for the control group ( P<.001 ) . Intracranial hemorrhage with neurological deterioration within 24 hours occurred in 10 % of r-proUK patients and 2 % of control patients ( P = .06 ) . CONCLUSION Despite an increased frequency of early symptomatic intracranial hemorrhage , treatment with IA r-proUK within 6 hours of the onset of acute ischemic stroke caused by MCA occlusion significantly improved clinical outcome at 90 days BACKGROUND Present mechanical devices are unable to achieve recanalisation in up to 20 - 40 % of large vessel occlusion strokes . We compared efficacy and safety of the Trevo Retriever , a new stent-like device , with its US Food and Drug Administration-cleared predecessor , the Merci Retriever . METHODS In this open-label r and omised controlled trial , we recruited patients at 26 sites in the USA and one in Spain . We included adults aged 18 - 85 years with angiographically confirmed large vessel occlusion strokes and US National Institutes of Health Stroke Scale ( NIHSS ) scores of 8 - 29 within 8 h of symptom onset . We r and omly assigned patients ( 1:1 ) with sequentially numbered sealed envelopes to thrombectomy with Trevo or Merci devices . R and omisation was stratified by age ( ≤68 years vs 69 - 85 years ) and NIHSS scores ( ≤18 vs 19 - 29 ) with alternating blocks of various sizes . The primary efficacy endpoint , assessed by an unmasked core laboratory , was thrombolysis in cerebral infa rct ion ( TICI ) scores of 2 or greater reperfusion with the assigned device alone . The primary safety endpoint was a composite of procedure-related adverse events . Analyses were done by intention to treat . This study is registered with Clinical Trials.gov , number NCT01270867 . FINDINGS Between Feb 3 , 2011 , and Dec 1 , 2011 , we r and omly assigned 88 patients to the Trevo Retriever group and 90 patients to Merci Retriever group . 76 ( 86 % ) patients in the Trevo group and 54 ( 60 % ) in the Merci group met the primary endpoint after the assigned device was used ( odds ratio 4·22 , 95 % CI 1·92 - 9·69 ; p(superiority)<0·0001 ) . Incidence of the primary safety endpoint did not differ between groups ( 13 [ 15 % ] patients in the Trevo group vs 21 [ 23 % ] in the Merci group ; p=0·1826 ) . INTERPRETATION Patients who have had large vessel occlusion strokes but are ineligible for ( or refractory to ) intravenous tissue plasminogen activator should be treated with the Trevo Retriever in preference to the Merci Retriever . FUNDING Stryker Neurovascular BACKGROUND Whether brain imaging can identify patients who are most likely to benefit from therapies for acute ischemic stroke and whether endovascular thrombectomy improves clinical outcomes in such patients remains unclear . METHODS In this study , we r and omly assigned patients within 8 hours after the onset of large-vessel , anterior-circulation strokes to undergo mechanical embolectomy ( Merci Retriever or Penumbra System ) or receive st and ard care . All patients underwent pretreatment computed tomography or magnetic resonance imaging of the brain . R and omization was stratified according to whether the patient had a favorable penumbral pattern ( substantial salvageable tissue and small infa rct core ) or a nonpenumbral pattern ( large core or small or absent penumbra ) . We assessed outcomes using the 90-day modified Rankin scale , ranging from 0 ( no symptoms ) to 6 ( dead ) . RESULTS Among 118 eligible patients , the mean age was 65.5 years , the mean time to enrollment was 5.5 hours , and 58 % had a favorable penumbral pattern . Revascularization in the embolectomy group was achieved in 67 % of the patients . Ninety-day mortality was 21 % , and the rate of symptomatic intracranial hemorrhage was 4 % ; neither rate differed across groups . Among all patients , mean scores on the modified Rankin scale did not differ between embolectomy and st and ard care ( 3.9 vs. 3.9 , P=0.99 ) . Embolectomy was not superior to st and ard care in patients with either a favorable penumbral pattern ( mean score , 3.9 vs. 3.4 ; P=0.23 ) or a nonpenumbral pattern ( mean score , 4.0 vs. 4.4 ; P=0.32 ) . In the primary analysis of scores on the 90-day modified Rankin scale , there was no interaction between the pretreatment imaging pattern and treatment assignment ( P=0.14 ) . CONCLUSIONS A favorable penumbral pattern on neuroimaging did not identify patients who would differentially benefit from endovascular therapy for acute ischemic stroke , nor was embolectomy shown to be superior to st and ard care . ( Funded by the National Institute of Neurological Disorders and Stroke ; MR RESCUE Clinical Trials.gov number , NCT00389467 . ) Rationale Self-exp and ing stent retrievers are a promising new device class design ed for rapid flow restoration in acute cerebral ischaemia . The SOLITAIRE ™ Flow Restoration device ( SOLITAIRE ) has shown high rates of recanalization in pre clinical models and in uncontrolled clinical series . Aims ( 1 ) To demonstrate non-inferiority of SOLITAIRE compared with a legally marketed device , the MERCI Retrieval System ® ; ( 2 ) To demonstrate safety , feasibility , and efficacy of SOLITAIRE in subjects requiring mechanical thrombectomy diagnosed with acute ischaemic stroke . Design Multicenter , r and omized , prospect i ve , controlled trial with blinded primary end-point ascertainment . Study Procedures Key entry criteria include : age 22–85 ; National Institute of Health Stroke Scale ( NIHSS ) ≥8 and < 30 ; clinical and imaging findings consistent with acute ischaemic stroke ; patient ineligible or failed intravenous tissue plasminogen activator ; accessible occlusion in M1 or M2 middle cerebral artery , internal carotid artery , basilar artery , or vertebral artery ; and patient able to be treated within 8 h of onset . Sites first participate in a roll-in phase , treating two patients with the SOLITAIRE device , before proceeding to the r and omized phase . In patients unresponsive to the initially assigned therapy , after the angiographic component of the primary end-point is ascertained ( reperfusion with the initial assigned device ) , rescue therapy with other reperfusion techniques is permitted . Outcomes The primary efficacy end-point is successful recanalization with the assigned study device ( no use of rescue therapy ) and with no symptomatic intracranial haemorrhage . Successful recanalization is defined as achieving Thrombolysis In Myocardial Ischemia 2 or 3 flow in all treatable vessels . The primary safety end-point is the incidence of device-related and procedure-related serious adverse events . A major secondary efficacy end-point is time to achieve initial recanalization . Additional secondary endpoints include clinical outcomes at 90 days and radiologic haemorrhagic transformation BACKGROUND Endovascular therapy is increasingly used after the administration of intravenous tissue plasminogen activator ( t-PA ) for patients with moderate-to-severe acute ischemic stroke , but whether a combined approach is more effective than intravenous t-PA alone is uncertain . METHODS We r and omly assigned eligible patients who had received intravenous t-PA within 3 hours after symptom onset to receive additional endovascular therapy or intravenous t-PA alone , in a 2:1 ratio . The primary outcome measure was a modified Rankin scale score of 2 or less ( indicating functional independence ) at 90 days ( scores range from 0 to 6 , with higher scores indicating greater disability ) . RESULTS The study was stopped early because of futility after 656 participants had undergone r and omization ( 434 patients to endovascular therapy and 222 to intravenous t-PA alone ) . The proportion of participants with a modified Rankin score of 2 or less at 90 days did not differ significantly according to treatment ( 40.8 % with endovascular therapy and 38.7 % with intravenous t-PA ; absolute adjusted difference , 1.5 percentage points ; 95 % confidence interval [ CI ] , -6.1 to 9.1 , with adjustment for the National Institutes of Health Stroke Scale [ NIHSS ] score [ 8 - 19 , indicating moderately severe stroke , or ≥20 , indicating severe stroke ] ) , nor were there significant differences for the predefined subgroups of patients with an NIHSS score of 20 or higher ( 6.8 percentage points ; 95 % CI , -4.4 to 18.1 ) and those with a score of 19 or lower ( -1.0 percentage point ; 95 % CI , -10.8 to 8.8 ) . Findings in the endovascular-therapy and intravenous t-PA groups were similar for mortality at 90 days ( 19.1 % and 21.6 % , respectively ; P=0.52 ) and the proportion of patients with symptomatic intracerebral hemorrhage within 30 hours after initiation of t-PA ( 6.2 % and 5.9 % , respectively ; P=0.83 ) . CONCLUSIONS The trial showed similar safety outcomes and no significant difference in functional independence with endovascular therapy after intravenous t-PA , as compared with intravenous t-PA alone . ( Funded by the National Institutes of Health and others ; Clinical Trials.gov number , NCT00359424 . ) |
14,037 | 30,006,033 | HIGHLIGHTSSocial presence alone may not affect the experience of experimentally‐induced pain .
The impact of social support on pain may be context ‐dependentForms of social support may decrease or increase pain and physiology differentlyVerbal communication of support may be important .
The mere presence of another person was not sufficient to modulate pain perception .
Together , our findings suggest that the impact of social support on pain is context ‐dependent with the verbal communication of support and intimate relationships being of particular importance | Intimate relationship may decrease pain through touching or viewing a romantic other .
ABSTRACT Social support is demonstrated to have mixed effects on both pain and related physiological arousal . | UNLABELLED Two experiments assessed how interpersonal transactions influence responses to cold pressor pain in women versus men . In Experiment 1 , 91 young adults ( 57 women , 34 men ) were r and omly assigned to either a no transaction ( NT ) condition in which they coped alone with the cold pressor test or a transaction opportunity ( TO ) condition in which they also had the option of interacting with an empathetic , reflecting experimenter . Compared to men , women had lower pain tolerance and reported more pain and catastrophizing , although there were no gender differences in support seeking or other ways of coping . Within the TO condition , women were no more likely than men to initiate a transaction , but female speakers were more pain-focused than male speakers , and speaking with the empathetic interaction partner had generally negative effects on pain perception and coping . In Experiment 2 , 126 young adults ( 76 women , 50 men ) were r and omly assigned to NT , TO , or experimenter-directed ( 1 ) Distraction ( DT ) , ( 2 ) Reinterpretation ( RT ) , or ( 3 ) Encouragement ( ET ) conditions . Although men had similar levels of pain tolerance across the 5 transaction conditions , women in NT and TO conditions exhibited reduced tolerance compared with those in the DT , RT , and ET conditions . Pain tolerance times among women in DT , RT , and ET conditions were equal to or exceeded those of men in these conditions . Together , findings suggest the nature of interpersonal transactions exerts a greater influence on women 's responses to noxious stimulation than those of men . PERSPECTIVE This study adds to literature indicating that women exhibit reduced tolerance for experimentally induced pain compared with men . These results suggest that the nature of interpersonal transactions also affects women 's responses to noxious stimulation , more than those of men OBJECTIVE The aim of this study was to test the hypothesis that greater global and situational relationship satisfaction would reduce the negative impact of threatening information on acute pain . DESIGN An experimental design was used to manipulate threat and elicit acute pain via a cold pressor task . SETTING The study was completed in a research laboratory at a large urban university in the Midwestern USA . SUBJECTS Participants were 134 couples , in which at least one individual was an undergraduate student . METHODS After administration of a global relationship satisfaction measure , couples were r and omly assigned to either receive high or low threatening information about the painful task . Following the threat manipulation , couples discussed the upcoming task and rated their satisfaction with the interaction ( i.e. , situational relationship satisfaction ) . The design ated pain participant then completed the painful task alone . RESULTS The threat manipulation altered couples ' perceived threat of pain . Situational relationship satisfaction moderated the effect of threat on pain trajectories such that situational relationship satisfaction predicted less pain intensity at an earlier point in the task for the low threat condition than the high threat condition . Greater global relationship satisfaction predicted greater likelihood of task completion among those in the low threat condition , whereas it was unrelated to task completion in the high threat condition . Greater global relationship satisfaction also predicted lower pain intensity throughout the task . CONCLUSIONS These findings demonstrate that the interpersonal context is independently related to acute pain and may also alter the effect of threatening information on acute pain Social contact promotes enhanced health and well-being , likely as a function of the social regulation of emotional responding in the face of various life stressors . For this functional magnetic resonance imaging ( fMRI ) study , 16 married women were subjected to the threat of electric shock while holding their husb and 's h and , the h and of an anonymous male experimenter , or no h and at all . Results indicated a pervasive attenuation of activation in the neural systems supporting emotional and behavioral threat responses when the women held their husb and 's h and . A more limited attenuation of activation in these systems occurred when they held the h and of a stranger . Most strikingly , the effects of spousal h and -holding on neural threat responses varied as a function of marital quality , with higher marital quality predicting less threat-related neural activation in the right anterior insula , superior frontal gyrus , and hypothalamus during spousal , but not stranger , h and -holding Objectives : Certain forms of social support have been shown to improve pain-coping behaviors and pain outcomes in older adults with chronic pain , but little is known about the effect of social support on pain outcomes in older adults following trauma exposure . Methods : We analyzed data from a prospect i ve longitudinal study of adults aged 65 years and older presenting to an emergency department after a motor vehicle collision ( MVC ) to characterize the relationship between perceived social support and MVC-related pain after trauma overall and by subgroups based on sex , depressive symptoms , and marital status . Results : In our sample ( N=176 ) , patients with low perceived social support had higher pain severity 6 weeks after MVC than patients with high perceived social support after adjustment for age , sex , race , and education ( 4.2 vs. 3.2 , P=0.04 ) . The protective effect of social support on pain severity at 6 weeks was more pronounced in men and in married individuals . Patients with low social support were less likely to receive an opioid prescription in the emergency department ( 15 % vs. 32 % , P=0.03 ) , but there was no difference in opioid use at 6 weeks ( 22 % vs. 20 % , P=0.75 ) . Discussion : Among older adults experiencing trauma , low perceived social support was associated with higher levels of pain at 6 weeks We tested whether the presence of a stranger reduces cardiovascular responses during stressful tasks if the evaluation potential of the stranger is minimized and whether cardiovascular responses are affected by the quality of support in a friendship . Undergraduate women performed stressful tasks in one of three conditions : Alone , with a same-sex Stranger , or with a same-sex best Friend . The stranger and friend could not hear participants ' responses . Alone women had the greatest increases in SBP and HR while women in the Stranger and Friend conditions did not differ in their responses . In the Friend condition , HR responses were smallest in women who were highly satisfied with the support that they generally received from their friend . We conclude that the presence of a nonevaluative friend or stranger can reduce cardiovascular responses and that the quality of supportive ties modulates the impact of those ties on responses to stress & NA ; The study was design ed to assess whether the social context of a pain experience impacted on the relation between catastrophizing and duration of pain behaviour . Based on a communal coping model , the prediction was that the presence of an observer during a pain procedure would differentially influence the display of pain behaviour in high and low catastrophizers . University undergraduates taking part in a cold pressor procedure were r and omly assigned to one of two conditions : ( 1 ) participant alone ( n=30 ) , or ( 2 ) observer present ( n=34 ) . Analysis of video records revealed that high pain catastrophizers displayed communicative pain behaviours ( e.g. facial displays , vocalizations ) for a longer duration when an observer was present compared to high pain catastrophizers who were alone during the pain procedure . The duration of pain management behaviours ( e.g. holding , rubbing ) did not vary significantly as a function of catastrophizing . When the observer was present , high catastrophizers also reported using fewer cognitive coping strategies than low catastrophizers . The pattern of findings suggests that in the presence of an observer , high pain catastrophizers show a propensity to engage in strategies that more effectively communicate their pain , and are less likely to engage in strategies that might minimize pain . Theoretical implication s of the findings are discussed UNLABELLED The objectives of this study were to demonstrate that empathy and validation could be increased in an observing partner who received a brief perspective-taking manipulation , result ing in less pain severity and greater pain tolerance in their partner , who experienced experimental pain . In addition , we examined the correlations between perceived empathy/validation and behavioral ratings of validation and invalidation . In 126 pain-free romantic couples , 1 partner was r and omly assigned to complete the cold pressor task while the other observed . The couples were r and omly assigned to a ) a perspective-taking group in which observing partners were privately instructed to take the perspective of the pain participant ; or b ) a control group in which observing partners received only a description of the task . Compared with the control group , pain participants in the perspective-taking group reported that observing partners had been more validating during the task and they also reported significantly lower pain severity . In addition , pain participants ' reports of their partners ' validation and observing partners ' self-reported empathic feelings were significantly related to lower pain severity over time . The results provide support that perspective taking may induce empathic feelings , in addition to perceptions of validation , which in turn promotes emotion regulation during pain . PERSPECTIVE The experimental evidence in this study suggests that empathic feelings can be induced in significant others with simple instructions , and this manipulation leads to less pain in their partners undergoing a painful task . The results suggest that perspective taking , empathy , and validation should be further investigated as pain intervention targets Objective : To investigate whether a support intervention ( warm touch enhancement ) influences physiological stress systems that are linked to important health outcomes . Growing evidence points to a protective effect of social and emotional support on both morbidity and mortality . Methods : In this study , 34 healthy married couples ( n = 68 ) , aged 20 to 39 years ( mean = 25.2 years ) , were r and omly assigned to a “ behavior monitoring ” control group or participated in a 4-week intervention study in which clinic levels of plasma oxytocin , 24-hour ambulatory blood pressure , and salivary cortisol and alpha amylase were obtained pre and post intervention , at the same time salivary oxytocin was taken at home during weeks 1 and 4 . Results : Salivary oxytocin was enhanced both early and late in the intervention group and alpha amylase was reduced at post treatment in intervention group husb and s and wives relative to controls . Husb and s in the intervention group had significantly lower post treatment 24-hour systolic blood pressure than the control group . Conclusion : Increasing warm touch among couples has a beneficial influence on multiple stress-sensitive systems . BP = blood pressure ; ABP = ambulatory blood pressure ; SBP = systolic blood pressure ; DBP = diastolic blood pressure ; OT = oxytocin ; HPA = hypothalamic-pituitary adrenocortical ; SNS = sympathetic nervous system ; AUC = area under the curve Oxytocin is a neuropeptide regulating social‐affiliative and reproductive behaviour in mammals . Despite robust pre clinical evidence for the antinociceptive effects and mechanisms of action of exogenous oxytocin , human studies have produced mixed results regarding the analgesic role of oxytocin and are yet to show a specific modulation of neural processes involved in pain perception . In the present study , we investigated the analgesic effects of 40 IU of intranasal oxytocin in 13 healthy male volunteers using a double‐blind , placebo‐controlled , cross‐over design and brief radiant heat pulses generated by an infrared laser that selectively activate Aδ‐ and C‐fibre nerve endings in the epidermis , at the same time as recording the ensuing laser‐evoked potentials ( LEPs ) . We predicted that oxytocin would reduce subjective pain ratings and attenuate the amplitude of the N1 , N2 and P2 components . We observed that oxytocin attenuated perceived pain intensity and the local peak amplitude of the N1 and N2 ( but not of P2 ) LEPs , and increased the latency of the N2 component . Importantly , for the first time , the present study reports an association between the analgesic effect of oxytocin ( reduction in subjective pain ratings ) and the oxytocin‐induced modulation of cortical activity after noxious stimulation ( attenuation of the N2 LEP ) . These effects indicate that oxytocin modulates neural processes contributing to pain perception . The present study reports preliminary evidence that is consistent with electrophysiological studies in rodents showing that oxytocin specifically modulates Aδ/C‐fibre nociceptive afferent signalling at the spinal level and provides further specificity to evidence obtained in humans indicating that oxytocin may be modulating pain experience by modulating activity in the cortical areas involved in pain processing BACKGROUND The presence of social support has been associated with decreased stress responsiveness . Recent animal studies suggest that the neuropeptide oxytocin is implicated both in prosocial behavior and in the central nervous control of neuroendocrine responses to stress . This study was design ed to determine the effects of social support and oxytocin on cortisol , mood , and anxiety responses to psychosocial stress in humans . METHODS In a placebo-controlled , double-blind study , 37 healthy men were exposed to the Trier Social Stress Test . All participants were r and omly assigned to receive intranasal oxytocin ( 24 IU ) or placebo 50 min before stress , and either social support from their best friend during the preparation period or no social support . RESULTS Salivary free cortisol levels were suppressed by social support in response to stress . Comparisons of pre- and poststress anxiety levels revealed an anxiolytic effect of oxytocin . More importantly , the combination of oxytocin and social support exhibited the lowest cortisol concentrations as well as increased calmness and decreased anxiety during stress . CONCLUSIONS Oxytocin seems to enhance the buffering effect of social support on stress responsiveness . These results concur with data from animal research suggesting an important role of oxytocin as an underlying biological mechanism for stress-protective effects of positive social interactions Objective The purpose of this experimental study was to supplement and exp and on clinical research demonstrating that the provision of social support is associated with lower levels of acute pain . Methods Undergraduates ( 52 men and 49 women ) performed the cold pressor task either alone or accompanied by a friend or stranger who provided active support , passive support , or interaction . Pain perception was measured on a 10-point scale . Results Participants in the active support and passive support conditions reported less pain than participants in the alone and interaction conditions , regardless of whether they were paired with a friend or stranger . Conclusions These data suggest that the presence of an individual who provides passive or active support reduces experimental pain OBJECTIVE To provide an experimental investigation of the impact of maternal behavior on children 's pain experiences . METHOD Participants were 120 healthy children ( 60 boys , 60 girls ) between the ages of 8 and 12 years and their mothers . Mothers were r and omly assigned and trained to interact with their children in one of three ways while the children were exposed to lab-induced cold pressor pain : ( 1 ) a pain-promoting interaction , ( 2 ) a pain-reducing interaction , and ( 3 ) a no training control group . Training was based on behaviors presumed to have the expected impact , as based on correlational studies reported in the literature . Children 's pain experiences during the cold pressor were assessed using self-reports of intensity and affect , coding of facial activity , tolerance , and heart rate responsiveness . RESULTS Girls whose mothers interacted with them in the pain-promoting manner reported more pain than daughters of mothers in the control group , who in turn reported more pain than girls whose mothers interacted with them in the pain-reducing manner . This effect was not significant for boys . Maternal interaction type had no effect on children 's pain affect , facial activity , tolerance , or heart rate . CONCLUSIONS Results indicate that maternal behavior can have a direct impact on their daughters ' subjective reports of pain . These data support the importance of social learning factors in influencing children 's pain experiences OBJECTIVE To evaluate the effects of a spouse-assisted pain-coping skills training intervention on pain , psychological disability , physical disability , pain-coping , and pain behavior in patients with osteoarthritis ( OA ) of the knees . METHODS Eighty-eight OA patients with persistent knee pain were r and omly assigned to 1 of 3 conditions : 1 ) spouse-assisted pain-coping skills training , ( spouse-assisted CST ) , 2 ) a conventional CST intervention with no spouse involvement ( CST ) , or 3 ) an arthritis education-spousal support ( AE-SS ) control condition . All treatment was carried out in 10 weekly , 2-hour group sessions . RESULTS Data analysis revealed that at the completion of treatment , patients in the spouse-assisted CST condition had significantly lower levels of pain , psychological disability , and pain behavior , and higher scores on measures of coping attempts , marital adjustment , and self-efficacy than patients in the AE-SS control condition . Compared to patients in the AE-SS control condition , patients who received CST without spouse involvement had significantly higher post-treatment levels of self-efficacy and marital adjustment and showed a tendency toward lower levels of pain and psychological disability and higher scores on measures of coping attempts and ratings of the perceived effectiveness of pain-coping strategies . CONCLUSION These findings suggest that spouse-assisted CST has potential as a method for reducing pain and disability in OA patients There are few systematic investigations of the potential benefits of incidental touch as it occurs in medical health care setting s. In the present laboratory study 60 college students participated in two testing sessions 1 month apart . These sessions involved counterbalanced conditions of baseline , pulse palpation ( touch ) , cold pressor test ( stressor ) , and combined cold pressor/pulse palpation . Heart rate and systolic and diastolic blood pressure were measured during each condition . Subjective pain ratings were recorded during stress conditions . Significant decreases in cardiovascular measures and pain ratings were associated with physical contact . However , these changes were small and individual responses to physical contact were not stable over time . Physical contact produces a small but significant decrease in cardiovascular variables and the experience of pain . However , the tendency to show a cardiovascular response to touch does not represent a stable trait for individuals in the laboratory setting OBJECTIVE To evaluate the long-term effects of a spouse-assisted coping skills intervention in patients with osteoarthritis ( OA ) of the knees , and to evaluate how pre- to posttreatment changes in marital adjustment and self-efficacy relate to long-term improvements in pain , psychological disability , physical disability , pain coping , and pain behavior . METHODS A followup study was conducted with 88 OA patients who had been r and omly assigned to 1 of 3 treatment conditions : 1 ) spouse-assisted coping skills training ( spouse-assisted CST ) , 2 ) a conventional CST intervention with no spouse involvement , and 3 ) an arthritis education-spousal support ( AE-SS ) control condition . To evaluate long-term outcome , comprehensive measures of self-efficacy , marital adjustment , pain , psychological disability , physical disability , pain coping , and pain behavior were collected from these individuals at 6 and 12 months posttreatment . RESULTS Data analysis revealed that , at 6-month followup , patients in the spouse-assisted CST condition scored higher on measures of coping and self-efficacy than those in the AE-SS control group . At 6-month followup , patients who received CST without spouse involvement showed a significantly higher frequency of coping attempts and reported higher levels of marital adjustment than those in the AE-SS control group . At 12-month followup , patients in the spouse-assisted CST condition had significantly higher overall self-efficacy than those in the AE-SS control condition . In addition , patients in both the spouse-assisted CST and CST only conditions tended to show improvements in physical disability at the 12-month followup . Individual differences in outcome were noted at the 12-month followup . Patients in the spouse-assisted CST condition who reported initial ( pre- to posttreatment ) increases in marital adjustment had lower levels of psychological disability , physical disability , and pain behavior at 12-month followup . However , for patients in the conventional CST and AE-SS control conditions , increases in marital adjustment occurring over the initial phase of treatment were related to increases in pain and decreases in scores on the Pain Control in Rational Thinking factor of the Coping Strategies Question naire . Finally , patients in the spouse-assisted CST condition who showed pre- to posttreatment increases in self-efficacy were more likely to show decreases in pain , psychological disability , and physical disability at 12-month followup . CONCLUSIONS These findings suggest that spouse-assisted CST can enhance self-efficacy and improve the coping abilities of OA patients in the long term . Individual differences in the long-term outcome of spouse-assisted CST were noted , with some patients ( those showing increases in marital satisfaction and self-efficacy ) showing much better outcomes than others This study examined whether highly cynical individuals benefit less from social support during an acute stressor than individuals low in cynicism . College students ( 52 men , 52 women ) performed a stressful speech task alone or in the presence of a supportive confederate . There was an interactive effect of social support and cynicism on cardiovascular reactivity : Low cynicism participants who received support has smaller increases in blood pressure during the speech than low cynicism participants without support and high cynicism participants with or without support . Participants ' psychological stress appeared to mediate the main effects of support on blood pressure reactivity , but not the Support x Cynicism interaction . Results suggest that cynical attitudes may undermine the stress buffering potential of interpersonal support & NA ; This study tested the separate and combined effects of spouse‐assisted pain coping skills training ( SA‐CST ) and exercise training ( ET ) in a sample of patients having persistent osteoarthritic knee pain . Seventy‐two married osteoarthritis ( OA ) patients with persistent knee pain and their spouses were r and omly assigned to : SA‐CST alone , SA‐CST plus ET , ET alone , or st and ard care ( SC ) . Patients in SA‐CST alone , together with their spouses , attended 12 weekly , 2‐h group sessions for training in pain coping and couples skills . Patients in SA‐CST+ET received spouse‐assisted coping skills training and attended 12‐weeks supervised ET . Patients in the ET alone condition received just an exercise program . Data analyses revealed : ( 1 ) physical fitness and strength : the SA‐CST+ET and ET alone groups had significant improvements in physical fitness compared to SA‐CST alone and patients in SA‐CST+ET and ET alone had significant improvements in leg flexion and extension compared to SA‐CST alone and SC , ( 2 ) pain coping : patients in SA‐CST+ET and SA‐CST alone groups had significant improvements in coping attempts compared to ET alone or SC and spouses in SA‐CST+ET rated their partners as showing significant improvements in coping attempts compared to ET alone or SC , and ( 3 ) self‐efficacy : patients in SA‐CST+ET reported significant improvements in self‐efficacy and their spouses rated them as showing significant improvements in self‐efficacy compared to ET alone or SC . Patients receiving SA‐CST+ET who showed increased self‐efficacy were more likely to have improvements in psychological disability . An intervention that combines spouse‐assisted coping skills training and exercise training can improve physical fitness , strength , pain coping , and self‐efficacy in patients suffering from pain due to osteoarthritis This study examined the comparative efficacy of three interventions : a spouse-assisted coping skills training protocol for patients undergoing a multidisciplinary pain management programme ( SA-MPMP ) , conventional patient-oriented multidisciplinary pain management programme ( P-MPMP ) and st and ard medical care ( SMC ) . Thirty-six chronic low back pain ( CLBP ) patients and their spouses were r and omly assigned to one of the three conditions . The SA-MPMP condition consisted of seven , weekly , 2-h , group sessions of training in dyadic pain coping and couple skills , delivered by a clinical psychologist with support of a multidisciplinary team of specialists , to patients together with their spouses . P-MPMP consisted of the SA-MPMP training delivered to the patient only ( i.e. , no spouse participation and assistance ) . The SMC condition entailed continuation of routine treatment , entailing medical care only . Data analysis revealed that , at the 12-month follow-up time point , patients receiving SA-MPMP had significant improvements in kinesiophobia and rumination about pain compared to those receiving P-MPMP and SMC . In patients suffering from CLBP , an intervention that combines spouse-assisted coping skills training with a multidisciplinary pain management programme can improve fear of movement and rumination about low back pain The purpose of this study was to examine the effects of social influence on responses to acute pain in women and men in a r and omized experimental design . Sixty-eight undergraduates ( 32 women ; 36 men ) were r and omly assigned to perform a cold pressor task either alone or in the presence of a same-sex friend . Expressions of pain were assessed with the short form of the McGill Pain Question naire . Overall social support was measured using the Krause social support assessment scale . The presence of a same-sex friend significantly increased pain reports in women , but not in men . Persons who reported high levels of social support on the Krause scale also reported greater cold pressor pain . Results suggest that the presence of a friend can increase pain report to an acute laboratory pain stimulus in women . These findings are consistent with models of social reinforcement in chronic pain syndromes |
14,038 | 30,023,364 | Conclusions Among four commonly used first-line chemotherapy regimens for R/M NPC , triplet combination regimen showed best short-term efficacy but failed to improve prognosis .
TP regimen demonstrated fairly good short-term efficacy and best long-term efficacy , followed by GP regimen , while FP regimen was the lowest | Background The st and ard first-line chemotherapy for patients with recurrent or metastatic nasopharyngeal carcinoma ( R/M NPC ) has not been well established .
We conducted a pooled meta- analysis to evaluate the efficacy of commonly used first-line chemotherapy in this disease . | BACKGROUND Paclitaxel has been demonstrated to have significant activity in recurrent or metastatic head and neck cancer ( HNC ) . In addition , the combination of paclitaxel and cisplatin is active in untreated patients with inoperable HNC . Substitution of carboplatin for cisplatin allows the treatment to be delivered on an outpatient basis . PURPOSE OF THE STUDY To evaluate the activity and toxicity of the combination of paclitaxel by three-hour infusion and carboplatin as first-line chemotherapy in patients with recurrent or metastatic HNC . PATIENTS AND METHODS From March 1994 until August 1996 , 49 patients with recurrent or metastatic HNC were treated with paclitaxel ( 200 mg/m2 , by three-hour infusion ) followed by carboplatin at an AUC of 7 mg.min/ml , every four weeks . G-CSF was administered prophylactically on days 2 to 12 of each cycle . There were 41 men and 8 women with a median age of 57 years ( range 23 - 73 ) . The majority of the patients were symptomatic and they had recurrent disease locoregionally . Fourteen patients had nasopharyngeal cancer ( NPC ) and 35 had squamous cell cancers of other areas of the head and neck region ( non-NPC ) . RESULTS At the completion of treatment , two patients with NPC demonstrated complete and six partial responses for an overall response rate of 57 % ( 95 % CI 29%-82 % ) . Among patients with non-NPC , the response rate was 23 % ( 95 % CI 9%-37 % ) . After a median follow up period of 15 months , the median time to progression was 4.3 months in the non-NPC group and 16.5 months in the NPC group . At the time of the analysis , median survival had not been reached in NPC while it was 7.3 months in non-NPC patients . Grade 3 - 4 toxicities included anemia ( 2 % ) and leukopenia , thrombocytopenia , stomatitis , nausea/vomiting and diarrhea ( 4 % each ) . CONCLUSIONS The combination of paclitaxel and carboplatin appears to be well tolerated but only moderately active in patients with advanced non-NPC of the head and neck region . However , its activity appears promising in NPC and deserves further investigation OBJECTIVE : To test the feasibility of creating a valid and reliable checklist with the following features : appropriate for assessing both r and omised and non-r and omised studies ; provision of both an overall score for study quality and a profile of scores not only for the quality of reporting , internal validity ( bias and confounding ) and power , but also for external validity . DESIGN : A pilot version was first developed , based on epidemiological principles , review s , and existing checklists for r and omised studies . Face and content validity were assessed by three experienced review ers and reliability was determined using two raters assessing 10 r and omised and 10 non-r and omised studies . Using different raters , the checklist was revised and tested for internal consistency ( Kuder-Richardson 20 ) , test-retest and inter-rater reliability ( Spearman correlation coefficient and sign rank test ; kappa statistics ) , criterion validity , and respondent burden . MAIN RESULTS : The performance of the checklist improved considerably after revision of a pilot version . The Quality Index had high internal consistency ( KR-20 : 0.89 ) as did the subscales apart from external validity ( KR-20 : 0.54 ) . Test-retest ( r 0.88 ) and inter-rater ( r 0.75 ) reliability of the Quality Index were good . Reliability of the subscales varied from good ( bias ) to poor ( external validity ) . The Quality Index correlated highly with an existing , established instrument for assessing r and omised studies ( r 0.90 ) . There was little difference between its performance with non-r and omised and with r and omised studies . Raters took about 20 minutes to assess each paper ( range 10 to 45 minutes ) . CONCLUSIONS : This study has shown that it is feasible to develop a checklist that can be used to assess the method ological quality not only of r and omised controlled trials but also non-r and omised studies . It has also shown that it is possible to produce a checklist that provides a profile of the paper , alerting review ers to its particular method ological strengths and weaknesses . Further work is required to improve the checklist and the training of raters in the assessment of external validity BACKGROUND The most active chemotherapy regimens in UCNT were those combining anthracyclines ( doxorubicin or epirubicin ) and cisplatin . Our previous pilot study on 37 patients treated with the zorubicin-cisplatin combination with a RR of 67 % and literature data about other anthracyclines such as epirubicin achieving a response rate of over 50 % were the basis of this r and omized study comparing efficacy and toxicity of the combination vs. zorubicin as monotherapy . PATIENTS AND METHODS A total of 80 patients entered the study . The diagnosis of UCNT was confirmed by two independent pathologists . All patients had their primary tumors in the nasopharynx . The patients were r and omized in two groups : group A ( zorubicin 325 mg/m2 , day 1 ) , and group B ( zorubicin 250 mg/m2 , day 1 and cisplatin 30 mg/m2 , days 2 - 5 ) . The inter-cycle interval was four weeks . The two groups were well balanced according to sex , age , stage Ho and TNM stage . RESULTS Group A : 40 patients included , 34/40 evaluable for activity . Activity on evaluable patient basis : CR 4/34 ( 11.75 % ) , PR 4/34 , SD 14/34 , PD 12/34 , response rate 8/34 ( 23.5 % ) ; response rate on intent to treat basis 8/40 ( 20 % ) . TOXICITY granulocytopenia grade 3 - 4 6/40 , thrombocytopenia grade 3 - 4 2/40 , no febrile neutropenias , nausea/vomiting any grade 3/40 , cardiac toxicity any grade ( rhythm ) 3/40 other toxicities minor or absent . Group B : 40 patients included , 36/40 evaluable for activity . Activity on evaluable patient basis : CR 10/36 ( 27.78 % ) , PR 17/36 , SD 3/36 , PD 6/36 , response rate 27/36 ( 75 % ) ; response rate on intent to treat basis 27/40 ( 67.5 % ) . TOXICITY granulocytopenia grade 3 - 4 10/40 , thrombocytopenia grade 3 - 4 8/40 , two febrile neutropenias , nausea/vomiting any grade 13/40 , other toxicities mild or absent . Of the group of patients achieving a CR , four relapsed following 7 , 11 , 22 and 23 months , one was lost to follow-up , one died after six months from fulminant hepatitis B and eight are in complete remission lasting for 30 + to 66 + months . Following CR achievement none received any consolidation radiotherapy , and the projected five years of freedom from relapse for complete responders is about 60 % . CONCLUSION Zorubicin is an effective drug in UCNT and its combination with cisplatin has a significant activity and an acceptable toxicity BACKGROUND Nasopharyngeal carcinoma ( NPC ) is a platinum-sensitive cancer and excision repair cross-complementing group 1 ( ERCC1 ) polymorphisms have been shown to predict survival in several cancers following platinum therapy . PATIENTS AND METHODS This multicenter study evaluated the activity of oxaliplatin and prolonged infusion of gemcitabine ( ' GEMOX ' regimen ) in recurrent NPC . Baseline blood sample s were genotyped for the presence of ERCC1 - 118 gene polymorphisms . RESULTS Forty-two patients were recruited , of whom most ( 61 % ) had metastatic disease . Of the 40 patients evaluated for response , the respective overall response and disease control rates were 56.1 % and 90.2 % . At a median follow-up of 14.8 months , the respective median overall survival and time to progression were 19.6 months [ 95 % confidence interval ( CI ) = 12.8 - 22 months ] and 9 months ( 95 % CI = 7.3 - 10 months ) . Grade 3 - 4 toxic effects were uncommon . The distribution of ERCC1 - 118 genotypes from 29 patients was C/C ( n = 17 , 40.5 % ) , C/T ( n = 10 , 23.8 % ) and T/T ( n = 2 , 4.8 % ) . No differences in survival or response rates were found between genotypes . CONCLUSIONS GEMOX is active in the treatment of recurrent NPC . Detection of single-nucleotide gene polymorphisms from genomic DNA in peripheral blood is feasible in NPC and further studies are warranted OBJECTIVE The purpose of this article is to compare the recently published revised Response Evaluation Criteria in Solid Tumors ( RECIST ) guidelines ( version 1.1 ) to the original guidelines ( RECIST 1.0 ) for advanced non-small cell lung cancer ( NSCLC ) after erlotinib therapy and to evaluate the impact of the new CT tumor measurement guideline on response assessment . MATERIAL S AND METHODS Forty-three chemotherapy-naive patients with advanced NSCLC treated with erlotinib in a single-arm phase 2 multicenter open-label clinical trial were retrospectively studied . CT tumor measurement records using RECIST 1.0 that were generated as part of the prospect i ve clinical trial were review ed . A second set of CT tumor measurements was generated from the records to meet RECIST 1.1 guidelines . The number of target lesions , best response , and time to progression were compared between RECIST 1.1 and RECIST 1.0 . RESULTS The number of target lesions according to RECIST 1.1 decreased in 22 patients ( 51 % ) and did not change in 21 patients ( 49 % ) compared with the number according to RECIST 1.0 ( p < 0.0001 , paired Student 's t test ) . Almost perfect agreement was observed between best responses using RECIST 1.1 and RECIST 1.0 ( weighted kappa = 0.905 ) . Two patients with stable disease according to RECIST 1.0 had progressive disease according to RECIST 1.1 criteria because of new lesions found on PET/CT . There was no significant difference in time to progression between RECIST 1.1 and RECIST 1.0 ( p = 1.000 , sign test ) . CONCLUSION RECIST 1.1 provided almost perfect agreement in response assessment after erlotinib therapy compared with RECIST 1.0 . Assessment with PET/CT was a major factor that influenced the difference in best response assessment between RECIST 1.1 and RECIST 1.0 PURPOSE To evaluate the role of aggressive combination chemotherapy in patients with poorly differentiated carcinoma of the nasopharynx ( NPC ) . PATIENTS AND METHODS In a prospect i ve phase I/II study , 90 chemotherapy-naive patients with NPC ( 21 with very advanced locoregional disease , 18 with locoregional persistent and /or recurrent disease postradiotherapy , and 51 with metastatic disease ) were treated with cyclophosphamide , doxorubicin , cisplatin , methotrexate , and bleomycin ( CAPABLE ) . Two schedules of this regimen were used over a 9-year period , with the second schedule being a modification of the first in an attempt to minimize treatment-related toxicity . RESULTS Of 21 patients with very advanced local disease , one had a complete response ( CR ) and 17 had partial responses ( PRs ) ( response rate , 86 % ) . Seventeen of these 21 patients had subsequent radiotherapy . Of 17 patients with measurable locoregional disease either persistent and /or recurrent postradiotherapy , there were four CRs and three PRs ( response rate , 41 % ) . Of 44 patients with measurable metastatic disease , there were three CRs and 32 PRs ( response rate , 80 % ) . The median survival duration s for these three groups of patients were 47 , 16 , and 14 months , respectively . The two chemotherapy schedules had similar received dose-intensities ( RDIs ) and produced similar response rates and survival . Toxicity was severe with frequent mucositis and myelosuppression . Overall , 37 patients required at least one hospital admission for management of toxic side effects and there were seven drug-related deaths . Three of the deaths were due to fulminant hepatitis , likely from reactivation of hepatitis B. CONCLUSION This aggressive regimen provides a high rate of tumor response , but limited palliation for most patients with recurrent or metastatic NPC . The results with chemotherapy followed by radiotherapy for patients with very advanced local disease are encouraging , but proof of benefit would require evaluation in a r and omized trial |
14,039 | 30,744,523 | Conclusions Infection remains a serious complication during treatment of lupus nephritis , but the reported rates and outcomes varied markedly .
Mycophenolate was associated with lower infection risk than cyclophosphamide in non-Asians .
Infection-related deaths appeared more common in Asian patients | Objectives Infection is an important concern in lupus nephritis treatment , but few studies have focused on this complication .
Available data suggest marked variation in occurrence and outcome .
This meta- analysis and review aims to provide an overview of infective complications , focusing on the risk factors and outcomes . | Treatment of lupus nephritis ( LN ) with cyclophosphamide ( CYC ) is effective but retains a certain severe adverse effect . Tacrolimus ( TAC ) may be a suitable treatment for LN . Forty patients with diffuse proliferative or membranous LN were recruited for this non-r and omized open-label study — 67.5 % ( 27/40 ) had nephrotic proteinuria ( > 3.5 g/day ) and 50.0 % ( 20/40 ) had low estimated glomerular filtration rate ( eGFR ) ( < 60 mL/min/1.73m2 ) . We compared the efficacy and adverse effects of TAC ( 0.04–0.08 mg/kg/d)/prednisone for 12 months ( TAC group , n = 20 ) with intravenous CYC ( 750 mg/m2 per month)/prednisone for six months followed by azathioprine ( Aza ) ( 100 mg/day)/prednisone for six months ( CYC group , n = 20 ) . The TAC target concentration was 6–8 ng/mL or 4–6 ng/mL , respectively , when induction or maintenance therapy was required and 4.0 ng/mL for patient with renal insufficiency . In the TAC group , mean urinary protein excretion decreased significantly from 5.00 ± 1.91 g/day at baseline to 2.54 ± 1.68 g/day after two weeks of therapy ( P < 0.001 ) , compared with the CYC group ( 4.9 ± 19.4 g/day ) , P = 0.001 , and 65.0 % ( 13/20 ) achieved partial remission at one month , compared with the CYC group ( 0/20 ) , P < 0.001 . The incidence of complete remission ( CR ) was significantly higher in the TAC group than in the CYC group ( 55.0 % vs.15.0 % by five months , P = 0.008 , and 75.0 % vs.40.0 % by 12 months , P = 0.025 , respectively ) . The significant improvement in serum anti-dsDNA and systemic lupus erythematosus ( SLE ) disease activity index ( DAI ) was in the TAC group relative to the CYC group at 12 months ( P = 0.031 , P = 0.003 , respectively ) . The eGFR improved in the TAC group from 59.90 ± 23.64 mL/min/1.73m2 at baseline to 93.75 ± 28.52 mL/min/1.73m2 after 12 months , P = 0.001 . In the CYC group , two patients developed end-stage renal disease ( ESRD ) , three patients experienced serious pneumonia , and one patient died . Our preliminary study showed TAC is a safe and effective treatment for LN with severe renal disease , and with less-severe adverse events compared with CYC followed Aza therapy . Further larger sample studies are needed to confirm our conclusion OBJECTIVE To investigate the efficacy and safety of ocrelizumab in patients with class III/IV lupus nephritis ( LN ) . METHODS Patients were r and omized 1:1:1 to receive placebo , 400 mg ocrelizumab , or 1,000 mg ocrelizumab given as an intravenous infusion on days 1 and 15 , followed by a single infusion at week 16 and every 16 weeks thereafter , accompanied by background glucocorticoids plus either mycophenolate mofetil ( MMF ) or the Euro-Lupus Nephritis Trial ( ELNT ) regimen ( cyclophosphamide followed by azathioprine ) . The study was terminated early due to an imbalance in serious infections in ocrelizumab-treated patients versus placebo-treated patients . We report week 48 efficacy data for patients receiving ≥32 weeks of treatment ( n = 223 ) and safety results for all treated patients ( n = 378 ) . RESULTS The overall renal response rate was 54.7 % , 66.7 % , 67.1 % , and 66.9 % in the placebo-treated , 400 mg ocrelizumab-treated , 1,000 mg ocrelizumab-treated , and combined ocrelizumab-treated groups , respectively . The associated treatment difference versus placebo for the combined ocrelizumab-treated groups was 12.7 % ( 95 % confidence interval [ 95 % CI ] -0.8 , 26.1 ) ( P = 0.065 ) , with similar differences observed for both ocrelizumab-treated groups . Ocrelizumab versus placebo treatment differences were apparent in patients receiving the background ELNT regimen , but not in those receiving background MMF . A numerically greater proportion of ocrelizumab-treated patients had a ≥50 % reduction in the urinary protein : urinary creatinine ratio at 48 weeks compared with placebo-treated patients ( placebo-treated patients , 58.7 % ; 400 mg ocrelizumab-treated patients , 70.7 % ; 1,000 mg ocrelizumab-treated patients , 68.5 % ) . Serious adverse events occurred in 27.2 % of placebo-treated patients , 35.7 % of 400 mg ocrelizumab-treated patients , and 22.0 % of 1,000 mg ocrelizumab-treated patients . Corresponding serious infection rates ( events/100 patient-years ) were 18.7 ( 95 % CI 12.2 , 28.7 ) , 28.8 ( 95 % CI 20.6 , 40.3 ) , and 25.1 ( 95 % CI 17.4 , 36.1 ) , respectively . The imbalance in serious infections with ocrelizumab occurred with background MMF but not with the background ELNT regimen . CONCLUSION In patients with active LN , overall renal response rates with ocrelizumab were numerically but not statistically significantly superior to those with placebo . Ocrelizumab treatment was associated with a higher rate of serious infections in the subgroup receiving background MMF BACKGROUND Intravenous cyclophosphamide with prednisone is an effective treatment for lupus nephritis , but with significant toxicities . We compared the efficacy and safety of tacrolimus versus intravenous cyclophosphamide as induction therapy . STUDY DESIGN Multicenter noninferiority r and omized controlled trial . SETTING & PARTICIPANTS 81 patients with biopsy-proven lupus nephritis from 9 nephrology centers in China from 2006 - 2008 . INTERVENTION Prednisone and either tacrolimus ( n = 42 ) or intravenous cyclophosphamide ( n = 39 ) for 6 months . Tacrolimus was started at 0.05 mg/kg/d and titrated to achieve a trough blood concentration of 5 - 10 ng/mL. Intravenous cyclophosphamide was initiated at 750 mg/m² of body surface area , then adjusted to 500 - 1,000 mg/m² every 4 weeks for a total of 6 pulse treatments . OUTCOMES & MEASUREMENTS The primary outcome was complete remission ( proteinuria with protein excretion < 0.3 g/24 h , serum albumin ≥3.5 g/dL , normal urinary sediment , and normal or stable serum creatinine level ) at 6 months . Response ( complete or partial remission ) , clinical parameters , and adverse effects were secondary end points . RESULTS After the 6-month induction therapy , the tacrolimus group achieved higher cumulative probabilities of complete remission and response ( 52.4 % vs 38.5 % and 90.5 % vs 82.1 % , respectively ) than the intravenous cyclophosphamide group , but differences were not statistically significant ( log-rank test , P = 0.2 and P = 0.7 , respectively ) . Proteinuria [ corrected ] was significantly decreased in tacrolimus- versus intravenous cyclophosphamide-treated patients after the first month of treatment , even with adjustment for baseline proteinuria ( protein excretion , 1.76 vs 2.40 g/d ; P = 0.02 for the log-transformed analysis ) . [ corrected ] After treatment , serum creatinine levels and estimated glomerular filtration rates were not significantly different between treatment groups . Adverse effects , such as leukopenia and gastrointestinal symptoms , were less frequent in the tacrolimus group . LIMITATIONS Nonblinded , small sample size , and short duration of follow-up . CONCLUSIONS In conjunction with prednisone , induction therapy with tacrolimus is at least as efficacious as intravenous cyclophosphamide and prednisone in producing complete remission of lupus nephritis and has a more favorable safety profile Treatment of class V+IV lupus nephritis remains unsatisfactory despite the progress made in the treatment of diffuse proliferative lupus nephritis . In this prospect i ve study , 40 patients with class V+IV lupus nephritis were r and omly assigned to induction therapy with mycophenolate mofetil , tacrolimus , and steroids ( multitarget therapy ) or intravenous cyclophosphamide ( IVCY ) . Patients were treated for 6 mo unless complete remission was not achieved , in which case treatment was extended to 9 mo . An intention-to-treat analysis revealed a higher rate of complete remission with multitarget therapy at both 6 and 9 mo ( 50 and 65 % , respectively ) than with IVCY ( 5 and 15 % , respectively ) . At 6 mo , eight ( 40 % ) patients in each group experienced partial remission , and at 9 mo , six ( 30 % ) patients receiving multitarget therapy and eight ( 40 % ) patients receiving IVCY experienced partial remission . There were no deaths during this study . Most adverse events were less frequent in the multitarget therapy group . Calcineurin inhibitor nephrotoxicity was not observed , but three patients developed new-onset hypertension with multitarget therapy . In conclusion , multitarget therapy is superior to IVCY for inducing complete remission of class V+IV lupus nephritis and is well tolerated BACKGROUND Although the use of aggressive immunosuppression has improved both patient and renal survival of patients with lupus nephritis ( LN ) , the optimal treatment of LN remains challenging . The objective of this study is to assess the efficacy and safety of mycophenolate mofetil ( MMF ) and tacrolimus compared with intravenous cyclophosphamide ( IVC ) as induction therapies for active lupus nephritis ( ALN ) . METHODS In this open-label , 24-week prospect i ve study , 60 patients with biopsy-proven ALN ( Classes III , IV , V or combination ) were r and omly assigned to receive MMF , tacrolimus or IVC in combination with corticosteroids . The remission of proteinuria , systemic lupus erythematosus disease active index and adverse events were compared . RESULTS The response rates at 24 weeks were 70 % ( 14/20 ) in the MMF group , 75 % ( 15/20 ) in the tacrolimus group and 60 % ( 12/20 ) in the IVC group ( P>0.05 ) . The complete remission rates were also similar in the three groups ( 40 , 45 and 30 % , respectively ; P>0.05 ) . There were more cases of infection in the IVC group ( 8/20 ) and the MMF group ( 8/20 ) than the tacrolimus group ( 3/20 ) and more hyperglycemia in the tacrolimus group ( 5/20 ) than the other two groups ( 2 or 3/20 ) , but the results were not statistically significant among the three groups . Proteinuria decreased and serum albumin increased more quickly in the patients treated with tacrolimus ( P=0.0051 and P=0.048 ) . CONCLUSIONS This pilot study suggests that both MMF and tacrolimus are possible alternatives to IVC as induction therapies for ALN in Chinese patients . Tacrolimus possibly results in a faster resolution of proteinuria and hypoalbuminemia . Further studies are necessary to determine the optimal dosage and duration of the therapies Recent studies have suggested that mycophenolate mofetil ( MMF ) may offer advantages over intravenous cyclophosphamide ( IVC ) for the treatment of lupus nephritis , but these therapies have not been compared in an international r and omized , controlled trial . Here , we report the comparison of MMF and IVC as induction treatment for active lupus nephritis in a multinational , two-phase ( induction and maintenance ) study . We r and omly assigned 370 patients with classes III through V lupus nephritis to open-label MMF ( target dosage 3 g/d ) or IVC ( 0.5 to 1.0 g/m(2 ) in monthly pulses ) in a 24-wk induction study . Both groups received prednisone , tapered from a maximum starting dosage of 60 mg/d . The primary end point was a prespecified decrease in urine protein/creatinine ratio and stabilization or improvement in serum creatinine . Secondary end points included complete renal remission , systemic disease activity and damage , and safety . Overall , we did not detect a significantly different response rate between the two groups : 104 ( 56.2 % ) of 185 patients responded to MMF compared with 98 ( 53.0 % ) of 185 to IVC . Secondary end points were also similar between treatment groups . There were nine deaths in the MMF group and five in the IVC group . We did not detect significant differences between the MMF and IVC groups with regard to rates of adverse events , serious adverse events , or infections . Although most patients in both treatment groups experienced clinical improvement , the study did not meet its primary objective of showing that MMF was superior to IVC as induction treatment for lupus nephritis Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more Patients with lupus membranous nephropathy ( LMN ) are at substantial long-term risk for morbidity and mortality associated with protracted nephrotic syndrome , including ESRD . The optimal treatment for this condition is controversial . Forty-two patients with LMN participated in a r and omized , controlled trial to compare adjunctive immunosuppressive drugs with prednisone alone . Adjunctive regimens included either cyclosporine ( CsA ) for 11 mo or alternate-month intravenous pulse cyclophosphamide ( IVCY ) for six doses ; the control group received alternate-day prednisone alone . Median proteinuria was 5.4 g/d ( range 2.7 to 15.4 g/d ) . We assessed the primary outcome , time to remission of proteinuria during the 12-mo protocol , by univariate survival analysis . At 1 yr , the cumulative probability of remission was 27 % with prednisone , 60 % with IVCY , and 83 % with CsA. Although both IVCY and CsA were more effective than prednisone in inducing remissions of proteinuria , relapse of nephrotic syndrome occurred significantly more often after completion of CsA than after IVCY . By multivariate survival analysis , treatment with prednisone and high- grade proteinuria ( > 5 g/d ) but not race or ethnicity were independently associated with a decreased probability of remission . Adverse effects during the 12-mo protocol included insulin-requiring diabetes ( one with prednisone and two with CsA ) , pneumonia ( one with prednisone and two with CsA ) , and localized herpes zoster ( two with IVCY ) . In conclusion , regimens containing CsA or IVCY are each more effective than prednisone alone in inducing remission of proteinuria among patients with LMN BACKGROUND The aim of the present study was to evaluate the efficacy of mycophenolate mofetil in the induction therapy of proliferative lupus nephritis . METHODS Forty-four patients from eight centres with newly diagnosed lupus nephritis World Health Organization class III or IV were r and omly assigned to either mycophenolate mofetil ( MMF ) 2 g/day for 6 months or intravenous cyclophosphamide ( IVC ) 0.75 - 1 g/m(2 ) monthly for 6 months in addition to corticosteroids . RESULTS Remission occurred in 13 out of 25 patients ( 52 % ) in the IVC group and 11 out of 19 patients ( 58 % ) in the MMF group ( P = 0.70 ) . There were 12 % in the IVC group and 26 % in the MMF group that achieved complete remission ( P = 0.22 ) . Improvements in haemoglobin , the erythrocyte sedimentation rate , serum albumin , serum complement , proteinuria , urinary activity , renal function and the Systemic Lupus Erythematosus Disease Activity Index score were similar in both groups . Twenty-four follow-up renal biopsies at the end of therapy showed a significant reduction in the activity score in both groups . The chronicity index increased in both groups but was only significant in the IVC group . Adverse events were similar . Major infections occurred in three patients in each group . There was no difference in gastrointestinal side-effects . CONCLUSIONS MMF in combination with corticosteroids is an effective induction therapy for moderately severe proliferative lupus nephritis To compare the efficacy and safety of intravenous ( IV ) abatacept , a selective T cell costimulation modulator , versus placebo for the treatment of active class III or IV lupus nephritis , when used on a background of mycophenolate mofetil and glucocorticoids Mycophenolic acid , in combination with glucocorticoids , has been shown in a series of trials to be safe and effective for treatment of lupus nephritis . Regimens that permit glucocorticoid dose reduction without loss of efficacy would be advantageous . MyLupus was a 24-week , multicentre , open-label , study in patients with active proliferative lupus nephritis treated with enteric-coated mycophenolate sodium ( EC-MPS ) , r and omized to st and ard-dose ( n = 42 ) or reduced-dose ( n = 39 ) glucocorticoids . Complete response at week 24 , the primary endpoint , was achieved in 19.8 % ( 16/81 ) of patients ( 19.0 % st and ard-dose , 20.5 % reduced-dose ; lower limit of 97.5 % CI for the difference −15.9 % , p = 0.098 , i.e. non-inferiority was not shown ) . Partial response occurred in 42.0 % of patients ( 34/81 ) . From baseline to week 24 , the mean global British Isles Lupus Assessment Group ( BILAG ) score decreased from 14.0 ± 5.4 to 5.0 ± 3.8 ( p < 0.001 ) . The incidence of adverse events was 80.2 % ( 65/81 ) , most frequently gastrointestinal complications ( 31/81 , 38.3 % ) . Infections were reported in 57.1 % and 35.9 % of st and ard- and reduced-dose glucocorticoid patients , respectively ( p = 0.056 ) , with herpes zoster in 16.7 % and 0 % ( p = 0.012 ) . Three patients discontinued study medication due to adverse events . This exploratory study suggests that EC-MPS may facilitate glucocorticoid reduction without loss of efficacy in patients with active lupus nephritis , but results require confirmation in a controlled , longer-term study versus the current st and ard of care To evaluate the outcome of low doses of cyclophosphamide ( Cyclo ) therapy in lupus nephritis ( LN ) patients , we studied 117 biopsy-proven , de novo LN WHO class IV patients double-blinded and r and omized in December 1997 to receive Cyclo in different doses ; Group I ( n=73 ) received Cyclo 10 mg/kg monthly for six months then every two months for 12 months . Group II ( n=44 ) received Cyclo 5 mg/kg monthly for six months then every two months for 36 months . The patients were followed-up till January 2007 . Six months post-induction values for creatinine clearance were significantly higher in Group I ( 67.7 ± 28.6 mL/min ) compared with Group II ( 55.1 ± 30.1 mL/min ) , P = 0.026 . Serum C4 and ANA were not significantly different between the groups ( P > 0.05 ) . At the mean follow-up of 6.77 ± 3.3 years , the mean creatinine clearance was 44.74 ± 31.7 mL/min in Group I vs. 49.3 ± 38.8 in Group II . Urinary protein was 1.65 ± 1.8 g/dL in Group I vs. 1.02 ± 1.01 in Group II ( P = 0.03 ) . The survival curve showed that kidney survival overtime was comparable in both groups ( P = 0.2 ) . Complete remission was observed in 25 ( 34.2 % ) patients in Group I vs. 11 ( 25 % ) in Group II ( P = 0.288 ) , while partial remission was similar in both groups ; 43 ( 58.9 % ) patients in Group I vs. 26 ( 59 % ) patients in Group II . End-stage renal disease was observed in 10 ( 13.7 % ) patients in Group I vs. 9 ( 20.4 % ) patients in Group II ( P = 0.359 ) . Side-effects were more frequent in Group I patients than in Group II patients ; gonadal toxicity and malignancy were lower in Group II patients ( P = 0.0000 ) . Moreover , different infections occurred in 23 ( 31.3 % ) patients vs. six ( 13.6 % ) , digital infa rcts occurred in 1.35 % vs. 0 % , diabetes in 4.1 % vs. 2.27 % , and vasculitis in 4.1 % vs. 2.27 % in Group I vs. Group II , respectively . Sustained amenorrhea without pregnancy was observed in both groups ; however , significantly more in Group I patients , P ≤ 0.05 . We conclude that low-dose Cyclo therapy is sufficiently effective for WHO class IV LN patients with lower side-effects compared with st and ard dose To assess the efficacy and safety of a 24‐week course of abatacept in the treatment of active lupus nephritis and to assess the potential of abatacept to induce “ clinical tolerance , ” defined as sustained clinical quiescence of lupus nephritis after discontinuation of immunosuppressive therapy Mycophenolate mofetil ( MMF ) and the sequential use of cyclophosphamide followed by azathioprine ( CTX-AZA ) demonstrate similar short-term efficacy in the treatment of diffuse proliferative lupus nephritis ( DPLN ) , but MMF is associated with less drug toxicity . Results from an extended long-term study , with median follow-up of 63 mo , that investigated the role of MMF as continuous induction-maintenance treatment for DPLN are presented . Thirty-three patients were r and omized to receive MMF , and 31 were r and omized to the CTX-AZA treatment arm , both in combination with prednisolone . More than 90 % in each group responded favorably ( complete or partial remission ) to induction treatment . Serum creatinine in both groups remained stable and comparable over time . Creatinine clearance increased significantly in the MMF group , but the between-group difference was insignificant . Improvements in serology and proteinuria were comparable between the two groups . A total of 6.3 % in the MMF group and 10.0 % of CTX-AZA-treated patients showed doubling of baseline creatinine during follow-up ( P = 0.667 ) . Both the relapse-free survival and the hazard ratio for relapse were similar between MMF- and CTX-AZA-treated patients ( 11 and nine patients relapsed , respectively ) and between those with MMF treatment for 12 or > /=24 mo . MMF treatment was associated with fewer infections and infections that required hospitalization ( P = 0.013 and 0.014 , respectively ) . Four patients in the CTX-AZA group but none in the MMF group reached the composite end point of end-stage renal failure or death ( P = 0.062 by survival analysis ) . It is concluded that MMF and prednisolone constitute an effective continuous induction-maintenance treatment for DPLN in Chinese patients This study assessed whether certain clinicopathologic variables could explain the impact of race on outcome in 86 patients who had severe lupus nephritis and were available for long-term follow-up after participating in a prospect i ve , controlled , clinical trial . Fifty-four ( 63 % ) patients were white , 21 ( 24 % ) were black , and 11 ( 13 % ) were categorized as other . The proportion of patients with anti-Ro , anti-nRNP , and anti-Sm was significantly greater among black patients . Biopsies with segmental active proliferative and necrotizing lesions that involved > or=50 % of glomeruli + /- membranous glomerulonephritis ( class III > or=50%+/-V ) were significantly more common ( white 44 % , black 76 % , other 36 % ; P < 0.05 ) and diffuse proliferative glomerulonephritis + /- membranous glomerulonephritis ( class IV+/-V ) was less common ( white 54 % , black 24 % , other 64 % ) among black patients . Attainment of a remission was greatest among white patients ( white 52 % , black 29 % , other 27 % ; P = 0.09 ) . Features that were predictive of a remission were white race , baseline serum creatinine , and class IV+/-V lesions . Patient survival at 10 yr ( white 81 % , black 59 % , other 73 % ; P = 0.029 ) and renal survival at 10 yr ( white 68 % , black 38 % , other 61 % ; P = 0.015 ) were significantly poorer in black patients . Predictors of ESRD were serum creatinine , the presence of anti-Ro antibodies , class III > or=50%+/-V lesions , and failure to achieve a remission . In conclusion , racial differences were observed in the serologic and histologic features at presentation , response to treatment , and outcome of patients with severe lupus nephritis . In a population of patients with severe lupus nephritis , black patients were significantly more likely to have a serologic profile and renal lesions that were associated with more aggressive renal disease and result ed in worse outcomes than white patients BACKGROUND The combination of cyclophosphamide and prednisolone is effective for the treatment of severe lupus nephritis but has serious adverse effects . Whether mycophenolate mofetil can be substituted for cyclophosphamide is not known . METHODS In 42 patients with diffuse proliferative lupus nephritis we compared the efficacy and side effects of a regimen of prednisolone and mycophenolate mofetil given for 12 months with those of a regimen of prednisolone and cyclophosphamide given for 6 months , followed by prednisolone and azathioprine for 6 months . Complete remission was defined as a value for urinary protein excretion that was less than 0.3 g per 24 hours , with normal urinary sediment , a normal serum albumin concentration , and values for serum creatinine and creatinine clearance that were no more than 15 percent above the base-line values . Partial remission was defined as a value for urinary protein excretion that was between 0.3 and 2.9 g per 24 hours , with a serum albumin concentration of at least 30 g per liter . RESULTS Eighty-one percent of the 21 patients treated with mycophenolate mofetil and prednisolone ( group 1 ) had a complete remission , and 14 percent had a partial remission , as compared with 76 percent and 14 percent , respectively , of the 21 patients treated with cyclophosphamide and prednisolone followed by azathioprine and prednisolone ( group 2 ) . The improvements in the degree of proteinuria and the serum albumin and creatinine concentrations were similar in the two groups . One patient in each group discontinued treatment because of side effects . Infections were noted in 19 percent of the patients in group 1 and in 33 percent of those in group 2 ( P = 0.29 ) . Other adverse effects occurred only in group 2 ; they included amenorrhea ( in 23 percent of the patients ) , hair loss ( 19 percent ) , leukopenia ( 10 percent ) , and death ( 10 percent ) . The rates of relapse were 15 percent and 11 percent , respectively . CONCLUSIONS For the treatment of diffuse proliferative lupus nephritis , the combination of mycophenolate mofetil and prednisolone is as effective as a regimen of cyclophosphamide and prednisolone followed by azathioprine and prednisolone but is less toxic Background Recent studies have suggested that mycophenolate mofetil ( MMF ) may offer advantages over intravenous cyclophosphamide ( IVC ) for the treatment of lupus nephritis . The aim of this study was to evaluate the efficacy of MMF compared with IVC in the induction therapy of proliferative lupus nephritis . Methods We r and omly assigned 47 patients with newly diagnosed active proliferative lupus nephritis class III or IV to open-label oral MMF 2 g/day for 6 months or intravenous cyclophosphamide 0.5–1 g/m2 monthly for 6 months in addition to corticosteroids . Results In the intention-to-treat analysis , 14 of the 24 patients ( 58.33 % ) receiving MMF and 12 of the 23 patients receiving cyclophosphamide ( 52.17 % ) had remission ( P = 0.48 ) ; complete remission occurred in 6 of the 24 patients ( 25 % ) and 5 of the 23 patients ( 21.74 % ) , respectively ( P = 0.53 ) . Improvements in packed cell volume , the erythrocyte sedimentation rate , anti-double-str and ed DNA antibodies titer ( anti-dsDNA ) , serum complement , proteinuria , urinary activity , renal function , serum soluble interleukin-2 receptor alpha concentration and the systemic lupus activity measure score were similar in both groups . Two patients assigned to MMF and another patient assigned to IVC developed end-stage renal failure with commencement of dialysis . Adverse events were similar . Major infections occurred in two patients in each group . There was no difference in gastrointestinal side effects , but more diarrhea occurred in those receiving MMF . Conclusion In this 24-week trial , MMF or IVC combined with corticosteroids demonstrated equal efficacy in inducing remission of proliferative lupus nephritis We evaluated the efficacy and safety of tacrolimus in patients receiving glucocorticoid therapy for lupus nephritis . Patients with persistent nephritis were r and omized to receive 28 weeks of double-blind treatment with tacrolimus ( 3 mg/day ) or placebo . The primary endpoint was the change in the lupus nephritis disease activity index ( LNDAI ) calculated from scores for daily urinary protein excretion , urinary red cells , serum creatinine , anti-double-str and ed DNA antibody , and serum complement . Statistical analysis was performed using the full analysis set . The LNDAI was decreased by 32.9 ± 31.0 % ( mean ± SD ) in the tacrolimus group ( n = 28 ) and was increased by 2.3 ± 38.2 % in the placebo group ( n = 35 ) at final evaluation . There was significant improvement in the tacrolimus group . Daily urinary protein excretion showed a significant decrease in the tacrolimus group ( p < 0.001 ) . The complement ( C3 ) level showed a significant increase in the tacrolimus group ( p = 0.001 ) . Treatment-related adverse events occurred in 92.9 % of the tacrolimus group and 80.0 % of the placebo group , but the difference was not significant . In patients on glucocorticoid therapy for lupus nephritis , addition of tacrolimus to basal therapy achieved significant improvement compared with placebo . Tacrolimus may therefore be a useful alternative treatment for lupus nephritis We evaluated renal function in 107 patients with active lupus nephritis who participated in long-term r and omized therapeutic trials ( median follow-up , seven years ) . For patients taking oral prednisone alone , the probability of renal failure began to increase substantially after five years of observation . Renal function was better preserved in patients who received various cytotoxic-drug therapies , but the difference was statistically significant only for intravenous cyclophosphamide plus low-dose prednisone as compared with high-dose prednisone alone ( P = 0.027 ) . The advantage of treatment with intravenous cyclophosphamide over oral prednisone alone was particularly apparent in the high-risk subgroup of patients who had chronic histologic changes on renal biopsy at study entry . Patients treated with intravenous cyclophosphamide have not experienced hemorrhagic cystitis , cancer , or a disproportionate number of major infections . We conclude that , as compared with high-dose oral prednisone alone , treatment of lupus glomerulonephritis with intravenous cyclophosphamide reduces the risk of end-stage renal failure with few serious complications Therapy for patients with life-threatening systemic lupus erythematosus has included high doses of corticosteroids and cytotoxic or cytostatic drugs [ 1 - 20 ] . Cyclophosphamide , given in intermittent intravenous boluses , has been widely used to treat renal [ 1 - 68 , 15 , 21 ] and central nervous system disease [ 2 , 3 , 6 , 7 , 19 - 21 ] , but this therapy is sometimes withheld in the hope that disease might be controlled with corticosteroids or other immunosuppressive drugs . Moreover , some patients do not respond adequately to therapy with intermittent boluses of cyclophosphamide , and these patients might benefit from more intensive therapy . In a previous study [ 3 ] , monthly administration of methylprednisolone ( 1.0 g/m2 body surface area ) was less effective than bolus therapy with cyclophosphamide . However , the limited duration of the methylprednisolone regimen [ 6 months ] might have been insufficient to treat lupus nephritis . To address this concern , we evaluated patients receiving methylprednisolone once a month for 1 year ; additional boluses were given as needed to control disease . We compared these patients with patients receiving our st and ard therapy : intermittent boluses of cyclophosphamide . A group of patients r and omly assigned to receive both cyclophosphamide and methylprednisolone was also included for three major reasons : 1 ) some patients with lupus nephritis respond inadequately to boluses of cyclophosphamide , 2 ) anecdotal experience had suggested that cyclophosphamide therapy might be more effective for all patients when given with substantial doses of corticosteroids , and 3 ) animal studies had shown the advantage of combined chemotherapy for lupus nephritis [ 22 , 23 ] . Our study design was modified from previous design s so that therapy could be intensified for patients with refractory or relapsing disease . Methods Patient Selection We enrolled 82 patients with lupus nephritis into this r and omized , parallel study at the Clinical Center of the National Institutes of Health ( Bethesda , Maryl and ) between 1986 and 1990 . To enter the study , patients had to have both glomerulonephritis and a diagnosis of systemic lupus erythematosus [ 24 ] . Glomerulonephritis was defined as a sediment on two or more urinalyses that showed either 10 or more erythrocytes per high-power field or erythrocyte or leukocyte casts ( without evidence of infection ) or both , plus histologic evidence of active proliferative lupus glomerulonephritis on a renal biopsy specimen obtained within 3 months of study entry ( provided that a biopsy could be done safely ) . Scores for renal histologic activity and chronicity were assessed as reported elsewhere [ 25 ] . All eligible patients were invited to participate . Exclusion criteria were 1 ) receipt of cytotoxic drug treatment for more than 2 weeks during the 6 weeks before study entry or receipt of cyclophosphamide therapy for more than 10 weeks at any time ; 2 ) receipt of pulse therapy with corticosteroids during the 6 weeks before study entry ; 3 ) need [ at the time of study entry ] for oral corticosteroids in dosages greater than 0.5 mg of a prednisone equivalent per kilogram of body weight per day to control extrarenal disease ; 4 ) active or chronic infection ; 5 ) pregnancy ; 6 ) the presence of only one kidney ; 7 ) insulin-dependent diabetes mellitus ; and 8) allergy to methylprednisolone or cyclophosphamide . Study Design The protocol that we used was approved by the NIDDK/NIAMS ( National Institute of Diabetes and Digestive and Kidney Diseases/National Institute of Arthritis and Musculoskeletal and Skin Diseases ) Institutional Review Board [ 86-AR-0189 ] . After giving signed , written informed consent , patients were r and omly assigned to one of three treatment groups by drawing from a masked card sequence arranged from a table of r and om numbers . Each group received one of the following regimens : 1 ) intravenous methylprednisolone [ 1 g/m2 body surface area ] , given as boluses over 60 minutes on 3 consecutive days followed by at least 12 consecutive monthly single infusions ; 2 ) intravenous cyclophosphamide , given as boluses once a month for 6 consecutive months and then once every 3 months for at least 2 more years ; and 3 ) the combination of these two regimens . After a patient completed 1 year of study , a decision about whether therapy would be modified was made on the basis of the patient 's renal status at that time ( Figure 1 ) . In patients receiving methylprednisolone , therapy was discontinued if urine studies showed that renal remission had occurred . Renal remission was defined as the presence of fewer than 10 dysmorphic erythrocytes per high-power field , the absence of cellular casts , and excretion of less than 1 g of protein per day . If a renal remission was not evident , the patient continued to receive methylprednisolone every month for 6 more months . After the additional 6 months , if renal remission was still not evident , the patient received treatment for another 6 months . Therapy with methylprednisolone was limited to a maximum of 36 monthly boluses . Figure 1 . Treatment regimens and decision pathways used in this clinical trial for lupus nephritis . At 1 year , patients who had been receiving cyclophosphamide alone or in combination with methylprednisolone continued to receive or began to receive cyclophosphamide alone , once every 3 months , if the results of urine studies were substantially improved . Substantial improvement was defined as a reduction of at least 50 % in 1 ) the number of dysmorphic erythrocytes seen in urine sample s , 2 ) the number of cellular casts , and 3 ) proteinuria , without a mmol of the serum creatinine level . Quarterly administration of cyclophosphamide was continued for 2 years after renal remission occurred , after which time therapy was stopped . After the first year of the study , patients in any treatment group who were no longer receiving monthly therapy but who had evidence of the reactivation of glomerular disease had their originally assigned regimens reinstituted as if they were beginning therapy from enrollment . Reactivation of glomerular disease was defined as new active nephritis with an increase of at least 50 % ( relative to the lowest reproducible values obtained during the study ) in at least two of the following : number of dysmorphic erythrocytes ( 10 per high-power field ) , number of cellular casts , proteinuria ( 1 g of protein per day ) , or serum creatinine level . One year after the reinstitution of therapy , patients were again evaluated for evidence of active glomerulonephritis ( as described above ) . As before , patients could be withdrawn from therapy , could restart treatment , or could continue to receive cyclophosphamide every 3 months . Patients could restart therapy no more than twice ; if therapy failed more than three times , patients were declared to be nonresponders . Treatment and Follow-up Cyclophosphamide was infused for 60 minutes at an initial dose of 0.75 g/m2 body surface area . If the leukocyte nadir was greater than 3000 cells/mm3 , the cyclophosphamide dose was increased by 25 % , to a maximum of 1 g/m2 body surface area . The dose was reduced by 25 % for leukocyte counts less than 1500 cells/mm3 . Patients with a creatinine clearance of less than 30 mL/min received an initial dose of 0.5 g/m2 body surface area , and subsequent doses were adjusted on the basis of the lowest leukocyte count . Patients treated with cyclophosphamide were hydrated , and diuretics were used to maintain neutral fluid balance . Thiethylperazine , 10 mg , with 25 mg of diphenhydramine or 0.25 mg of lorazepam , was administered orally or intravenously every 6 hours for nausea . After the middle of 1990 , patients were treated in a day hospital setting , where they received intravenous saline , 200 mL per hour for 10 hours . Mesna ( 2-mercaptoethanesulfonate ) , at 20 % of the cyclophosphamide dose , was infused intravenously for 10 minutes before cyclophosphamide was administered and every 3 hours thereafter , for a total of four doses . Ondansetron , 8 mg , was given every 4 hours beginning 4 hours after infusion of cyclophosphamide , for a total of three doses . Dexamethasone , 10 mg , was given 4 hours after administration of cyclophosphamide [ 26 ] . Patients were instructed to continue oral hydration after discharge from the day hospital to maintain a dilute and frequent diuresis for at least 24 hours after infusion of cyclophosphamide . All patients were initially given oral prednisone , 0.5 mg/kg per day for 4 weeks . The prednisone dose was then tapered by 5 mg every other day each week to the minimal dose required to control extrarenal disease or 0.25 mg/kg every other day , whichever was greater . For severe extrarenal flares of lupus , patients were permitted to receive prednisone , 1.0 mg/kg per day for 2 weeks . Blood pressure was closely monitored and was maintained within 110 to 130/70 to 85 mm Hg with antihypertensive therapy . The intervals at which patients were followed were dictated by the activity of lupus and nephritis . In general , all patients were seen monthly during the first year of the study and every 3 months thereafter . At each study visit , patients were question ed about and examined for adverse events . Outcome Measures The primary study outcome was the response to the study drugs as defined by 1 ) the percentage of patients who achieved renal remission , 2 ) the number of nonresponders ( nonresponse was defined as 10 erythrocytes per high-power field , cellular casts , proteinuria [ > 1 g of protein per day ] , and doubling of the serum creatinine level ) , and 3 ) the percentage of adverse events . The outcome data , with the exception of data on adverse events , were collected in a blinded manner on 1 May 1995 , 5 years after the last patient was enrolled in the study . Secondary outcome measures were renal failure that required dialysis ( end-stage renal disease ) , stable doubling of the serum creatinine level , and number of renal relapses ( renal relapse was defined as a reactivation of renal disease after 6 or more months of BACKGROUND Since anecdotal series and small , prospect i ve , controlled trials suggest that mycophenolate mofetil may be effective for treating lupus nephritis , larger trials are desirable . METHODS We conducted a 24-week r and omized , open-label , noninferiority trial comparing oral mycophenolate mofetil ( initial dose , 1000 mg per day , increased to 3000 mg per day ) with monthly intravenous cyclophosphamide ( 0.5 g per square meter of body-surface area , increased to 1.0 g per square meter ) as induction therapy for active lupus nephritis . A change to the alternative regimen was allowed at 12 weeks in patients who did not have an early response . The study protocol specified adjunctive care and the use and tapering of corticosteroids . The primary end point was complete remission at 24 weeks ( normalization of abnormal renal measurements and maintenance of baseline normal measurements ) . A secondary end point was partial remission at 24 weeks . RESULTS Of 140 patients recruited , 71 were r and omly assigned to receive mycophenolate mofetil and 69 were r and omly assigned to receive cyclophosphamide . At 12 weeks , 56 patients receiving mycophenolate mofetil and 42 receiving cyclophosphamide had satisfactory early responses . In the intention-to-treat analysis , 16 of the 71 patients ( 22.5 percent ) receiving mycophenolate mofetil and 4 of the 69 patients receiving cyclophosphamide ( 5.8 percent ) had complete remission , for an absolute difference of 16.7 percentage points ( 95 percent confidence interval , 5.6 to 27.9 percentage points ; P=0.005 ) , meeting the prespecified criteria for noninferiority and demonstrating the superiority of mycophenolate mofetil to cyclophosphamide . Partial remission occurred in 21 of the 71 patients ( 29.6 percent ) and 17 of the 69 patients ( 24.6 percent ) , respectively ( P=0.51 ) . Three patients assigned to cyclophosphamide died , two during protocol therapy . Fewer severe infections and hospitalizations but more diarrhea occurred among those receiving mycophenolate . CONCLUSIONS In this 24-week trial , mycophenolate mofetil was more effective than intravenous cyclophosphamide in inducing remission of lupus nephritis and had a more favorable safety profile Objective To compare the efficacy of tacrolimus ( TAC ) and mycophenolate mofetil ( MMF ) for the initial therapy of lupus nephritis ( LN ) . Study design This is an open r and omised controlled parallel group study . Methods Adult patients with biopsy-confirmed active LN ( class III/IV/V ) were r and omised to receive prednisolone ( 0.6 mg/kg/day for 6 weeks and tapered ) in combination with either TAC ( 0.06–0.1 mg/kg/day ) or MMF ( 2–3 g/day ) for 6 months . Good responders were shifted to azathioprine for maintenance . The primary outcome was the rate of complete renal response ( CR ) at 6 months and the secondary outcomes included partial renal response , renal flares and decline of renal function over time . Results 150 patients ( 92 % women ; aged 35.5±12.8 years ; 81 % class III/IV ) were r and omised ( 76 MMF , 74 TAC ) . At month 6 , the rate of CR was 59 % in the MMF and 62 % in the TAC group ( treatment difference : 3.0 % ( −12 % , 18 % ) ; p=0.71 ) . Major infective episodes occurred in 9.2 % patients treated with MMF and in 5.4 % patients treated with TAC ( p=0.53 ) . Maintenance therapy with azathioprine was given to 79 % patients . After 60.8±26 months , proteinuric and nephritic renal flares developed in 24 % and 18 % of patients in the MMF group and 35 % ( p=0.12 ) and 27 % ( p=0.21 ) in the TAC group , respectively . The cumulative incidence of a composite outcome of decline of creatinine clearance by ≥30 % , development of chronic kidney disease stage 4/5 or death was 21 % in the MMF and 22 % in the TAC group of patients ( p=0.35 ) . Conclusions TAC is non-inferior to MMF , when combined with prednisolone , for induction therapy of active LN . With azathioprine maintenance for 5 years , a non-significant trend of higher incidence of renal flares and renal function decline is observed with the TAC regimen . Trial registration number Hospital Authority Research Ethics Committee Clinical Trial Registry ( HARECCTR0500018 ; Hong Kong ) and US Clinical Trials.gov ( NCT00371319 ) OBJECTIVE To determine whether plasmapheresis increases the risk for infection in immunosuppressed patients . DESIGN R and omized , controlled trial . SETTING Multicenter . PATIENTS Eighty-six patients enrolled in a trial of plasmapheresis for severe diffuse proliferative lupus nephritis . INTERVENTIONS Forty-six of the patients received high-dose steroid therapy plus cyclophosphamide therapy for 8 weeks . Thereafter , cyclophosphamide therapy was discontinued , and steroid therapy was tapered ( st and ard treatment group ) . Forty patients received identical treatment and had 12 plasmapheresis procedures during the first 4 weeks of the treatment . MEASUREMENTS Patients were examined for the development of infection . MAIN RESULTS No statistical difference in age , sex , race , serum creatinine level , proteinuria , or complement levels was found between the two groups . Over a follow-up period of 5376 patient-weeks , 74 % of patients in the st and ard treatment group had 62 infections , yielding an aggregate infection rate of 1.15 infections per 100 weeks ( median individual infection rate , 1.08 ; 25th and 75th percentiles , 0.0 and 2.44 ) . This rate was comparable to that seen in the plasmapheresis-treated patients who were followed for 4187 patient-weeks : 68 % had 51 infections , for an aggregate infection rate of 1.22 infections per 100 weeks ( median individual infection rate , 0.94 ; 25th and 75th percentiles , 0.0 and 2.32 ) . The infection rate was also comparable in the initial acute phase of the study , despite the fact that patients who received plasmapheresis then had significantly lower immunoglobulin ( IgG ) levels ( P less than 0.001 ) . Neither the site ( superficial compared with systemic ) nor the nature ( conventional compared with unconventional ) of infection differed statistically between the two groups . Of 14 patient deaths , 7 were from infection ( 4 in control group and 3 in the plasmapheresis group ) . CONCLUSION Plasmapheresis did not increase the risk for infection in immunosuppressed patients with severe lupus nephritis In the present study , we assessed the frequency and characteristics of the main causes of morbidity and mortality in systemic lupus erythematosus ( SLE ) during a 10-year period and compared the frequency of early manifestations with those that appeared later in the evolution of the disease . In 1990 , we started a multicenter study of 1,000 patients from 7 European countries . All had medical histories documented and underwent medical interview and routine general physical examination when entered in the study , and all were followed prospect ively by the same physicians during the ensuing 10 years (1990–2000).A total of 481 ( 48.1 % ) patients presented 1 or more episodes of arthritis at any time during the 10 years , 311 ( 31.1 % ) patients had malar rash , 279 ( 27.9 % ) active nephropathy , 194 ( 19.4 % ) neurologic involvement , 166 ( 16.6 % ) fever , 163 ( 16.3 % ) Raynaud phenomenon , 160 ( 16.0 % ) serositis ( pleuritis and /or pericarditis ) , 134 ( 13.4 % ) thrombocytopenia , and 92 ( 9.2 % ) thrombosis . When the prevalences of the clinical manifestations during the initial 5 years of follow-up ( 1990–1995 ) were compared with those during the ensuing 5 years ( 1995–2000 ) , most manifestations were found to be more frequent during the initial 5 years . Of the 1,000 patients , 360 ( 36 % ) presented infections , 169 ( 16.9 % ) hypertension , 121 ( 12.1 % ) osteoporosis , and 81 ( 8.1 % ) cytopenia due to immunosuppressive agents . Twenty-three ( 2.3 % ) patients developed malignancies ; the most frequent primary localizations were the uterus and the breast . Sixty-eight ( 6.8 % ) patients died , and the most frequent causes of death were similarly divided between active SLE ( 26.5 % ) , thromboses ( 26.5 % ) , and infections ( 25 % ) . A survival probability of 92 % at 10 years was found . A lower survival probability was detected in those patients who presented at the beginning of the study with nephropathy ( 88 % versus 94 % in patients without nephropathy , p = 0.045 ) . When the causes of death during the initial 5 years of follow-up ( 1990–1995 ) were compared with those during the ensuing 5 years ( 1995–2000 ) , active SLE and infections ( 28.9 % each ) appeared to be the most common causes during the initial 5 years , while thromboses ( 26.1 % ) became the most common cause of death during the last 5 years . In conclusion , most of the SLE inflammatory manifestations appear to be less common after a long-term evolution of the disease , probably reflecting the effect of therapy as well as the progressive remission of the disease in many patients . Meanwhile , a more prominent role of thrombotic events is becoming evident , affecting both morbidity and mortality in SLE OBJECTIVE To evaluate the efficacy and safety of rituximab in a r and omized , double-blind , placebo-controlled phase III trial in patients with lupus nephritis treated concomitantly with mycophenolate mofetil ( MMF ) and corticosteroids . METHODS Patients ( n = 144 ) with class III or class IV lupus nephritis were r and omized 1:1 to receive rituximab ( 1,000 mg ) or placebo on days 1 , 15 , 168 , and 182 . The primary end point was renal response status at week 52 . RESULTS Rituximab depleted peripheral CD19 + B cells in 71 of 72 patients . The overall ( complete and partial ) renal response rates were 45.8 % among the 72 patients receiving placebo and 56.9 % among the 72 patients receiving rituximab ( P = 0.18 ) ; partial responses accounted for most of the difference . The primary end point ( superior response rate with rituximab ) was not achieved . Eight placebo-treated patients and no rituximab-treated patients required cyclophosphamide rescue therapy through week 52 . Statistically significant improvements in serum complement C3 , C4 , and anti-double-str and ed DNA ( anti-dsDNA ) levels were observed among patients treated with rituximab . In both treatment groups , a reduction in anti-dsDNA levels greater than the median reduction was associated with reduced proteinuria . The rates of serious adverse events , including infections , were similar in both groups . Neutropenia , leukopenia , and hypotension occurred more frequently in the rituximab group . CONCLUSION Although rituximab therapy led to more responders and greater reductions in anti-dsDNA and C3/C4 levels , it did not improve clinical outcomes after 1 year of treatment . The combination of rituximab with MMF and corticosteroids did not result in any new or unexpected safety signals |
14,040 | 21,154,372 | People are less likely to leave the study early if they remain on olanzapine compared to switching to quetiapine or aripiprazole .
There was no significant difference in outcomes of mental state , global state , and adverse events between groups which switched medications and those that remained on previous medication .
Three different switching strategies were compared and no strategy was found to be superior to the others for outcomes of weight gain , mental state and global state .
There was no difference in mental state , global state and other treatment related adverse events between switching to another medication and continuing on the previous one .
When the three switching strategies were compared none of them had an advantage over the others in their effects on the primary outcomes considered in this review . | BACKGROUND Weight gain is common for people with schizophrenia and this has serious implication s for a patient 's health and well being .
Switching strategies have been recommended as a management option .
OBJECTIVES To determine the effects of antipsychotic medication switching as a strategy for reducing or preventing weight gain and metabolic problems in people with schizophrenia . | Weight gain is a major adverse effect of several second-generation antipsychotic medications . Rimonabant is a cannabinoid-1 receptor antagonist that promotes weight loss in the general population . We conducted a 16-week , double-blind , placebo-controlled study of rimonabant ( 20 mg/d ) in people with schizophrenia or schizoaffective disorder , based on the Diagnostic and Statistical Manual of Mental Disorders , Fourth Edition criteria , who were clinical ly stable on second-generation antipsychotics . Participants had a body mass index of 27 kg/m2 or higher with hyperlipidemia or body mass index of 30 kg/m2 or higher , and no current substance abuse/dependence ( except nicotine ) , more than weekly cannabis use , or recent depressive symptoms/suicidality . An exercise and dietary counseling group was offered weekly . Target enrollment was 60 ; the trial was terminated early because of withdrawal of rimonabant from the European market . Fifteen participants were r and omized ( 7 rimonabant , 8 placebo ) ; 5 completed in each group . Rimonabant was associated with a greater reduction in Brief Psychiatric Rating Scale total score versus placebo ( mean ± SE difference , −1.9 ± 0.8 , P = 0.02 ) , driven by differences in the Brief Psychiatric Rating Scale anxiety/depression ( −1.4 ± 0.35 , P = 0.0004 ) and hostility ( −0.7 ± 0.3 , P = 0.02 ) factors . Group differences were not significant for the Calgary Depression Scale total score ( P = 0.24 ) , Scale for the Assessment of Negative Symptoms total score ( P = 0.13 ) , weight , blood pressure , or fasting lipids or glucose . Rimonabant was well tolerated with no significant adverse events . No significant weight loss , metabolic effects , or adverse psychiatric effects were associated with the cannabinoid-1 receptor antagonist rimonabant in this small sample of people with schizophrenia . The endocannabinoid system remains a promising target for pharmacotherapy of schizophrenia and obesity We examined the potential risks and benefits of switching from olanzapine to quetiapine in mentally stable , obese , or overweight patients with schizophrenia or schizoaffective disorder . Patients receiving olanzapine were r and omized to continuing olanzapine treatment ( N = 68 ; 7.5–20 mg/day ) or switching to quetiapine ( N = 65 ; 300–800 mg/day ) . Time to relapse was the primary study objective ; secondary objectives included changes in weight , metabolic parameters , and psychiatric symptoms , and discontinuation rates . No significant difference in time to relapse was observed ( p = 0.293 ) , but significantly more patients remained on treatment in the olanzapine group compared with the quetiapine group ( 70.6 % vs 43.1 % ; p = 0.002 ) . Olanzapine-treated patients had significantly lower rates of study discontinuation for lack of efficacy and psychiatric adverse events ( AEs ) compared to quetiapine ( 2.94 % vs 15.38 % , p = 0.015 ) . Significantly more patients in the olanzapine group experienced an increase in BMI ≥1 kg/m2 . Olanzapine-treated patients experienced significantly greater increases in weight from Weeks 2 through 13 . Switching patients with stable disease from olanzapine to quetiapine did not significantly shorten time to relapse , but produced more frequent study discontinuations due to lack of efficacy or psychiatric AEs with moderate but variable improvement in weight and no significant between-group differences in mean changes in metabolic laboratory parameters Clozapine is associated with significant weight gain and metabolic disturbances . This multicentre , r and omized study comprised a double-blind , placebo-controlled treatment phase of 16 wk , and an open-label extension phase of 12 wk . Out patients who met DSM-IV-TR criteria for schizophrenia , who were not optimally controlled while on stable dosage of clozapine for > or =3 months and had experienced weight gain of > or = 2.5 kg while taking clozapine , were r and omized ( n=207 ) to aripiprazole at 5 - 15 mg/d or placebo , in addition to a stable dose of clozapine . The primary endpoint was mean change from baseline in body weight at week 16 ( last observation carried forward ) . Secondary endpoints included clinical efficacy , body mass index ( BMI ) and waist circumference . A statistically significant difference in weight loss was reported for aripiprazole vs. placebo ( -2.53 kg vs. -0.38 kg , respectively , difference=-2.15 kg , p<0.001 ) . Aripiprazole-treated patients also showed BMI ( median reduction 0.8 kg/m(2 ) ) and waist circumference reduction ( median reduction 2.0 cm ) vs. placebo ( no change in either parameter , p<0.001 and p=0.001 , respectively ) . Aripiprazole-treated patients had significantly greater reductions in total and low-density lipoprotein ( LDL ) cholesterol . There were no significant differences in Positive and Negative Syndrome Scale total score changes between groups but Clinical Global Impression Improvement and Investigator 's Assessment Question naire scores favoured aripiprazole over placebo . Safety and tolerability were generally comparable between groups . Combining aripiprazole and clozapine result ed in significant weight , BMI and fasting cholesterol benefits to patients suboptimally treated with clozapine . Improvements may reduce metabolic risk factors associated with clozapine treatment Objective : Few interventions have been successful to prevent or reverse the medical complications associated with antipsychotic agents in the schizophrenia population . In particular , no single agent can correct multiple metabolic abnormalities such as insulin resistance , hyperlipidemia , inflammation , obesity , and fat distribution . We now report a r and omized placebo-controlled pilot study to examine the effects of ramelteon on obesity and metabolic disturbances among subjects with schizophrenia . Methods : A double-blind , placebo-controlled , 8-week pilot trial was conducted , adding ramelteon 8 mg/d to stable out patients with schizophrenia . Vital signs and anthropometric measurements , including height , weight , waist circumference , and body fat were assessed , and laboratory assays were tracked to monitor changes in metabolic markers . Results : Twenty-five subjects were r and omly assigned to treatment with study drug or placebo , and 20 subjects were included in the final analysis . Ramelteon did not improve anthropometric measurements , glucose metabolism , and inflammatory markers . There was , however , a significant decrease in total cholesterol and ratio of cholesterol to high-density lipoprotein in the ramelteon group . Although the st and ard anthropometric measures did not show significant change , the dual-energy x-ray absorptiometry scan showed a trend toward reduction in fat in the abdominal and trunk areas with a moderate effect size . Conclusions : Although ramelteon decreased cholesterol , treatment may have to be longer than 8 weeks and with a higher dose for maximal effect of ramelteon for body fat and lipid changes . Future studies are needed for patients with schizophrenia with a larger sample size to fully underst and ramelteon 's effects on abdominal adiposity and lipids In this issue , we answer three questions with respect to loss to follow-up in a clinical trial : How important is loss to follow-up ? How is loss to follow-up calculated ? How many patients can be lost to follow-up without mistrusting the results ? 1 . How important is loss to follow-up ? The simple answer to this question is “ very important ” because loss to follow-up can severely compromise a study 's validity . Incomplete follow-up biases the results when either : The dropout rates are different between study groups ; or The patients who drop out are different from those who do not drop out . Why do these situations make a difference ? Because in each situation , those lost to follow-up often have a different prognosis than those who complete the study . For example , patients who receive treatment for cervical myelopathy may not return for follow-up because they became asymptomatic and felt no need to return to see the surgeon . Conversely , some patients may not return because they had a particularly bad outcome ( worse pain or function ) or complication , or because they died . In either case , bias can affect the validity of the inferences drawn from the study . 2 . How is loss to follow-up calculated ? There is much confusion about how to determine the proportion of patients lost to follow-up . In order to correctly calculate the follow-up rate , one needs to know the denominator . In a r and omized controlled trial ( RCT ) , the denominator for each group is the number of patients who were r and omized , not the number who received the treatment . For example , suppose we have an RCT comparing two treatment groups , Group A and Group B. The investigators evaluate 178 patients and r and omize 120 ; 61 to Group A and 59 to Group B ( Fig 1 ) . Following the figure , we note that 49 patients received treatment A and 52 received treatment B. At the final follow-up 40 were analyzed in Group A and 41 in Group B. How many were considered lost to follow-up ? Many would consider the loss to follow-up rate to be 9 ( 18 % ) of 49 in treatment A and 11 ( 21 % ) of 52 in treatment B using as the denominator only those that were treated . However , the real proportion lost to follow-up must consider those who were r and omly assigned , even if they did not receive treatment . In the present example , this is calculated as 21 ( 34 % ) of 61 for treatment A and 18 ( 31 % ) of 59 for treatment B. Fig 1 Hypothetical example of patients lost to follow-up in a r and omized controlled trial . When calculating loss to follow-up in a retrospective cohort study , all individuals receiving treatment during the study period should be used as the denominator , not just those with complete data . For example , let 's say you want to compare decompression plus lumbar fusion with decompression alone in disc herniation and the data available are all patients receiving either treatment in the last 5 years ( N = 275 ) . However , the data base from which the data are obtained is incomplete and only 190 have the necessary data available . Since the investigators stated as part of the inclusion criteria that only those patients with complete data are included , they consider the follow-up to be 100 % ( 190/190 ) . This conclusion is wrong . The denominator should include all patients who underwent the surgery irrespective of completeness of data . The follow-up rate for this example is 69 % ( 190/275 ) . 3 . How many patients can be lost to follow-up without mistrusting the results ? Some have suggested that 20 % poses serious threats to validity 1 . This may be a good rule of thumb , but keep in mind that even small proportions of patients lost to follow-up can cause significant bias 2 . One way to determine if loss to follow-up can seriously affect results is to assume a worst-case scenario with the missing data and look to see if the results would change . Here is an example : Let 's assume a multicenter study enrolled 500 patients into each arm of a study comparing artificial disc replacement ( ADR ) with fusion , and the end point is adjacent segment disease ( ASD ) . The trial numbers are found in Fig 2 . Fig 2 Hypothetical example of the effect of loss to follow-up considering a worst-case scenario . ADR indicates artificial disc replacement ; ASD , adjacent segment disease . The proportion of patients with ASD in the ADR group is half as much versus the fusion group , 25 % ( 100/400 ) compared with 50 % ( 200/400 ) . If we assume that the 100 lost to follow-up in the ADR group had ASD and the 100 lost to follow-up in the fusion group did not , then the rate of ASD in each group would be 40 % ( 200/500 ) . In this case , adopting the worst-case scenario for the intervention group with respect to those lost to follow-up causes the results to change significantly from half the rate of ASD with ADR to the same rate . When this happens , loss to follow-up can threaten the internal validity of the trial . Only when the worst case does not change the inferences derived from the results is lost to follow-up not a problem While weight-management interventions are effective in attenuating antipsychotic-induced weight , there is no available evidence on their long-term effectiveness . This study sought to investigate the 2-year effects of an early behavioural intervention ( EBI ) design ed to prevent antipsychotic-induced weight gain in first-episode psychosis ( FEP ) patients . Sixty-one FEP patients were r and omized to receive either EBI or treatment-as-usual . Intention-to-treat and observed-cases analysis showed that patients in the EBI group gained significantly less weight than those allocated to routine care at intervention completion ( 3-month follow-up ) with treatment effects maintained over 3months . Differences between groups were no longer significant by 12months . Weight-management interventions may need to be offered for longer periods to maintain preventative effects . Alternatively , booster sessions may need to be regularly delivered after intervention completion BACKGROUND Patients with schizophrenia and bipolar disorder have frequently reported weight gain during olanzapine treatment . Previous studies have observed a decrease in weight gain , or weight loss , in patients switching from st and ard olanzapine tablets ( SOT ) to orally disintegrating olanzapine ( ODO ) tablets . The primary objective of this study was to investigate the change in body mass index ( BMI ) in patients who had previously gained weight with SOT and continued with this therapy during the study period , compared with those patients who switched to ODO during the study period . METHODS This was a 16-week , multicentre , r and omized , double-blind , double-dummy , study of out patients diagnosed with schizophrenia , schizoaffective disorder , related psychotic disorder or bipolar disorder , who were taking 5 - 20 mg SOT daily . Patients continued treatment with 5 - 20 mg olanzapine in a flexible single daily dose , and were r and omized to either receive sublingual ODO plus an oral placebo , or sublingual placebo plus SOT . RESULTS No statistically significant between group differences in mean change from baseline in BMI , weight or waist circumference were observed . Analysis of change in body weight from baseline , by pre-specified category ( no change , loss of > or=1.5 kg , gain of > or=1.5 kg ) , revealed a significant difference between groups , favoring ODO patients , who also experienced a significant reduction in subjective appetite and better treatment compliance , compared to patients in the SOT group . CONCLUSIONS In this study , patients treated with ODO experienced a similar mean change in BMI and weight from baseline , to those patients treated with SOT UNLABELLED GENERAL PURPOSE : To evaluate the social functioning of schizophrenic out patients after switching to second-generation antipsychotics . METHODOLOGY Multi-center , r and omized , open-label , parallel , flexible-dose , 1-year study of schizophrenic out patients with prominent negative symptoms ( defined as a SANS Global score > or = 10 ) , previously treated with conventional antipsychotics . Patients were r and omly assigned ( 1:1 ratio ) to treatment with an initial dose of at least 10 mg/day olanzapine ( N = 120 ) or at least 3 mg/day risperidone ( N = 115 ) . Dosage could be modified during the study according to clinical criteria . Social functioning was evaluated using the total and subscales scores of the Social Functioning Scale ( SFS ) ( vali date d Spanish version ) . Other efficacy measures included the SANS , SAPS , and CGI-S scales . Response was defined in advance as a 30 % improvement in the SANS Global score . RESULTS The mean doses during the trial were 12.2 mg/day ( S.D. = 5.8 ) of olanzapine and 4.9 mg/day ( S.D. = 2 ) of risperidone . There were no significant baseline differences in SFS total scores or other relevant clinical variables . At 1 year , olanzapine-treated patients presented a mean improvement in SFS total scores ( 7.75 ) that were significantly higher ( p = 0.0028 ) than for risperidone-treated patients ( -0.92 ) . Treatment with olanzapine result ed in a greater numerical improvement than risperidone in all SFS domains and reached statistical significance in such categories as social engagement or withdrawal ( p = 0.01 ) , independence ( performance ) ( p = 0.0098 ) , independence ( competence ) ( p = 0.04 ) , recreational activities ( p = 0.0391 ) , and occupation/employment ( p = 0.0024 ) in which the greatest difference between the olanzapine and risperidone groups was found ( 0.86 vs. -3.06 ) . Significantly more patients treated with olanzapine reached or surpassed the SFS typified total scores corresponding to a functional level that is representative of a sample of stabilized Spanish out patients with schizophrenia without prominent negative symptoms ( p = 0.0009 ) . Associated factors were treatment with olanzapine and a 30 % improvement or more in SANS global score or SAPS global score . CONCLUSIONS Long-term treatment with olanzapine was associated with overall greater improvement in social functioning ( as measured by SFS ) compared to risperidone-treated patients Although recent treatment guidelines for schizophrenia recommend that the prior antipsychotic agent should remain stable for at least 2 weeks when aripiprazole is introduced , there is no trial-based evidence to support this strategy . This study was design ed to compare this strategy with another conventional one in patients with schizophrenia . We conducted a r and omized , 14-week , open-label trial to compare the following 2 switching strategies : ( 1 ) add-on of aripiprazole on a current regimen , wait for 4 weeks , and the tapering of prior antipsychotics and ( 2 ) add-on of aripiprazole and the simultaneous tapering of prior antipsychotics in patients with schizophrenia . Aripiprazole was initiated at 12 mg/d and then titrated between 12 and 30 mg . The previous antipsychotic medication was reduced biweekly by 25 % . Assessment s included the Clinical Global Impression Scale Schizophrenia version , the Drug-Induced Extrapyramidal Symptoms Scale , and the Subjective Well-being Under Neuroleptics , Short Version , Japanese Edition . Impressions toward their assigned strategy were also subjectively evaluated at baseline and end point . Fifty-three patients were enrolled , and 48 patients completed this trial . No significant differences were found in changes from the baseline in the total Clinical Global Impression Scale Schizophrenia version severity , Drug-Induced Extrapyramidal Symptoms Scale , and Subjective Well-being Under Neuroleptics , Short Version , Japanese Edition scores throughout the study period between the 2 strategies . Both strategies were judged by subjects to be tolerable and favorable without between-group differences . In conclusion , both strategies were found to be objective ly safe and well tolerated . Taken together with similar results from subjective assessment s , it would be reasonable to choose either of these 2 strategies in clinical practice based on a patients ' preference The topic of antipsychotic-induced weight-gain and its relationship to glucose metabolism is under-studied . We evaluated the long-term effects of a new-generation antipsychotic , quetiapine and a conventional antipsychotic , haloperidol on body mass index ( BMI ) and glycaemic control in patients with schizophrenia previously treated with conventional antipsychotics . Forty-five clinical ly stable patients with schizophrenia participated in this r and omized , investigator-blinded , parallel-group comparison of flexible doses of quetiapine and haloperidol treatment over 52 wk . Primary outcome measures were change from baseline in BMI and glycosylated haemoglobin ( HBA1c ) levels . There were no between-group differences at any of the time-points for BMI ( F = 1.90 , p = 0.1 ) and HBA1c ( F = 1.17 , p = 0.3 ) values , and there were no significant changes in BMI from baseline for either group . HBA1c levels decreased significantly at end-point for the haloperidol group ( -1.5 % , p = 0.04 ) , but not for the quetiapine group ( -0.3 % , p = 0.5 ) . Although the sample was not generally obese ( mean baseline BMI 25.5 + /- 6.3 kg/m2 ) , a large proportion exhibited evidence of abnormal glycaemic control prior to r and omization ( mean HBA1c 6.7 + /- 1.9 % ) , with 48 % having values that were at least mildly elevated ( HBA1c > 6.1 % ) and 19 % markedly elevated ( HBA1c > 7 % ) . The number of subjects with elevated HBA1c values decreased from baseline in both the haloperidol and quetiapine treatment groups . These findings suggest that switching treatment from a conventional antipsychotic to quetiapine is not associated with weight gain or worsening of glycaemic control , even in the long term . The study also highlights the high incidence of unrecognized glucose dysregulation in patients with schizophrenia receiving conventional antipsychotic treatment The authors estimated components of variance and intraclass correlation coefficients ( ICCs ) to aid in the design of complex surveys and community intervention studies by analyzing data from the Health Survey for Engl and 1994 . This cross-sectional survey of English adults included data on a range of lifestyle risk factors and health outcomes . For the survey , households were sample d in 720 postal code sectors nested within 177 district health authorities and 14 regional health authorities . Study subjects were adults aged 16 years or more . ICCs and components of variance were estimated from a nested r and om-effects analysis of variance . Results are presented at the district health authority , postal code sector , and household levels . Between-cluster variation was evident at each level of clustering . In these data , ICCs were inversely related to cluster size , but design effects could be substantial when the cluster size was large . Most ICCs were below 0.01 at the district health authority level , and they were mostly below 0.05 at the postal code sector level . At the household level , many ICCs were in the range of 0.0 - 0.3 . These data may provide useful information for the design of epidemiologic studies in which the units sample d or allocated range in size from households to large administrative areas OBJECTIVE To evaluate the effect of metformin treatment on the risperidone-induced body weight gain in patients . METHODS In a 12-weeks , double-blind , placebo controlled , r and omized trial between October 2006 and October 2007 which was conducted in the Child and Adolescent Psychiatric Consultation Center of Isfahan University of Medical Sciences , 49 patients were entered the study with schizophrenia diagnosis . Then metformin ( 500 mg bid ) or placebo was administrated with risperidone ( 6 mg ) for the patients . Weight , height , and body mass index BMI were measured at the beginning , at 4 weeks , and at 12 weeks of the study . Changes in weight and BMI were evaluated by using repeated measures analysis of variance . RESULTS Seventeen patients were excluded from the study . Repeated measure analysis of variances showed a significant difference between weight and BMI in both metformin ( p<0.001 , p<0.015 ) and placebo group ( p<0.013 , p<0.005 ) . CONCLUSION Metformin treatment did not show a significant effect to control the body weight of patients after 12 weeks BACKGROUND This study compared the efficacy and safety of 4 therapeutically relevant strategies for switching clinical ly stable patients from a conventional antipsychotic drug or risperidone to olanzapine . METHOD Two hundred nine out patients with a DSM-IV diagnosis of schizophrenia or schizo-affective disorder who were clinical ly stable while being treated with a conventional antipsychotic drug or risperidone were openly r and omly assigned to either abrupt or gradual discontinuation of their prior antipsychotic drug . Patients were further r and omly assigned in a double-blind fashion to immediate olanzapine initiation ( olanzapine , 10 mg q.d . for 3 weeks ) or stepwise initiation ( a sequence of 1 week each on placebo ; olanzapine , 5 mg q.d . ; and olanzapine , 10 mg q.d . ) . The efficacy of these 4 switching paradigms was assessed using the Clinical Global Impressions (CGI)-Improvement scale , Patient 's Global Impressions (PGI)-Improvement scale , and Positive and Negative Syndrome Scale ( PANSS ) . Safety assessment s included ratings for extrapyramidal symptoms , cognitive impairment , adverse events , laboratory parameters , weight change , and vital signs . RESULTS The paradigm of gradual antipsychotic drug discontinuation combined with an initial full dose of olanzapine , 10 mg/day , had the most favorable efficacy and tolerability profile overall . By week 3 , the majority of completing patients on all 4 switching paradigms were either improved or clinical ly unchanged ( > 90 % ) . No clinical ly significant differences between switching paradigms were seen in laboratory values or vital signs . CONCLUSION In this study , switching clinical ly stable out patients with a diagnosis of schizophrenia or schizoaffective disorder to olanzapine was most successful when a full therapeutic dose of olanzapine was immediately initiated while gradually discontinuing prior conventional antipsychotic drug or risperidone treatment . Overall , switching was achieved without increased vulnerability to relapse or to occurrence of clinical ly burdensome antipsychotic drug withdrawal symptoms in the majority of patients Background In clinical practice , physicians often need to change the antipsychotic medications they give to patients because of an inadequate response or the presence of unacceptable or unsafe side effects . However , there is a lack of consensus in the field as to the optimal switching strategy for antipsychotics , especially with regards to the speed at which the dose of the previous antipsychotic should be reduced . This paper assesses the short-term results of strategies for the discontinuation of olanzapine when initiating risperidone . Methods In a 6-week , r and omized , open-label , rater-blinded study , patients with schizophrenia or schizoaffective disorder , on a stable drug dose for more than 30 days at entry , who were intolerant of or exhibiting a suboptimal symptom response to more than 30 days of olanzapine treatment , were r and omly assigned to the following switch strategies ( common risperidone initiation scheme ; varying olanzapine discontinuation ) : ( i ) abrupt strategy , where olanzapine was discontinued at risperidone initiation ; ( ii ) gradual 1 strategy , where olanzapine was given at 50 % entry dose for 1 week after risperidone initiation and then discontinued ; or ( iii ) gradual 2 strategy , where olanzapine was given at 100 % entry dose for 1 week , then at 50 % in the second week , and then discontinued . Results The study enrolled 123 patients on stable doses of olanzapine . Their mean age was 40.3 years and mean ( ± st and ard deviation ( SD ) ) baseline Positive and Negative Syndrome Scale ( PANSS ) total score of 75.6 ± 11.5 . All-cause treatment discontinuation was lowest ( 12 % ) in the group with the slowest olanzapine dose reduction ( gradual 2 ) and occurred at half the discontinuation rate in the other two groups ( 25 % in abrupt and 28 % in gradual 1 ) . The relative risk of early discontinuation was 0.77 ( confidence interval 0.61–0.99 ) for the slowest dose reduction compared with the other two strategies . After the medication was changed , improvements at endpoint were seen in PANSS total score ( -7.3 ; p < 0.0001 ) and in PANSS positive ( -3.0 ; p < 0.0001 ) , negative ( -0.9 ; p = 0.171 ) and anxiety/depression ( -1.4 ; p = 0.0005 ) subscale scores . Severity of movement disorders and weight changes were minimal . Conclusion When switching patients from olanzapine to risperidone , a gradual reduction in the dose of olanzapine over 2 weeks was associated with higher rates of retention compared with abrupt or less gradual discontinuation . Switching via any strategy was associated with significant improvements in positive and anxiety symptoms and was generally well tolerated . Trial registration Clinical Trials.gov BACKGROUND This open-label , multicenter , r and omized study compared the efficacy and safety of switching moderately ill Asian patients with schizophrenia from their current regimen of antipsychotic medication to the atypical antipsychotic olanzapine using either a direct switch method or a start-taper switch method . METHOD Asian in patients and out patients with DSM-IV schizophrenia ( N = 108 ) currently treated with predominantly typical antipsychotics were switched to olanzapine ( initial dose of 10 mg/day ) for 6 weeks . Patients were r and omly assigned to 1 of 2 groups : the direct switch group ( N = 54 ) received only olanzapine , while the start-taper switch group ( N = 54 ) received olanzapine and their usual antipsychotic in decreasing doses for the first 2 weeks . A successful switch was defined as completing 6 weeks of therapy without worsening of symptoms ( Clinical Global Impressions-Severity of Illness scale [ CGI-S ] ) or extrapyramidal side effects ( Simpson-Angus Scale ) . Overall efficacy was assessed using the Positive and Negative Syndrome Scale ( PANSS ) , and safety was assessed by recording adverse events and measuring vital signs . RESULTS Statistically significant ( p < .001 ) improvements from baseline to endpoint occurred in both switch groups in the CGI-S score and the PANSS total score and subscores . However , no significant differences were observed between the switch groups for any efficacy measure . Both techniques had comparable rates of successful switching ( direct switch , 74.1 % vs. start-taper switch , 67.9 % ) . The frequency of treatment-emergent adverse events was similar between switch groups with no clinical ly significant differences in any laboratory value or vital sign . Weight gain occurred in both switch groups ( p < .001 ) , but the groups were not statistically different from each other . Both switch groups showed statistically significant ( p < .01 ) improvements from baseline to endpoint on the Simpson-Angus Scale and Barnes Akathisia Scale . CONCLUSION Moderately ill Asian patients with schizophrenia may experience a decrease in symptom severity and improvement in extrapyramidal symptoms when switched from their current medication to olanzapine therapy BACKGROUND The main objective was to assess the efficacy of a weight management program design ed for out patients taking olanzapine for schizophrenia or schizoaffective disorder and to compare these patients with a r and omized control group . The effects of the weight management program were also assessed with regard to safety and quality of life . METHOD Forty-eight patients were enrolled in a 12-week , r and omized , multicenter weight management study . Thirty-three patients were r and omly allocated to an intervention group in which they received olanzapine within a weight management program . Fifteen patients were allocated to a control group in which they were given olanzapine treatment as usual out patients . Weight , body mass index ( BMI ) , and measurements of safety and quality of life were evaluated . The study was conducted from January 7 , 2003 , to September 16 , 2003 . RESULTS Thirty-six patients ( 75 % ) completed this study . We found significant differences in weight ( -3.94 + /- 3.63 kg vs. -1.48 + /- 1.88 kg , p = .006 ) and BMI ( -1.50 + /- 1.34 vs. -0.59 + /- 0.73 , p = .007 ) change from baseline to endpoint between the intervention and control groups , respectively . Significant differences in weight reduction were initially observed at week 8 ( p = .040 ) . No significant differences were found with regard to the safety outcomes . When the ratio of low-density lipoproteins to high-density lipoproteins was calculated , change from baseline was greater in the intervention group than the control group ( -0.19 vs. -0.04 ) , but the difference was not statistically significant ( p = .556 ) . After the completion of the weight management program , there was a trend toward statistical difference in the physical health score changes between the weight management and control groups ( 1.12 in the intervention group vs. -0.93 in the control group , p = .067 ) . CONCLUSION The weight management program was effective in terms of weight reduction in patients with schizophrenia or schizoaffective disorder taking olanzapine and was also found to be safe in terms of psychiatric symptoms , vital signs , and laboratory data . In addition , such a weight management program might improve quality of life in patients with schizophrenia or schizoaffective disorder with respect to their physical well-being Objective To compare the long-term efficacy and safety of aripiprazole with olanzapine in patients with either acute relapsing or chronic , stable schizophrenia . Material s and methods A 52-week , open-label extension to a 26-week , multicenter , r and omized , double-blind , placebo-controlled trial in patients with chronic schizophrenia . Patients who completed the initial treatment or who met the protocol definition of relapse after ≥2 weeks of double-blind treatment were r and omized to aripiprazole ( 15–30 mg/day , n = 104 ) or olanzapine ( 10–20 mg/day , n = 110 ) for 52 weeks . Results Sixty-nine percent of patients completed the study . Efficacy improvements were similar between groups at endpoint , mean reductions in Positive and Negative Syndrome Scale ( PANSS ) Total scores from baseline for patients completing the study ( observed cases ) were similar in chronic stable patients ( aripiprazole , −7.94 ; olanzapine , −7.36 ) and in patients with acute relapse ( aripiprazole , −31.19 ; olanzapine , −29.55 ) . Olanzapine-treated patients reported more extrapyramidal symptoms (EPS)-related adverse events ( 18 % ) than aripiprazole-treated patients ( 10 % ) . No significant differences in EPS were seen between treatments at endpoint . Olanzapine was associated with significantly greater weight gain than aripiprazole at all time points ( week 52 [ LOCF ] : + 2.54 vs + 0.04 kg ; p < 0.001 ) . Changes in fasting glucose and lipid levels at endpoint favored aripiprazole over olanzapine , with significant differences observed for total cholesterol , low- and high-density lipoprotein . While differences observed for changes in fasting glucose and triglycerides favored aripiprazole , they were not statistically significant . Conclusion Aripiprazole showed similar efficacy to olanzapine for long-term treatment of acutely psychotic and chronic , stable schizophrenia patients , with a lower liability for weight gain or increased lipid levels To measure the long-term changes in weight and plasma lipids after switching antipsychotic treatment to ziprasidone , three 52-week , open-label extension studies of ziprasidone in out patients ( N=185 ) with schizophrenia or schizoaffective disorder successfully completing one of three , 6-week switch studies were carried out . Pre-switch treatment consisted of risperidone ( n=43 ) , olanzapine ( n=71 ) , or conventional antipsychotic agents ( n=71 ) . The maximum length of exposure to ziprasidone was 58 weeks . Nonfasting total cholesterol and triglyceride levels were obtained at baseline and at weeks 6 , 19 , 32 , 45 , and 58 . Weight was measured at baseline and during each follow-up visit ; height was recorded at baseline for the purpose of body mass index ( BMI ) calculation . Efficacy measures included the Positive and Negative Syndrome Scale and Clinical Global Impression — Severity scale which were obtained at baseline and major follow-up points . Clinical ly significant sustained improvements in weight , BMI , total cholesterol , and triglyceride levels were observed among patients switched to ziprasidone from risperidone or olanzapine . Switching from conventional antipsychotics was not associated with significant changes in weight and lipid parameters . Mean reductions in weight from baseline to study endpoint were 9.8 kg ( p<0.001 ) and 6.9 kg ( p<0.005 ) for patients previously treated with olanzapine and risperidone , respectively . These findings demonstrate that switching from risperidone or olanzapine to ziprasidone is associated with sustained , clinical ly significant improvements in weight and plasma lipids This open-label , prospect i ve , 4-month study in hyperprolactinemic patients with schizophrenia explored whether prolactin levels decrease after switching antipsychotic therapy to olanzapine . A secondary objective was to determine if reproductive morbidities and sexual dysfunction occurring with hyperprolactinemia improved with prolactin normalization . Clinical ly stable patients with schizophrenia , who had hyperprolactinemia defined as > 18.8 ng/ml for males and > 24.2 ng/ml for females , were r and omized to : remain on current therapy ( n=27 ) or switch to olanzapine , 5 - 20 mg/day , ( n=27 ) . Baseline prolactin levels in female patients r and omized to receive olanzapine ( n=14 ) were 66.3+/-38.7 ng/ml and were 82.0+/-37.6 ( p=.32 ) in those remaining on their pre- study antipsychotic medication ( n=14 ) . In male patients , baseline prolactin levels were 33.7+/-12.1 and 33.5+/-13.8 ng/ml ( p=.97 ) , respectively , for those r and omized to olanzapine ( n=13 ) or remaining on pre- study treatment ( n=13 ) . At study end , patients switched to olanzapine experienced significant reductions in mean serum prolactin levels of 19.8+/-18.1 ng/ml in males ( p=.02 ) , and 32.3+/-47.5 ng/ml in females ( p=.01 ) , but prolactin continued to be elevated in patients who remained on pre- study antipsychotic treatment . After switching to olanzapine treatment , male patients experienced significantly ( p=.03 ) increased free testosterone levels but there were no significant improvements in total testosterone levels ; some female patients experienced improved menstrual cycling , as well as resolution of galactorrhea and gynecomastia , and sexual functioning was significantly improved in both genders . Patients switched to olanzapine , as well as those remaining on their pre- study medication , maintained clinical stability , their symptoms continued to improve , although there were no significant between-treatment differences in improvement . Treatment-emergent adverse events did occur in both treatment groups ; however , they were not significantly different between groups . Olanzapine-treated patients experienced significantly lower eosinophil counts and higher elevations in low-density lipoproteins and st and ing blood pressure than non-switched patients . Olanzapine treatment may offer sustained reduction in serum prolactin and improvement in sexual and reproductive comorbid symptoms in patients with schizophrenia who have treatment-emergent hyperprolactinemia Rationale Search for safe and effective strategies to diminish weight gain associated with second generation antipsychotics ( SGAs ) is imperative . In the present study , we sought to replicate our preliminary findings , which indicated that coadministration of the selective norepinephrine reuptake inhibitor reboxetine attenuates olanzapine-induced weight gain . Material s and method Fifty-nine patients hospitalized for first-episode DSM-IV schizophrenic disorder participated in this r and omized double-blind study . Reboxetine ( 4 mg/day ; 31 patients ) or placebo ( 29 patients ) was coadministered with olanzapine ( 10 mg/day ) for 6 weeks . Analysis was by intention-to-treat . Results Nine patients in each group prematurely discontinued the trial . Olanzapine/reboxetine-treated patients showed a significantly lower increase in body weight ( mean = 3.31 kg , SD = 2.73 ) than their olanzapine/placebo-treated counterparts ( mean = 4.91 kg , SD = 2.45 ) . Significantly fewer olanzapine/reboxetine-treated patients gained at least 7 % of their initial weight , the cutoff for clinical ly significant weight gain ( 6 [ 19.4 % ] of 31 patients vs 13 [ 46.4 % ] of 28 patients ) . Seven ( 22.6 % ) olanzapine/reboxetine-treated patients compared to only one patient ( 3.6 % ) in the olanzapine/placebo group revealed no weight change or even modest weight loss . Appetite increase was significantly lower in the olanzapine/reboxetine than olanzapine/placebo group and was correlated with attenuation of weight gain . Reboxetine addition was safe and well tolerated . Conclusions The results confirm that coadministration of reboxetine promotes a clinical ly meaningful attenuation of olanzapine-induced weight gain in schizophrenia patients . If substantiated in long-term studies , along with behavioral management and diet counseling , reboxetine may have a clinical utility in controlling SGA-induced weight gain OBJECTIVE The purpose of this study was to assess the efficacy of metformin in preventing olanzapine-induced weight gain . METHOD Forty patients with schizophrenia were r and omly assigned to treatment for 12 weeks with olanzapine , 15 mg/day , plus metformin , 750 mg/day ( N=20 ) , or olanzapine , 15 mg/day , plus placebo ( N=20 ) . This investigation was conducted in a double-blind fashion . Planned assessment s included body weight , body mass index , proportion of patients who gained more than 7 % of their baseline weight at the end of the 12-week treatment , waist circumference , waist-to-hip ratio , fasting glucose and insulin , insulin resistance index , and scores on the Scale for the Assessment of Positive Symptoms ( SAPS ) and Scale for the Assessment of Negative Symptoms ( SANS ) . RESULTS Of the 40 patients who were r and omly assigned , 37 ( 92.5 % ) completed treatments . The weight , body mass index , waist circumference , and waist-to-hip ratio levels increased less in the olanzapine plus metformin group relative to the olanzapine plus placebo group during the 12-week follow-up period . The insulin and insulin resistance index values of the olanzapine plus placebo group increased significantly at weeks 8 and 12 . In contrast , the insulin and insulin resistance index levels of the olanzapine plus metformin group remained unchanged . Significantly fewer patients in the olanzapine plus metformin group relative to patients in the olanzapine plus placebo group increased their baseline weight by more than 7 % , which was the cutoff for clinical ly meaningful weight gain . There was a significant decrease in SAPS and SANS scores within each group from baseline to week 12 , with no between-group differences . Metformin was tolerated well by all patients . CONCLUSIONS Metformin was effective and safe in attenuating olanzapine-induced weight gain and insulin resistance in drug-naive first-episode schizophrenia patients . Patients displayed good adherence to this type of preventive intervention OBJECTIVE St and ardized mortality rates are elevated in schizophrenia compared to the general population . The incidence of coronary heart disease ( CHD ) and the relative contribution of CHD to increased mortality in schizophrenia patients are not clear , despite recent concerns about metabolic complications of certain atypical antipsychotics . METHOD Ten-year risk for CHD was calculated for 689 subjects who participated in the Clinical Trials of Antipsychotic Treatment Effectiveness ( CATIE ) Schizophrenia Trial at baseline using the Framingham CHD risk function and were compared with age- , race- and gender-matched controls from the National Health and Nutrition Examination Survey ( NHANES ) III . RESULTS Ten-year CHD risk was significantly elevated in male ( 9.4 % vs. 7.0 % ) and female ( 6.3 % vs. 4.2 % ) schizophrenia patients compared to controls ( p = 0.0001 ) . Schizophrenia patients had significantly higher rates of smoking ( 68 % vs. 35 % ) , diabetes ( 13 % vs. 3 % ) , and hypertension ( 27 % vs. 17 % ) and lower HDL cholesterol levels ( 43.7 vs. 49.3 mg/dl ) compared to controls ( p < 0.001 ) . Only total cholesterol levels did not differ between groups . Ten-year CHD risk remained significantly elevated in schizophrenia patients after controlling for body mass index ( p = 0.0001 ) . CONCLUSIONS These results are consistent with recent evidence of increased cardiac mortality in schizophrenia patients . While the impact of cigarette smoking is clear , the relative contributions to cardiac risk of specific antipsychotic agents , diet , exercise , and quality of medical care remain to be clarified OBJECTIVE Undesirable metabolic effects of modern antipsychotics , especially clozapine and olanzapine , merit development of new weight-control strategies , including pharmacologic ones . We investigated the feasibility of treatment with orlistat , a weight-control drug with no central effects , for overweight/obesity in clozapine- or olanzapine-treated male and female patients . METHOD Add-on orlistat was prescribed for 16 weeks in a r and omized , double-blind , placebo-controlled clinical trial to patients who were receiving stable clozapine or olanzapine medication and were aged 18 to 65 years , with no compliance with nonpharmacologic programs or hypocaloric diet required . The primary efficacy variable was body weight change . The study was conducted from 2004 through 2005 . RESULTS Of 71 r and omly assigned subjects , 63 were eligible for modified intent-to-treat analysis . While no statistically significant effect was observed in the whole population , male ( but not female ) patients benefited from treatment with orlistat ( -2.36 kg vs. 0.62 kg on placebo , p = .011 ) . There were 5 responders ( 16.1 % ) ( those with > or= 5 % weight loss ) that received orlistat versus 2 responders ( 6.3 % ) that received placebo ( number needed to treat = 11 ) , but the difference was not statistically significant . CONCLUSIONS Without a hypocaloric diet , the effect of orlistat in overweight/obese clozapine-or olanzapine-treated patients is modest and may only be seen in men . More studies should define the optimal length of treatment and feasibility of combination of orlistat with behavioral programs in this population BACKGROUND Many out patients with schizophrenia experience persistent symptoms or side effects on their current antipsychotic regimen . Few studies have prospect ively examined the effects of the prior medication or switching method on the safety and efficacy of a newly available antipsychotic . Efficacy and tolerability of ziprasidone were evaluated in patients with DSM-IV schizophrenia or schizoaffective disorder who were switched from conventional or atypical antipsychotics in three 6-week , multicenter , r and omized , open-label , parallel-group trials . METHOD Stable out patients with persistent symptoms or troublesome side effects on ( 1 ) conventional antipsychotic ( N = 108 ) , ( 2 ) olanzapine ( N = 104 ) , or ( 3 ) risperidone ( N = 58 ) therapy were switched to an open-label , 6-week , flexible-dose trial of ziprasidone ( 40 - 160 mg/day ) . Patients were r and omly assigned at baseline to 1 of 3 switching schedules during the first week of ziprasidone therapy . Baseline and outcome assessment s included Positive and Negative Syndrome Scale ( PANSS ) and Clinical Global Impressions of Severity ( CGI-S ) ratings . RESULTS All 3 switching strategies were well tolerated for all 3 patient groups . After 6 weeks on ziprasidone therapy , significant ( p < .05 ) improvements were observed on all major symptom measures and almost all subscales for all switched subgroups . CONCLUSION Switching stable but symptomatic out patients from their previous antipsychotic to ziprasidone was generally well tolerated and was associated with symptom improvements 6 weeks later . Improvements occurred in patients recently on other first-line atypical antipsychotic , as well as in those on conventional antipsychotic , treatment . While limitations of switching study design s do not permit interpretation of comparative efficacy , these studies suggest that out patients who partially respond to conventional antipsychotics , risperidone , or olanzapine may experience improved control of psychotic symptoms following a switch to ziprasidone Side effect and health status changes were measured in 3 studies in which out patients experiencing suboptimal efficacy or tolerability with their current antipsychotic were switched to 6 weeks of open-label ziprasidone . The studies differed only in the patient ’s prior antipsychotic ; 1 study group was on olanzapine ( n = 104 ) , a second on risperidone ( n = 58 ) , and third on a conventional antipsychotic ( n = 108 ) . Baseline and end point health status measures included weight and height , nonfasting cholesterol , and triglyceride levels , prolactin levels , and extrapyramidal side effects . Improvements in health indices and side effects were seen among all 3 groups , but the specific benefits depended on the preswitch antipsychotic . For example , patients switched from olanzapine experienced a mean weight loss of 1.76 kg ( P < 0.0001 ) , those switched from risperidone had a lesser reduction in weight ( −0.86 kg ; P = 0.015 ) , and those switched from conventionals had a nonsignificant increase ( + 0.27 kg ; P = 0.3 ) . Prolactin levels decreased among those switched from risperidone ( P < 0.0001 ) or conventionals ( P = 0.05 ) , but not for patients switched from olanzapine . EPS improved among those switched from conventionals ( P < 0.0001 ) and to a lesser extent among those switched from risperidone ( P < 0.01 ) , but not in those changed from olanzapine ( NS ) . Thus , in these studies , switching to ziprasidone in patients with continuing symptoms or side effects on their current medication was often associated with improved health status indices , lowered prolactin levels , or less EPS , with the magnitude benefit consistent with the known side-effect profile of the preswitch antipsychotic BACKGROUND Patients with chronic schizophrenia ( DSM-IV criteria ) often receive depot antipsychotic medications to assure longer administration and better compliance with their treatment regimen . This study evaluated whether patients stabilized on depot antipsychotic medication could be successfully transitioned to oral olanzapine . METHOD In a 3-month open-label study , 26 clinical ly stable patients with schizophrenia taking depot antipsychotics for over 3 years were r and omly assigned to continue on their current depot dose or to switch to oral olanzapine . Clinical ratings ( Positive and Negative Syndrome Scale [ PANSS ] , Global Assessment of Functioning [ GAF ] scale , and Clinical Global Impressions [ CGI ] scale ) and side effect parameters ( Abnormal Involuntary Movement Scale [ AIMS ] , Barnes Akathisia Scale , AMDP-5 scale , vital signs , and weight ) were obtained monthly . RESULTS Oral olanzapine patients ( N = 13 ) demonstrated significant clinical improvement over the depot control group ( N = 13 ) from baseline to 3-month endpoint ( PANSS total , p = .012 ; PANSS general , p = .068 ; PANSS negative , p = .098 ; CGI-Improvement , p = .007 ; CGI-Severity , p = .026 ; GAF , p = .015 ) . Side effect rating scales showed no statistical differences between the 2 groups ( AIMS , Barnes Akathisia Scale , AMDP-5 , vital signs ) . The depot control group showed no statistical superiority in any measure except weight change ( p = .0005 ) . After 3 months , all olanzapine patients preferred olanzapine to their previous depot medications and chose to continue on olanzapine treatment . CONCLUSION Clinicians may expect clinical improvement when switching chronically psychotic patients from traditional depot antipsychotic drugs to oral olanzapine . Switching may be completed within a 4-week period with relative compliance being maintained and patients preferring oral olanzapine to their previous depot medications BACKGROUND We conducted exploratory analyses of the data from a multinational , r and omised study to identify factors associated with weight change after 16 weeks of treatment with st and ard olanzapine tablets ( SOT ) or sublingual orally disintegrating olanzapine ( ODO ) . METHODS One hundred and forty nine out patients who gained weight during prior SOT therapy were enrolled into the study and treated with ODO ( N = 84 ) or SOT ( N = 65 ) . Exploratory analyses were conducted with the subset of compliant patients ( ODO : n = 60 ; SOT : n = 47 ) . RESULTS The decrease in the rate of weight gain at the end of study therapy ( change from baseline ) was greater in the ODO group than the SOT group ( -0.59 kg/week vs. -0.38 kg/week , p = 0.0246 ) . Age was negatively associated with weight change ( p = 0.0203 ) in both treatment groups combined : patients gained 0.7 kg less for every 10 years of age . The least squares mean weight gain was lower with ODO than SOT in male patients ( 0.35 kg vs. 3.04 kg , p = 0.061 ) , but not female patients and in American patients ( 0.55 kg vs. 6.21 kg , p < 0.0001 ) , but not Canadian or Mexican patients . CONCLUSIONS Although not conclusive , these data suggest that ODO may be a reasonable treatment option for some patients who gain weight with SOT . Further research is required to confirm these findings The second generation antipsychotics clozapine and olanzapine are known to cause weight gain . However , only clozapine is associated with drug-induced fever . Cytokines have been linked to the induction of both weight gain and drug-induced fever . We investigated these potential side effects of clozapine and olanzapine and studied their differential effects on cytokine secretion . Thirty patients suffering from schizophrenia , schizophreniform disorder or schizoaffective disorder were treated with either clozapine ( mean modal dose : 266.7+/-77.9 mg ) or olanzapine ( 21.2+/-2.5 mg ) in a r and omized , double-blind , 6-week study . Body mass index ( BMI ) , tympanic temperature , and plasma levels of leptin and cytokines ( tumor necrosis factor-alpha ( TNF-alpha ) , soluble TNF receptor 1 and 2 ( sTNFR-1/2 ) , soluble interleukin-2 receptors ( sIL-2R ) , interleukin-6 ) were determined weekly . BMI , leptin and cytokines significantly increased over time , except interleukin-6 and sTNFR-1 in the olanzapine group . All cytokines numerically increased compared to baseline already during the first week of treatment in both groups . Leptin , TNF-alpha , sTNFR-1 , sTNFR-2 and sIL-2R levels correlated with the BMI . Five patients who received clozapine ( 33 % ) developed drug-induced fever ( > /=38 degrees C ) . In these , interleukin-6 peak levels were significantly ( p<0.01 ) higher than in those patients treated with clozapine who did not develop fever . In conclusion , increase of BMI appears to be related to clozapine 's and olanzapine 's similar effects on cytokine systems , whilst drug-induced fever appears to be related to clozapine 's differential effects on interleukin-6 Many antipsychotic medications carry a substantial liability for weight gain , and one mechanism common to all antipsychotics is binding to the dopamine D2 receptor . We therefore examined the relationship between -141C Ins/Del ( rs1799732 ) , a functional promoter region polymorphism in DRD2 , and antipsychotic-induced weight gain in 58 first episode schizophrenia patients enrolled in a r and omized trial of risperidone versus olanzapine . Carriers of the deletion allele ( n=29 ) were compared with Ins/Ins homozygotes ( noncarriers , n=29 ) in a mixed model encompassing 10 weight measurements over 16 weeks . Deletion allele carriers showed significantly more weight gain after 6 weeks of treatment regardless of assigned medication . Although deletion carriers were prescribed higher doses of olanzapine ( but not risperidone ) , dose did not seem to account for the genotype effects on weight gain . Given earlier evidence that deletion carriers show reduced symptom response to medication , additional study of appropriate treatment options for these patients seems warranted Individuals with severe and persistent mental illness ( SPMI ) have a preponderance of weight problems , possibly even greater than the obesity epidemic in the general population . Although atypical antipsychotics cause weight gain , their contribution to obesity has not been characterized in a community setting where individuals may take multiple psychotropics associated with weight gain . Using survey information including measured height and weight from a r and om sample of Maryl and Medicaid recipients with SPMI , we compared obesity prevalence to the National Health and Nutrition Examination Survey ( NHANES III ) sample and a Maryl and sample ( Behavioral Risk Factor Surveillance System ) of the general population adjusted to SPMI demographic characteristics . We investigated correlates of obesity in the SPMI sample . The results indicate that both men and especially women with SPMI had a higher prevalence of obesity than the general population ; this portends substantial health implication s. A fourfold association between atypical antipsychotics and prevalent obesity was found in men but not in women ; further work should clarify mechanisms of obesity in the SPMI BACKGROUND Obesity is common in persons with schizophrenia . Besides its adverse health effects , obesity reduces quality of life and contributes to the social stigma of schizophrenia . METHOD This 14-week , multicenter , open-label , rater-blinded , r and omized study evaluated the effects of a group-based behavioral treatment ( BT ) for weight loss in overweight and obese stable patients with DSM-IV schizophrenia or schizoaffective disorder who had been switched from olanzapine to risperidone . Participants were r and omly assigned to receive BT or usual clinical care ( UC ) . BT included 20 sessions during which patients were taught to reduce caloric intake . In UC , patients were encouraged to lose weight but received no special advice about weight reduction . The primary outcome measure was change in body weight . RESULTS Seventy-two patients were enrolled . The mean + /- SD weight loss at endpoint was significant in both groups ( p < .05 ) and numerically greater in patients receiving BT than in those receiving UC ( -2.0 + /- 3.79 and -1.1 + /- 3.11 kg , respectively ) . More patients in the BT group than in the UC group had lost > or = 5 % of their body weight at endpoint ( 26.5 % [ 9/34 ] and 10.8 % [ 4/37 ] , respectively ; p = .082 ) . A post hoc analysis of patients attending at least 1 BT session showed that significantly more patients in the BT than the UC group had lost > or = 5 % of their body weight at endpoint ( 32.1 % [ 9/28 ] vs. 10.8 % [ 4/37 ] , respectively , p = .038 ) and at week 14 ( complete population ; 40.9 % [ 9/22 ] and 14.3 % [ 4/28 ] , respectively , p = .027 ) . CONCLUSION BT may be an effective method for weight reduction in patients with chronic psychotic illness OBJECTIVE Major mental disorders are associated with an increased risk for obesity-related cardiovascular mortality , leading to interest in risk-reduction approaches that target weight and risk-related plasma lipids , including use of antipsychotic agents with low metabolic risk . This multicenter , r and omized , double-blind study compared the metabolic effects of aripiprazole versus olanzapine in overweight persons with schizophrenia or schizoaffective disorder who were previously on olanzapine treatment . METHOD In total , 173 subjects with DSM-IV-TR-defined schizophrenia or schizoaffective disorder were r and omly assigned to receive aripiprazole ( N = 88 ) or olanzapine ( N = 85 ) for 16 weeks in a study conducted from March 30 , 2004 , to August 8 , 2006 . Primary and secondary endpoints were mean weight change from baseline and percentage change from baseline in fasting triglyceride levels , respectively . RESULTS At week 16 , weight decreased significantly with aripiprazole versus olanzapine ( -1.8 vs. + 1.41 kg ; p < .001 ) . Significant differences in percentage change in triglyceride levels were observed with aripiprazole ( decreases ) versus olanzapine ( increases ) at all time-points . In addition , significantly more subjects receiving aripiprazole had clinical ly relevant ( > or = 7 % ) weight loss versus olanzapine ( 11.1 % vs. 2.6 % ; p = .038 ) , and a lower percentage of subjects receiving aripiprazole had clinical ly relevant weight gain ( 2.5 % vs. 9.1 % ; p = .082 ) . Mean percentage changes in fasting total cholesterol and high-density lipoprotein cholesterol at week 16 were significantly different with aripiprazole versus olanzapine , with no significant effects on glycemic laboratory measures . Mean Clinical Global Impressions-Improvement ( CGI-I ) scores for both groups were in the range of " no change " to " minimal improvement . " CGI-I endpoint scores were statistically significantly better with olanzapine ( mean + /- SE = 3.09 + /- 0.16 ) versus aripiprazole ( mean + /- SE = 3.74 + /- 0.15 ; p < .001 ) , and more subjects discontinued aripiprazole ( N = 32/88 ; 36 % ) than olanzapine ( N = 22/85 ; 26 % ) . CONCLUSION Significant improvements in weight and lipids observed during discontinuation of olanzapine and switch to aripiprazole treatment occurred with limited evidence of negative psychiatric effects , relative to uninterrupted continuation of olanzapine treatment . The results suggest that the potential value of therapeutic substitutions involving specific antipsychotic medications should be considered in overall efforts to reduce cardiovascular risk in this population The objective of the study was to examine whether patients with schizophrenia who were judged to be stable on long-term treatment with conventional antipsychotic medications would further benefit from a switch to an atypical antipsychotic drug . Thirty-six subjects with schizophrenia spectrum disorder , on conventional antipsychotic medication therapy for at least 2 years , were r and omized in double-blind fashion to risperidone versus olanzapine . Patients were titrated up to 6 mg risperidone or 15 mg olanzapine as tolerated , followed by tapering and discontinuation of conventional antipsychotic medication . Atypical antipsychotic agents were then administered alone ( monotherapy ) for 12 weeks . Efficacy and tolerability were assessed using the Positive and Negative Syndrome Scale ( PANSS ) , Clinical Global Impression Scale , and Simpson Angus Scale . Body weight was measured at each visit . Both treatment groups exhibited marked and similar improvement in the total PANSS score from baseline to study endpoint ( 22 weeks ) [ risperidone : baseline=59.3 ( SE 3.1 ) , 22 weeks=44.3 ( SE 2.3 ) ( p<0.001 ) ; olanzapine : baseline=55.9 ( SE 3.3 ) , 22 weeks=46.9 ( SE 3.2 ) ( p<0.001 ) . Both groups also exhibited significant reductions in PANSS factor scores for positive and negative symptoms and disorganized thoughts . Only risperidone-treated patients exhibited significant decreases in uncontrolled hostility/excitement and anxiety and depression . Of note , while positive factor scores exhibited the majority of change within the first 10 weeks , negative factor scores continued to decline significantly in both treatment groups throughout the study . Tolerability assessment s did not differ between groups . The results indicate that both atypical antipsychotic medications provided significant additional improvement in symptom severity in patients with schizophrenia previously on conventional antipsychotic agents OBJECTIVE Atypical antipsychotics induce weight gain and are linked to increased diabetes risk , but their relative impact on factors that elevate disease risk are unknown . METHODS We performed a 6-month , r and omized , double-blind study to evaluate the effects of risperidone and olanzapine in patients with schizophrenia . At baseline and weeks 6 and 24 , we quantified : ( 1 ) total adiposity by DEXA , ( 2 ) visceral adiposity by abdominal CT , and ( 3 ) insulin sensitivity ( SI ) and ( 4 ) pancreatic function ( " disposition index " , DI ) by intravenous glucose tolerance test . RESULTS At baseline , groups ( risperidone : n=28 ; olanzapine : n=31 ) were overweight or obese by body mass index ( risperidone : 28.4+/-5.4 , olanzapine : 30.6+/-7.0kg/m2 ) . Both drugs induced weight gain ( p<0.004 ) . Total adiposity was increased by olanzapine at 6 weeks ( p=0.0006 ) and by both treatments at 24 weeks ( p<0.003 ) . Visceral adiposity was increased by olanzapine and risperidone by 24 weeks ( p<0.003 ) . S(I ) did not deteriorate appreciably , although a downward trend was observed with risperidone . Given known ethnic differences in adiposity and S(I ) , we performed secondary analysis in African American and Hispanic subjects . In this subset , olanzapine exp and ed both total and visceral adiposity ( p<0.02 ) ; no increase was observed with risperidone . There were modest downward trends for SI with both treatments . By week 24 , olanzapine-treated subjects exhibited diminished DI ( p=0.033 ) , indicating inadequate pancreatic compensation for insulin resistance . CONCLUSIONS This is the first prospect i ve study in psychiatric patients that quantified antipsychotic effects on the multiple metabolic processes that increase diabetes risk . Results indicate that ethnic minorities may have greater susceptibility to antipsychotic-induced glucoregulatory complications BACKGROUND There is little information about weight gain induced by antipsychotics at long-term . OBJECTIVE To quantify the weight gain induced by first ( haloperidol ) and second generation antipsychotics ( olanzapine and risperidone ) in a cohort of drug-naïve subjects after 1 year of treatment . METHODS This is a prospect i ve , r and omized clinical trial , including a representative sample of first episode psychotic incident cases from a population area of 555.000 people . The main outcome measures were changes in body weight and body mass index at 3 months and at 12 months . Both a per protocol analysis and an intention to treat analysis were conducted . RESULTS A total of 164 drug-naïve patients were included . At 12 months 144 patients were evaluated . Of them , 66 % completed the protocol and 34 % needed treatment switch . We found statistically significant differences in weight gain at 3 months : 3.8 kg ( + /-4.1 ) for haloperidol , 5.9 kg ( + /-5.1 ) for risperidone and 8.4 kg ( + /-5.0 ) for olanzapine ( F=7.045 ; p=0.002 ) . After 1 year the difference in weight gain had disappeared : 9.7 kg ( + /-5.7 ) for haloperidol , 8.9 kg ( + /-8.8 ) for risperidone and 10.9 kg ( + /-7.2 ) for olanzapine ( F=0.817 ; p=0.445 ) . CONCLUSIONS Drug-naïve patients experience an extraordinary weight gain after 1 year of treatment with haloperidol , olanzapine or risperidone . The main difference among these treatments is the pattern of weight gain but not the final amount of weight gain Objectives of the study were to evaluate the relationship between olanzapine plasma concentrations and efficacy , prolactin , and weight and to assess effects of smoking , sex , and race on the pharmacokinetic characteristics of oral olanzapine up to 40 mg/d . Patients were r and omly allocated to olanzapine 10 , 20 , or 40 mg/d for 8 weeks . Olanzapine concentrations in 634 sample s from 380 patients were analyzed . Mean sample collection time was approximately 15 hours after dose for all groups . Mean olanzapine concentrations were 19.7 ± 11.4 , 37.9 ± 22.8 , and 74.5 ± 43.7 ng/mL for 10- , 20- , and 40-mg doses , respectively . Olanzapine concentration and Positive and Negative Syndrome Scale improvement were not significantly correlated . Change in both weight and prolactin showed significant dose response . Prolactin concentration was correlated with olanzapine concentration ( r = 0.46 , P < 0.001 ) . No significant correlation between olanzapine concentration and weight change was observed . Olanzapine concentrations were lower in self-reported smokers ( 16.5 ± 9.6 , 34.2 ± 20.8 , and 60.9 ± 34.6 ng/mL ) than in self-reported nonsmokers ( 25.6 ± 12.3 , 43.4 ± 24.7 , and 113.2 ± 44.0 ng/mL ) for 10- , 20- , and 40-mg doses , respectively ( P ≤ 0.022 ) . In the 40-mg group only , African Americans had a lower mean olanzapine concentration than whites ( 65.6 ± 44.1 and 84.8 ± 44.1 ng/mL , respectively , P = 0.048 ) . Women had numerically but not significantly higher mean olanzapine concentrations than men . In conclusion , olanzapine pharmacokinetics of doses up to 40 mg/d was generally consistent with prior findings in studies with fewer subjects and /or lower doses Objective : To evaluate the efficacy of olanzapine compared with risperidone in negative symptoms , after 1 year of treatment , in schizophrenic out patients with prominent negative symptoms . Methods : This was a multicenter , r and omized , monitored , open-label , parallel , dose-flexible , 1-year study of out patients with schizophrenia ( Diagnostic and Statistical Manual of Mental Disorders , Fourth Edition criteria ) with prominent negative symptoms ( Scale for the Assessment of Negative Symptoms [ SANS ] summary score > 10 ) previously treated with conventional antipsychotics . Patients were r and omly assigned to treatment with an initial dose of olanzapine 10 mg/d or more ( n = 120 ) or risperidone 3 mg/d or more ( n = 115 ) . The primary efficacy measure was the SANS summary score . Secondary efficacy measures included Scale for the Assessment of Positive Symptoms , Clinical Global Impression of Severity Scale , Calgary Depression Scale , and Social Functioning Scale . The response rate was defined as 30 % or more of improvement in the SANS summary score . Results : The mean dose throughout the study was 12.2 mg/d ( ±5.8 mg/d ) for olanzapine and 4.9 mg/d ( ±2.0 mg/d ) for risperidone . At 1 year , olanzapine patients showed significantly higher improvement than risperidone patients on the SANS summary ( P = 0.015 ) and on the affective flattening ( P = 0.007 ) and avolition/apathy ( P = 0.028 ) SANS subscales . There were also significant improvements in favor of olanzapine in the Scale for the Assessment of Positive Symptoms summary ( P = 0.021 ) , Clinical Global Impression of Severity ( P = 0.008 ) , and Social Functioning Scale total ( P < 0.001 ) scores . The response rate was greater ( P = 0.001 ) in the olanzapine cohort ( 69.2 % ) than in the risperidone cohort ( 48.7 % ) . Olanzapine patients reported less extrapyramidal side effects but a higher incidence of clinical ly important body weight increase than risperidone patients . Conclusions : Long-term treatment with olanzapine was associated with significantly better improvement in negative symptoms as compared with risperidone-treated schizophrenic out patients with prominent negative symptoms INTRODUCTION The aim of this study was to evaluate the efficacy of a psychoeducational program ( PEP ) for weight control in patients who had experienced an increase of body weight during treatment with olanzapine . METHODS Eligible patients were r and omised to the PEP ( Group 1 ) or to no intervention ( Group 2 ) and continued on olanzapine . After 12 weeks , the PEP was also started in Group 2 and continued in Group 1 , up to week 24 . Body weight was measured every month . Other measures included quality of life , and change in plasma glucose and lipids levels . RESULTS Patients in Group 1 ( n=15 ) had a mean weight loss of 3.6 kg at week 12 and 4.5 kg at week 24 ( p<0.01 at both times , p<0.01 between groups at week 12 ) , while those in Group 2 ( n=18 ) had no changes at week 12 and a significant weight loss at week 24 ( -3.6 kg from week 12 , p<0.01 ) . Changes of BMI paralleled those of body weight . Quality of life ( Q-LES-Q-SF categorisation ) and functioning ( GAF ) significantly improved in the total population at endpoint ( p<0.01 ) . No significant changes were observed in fasting glucose and lipid profile , while insulin levels significantly decreased from baseline to endpoint in both groups ( p<0.05 ) . HOMA index and hepatic insulin sensitivity improved , too . DISCUSSION Patients with increased BMI during treatment with olanzapine experienced significant weight and BMI loss following a structured psychoeducational program Schizophrenic patients commonly suffer weight gain , which is often associated with widely prescribed antipsychotic medicines . It is distressing to most patients who experience it and may affect their response to treatment of schizophrenia . Weight gain is also associated with treatment noncompliance and several medical conditions . This study explored the efficacy and tolerability of topiramate as an adjuvant treatment of patients with schizophrenia who were carrying excess weight . In this 12-week , r and omized , placebo-controlled prospect i ve study , 66 hospitalized patients with schizophrenia who were carrying excess weight were given topiramate at doses of 100 mg/day or 200 mg/day , or a placebo . The primary measures made were body weight , body mass index , waist measurement , hip measurement , and waist-to-hip ratio . Safety measures included physical examinations and the monitoring of adverse effects , clinical laboratory data , and vital signs . The Clinical Global Impression-Severity of Illness scale ( CGI-S ) and the Brief Psychiatric Rating Scale ( BPRS ) were used to quantify changes in schizophrenic symptoms and signs . In the 200-mg/day topiramate group , body weight , body mass index , waist measurement , and hip measurement decreased significantly compared with the 100-mg/day topiramate and placebo groups over 12 weeks . However , the waist-to-hip ratio did not change in any group . Scores on the CGI-S and BPRS decreased significantly over the 12-week period in both topiramate groups , but the decrease was not clinical ly meaningful . These results suggest that a higher dose of topiramate is efficacious as an adjuvant treatment of patients with schizophrenia experiencing excess weight gain . Further clinical research is required to establish guidelines for the use of topiramate as an antiobesity agent in schizophrenic patients Significant weight gain is a side effect associated with olanzapine treatment in some patients . We investigated the efficacy of high-dose fluoxetine as a weight-reducing agent for patients who develop early weight gain with olanzapine treatment . Patients that gained ⩾3 % of their baseline weight in the initial 8 weeks of olanzapine treatment ( n=31 ) were r and omized to double-blind treatment with placebo or fluoxetine ( 60 mg/day ) . Clinical , weight , and weight-related measures were assessed . Fluoxetine failed to demonstrate weight-reducing effects ( fluoxetine group : baseline mean 80.5 kg , SD=19.1 , last mean=83.5 kg , SD=19.8 ; placebo group : baseline mean=77.1 kg , SD=12.1 , last mean=78.8 kg , SD=10.6 ; F=1.3 ; df=1 , 18 ; p=0.3 ) . There were no differential effects in psychopathology , extrapyramidal side effects or weight-related measures between the placebo and fluoxetine groups . Serotonin reuptake inhibitors are probably not a practical option to counteract weight gain induced by atypical antipsychotics . Atypical-induced weight gain may result from mechanisms other than 5HT reuptake blockade Objective : To determine the potential effectiveness of a behavioural weight control programme including physical exercise in the prevention of antipsychotic-induced weight gain and associated comorbid conditions in out patients with schizophrenia and mood disorders . Methods : A prospect i ve , comparative , open and naturalistic study was carried out for a total of 110 patients with schizophrenia , schizoaffective or bipolar disorders ( DSM-IV ) , on treatment with atypical antipsychotics . Of these , 59 patients participated in an 18 month weight control programme that included an educational activity about dietary and physical activity counselling as well as a structured , supervised , facility-based exercise programme . The control group consisted of 51 patients with the same baseline characteristics who did not receive the clinical programme . Anthropometric measurements , plasma lipid – lipoprotein profile , and fasting plasma glucose concentrations were assessed at 11 time-points over the study . In addition , serum concentrations of prolactin , thyrotropin-stimulating hormone ( TSH ) , and glycated haemoglobin ( HbA1c ) were assessed at four time-points . Finally , the Clinical Global Impression scale ( CGI ) , the Brief Psychiatric Rating Scale ( BPRS ) and the Short Form (SF)-36 Health Survey were used . Results : The adherence rate of patients was 85 % , both in the active and in the control group . Whereas the control group experienced a significant increase in bodyweight ( 4.1 % ) , body mass index ( BMI ; 5.5 % ) and waist circumference ( WC ; 4.2 % ) , the active group significantly reduced their bodyweight ( −3.5 % ) , BMI ( −4.4 % ) , and WC ( −4.6 % ) at the study end-point . In addition , a significant increase in low-density lipoprotein (LDL)-cholesterol ( 14.8 % ) and in triglyceride concentrations ( 12.3 % ) was observed at month 18 in the control group . In contrast , high-density lipoprotein-cholesterol ( HDL ) significantly increased ( 21.4 % ) , and LDL cholesterol ( −13.7 % ) , triglycerides ( −26.2 % ) , total cholesterol ( −12.1 % ) , fasting glucose concentrations ( −12.0 % ) , and HbA1c ( −11.4 % ) significantly decreased compared to baseline in the active group . No significant changes were observed regarding serum concentrations of prolactin and TSH during the study . In regard to the changes observed in psychological measures , no between-group differences were seen in the clinical ratings of CGI and BPRS . However , the SF-36 showed that physical health was improved only for subjects in the active group at months 12 and 18 compared to baseline ( p<0.05 ) , and mental health was significantly improved for both groups at months 12 and 18 compared to baseline . Conclusion : Bodyweight and metabolic risk profile in patients receiving atypical antipsychotic medications can be effectively managed with a weight control programme including physical activity OBJECTIVE Treatment-resistant schizophrenia poses a major therapeutic challenge . This multicenter , double-blind , r and omized study compared the efficacy and safety of aripiprazole and perphenazine in treatment-resistant patients with schizophrenia . METHOD Schizophrenia patients ( DSM-IV diagnosis ) with a history of antipsychotic resistance underwent 4 to 6 weeks of open-label treatment with olanzapine or risperidone to confirm treatment resistance . Only patients who completed this open-label period and failed to respond ( < 20 % improvement in Positive and Negative Syndrome Scale [ PANSS ] total score or a Clinical Global Impressions-Severity of Illness score > or= 4 ) entered the 6-week , double-blind treatment phase . In all , 300 patients with confirmed treatment resistance were r and omly assigned to aripiprazole ( 15 - 30 mg/day ) or perphenazine ( 8 - 64 mg/day ) . The primary outcome measure was change in PANSS score from baseline . The study was conducted between August 30 , 2000 , and March 18 , 2002 . RESULTS Both aripiprazole and perphenazine treatment were associated with clinical ly relevant improvements in PANSS total scores from baseline . After 6 weeks , 27 % of aripiprazole-treated patients and 25 % of perphenazine-treated patients were responders ( > or= 30 % decrease in PANSS total score or a Clinical Global Impressions-Improvement score of 1 or 2 ) . Perphenazine-treated patients had a higher incidence of extrapyramidal symptom-related adverse events , mean increases ( i.e. , worsening ) in extrapyramidal symptom rating scale scores , and a higher rate of elevated prolactin levels than aripiprazole ( 57.7 % vs. 4.4 % , p < .001 ) . Improvements in quality of life considered to be clinical ly relevant ( > or= 20 % improvement in Quality of Life Scale score ) occurred in 36 % of the aripiprazole-treated patients and in 21 % of those treated with perphenazine ( p = .052 ) . CONCLUSIONS Aripiprazole and perphenazine , at the doses used here , can improve the symptoms of schizophrenia in treatment-resistant patients who have failed to respond to olanzapine or risperidone The second generation antipsychotics clozapine and olanzapine frequently induce weight gain . R and omized studies investigating abnormal eating behavior ( food craving , binge eating ) possibly associated with weight gain are lacking . Thirty patients with schizophrenia , schizophreniform , or schizoaffective disorder were included in this r and omized , double-blind , parallel study comparing abnormal eating behavior using a st and ardized scale , clinical efficacy using the Brief Psychiatric Rating Scale0 - 6 and Clinical Global Impression-Severity scale , and tolerability of clozapine and olanzapine . In both treatment groups , the number of patients reporting food craving , binge eating , or both increased over time . The likelihood to experience food craving at any time during drug treatment showed a trend ( P = 0.068 ) to be higher in the olanzapine group ( 48.9 % ) compared with the clozapine group ( 23.3 % ) . The likelihood to experience binge eating at any time during drug treatment was numerically but not statistically significantly higher in the olanzapine group ( 16.7 % ) than in the clozapine group ( 8.9 % ) . In both groups , significant baseline-to-end point improvements of clinical symptoms ( Brief Psychiatric Rating Scale0 - 6 : clozapine , 36.6 ± 8.8 to 15.9 ± 13.7 ; olanzapine , 36.7 ± 9.9 to 19.1 ± 13.8 ) and severity of illness ( Clinical Global Impression-Severity scale : clozapine , 4.7 ± 0.6 to 2.5 ± 1.5 ; olanzapine , 4.5 ± 0.6 to 2.3 ± 1.2 ) were observed . These improvements did not differ significantly between groups . Olanzapine was more tolerable than clozapine ; adverse events occurred significantly ( P < 0.01 ) less frequently than in the clozapine group . These results suggest that both clozapine and olanzapine can induce food craving and binge eating , however , olanzapine possibly to a greater extent . Findings on clinical efficacy and safety are in accordance with previous reports Patients with treatment-resistant schizophrenia pose a major challenge to caregivers since only clozapine is documented as having superior efficacy in this population . Although olanzapine is similar to clozapine in structure and receptor profile , it has not been proven to have superior efficacy for this patient group . Nonetheless , olanzapine is being increasingly used in higher doses as clinicians attempt to find a more effective and tolerable therapy for refractory patients . Furthermore , there are little data comparing olanzapine and clozapine in this population . Thirteen patients participated in a r and omized double-blind 16-week crossover study of clozapine therapy ( 450 mg/day ) compared to high doses of olanzapine ( 50 mg/day ) . No patients on olanzapine responded while 20 % responded to clozapine treatment . Olanzapine patients tended to experience higher rates of anticholinergic effects such as dry mouth ( 80 vs. 20 % ) and blurry vision ( 40 vs. 0 % ) . Clozapine-treated patients had higher rates of sialorrhea ( 80 vs. 10 % ) , sweating ( 50 vs. 10 % ) , dyspepsia ( 70 vs. 30 % ) , and lethargy ( 90 vs. 60 % ) . Neither treatment was associated with significant akathisia . Liver enzyme elevation and lipids were higher with clozapine treatment . Mean weight gain in the initial 8 weeks was 3.4 kg for olanzapine and 1.2 kg for clozapine . High doses of olanzapine during 8 weeks of treatment did not increase lipids and liver enzymes like clozapine did . Olanzapine at 50 mg/day may be associated with more anticholinergic effects and weight gain than clozapine OBJECTIVE Changing antipsychotics is common despite the dearth of information on risks and benefits associated with medication changes . The authors examined phase 1 findings from the Clinical Antipsychotic Trials of Intervention Effectiveness ( CATIE ) study to explore whether it was more advantageous to continue taking the medication being received at baseline or to switch to a different antipsychotic . METHOD First , for patients r and omly assigned to treatment with olanzapine ( N=314 ) or risperidone ( N=321 ) , the authors assessed the impact of being assigned to stay with the medication they were receiving at entry into the study versus being assigned to switch to these medications from a different antipsychotic . Second , for patients whose baseline antipsychotic was olanzapine ( N=319 ) , risperidone ( N=271 ) , or quetiapine ( N=94 ) , the authors examined the impact of being r and omly assigned to stay with the same antipsychotic versus switch . Finally , the authors assessed the impact of removing the data of 209 patients whose r and om assignment was to stay with their baseline antipsychotic . The authors followed analysis strategies for CATIE ; primary outcome was time until all-cause treatment discontinuation . RESULTS Individuals r and omly assigned to olanzapine and risperidone who were continuing with their baseline medication had significantly longer times until discontinuation than did those assigned to switch antipsychotics . When these " stayers " were removed , differences seen in the original CATIE phase 1 analyses were attenuated , although the original pattern of results remained . CONCLUSIONS Comparisons of medication effectiveness should take into account whether medications being compared were each newly initiated . Further , unless the clinical situation requires a medication change , prescribers may want to take steps to optimize current medication regimens ( e.g. , dosage adjustments , behavioral or psychosocial interventions ) before switching medications BACKGROUND A recent review suggested an association between using unpublished scales in clinical trials and finding significant results . AIMS To determine whether such an association existed in schizophrenia trials . METHOD Three hundred trials were r and omly selected from the Cochrane Schizophrenia Group 's Register . All comparisons between treatment groups and control groups using rating scales were identified . The publication status of each scale was determined and cl aims of a significant treatment effect were recorded . RESULTS Trials were more likely to report that a treatment was superior to control when an unpublished scale was used to make the comparison ( relative risk 1.37 ( 95 % CI 1.12 - 1.68 ) ) . This effect increased when a ' gold-st and ard ' definition of treatment superiority was applied ( RR 1.94 ( 95 % CI 1.35 - 2.79 ) ) . In non-pharmacological trials , one-third of ' gold-st and ard ' cl aims of treatment superiority would not have been made if published scales had been used . CONCLUSIONS Unpublished scales are a source of bias in schizophrenia trials A one year double-blind trial of haloperidol decanoate and fluphenazine decanoate was conducted in nineteen out- patients who had previously received at least one year 's treatment with fluphenazine decanoate and were already overweight , as judged by a Body Mass Index of 25 + . Although the difference was not statistically significant , patients treated with haloperidol decanoate showed a trend to less weight gain than patients who continued on fluphenazine decanoate , even though the haloperidol to fluphenazine dose ratio was 4:1 . No statistically significant changes in mental state were observed and the incidence of extrapyramidal side-effects in the two treatment groups was similar OBJECTIVE To assess changes in cognitive function in stable out patients with schizophrenia switched to ziprasidone from conventional antipsychotics ( n = 108 ) , olanzapine ( n = 104 ) , or risperidone ( n = 58 ) because of suboptimal efficacy or poor tolerability . METHODS In three separate 6-week trials , patients received ziprasidone 40 mg b.i.d . for 2 days , followed by 20 - 80 mg b.i.d . for the next 40 days . Before switching , and at endpoint , patients were evaluated with tests of working and secondary verbal memory , vigilance , visuomotor speed , verbal fluency , and executive functioning . Principal components factor analysis was performed to test for clustering of cognitive variables . RESULTS Significant improvements were seen at endpoint in secondary verbal memory ( in all three groups ) , vigilance ( in patients switched from conventional antipsychotics or risperidone ) , executive function ( in patients switched from conventional antipsychotics or risperidone ) , and verbal fluency . Factor analysis on baseline scores suggested reduction of the cognitive variables to three factors : verbal skills , attention and short-term memory , and executive functioning . Analysis of z-transformed mean change in factor scores showed significant improvement in verbal skills and global score following the switch from conventional antipsychotics , olanzapine , or risperidone . CONCLUSIONS Patients requiring a change in antipsychotic therapy may exhibit cognitive improvement following a switch to ziprasidone INTRODUCTION Body mass index ( BMI ) increase is an undesired effect associated with antipsychotics , and crucial for patients ' global health and treatment compliance . We aim ed to investigate the relation between BMI during olanzapine or haloperidol treatments and leptin , neuropeptide Y ( NPY ) , adiponectin and lipid serum levels . METHODS In this 9-month , r and omized and naturalist study , 34 male patients , 18 on olanzapine and 16 on haloperidol group were enrolled , all were under monotherapy . Patient outcome was evaluated with positive and negative syndrome scale ( PANSS ) at every 3-month period . In each visit , BMI , leptin , NPY , lipid , olanzapine or haloperidol levels were also monitored . RESULTS AND DISCUSSION Leptin levels positively correlated with BMI in olanzapine ( r=0.64 , p<0.001 ) and haloperidol ( r=0.73 , p<0.001 ) groups ; only in olanzapine patients , the former also correlated with PANSS score ( r=0.54 , p<0.05 ) . NPY levels negatively correlated with olanzapine levels ( r=− 0.65 , p<0.01 ) . Adiponectin levels had not significantly varied . CONCLUSION Antipsychotics probably interfere on leptin and NPY signalling ways and disturb these hormones in eating behaviour control Rationale Switching patients from one antipsychotic to another can lead to tolerability problems or transient symptom exacerbations . It is important to compare switching strategies to determine which methods produce the best possible patient outcomes . Objective To investigate the efficacy , safety and tolerability of three dosing strategies for switching chronic , stable patients with schizophrenia from current oral antipsychotic monotherapy to once-daily oral aripiprazole monotherapy . Method Patients in this 8-week , open-label , outpatient study were r and omized to : 1 ) immediate initiation of 30 mg/day aripiprazole with simultaneous immediate discontinuation of current antipsychotic ; 2 ) immediate initiation of 30 mg/day aripiprazole while tapering off current antipsychotic over 2 weeks ; or 3 ) up-titrating aripiprazole to 30 mg/day over 2 weeks , while simultaneously tapering off current antipsychotic . Efficacy assessment s included PANSS , CGI-S , and CGI-I scores . Safety assessment s included : adverse events ( AEs ) recording , evaluation of extrapyramidal symptoms ( EPS ) , vital signs , ECG , and clinical laboratory tests . Results Efficacy with aripiprazole was maintained during the study with numerical improvements compared with baseline in all three groups . The overall incidence of AEs was broadly comparable across all groups , and AEs were generally mild to moderate in severity and time-limited . Discontinuations due to AEs were comparable across the groups . No deterioration in EPS occurred in any group . The reduction in body weight and plasma prolactin levels following switch to aripiprazole were comparable across the three groups . Conclusion Any of the three strategies evaluated can be used safely for switching patients to aripiprazole from antipsychotic monotherapy . Furthermore , patients ' symptoms may continue to improve after switching to aripiprazole |
14,041 | 24,353,078 | There was insufficient evidence to determine whether interdental brushing reduced or increased levels of plaque when compared to flossing | BACKGROUND Effective oral hygiene is a crucial factor in maintaining good oral health , which is associated with overall health and health-related quality of life .
Dental floss has been used for many years in conjunction with toothbrushing for removing dental plaque in between teeth , however , interdental brushes have been developed which many people find easier to use than floss , providing there is sufficient space between the teeth .
OBJECTIVES To evaluate the effects of interdental brushing in addition to toothbrushing , as compared with toothbrushing alone or toothbrushing and flossing for the prevention and control of periodontal diseases , dental plaque and dental caries . | PURPOSE The aim of the present study was to evaluate the recommendations relating to the use of approximal cleaning aids given by dental hygienists and dentists , the self-care practice s in a Swedish population and the ability to remove dental plaque . MATERIAL S AND METHODS A structured question naire was r and omly distributed to 500 dental hygienists and 500 dentists and a similar question naire was distributed to 1000 r and omly selected individuals , divided equally into the following age groups : 15 to 20 , 21 to 40 , 41 to 60 and > 60 years . A clinical examination evaluating the ability to remove approximal dental plaque was also carried out in a total of 60 regular users of approximal cleaning aids . Plaque was scored before and after cleaning with a toothpick , dental floss or an interdental brush . RESULTS The response rate was 82 % , 79 % and 68 % for the three groups . The results reveal that dental hygienists give more detailed information about a majority of the aspects that are related to the use of approximal cleaning aids compared with dentists ( P < 0.01 or P < 0.001 ) . The majority of the dental staff give recommendations to children and adolescents firstly to prevent dental caries and to older individuals to improve periodontal health . The use of different approximal cleaning aids on a daily basis varied with respect to age group ( 2 % to 42 % ) ; dental floss dominated in the younger age groups and interdental brushes in the two oldest groups . In the clinical study , the largest plaque reduction was produced by the interdental brush ( 83 % ) , followed by toothpicks ( 74 % ) and dental floss ( 73 % ) . CONCLUSIONS The present study indicated the importance of individual recommendations related to the use of approximal cleaning aids This clinical study was conducted to compare the efficacy and safety of the new Braun Oral-B Interclean ( ID2 ) with that of dental floss in healthy adults . Volunteers with sufficient dental plaque and gingivitis were r and omized to use the ID2 ( n = 24 ) or American Dental Association-approved dental floss ( n = 24 ) in conjunction with toothbrushing once nightly for 6 weeks . All subjects received a supragingival prophylaxis and polishing at the start of the study . Over the study period , both devices produced significant reductions in interproximal plaque , gingivitis and bleeding ( p < 0.01 ) . With the ID2 , there were reductions in interproximal plaque scores ( all sites ) of approximately 40 % compared with 28 % with dental floss . A decrease in gingivitis of 15 % was observed with the ID2 compared with 12 % for floss users . Bleeding on probing was reduced by 25 % with the ID2 and by 34 % with dental floss . There was a trend in favor of the ID2 with respect to reduction in plaque which achieved statistical significance ( p = 0.05 ) for the posterior three interproximal sites . Differences between treatment groups with respect to gingivitis and bleeding reductions were not statistically significant . No adverse events were reported or observed during the study . It is concluded that the ID2 has equivalent efficacy to dental floss for the reduction of interproximal plaque and gingivitis The purpose of the present study was to compare in untreated patients suffering from moderate to severe periodontitis the efficacy of dental floss ( DF ) and interdental brushes ( IDB ) in the reduction of plaque , gingival inflammation , and probing depth in a 6-week period prior to subgingival debridement . Twenty-six patients ( 12 female , 14 male ; mean age 37.4 years ; range 27 to 72 years ) were instructed to use DF for one side of the dentition and IDB for the other side as an adjunct to the daily toothbrushing for 6 weeks . Oral hygiene instructions for toothbrushing and the use of the two devices were given at baseline and at week 3 . Measurements were carried out at baseline and at 6 weeks including plaque scores , probing depth , and 2 bleeding scores ( periodontal pocket bleeding index and angulated bleeding index ) . With the IDB , the approximal plaque score at baseline of 3.09 reduced to 2.15 at 6 weeks and with DF from 3.10 to 2.47 , respectively . IDB proved to remove significantly more plaque than DF . Baseline probing depth of 5.84 mm for IDB sites and 5.59 mm for DF sites was reduced to 5.01 mm at 6 weeks for both regimens . Analysis showed that the use of IDB result ed in a greater pocket reduction . Both bleeding indices were slightly reduced with IDB and DF , but no differences between devices were found . In relation to patient acceptance , more problems were observed with DF , and IDB were felt to be more efficacious . In conclusion , the results of the present study indicate that in combination with a manual toothbrush , the use of interdental brushes is more effective in removal of plaque and results in a larger reduction of probing depth than the use of dental floss . Although the differences were small , they indicate , in combination with patient preferences , that interdental brushes are to be considered preferable to floss for interdental plaque removal in patients suffering from moderate to severe periodontitis OBJECTIVE The study was conducted to compare the performance of three interdental products to dental floss in the control and removal of plaque , and in the reduction of gingivitis . METHODOLOGY One-hundred and twenty subjects were screened for the presence of interproximal sites of a size suitable for a GUMO Go-Betweens cleaner , and for being in compliance with inclusion and exclusion criteria . They were then assessed with the Plaque , Gingivitis , and Eastman Interdental Bleeding Indices ( EIBI ) at baseline , given a prophylaxis , r and omly assigned to one of four products ( Glide dental floss , Butler flossers , GUM Go-Betweens cleaners , and GUM Soft-Picks cleaners ) , and given product use instructions . Subjects returned at three weeks for a compliance review and at six weeks for a final visit . Plaque was assessed at the final visit before and after using the assigned products . Plaque , gingivitis , and bleeding scores were evaluated by analysis of covariance using the baseline measurements as the covariate . RESULTS All four interdental products significantly reduced interdental plaque from baseline to before-use at the final visit ( after six weeks ) employing baseline plaque as a covariate . Reductions were 16 % to 24 % . Similarly , use of the products at the final visit result ed in 26 % to 31 % reductions in plaque with the before-use plaque as a covariate . Interdental gingivitis scores showed a reduction both lingually and buccally , with reductions ranging from 27 % to 36 % for the former and 34 % to 53 % for the latter ( baseline was the covariate ) . No statistical differences were found between the products on the lingual interdental sites . The Go-Betweens cleaners showed a statistically greater reduction in the Gingival Index score buccally than the other three products . No differences were noted among the products for the EIBI . CONCLUSION In this study , dental floss , the recognized " gold st and ard " for gingivitis reduction , was matched in performance by flossers and an interdental cleaner with small elastomeric fingers , and surpassed by an interdental brush . All products performed comparably for plaque reduction and removal Quality assurance ( QA ) and continuing competence ( CC ) programs aim to ensure acceptable levels of health care provider competence , but it is unknown which program methods most successfully achieve this goal . The objectives of the study reported in this article were to compare two distinct QA/CC programs of Canadian dental hygienists and assess the impact of these two programs on practice behavior change , a proxy measure for quality . British Columbia ( BC ) and Ontario ( ON ) were compared because the former m and ates continuing education ( CE ) time requirements . A two-group comparison survey design using a self-administered question naire was implemented in r and omly selected sample s from two jurisdictions . No statistical differences were found in total activity , change opportunities , or change implementation , but ON study subjects participated in significantly more activities that yielded change opportunities and more activities that generated appropriate change implementation , meaning positive and correct approaches to providing care , than BC dental hygienists . Both groups reported implementing change to a similarly high degree . The findings suggest that ON dental hygienists participated in more learning activities that had relevancy to their practice and learning needs than did BC subjects . The findings indicate that the QA program in ON may allow for greater efficiency in professional learning Abstract Objective . To investigate associations between oral health-related quality of life assessed with the Oral Health Impact Profile (OHIP)-14 and demographic factors , number of teeth present , dental visits , dental health behaviour and self-rated oral health in a representative sample of 20–80-year-old Norwegians . Material and methods . The study was conducted in a stratified r and om sample of 3538 individuals . Question naires including questions on demographic factors , number of remaining teeth , dental visits , dental health behaviour , self-rated oral health and OHIP-14 were mailed to the sample . Bivariate and multivariate analyses were performed . Results . The response rate was 69 % . The mean OHIP-14 score was 4.1 ( st and ard deviation = 6.2 ) . No problem was reported by 35 % of the respondents . The most frequently reported problems were : physical pain ( 56 % ) , psychological discomfort ( 39 % ) and psychological disability ( 30 % ) . When the effect of all independent variables was analysed in multivariate analysis , self-rated oral health , frequency of dental visits , number of teeth , age and sex were significantly ( P < 0.05 ) associated with the prevalence of having problems and frequent problems . Self-rated oral health had the strongest association with having problems [ odds ratio ( OR ) 4.5 ; 95 % confidence interval ( CI ) 3.4–6.0 ] and with having frequent problems ( OR 4.0 ; 95 % CI 2.7–5.8 ) . Dental health behaviour , use of floss and toothpicks and oral rinsing were not associated with having problems related to oral quality of life in multivariate analyses . Conclusion . In this Norwegian adult sample , self-rated oral health , frequency of dental visits , number of teeth , age and sex were associated with having problems as estimated using the OHIP-14 The aim of the present study was to examine the dental status and smoking habits in r and omized sample s of 35- , 50- , 65- , and 75-year-old subjects ( n = 1093 ) , recruited for a cross-sectional epidemiological study in the County of Värml and , Sweden . The following clinical variables were recorded by 4 well-calibrated dentists : number of edentuolous subjects , number of missing teeth , probing attachment level , furcation involvement , CPITN scores , DMF surfaces , plaque and stimulated salivary secretion rate ( SSSR ) . In addition , the subjects reported in a question naire their tobacco habits , oral hygiene habits , dietary habits etc . The percentage of smokers in 35- , 50- , 65- , and 75-year-olds was 35 % , 35 % , 24 % and 12 % , respectively . In 75-year-olds , 41 % of the smokers were edentulous compared to 35 % of non-smokers . The difference in number of missing teeth between smokers and non-smokers was 0.6 ( p=0.15 ) , 1.5 ( p=0.013 ) , 3.5 ( p=0.0007 ) and 5.8 ( p=0.005 ) in the 4 age groups . Smokers had the largest mean probing attachment loss in all age groups . The differences between smokers and non-smokers in mean attachment level were 0.37 ( p=0.001 ) , 0.88 ( p=0.001 ) , 0.85 ( p=0.001 ) and 1.33 mm ( p=0.002 ) in the 35- , 50- , 65- , and 75-year-olds , respectively . Treatment need assessed by CPITN was in all age groups greatest among smokers . The number of intact tooth surfaces was fewer in 35- , 50- , and 75-year-old smokers than in non-smokers . The number of missing surfaces ( MS ) was higher in 50- , 65- , and 75-year-old smokers than in non-smokers . In addition , 35-year-old smokers exhibited a significantly larger number of decayed and filled tooth surfaces ( DFS ) than non-smokers . Male smokers had significantly higher SSSR than non-smoking males ( p=0.012 ) . Plaque index and oral hygiene were similar in smokers and non-smokers . Smokers reported a more frequent intake of sugar containing soft drinks ( p=0.000 ) and snacks ( p=0.003 ) than non-smokers . The opposite was reported for consumption of fruit ( p=0.003 ) . It was concluded that smoking is a significant risk indicator for tooth loss , probing attachment loss and dental caries The objective of this double-blind , four-week clinical study was to evaluate the efficacy of BrushPicks , a new cleaning aid , and Glide floss on the reduction of plaque area , gingivitis and bleeding on probing , and to monitor safety when these products were used in addition to toothbrushing with an ADA-Accepted toothbrush ( Oral-B P35 ) and an ADA-Accepted fluoride-containing dentifrice ( Crest Regular ) . No special instructions on or supervision of product use was conducted , other than requesting twice-a-day ( morning and evening ) use of the assigned products . Following a baseline examination , 63 qualifying adult male and female subjects from the Philadelphia , Pennsylvania area were r and omized into two groups . Subjects were also told to use their assigned dental aid after each toothbrushing . Examinations for efficacy and safety were repeated after two and four weeks ' use of the products . Sixty-two subjects completed all aspects of the study . There were no untoward side effects attributed to product use , reported or observed , at the two- or four-week examination times . At baseline , there were no significant differences in plaque , gingivitis or bleeding on probing mean scores between the BrushPicks and Glide floss groups . At the two- and four-week evaluation times , both the BrushPicks and Glide floss had numerically lower plaque scores compared to baseline levels . The only statistically significant reduction ( p < 0.01 ) was in the BrushPicks group , comparing the week two mean with the baseline value . Gingivitis ( GI ) at four weeks was statistically ( p < 0.05 ) lower in the BrushPicks group as compared to the Glide floss mean value . When the changes in scores from baseline to two weeks and to four weeks were assessed , the mean GI score for the Glide floss group was significantly lower at two weeks ( p < 0.01 ) compared to baseline , and also from two weeks to four weeks ( p < 0.001 ) . The change in mean GI score for the Glide floss group from baseline to four weeks was also significant statistically ( p < 0.001 ) . When the changes in mean GI scores for the BrushPicks group were assessed , there was a significant decrease from baseline to two weeks ( p < 0.001 ) , from two weeks to four weeks ( p < 0.001 ) , and from baseline to four weeks ( p < 0.001 ) . For bleeding on probing , when the baseline to two- and four-week mean values were compared , only the BrushPicks produced significant ( p < 0.001 ) decreases . At two and four weeks , the BrushPicks group mean bleeding on probing scores were significantly ( p < 0.05 - 0.01 ) lower than the Glide floss group scores . At the end of this four-week study , the BrushPicks product was significantly more effective than Glide floss in the reduction of gingivitis and bleeding on probing , important attributes of soft-tissue health A single-blind , r and omized clinical study compared plaque removal efficacy of three toothbrush design s under conditions simulating normal use . Ninety ( 90 ) subjects with substantially complete dentition used one of the three toothbrushes : Advanced Design Reach , Crest Complete and Oral-B 40 . Subjects were examined for plaque before and after a single brushing using the Global Plaque Index to estimate plaque on the entire tooth surface , and the Proximal/Marginal Plaque Index ( PMI ) , a new index , was used to estimate plaque at proximal and marginal surfaces of the teeth . The Advanced Design Reach toothbrush reduced plaque scores significantly more than did the other toothbrushes tested ( p < 0.05 ) using either scoring method . At marginal and proximal sites , combined or separate , Advanced Design Reach toothbrush was significantly more effective than the other toothbrushes in plaque removal and produced significantly more plaque free sites than the other two toothbrushes . Evaluation of all anterior and posterior parts of the dentition with the Global Plaque Index indicated that Advanced Design Reach was superior in removing plaque in these regions . Both plaque indices were highly correlated ( correlation coefficient 0.91 ) indicating excellent consistency by the dental examiner The purpose of this study was to evaluate different methods of eliciting gingival bleeding as indicators of gingival inflammation in the experimental gingivitis model . Following a period of stringent oral hygiene , 103 dental students were scored for plaque and gingival bleeding assessed by 4 methods . From this group , 41 volunteers were r and omly allocated to 2 treatment groups . Dental students with clean teeth and healthy gingivae were asked to abolish all mechanical tooth cleaning in the lower jaw for a period of 3-weeks . During the 21-day experimental period , chlorhexidine ( Peridex ) or a placebo mouthrinse was applied to the lower jaw . Subjects brushed the upper jaw with a st and ard toothpaste . In principal , 2 different methods were employed to provoke bleeding : ( 1 ) at the marginal gingival tissue by running a probe along the soft tissue wall at the orifice of the pocket , and ( 2 ) by probing to the " bottom " of the pocket . Variations in the methods were based on angulation ( AngBI , ParBI ) of the probe in relation to the tooth surface and to the probing force ( PPBI.25N , PPBI.75N ) . 1 r and omly selected quadrant in the lower jaw was scored using the AngBI . The opposing quadrant was scored with a r and omly-allocated bleeding index , either ParBI , PPBI.25N or PPBI.75N . The results of this study confirm earlier findings that the angulation of the probe determines the number of sites with bleeding observed . It also indicates that bleeding as elicited by probing to the bottom of the pocket is a poor indicator of early gingivitis . It is recommended that gingivitis should be assessed by probing the marginal gingiva OBJECTIVES The study was design ed to determine whether the British public perceived oral health as being important to quality of life ( QoL ) and if so , to identify in which most important ways . In addition , to identify socio-demographic variations in these perceptions . METHOD In a national survey conducted with the assistance of the Office for National Statistics , attempts were made to conduct face to face interviews with a r and om probability sample of 2,668 United Kingdom residents . RESULTS The response rate was 67 % with 1,778 adults ( aged 16 or older ) participating in the study . Most ( 75 % , 1,332/1778 ) perceived their oral health as being important to their QoL , and did so through a wide variety of physical , social and psychological ways . Overall oral health 's impact on physical aspects were more frequently cited as important to life quality than social or psychological . Marked age and gender variations were apparent in the prioritisation of what domains were most important to quality of life . CONCLUSION The British public perceive oral health as being important to life quality in a variety of different ways and various sub groups of the population rate what is important differently . This has implication s for assessing patients needs and assessing oral health related quality of life The plaque-removing efficacy when using waxed dental floss and three interdental brushes was compared in an intraindividual clinical trial . Nine adult patients treated for periodontal disease , with a reduced but healthy periodontium and large interdental spaces were subjects in the study . Each subject tested the four interdental cleaning aids in r and om sequence over a 2-wk period . The duration of the study was 8 wk . The results indicated that the use of interdental brushes is preferable to that of dental floss in cleaning interdental areas where the papilla is missing . No difference in achieved cleanliness was noted after use of the different interdental brushes tested . No gingival damage or damage to the hard tissue of the teeth was observed after use of interdental brushes or dental floss OBJECTIVES To study the outcome of intensified mechanical oral hygiene compared with the effect of an adjunctive antibacterial mouth rinse on plaque and gingivitis in elderly people . MATERIAL AND METHODS In a r and omized , single-blind , 6-month controlled clinical study , 106 subjects , 55 years or older , were divided into four groups : ( I ) Participants were instructed on improved mechanical oral hygiene , including interdental hygiene ; ( II ) subjects used an antibacterial mouth rinse containing amine and stannous fluoride in addition to their usual oral hygiene practice s ; ( III ) both intensive mechanical and antibacterial measures were combined ; and ( IV ) a control group with no specific regimen . Gingivitis and plaque were examined . RESULTS After 6 months , both plaque and gingivitis scores were significantly lower than at baseline in all groups . Reductions in gingivitis differed significantly between the control group and all other groups but not between the three intervention groups . Only groups with improved mechanical oral hygiene showed significant improvements in plaque scores compared with control . CONCLUSIONS Intensive mechanical oral hygiene result ed in greater plaque reduction than the combination of an antibacterial rinse and usual oral hygiene procedures . Gingivitis was reduced by both intensive oral hygiene and use of the amine/stannous fluoride rinse . Combining intensive mechanical oral hygiene with the antibacterial rinse did not result in further gingivitis reduction BACKGROUND Although interdental cleaning is an integral component of home plaque control for periodontally involved patients , limited data exist on the periodontal benefits of commonly used interdental cleaning methods before definitive root surface debridement is undertaken . Therefore , the aim of this study was to compare the effects of a customized interdental brushing technique and a customized flossing technique on clinical periodontal outcomes prior to root surface debridement in chronic periodontitis cases . METHODS This was a single-blind , r and omized controlled clinical trial . Seventy-seven patients with chronic periodontitis were measured for plaque , relative interdental papillae level , Eastman interdental bleeding index , probing depths , and bleeding on probing at interdental sites and underwent a 10-minute h and scaling to remove easily accessible calculus deposits . Before group allocation , patients were advised on toothbrushing and instructed in two customized methods of interdental cleaning involving dental floss and precurved interdental brushes . Material s were supplied after r and om allocation . Participants were recalled at 6 and 12 weeks for clinical measurements , reinforcement of instructions , and fresh material s. RESULTS There were significant reductions from baseline for all indices in both groups ( P < 0.01 ) . At 6 weeks , the interdental brush group improved more than the floss group in every parameter ( P < 0.05 ) . By 12 weeks , the changes in plaque , papillae level , and probing depths were significantly greater in the interdental brush group than the floss group ( P < 0.01 ) . CONCLUSION This trial demonstrated that patients were able to improve clinical periodontal outcomes by interdental cleaning , particularly with interdental brushes , even before thorough root surface debridement was undertaken OBJECTIVES The objectives of this study were two-fold : ( 1 ) to determine ( by surfometry ) loss of deciduous and permanent enamel and dentine following consumption of a single low pH orange drink for 15days ; and ( 2 ) to determine ( by surfometry ) loss of deciduous and permanent enamel and dentine following consumption of the product 2 versus 4 times per day for 15days . METHODS Sixteen healthy volunteers participated in a single centre , single blind , 2-phase crossover study , conducted according to Good Clinical Practice , and employing the vali date d model described by West and co-workers ( Journal of Dentistry 1998 ; 26:329 - 335 ) . RESULTS In all tissues , erosion was progressive over time , the pattern being more linear in enamel than in dentine . In general , erosion of deciduous enamel was greater than that of permanent enamel , though this difference was significant only for those specimens exposed to 4 drinks per day . Conversely , erosion of dentine was generally greater in the permanent tissue , though differences rarely reached conventional levels of statistical significance . Increasing frequency of consumption result ed in increased loss of tissue , but this difference was neither proportional nor consistently statistically significant . CONCLUSIONS It is concluded that statistically significant differences in susceptibility of deciduous and permanent enamel to erosion appear to emerge over time and with increasing frequency of consumption . This is of importance clinical ly given the reduced dimensions of the deciduous dentition and the element of ' abuse ' of soft drinks by the child population . Further development of soft drinks with low erosive potential is recommended The effectiveness of the Interspace brush , Inter-Dens , and waxed dental floss as proximal surface cleansing agents was compared in 35 subjects . Each subject used all three methods of cleansing in r and om order of selection . Statistical analysis of the results showed that there was no difference in the effectiveness of any one of these three agents . However , proximal surfaces of anterior teeth where cleaned more effectively than posterior teeth . The coronal half of the proximal surfaces was cleaned more effectively than the apical half and the facial half more effectively than the lingual half when Inter-Dens was used . Comparison of cleansing effectiveness between facial and lingual halves of proximal surfaces for the Interspace brush and waxed dental floss showed no significant difference . Mesial and distal proximal surfaces were cleaned with similar effectiveness . Plaque control was only satisfactory on approximately half of the proximal surfaces , though a wide variation occurred . Significantly lower plaque scores were found 1 week after the initial instruction session , irrespective of the agent used . The majority of subjects preferred Inter-Dens whilst waxed dental floss was the least-liked method of cleansing BACKGROUND Although routine interdental cleaning is important and recommended by dental professionals , compliance has been relatively low . To aid in improving compliance , an electrically powered device has been developed . METHODS This six-month r and omized , single-blinded , parallel-group study was conducted to compare the long-term efficacy and safety of a new interdental cleaning device ( Braun Oral-B Interclean , model ID2 ) with those of an ADA-approved waxed dental floss in healthy adults . RESULTS The authors found no statistically significant difference between the two products with respect to the gingival index or gingival bleeding index after three or six months of use . A one-time product use , at the six-month examination , confirmed the equivalency of the two methods with respect to removal of dental plaque . The oral soft-tissue status of both groups of subjects also remained comparable throughout the study . CONCLUSION Use of the interdental cleaning device and dental floss result ed in comparable benefits with respect to gingival health and plaque removal . CLINICAL IMPLICATION S Although it was not shown to be an improvement over dental floss , the cleaning device was comparable in every respect . Since it can be used with one h and and does not require as much dexterity as floss , the device warrants consideration by those who lack the motivation or are unable to use dental floss OBJECTIVES To assess the periodontal status of relatives of Aggressive Periodontitis ( AgP ) patients , and to evaluate the reliability of the family history report as provided by the prob and . MATERIAL AND METHODS Data from 54 AgP patients were gathered along with a family history report for each of their relatives . Only 27 patients ( prob and s ) had relatives willing to be examined . This yielded a total of 61 relatives from whom the periodontal status was obtained . The family history report for each examined relative was compared with the periodontal diagnosis made at examination to assess reliability . RESULTS Eight percentage of the examined relatives , aged between 12 - 76 , were diagnosed with AgP , while chronic periodontitis was present in 39 % , gingivitis in 38 % and 15 % were healthy . If the report provided by the prob and was positive , the likelihood of finding any type of periodontitis in that relative was 85.7 % , whereas if the report was negative the likelihood of the absence of periodontitis was 70.6 % . CONCLUSION The percentage of examined relatives who were affected with AgP ( 8 % ) , although lower than percentages reported in other AgP family studies , was still higher than the prevalence of the condition in r and om population s. Reliability of periodontal family history was considered good and more reliable when it was positive This study compared the efficacy of an antimicrobial mouthrinse ( 0.12 % chlorhexidine gluconate ) plus toothbrushing ( mouthrinse group ) , mechanical interdental cleaning plus toothbrushing ( mechanical group ) , and toothbrushing alone ( control group ) , at reducing and preventing interdental gingival inflammation . 92 male subjects were examined for interdental inflammation using the Eastman interdental bleeding index at baseline , then monthly for 3 months after using one of the above oral hygiene regimens . The mechanical cleaning group had significant reductions in bleeding sites compared to baseline at 1 month ( 56.90 % versus 13.17 % ) that persisted throughout the study ( 2 months = 6.65 % , 3 months = 5.70 % ) . The other regimens showed no significant bleeding reduction at any time point in the study . The mechanical interdental cleaning group showed improvement over baseline at 1 month with the full benefit apparent after 2 months . The effect of location in the mouth on bleeding reduction was also assessed . The % of posterior sites which bled was always higher than anterior sites . Analysis of maxillary versus m and ibular , and buccal versus lingual sites showed no significant differences . Additional observations of the data demonstrated that sites which bled at baseline were more likely to stop bleeding in the mechanical cleaning group . Also , sites which did not bleed at baseline were unlikely to bleed subsequently when mechanical cleaning was used . Neither of these observations were true for the other cleaning regimens . These data show that only mechanical interdental plaque removal combined with toothbrushing is effective at reducing or preventing interdental inflammation . This underscores the importance of instituting mechanical interdental cleaning to eliminate interdental inflammation OBJECTIVE This single-blind , five parallel-arm , four-week r and omized clinical trial was design ed to compare the efficacy of a 0.05 % cetylpyridinium chloride gel-releasing interdental brush ( IDB ) with st and ard interproximal cleaning devices for plaque and gingivitis reduction , and decreased frequency in interproximal gingival bleeding . METHODOLOGY After consenting , participants meeting inclusion criteria brushed their teeth , received a baseline examination and a professional cleaning , and were then block-r and omized into five groups , with the plaque level serving as the blocking variable . All five groups performed st and ard tooth brushing as a background regimen . Three of the groups were respectively assigned to one of three interdental brush regimens , the fourth group was assigned to a st and ard flossing regimen ( positive control ) , and the fifth group was assigned to a st and ard tooth brushing only regimen ( control ) . Clinical outcome data were collected at two and four weeks . RESULTS Of a total of 162 starting participants , 152 completed the study . There were no baseline differences among the five groups with respect to age , interproximal plaque score , interproximal gingivitis score , or percent of interproximal bleeding on probing . After two and four weeks , the 3 IDB groups exhibited 30 - 40 percent lower plaque levels than the control ( p < 0.05 ) . With respect to interproximal gingival scores , the active agent IDB group exhibited a statistically significant effect after two weeks , and all three IDB groups demonstrated significantly better outcomes after four weeks ( p < 0.05 ) . At two and four weeks , the three IDB groups demonstrated a greater reduction in interproximal bleeding points upon probing compared to the two control groups ( p < 0.05 ) . The group using the 0.05 % cetylpyridinium gel-releasing IDB system did not demonstrate superior clinical results when compared to the two other IDB groups . CONCLUSION When compared to control and positive control interdental cleaning procedures , daily use of IDBs was effective in reducing interproximal plaque and gingivitis scores , as well as interproximal bleeding on probing . The benefits were evident at two weeks , but were more consistent after four weeks . The 0.05 % cetylpyridinium gel-releasing IDB system did not appear to confer a consistently independent incremental benefit |
14,042 | 25,708,852 | Exploratory subgroup analysis showed no effect of treatment regimen on the RRs of the relevant adverse events .
Our meta- analysis has demonstrated that lapatinib is associated with a significantly increased risk of all- grade skin rash , h and foot skin reaction and pruritus . | BACKGROUND We performed a systematic review and meta- analysis to determine the risk of mucocutaneous adverse events associated with lapatinib . | BACKGROUND We compared the efficacy and safety of the addition of lapatinib versus trastuzumab to anthracycline-taxane-based neoadjuvant chemotherapy . METHODS In the GeparQuinto r and omised phase 3 trial , patients with untreated HER2-positive operable or locally advanced breast cancer were enrolled between Nov 7 , 2007 , and July 9 , 2010 . Patients were eligible if their tumours were classified as cT3/4a-d , or hormone receptor (HR)-negative , HR-positive with clinical ly node-positive and cT2 disease ( cT2 cN+ ) , or HR-positive and pathologically node-positive in the sentinel lymph node for those with cT1 disease ( cT1 pN(SLN+ ) ) . Patients were r and omly assigned in a 1:1 ratio to receive neoadjuvant treatment with four cycles of EC ( epirubicin [ 90 mg/m(2 ) intravenously ] plus cyclophosphamide [ 600 mg/m(2 ) intravenously ] , every 3 weeks ) , and four cycles of docetaxel ( 100 mg/m(2 ) intravenously every 3 weeks ) with either trastuzumab ( 6 mg/kg intravenously , with a starting loading dose of 8 mg/kg , for eight cycles , every 3 weeks ) or lapatinib ( 1000 - 1250 mg per day orally ) throughout all cycles before surgery . R and omisation was done by dynamic allocation with the minimisation method of Pocock and patients were stratified by participating site , HR status , and extent of disease ( cT1 - 3 cN0 - 2 vs T4 or N3 ) . The primary endpoint was pathological complete response ( defined as ypT0 and ypN0 ) and was analysed in all patients who received at least one cycle of EC . Participants and investigators were not masked to treatment assignment . Pathologists in centres assessing surgery outcomes were masked to group assignment . This trial is registered with Clinical Trials.gov , number NCT00567554 . FINDINGS Of 620 eligible patients , 309 were r and omly assigned to chemotherapy with trastuzumab ( ECH-TH group ) and 311 to chemotherapy with lapatinib ( ECL-TL group ) . Two patients in the ECH-TH group and three patients in the ECL-TL group did not start treatment because of withdrawal of consent or immediate surgery . 93 ( 30·3 % ) of 307 patients in the ECH-TH group and 70 ( 22·7 % ) of 308 patients in the ECL-TL group had a pathological complete response ( odds ratio [ OR ] 0·68 [ 95%CI 0·47 - 0·97 ] ; p=0·04 ) . Chemotherapy with trastuzumab was associated with more oedema ( 119 [ 39·1 % ] vs 88 [ 28·7 % ] ) and dyspnoea ( 90 [ 29·6 % ] vs 66 [ 21·4 % ] ) , and ECL-TL with more diarrhoea ( 231 [ 75·0 % ] vs 144 [ 47·4 % ] ) and skin rash ( 169 [ 54·9 % ] vs 97 [ 31·9 % ] ) . 43 ( 14·0 % ) patients discontinued in the ECH-TH group and 102 ( 33·1 % ) in the ECL-TL group . 70 serious adverse events were reported in the ECH-TH group and 87 in the ECL-TL group . INTERPRETATION This direct comparison of trastuzumab and lapatinib showed that pathological complete response rate with chemotherapy and lapatinib was significantly lower than that with chemotherapy and trastuzumab . Unless long-term outcome data show different results , lapatinib should not be used outside of clinical trials as single anti-HER2-treatment in combination with neoadjuvant chemotherapy . FUNDING GlaxoSmithKline , Roche , and Sanofi-Aventis BACKGROUND We studied the effect on tumour response to neoadjuvant therapy of the substitution of lapatinib for trastuzumab in combination with weekly paclitaxel after doxorubicin plus cyclophosphamide treatment , and of the addition of lapatinib and trastuzumab combined after doxorubicin plus cyclophosphamide treatment in patients with HER2-positive operable breast cancer to determine whether there would be a benefit of dual HER2 blockade in these patients . METHODS For this open-label , r and omised phase 3 trial we recruited women aged 18 years or older with an ECOG performance status of 0 or 1 with operable HER2-positive breast cancer . Each received four cycles of st and ard doxorubicin 60 mg/m(2 ) and cyclophosphamide 600 mg/m(2 ) intravenously on day 1 every 3 weeks followed by four cycles of weekly paclitaxel ( 80 mg/m(2 ) ) intravenously on days 1 , 8 , and 15 , every 4 weeks . Concurrently with weekly paclitaxel , patients received either trastuzumab ( 4 mg/kg load , then 2 mg/kg intravenously ) weekly until surgery , lapatinib ( 1250 mg orally ) daily until surgery , or weekly trastuzumab plus lapatinib ( 750 mg orally ) daily until surgery . After surgery , all patients received trastuzumab to complete 52 weeks of HER2-targeted therapy . R and omisation ( ratio 1:1:1 ) was done central ly with stratification by clinical tumour size , clinical nodal status , hormone-receptor status , and age . The primary endpoint was the pathological complete response in the breast , and analysis was performed on an intention-to-treat population . FINDINGS Patient accrual started on July 16 , 2007 , and was completed on June 30 , 2011 ; 529 women were enrolled in the trial . 519 patients had their pathological response determined . Breast pathological complete response was noted in 93 ( 52·5 % , 95 % CI 44·9 - 59·5 ) of 177 patients in the trastuzumab group , 91 ( 53·2 % , 45·4 - 60·3 ) of 171 patients in the lapatinib group ( p=0·9852 ) ; and 106 ( 62·0 % , 54·3 - 68·8 ) of 171 patients in the combination group ( p=0·095 ) . The most common grade 3 and 4 toxic effects were neutropenia ( 29 [ 16 % ] patients in the trastuzumab group [ grade 4 in five patients ( 3 % ) , 28 [ 16 % ] in the lapatinib group [ grade 4 in eight patients ( 5 % ) ] , and 29 [ 17 % ] in the combination group [ grade 4 in nine patients ( 5 % ) ] ) and grade 3 diarrhoea ( four [ 2 % ] patients in the trastuzumab group , 35 [ 20 % ] in the lapatinib group , and 46 [ 27 % ] in the combination group ; p<0·0001 ) . Symptomatic congestive heart failure defined as New York Heart Association Class III or IV events occurred in seven ( 4 % ) patients in the trastuzumab group , seven ( 4 % ) in the lapatinib group , and one ( < 1 % ) in the combination group ; p=0·185 ) . INTERPRETATION Substitution of lapatinib for trastuzumab in combination with chemotherapy result ed in similar high percentages of pathological complete response . Combined HER2-targeted therapy produced a numerically but insignificantly higher pathological complete response percentage than single-agent HER2-directed therapy ; these findings are consistent with results from other studies . Trials are being undertaken to further assess these findings in the adjuvant setting Background : Phase-IV , open-label , single-arm study ( NCT01203917 ) to assess efficacy and safety/tolerability of first-line gefitinib in Caucasian patients with stage IIIA/B/IV , epidermal growth factor receptor ( EGFR ) mutation-positive non-small-cell lung cancer ( NSCLC ) . Methods : Treatment : gefitinib 250 mg day−1 until progression . Primary endpoint : objective response rate ( ORR ) . Secondary endpoints : disease control rate ( DCR ) , progression-free survival ( PFS ) , overall survival ( OS ) and safety/tolerability . Pre-planned exploratory objective : EGFR mutation analysis in matched tumour and plasma sample s. Results : Of 1060 screened patients with NSCLC ( 859 known mutation status ; 118 positive , mutation frequency 14 % ) , 106 with EGFR sensitising mutations were enrolled ( female 70.8 % ; adenocarcinoma 97.2 % ; never-smoker 64.2 % ) . At data cutoff : ORR 69.8 % ( 95 % confidence interval ( CI ) 60.5–77.7 ) , DCR 90.6 % ( 95 % CI 83.5–94.8 ) , median PFS 9.7 months ( 95 % CI 8.5–11.0 ) , median OS 19.2 months ( 95 % CI 17.0–NC ; 27 % maturity ) . Most common adverse events ( AEs ; any grade ): rash ( 44.9 % ) , diarrhoea ( 30.8 % ) ; CTC ( Common Toxicity Criteria ) grade 3/4 AEs : 15 % ; SAEs : 19 % . Baseline plasma 1 sample s were available in 803 patients ( 784 known mutation status ; 82 positive ; mutation frequency 10 % ) . Plasma 1 EGFR mutation test sensitivity : 65.7 % ( 95 % CI 55.8–74.7 ) . Conclusion : First-line gefitinib was effective and well tolerated in Caucasian patients with EGFR mutation-positive NSCLC . Plasma sample s could be considered for mutation analysis if tumour tissue is unavailable Dual epidermal growth factor receptor ( EGFR ) and HER2 targeting with the tyrosine kinase inhibitor lapatinib is approved for treating advanced HER2-positive breast cancer and can prevent estrogen receptor (ER)-negative mammary tumors in HER2 transgenic mouse models . Ki-67 labeling index ( LI ) has prognostic and predictive value and can be used to screen drugs ' therapeutic and preventive potential in a clinical model of short-term presurgical therapy of breast cancer . We conducted a r and omized , placebo-controlled trial of lapatinib ( 1500 mg/d ) administered orally for three weeks between biopsy and surgery in 60 women with HER-2–positive breast cancer to assess lapatinib biomarker ( including the primary endpoint , Ki-67 LI ) and clinical activity in invasive breast cancer , adjacent ductal intraepithelial neoplasia ( DIN , which comprises ductal carcinoma in situ and atypical ductal hyperplasia ) , and distant ductal hyperplasia without atypia ( DH ) . Ki-67 LI increased progressively in association with disease stage , increasing in the placebo arm , for example , by medians of 3 % in DH to 20 % in DIN to 30 % in invasive cancer . Ki-67 LI in cancer tissue decreased by a mean ( ±SD ) of 9.3 % ( ±34.2 ) in the lapatinib arm and increased by 15.1 % ( ±30.9 ) in the placebo arm ( P = 0.008 ) . Compared with placebo , lapatinib reduced Ki-67 significantly more in ER-negative tumors ( by 34.8 % ; P = 0.01 ) but not significantly more in ER-positive tumors ( by 12.3 % ; P = 0.2 ) and reduced Ki-67 more ( nonsignificantly ) in cytosol PTEN-overexpressing tumors ( P = 0.057 ) . The prevalence of DIN in post-treatment surgical specimens of both arms was similar ( 70%–76 % ) , with a median Ki-67 of 15 % ( range , 5%–35 % ) on lapatinib versus 20 % ( 5%–60 % ) on placebo ( P = 0.067 ) . The prevalence of DH also was similar in both arms ( > 90 % ) , with a median Ki-67 of 1 % ( 1%–7 % ) on lapatinib versus 3 % ( 1%–5 % ) on placebo ( P = 0.006 ) . Other results of lapatinib versus placebo , respectively , were as follows : Median tumor diameter at surgery of 18 mm ( 11 mm–57 mm ) versus 24 mm ( 10 mm–37 mm ; P = 0.009 ) ; partial response of 13.6 % versus 3.7 % , stable disease of 59.1 % versus 40.7 % , and progression of 27.3 % versus 55.6 % ( P-trend = 0.035 ) . In conclusion , short-term lapatinib decreased cell proliferation in DIN , DH , and invasive HER-2–positive ( especially ER-negative ) breast cancer , thus providing the rationale for further clinical development of lapatinib for breast cancer prevention in high-risk patients , including those with HER-2–positive DIN . Cancer Prev Res ; 4(8 ) ; 1181–9 . © 2011 AACR This phase II study ( VEG20007 ; NCT00347919 ) with r and omized and open-label components evaluated first-line lapatinib plus pazopanib therapy and /or lapatinib monotherapy in patients with human epidermal growth factor receptor type 2 (HER2)-positive advanced/metastatic breast cancer . Patients were enrolled sequentially into two cohorts : Cohort 1 , patients were r and omly assigned to lapatinib 1,000 mg plus pazopanib 400 mg or lapatinib 1,500 mg monotherapy ; Cohort 2 , patients received lapatinib 1,500 mg plus pazopanib 800 mg . The primary endpoint was week-12 progressive disease rate ( PDR ) for Cohort 1 . The principal secondary endpoint was week-12 response rate ( RR ) for Cohort 2 . Efficacy was assessed in patients with central ly confirmed HER2 positivity ( modified intent-to-treat population [ MITT ] ) . The study enrolled 190 patients ( Cohort 1 , combination n = 77 , lapatinib n = 73 ; Cohort 2 , n = 40 ) . The MITT population comprised n = 141 ( Cohort 1 ) and n = 36 ( Cohort 2 ) . In Cohort 1 , week-12 PDRs were 36.2 % ( combination ) versus 38.9 % ( lapatinib ; P = 0.37 for the difference ) . Week-12 RRs were 36.2 % ( combination ) versus 22.2 % ( lapatinib ) . In Cohort 2 , week-12 RR was 33.3 % . In Cohort 1 , grade 3/4 adverse events ( AEs ) included diarrhea ( combination , 9 % ; lapatinib , 5 % ) and hypertension ( combination , 5 % ; lapatinib , 0 % ) . Grade s 3/4 AEs in Cohort 2 included diarrhea ( 40 % ) , hypertension ( 5 % ) , and fatigue ( 5 % ) . Alanine aminotransferase elevations > 5 times the upper limit of normal occurred in Cohort 1 ( combination , 18 % ; lapatinib , 5 % ) and Cohort 2 ( 20 % ) . Upon conclusion , the combination of lapatinib plus pazopanib did not improve PDR compared with lapatinib monotherapy , although RR was increased . Toxicity was higher with the combination , including increased diarrhea and liver enzyme elevations This multi-center Phase II study evaluated lapatinib , pazopanib , and the combination in patients with relapsed HER2 + inflammatory breast cancer . In Cohort 1 , 76 patients were r and omized 1:1 to receive lapatinib 1,500 mg + placebo or lapatinib 1,500 mg + pazopanib 800 mg ( double-blind ) once daily until disease progression , unacceptable toxicity , or death . Due to high- grade diarrhea observed with this dose combination in another study ( VEG20007 ) , Cohort 1 was closed . The protocol was amended such that an additional 88 patients ( Cohort 2 ) were r and omized in a 5:5:2 ratio to receive daily monotherapy lapatinib 1,500 mg , lapatinib 1,000 mg + pazopanib 400 mg , or monotherapy pazopanib 800 mg , respectively . The primary endpoint was overall response rate ( ORR ) . Secondary endpoints included duration of response , progression-free survival ( PFS ) , overall survival , and safety . In Cohort 1 , ORR for the lapatinib ( n = 38 ) and combination ( n = 38 ) arms was 29 and 45 % , respectively ; median PFS was 16.1 and 14.3 weeks , respectively . Grade ≥3 adverse events ( AEs ) were more frequent in the combination arm ( 71 % ) than in the lapatinib arm ( 24 % ) . Dose reductions and interruptions due to AEs were also more frequent in the combination arm ( 45 and 53 % , respectively ) than in the lapatinib monotherapy arm ( 0 and 11 % , respectively ) . In Cohort 2 , ORR for patients treated with lapatinib ( n = 36 ) , lapatinib + pazopanib ( n = 38 ) , and pazopanib ( n = 13 ) was 47 , 58 , and 31 % , respectively ; median PFS was 16.0 , 16.0 , and 11.4 weeks , respectively . In the lapatinib , combination , and pazopanib therapy arms , grade ≥3 AEs were reported for 17 , 50 , and 46 % of patients , respectively , and the incidence of discontinuations due to AEs was 0 , 24 , and 23 % , respectively . The lapatinib – pazopanib combination was associated with a numerically higher ORR but no increase in PFS compared to lapatinib alone . The combination also had increased toxicity result ing in more dose reductions , modifications , and treatment delays . Activity with single-agent lapatinib was confirmed in this population Background : Lapatinib is a dual inhibitor of epidermal growth factor receptor ( EGFR ) and human EGFR-2 ( HER-2 ) tyrosine kinases . This study investigated the pharmacodynamic and clinical effects of lapatinib in patients with locally advanced squamous cell carcinoma of the head and neck ( SCCHN ) . Methods : In total , 107 therapy-naive patients with locally advanced SCCHN were r and omised ( 2 : 1 ) to receive lapatinib or placebo for 2–6 weeks before chemoradiation therapy ( CRT ) . Endpoints included apoptosis and proliferation rates , clinical response , and toxicity . Results : Versus placebo , lapatinib monotherapy did not significantly increase apoptosis detected by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick-end labelling or caspase-3 assays . A statistically significant decrease in proliferation using Ki67 assay was observed ( P=0.030 ) . In a subset of 40 patients that received ⩾4 weeks of lapatinib or placebo , objective response rate ( ORR ) was 17 % ( n=4/24 ) vs 0 % ( n=0/16 ) . In the lapatinib single-agent responders , all had EGFR overexpression , 50 % had EGFR amplification , and 50 % had HER2 expression by immunohistochemistry ( including one patient with HER2 amplification ) . However , these patients showed variable modulation of apoptosis , proliferation , and phosphorylated EGFR on drug treatment . Following CRT , there was a statistically non-significant difference in ORR between lapatinib ( 70 % ) and placebo ( 53 % ) . There was no clear correlation between changes in apoptosis or proliferation and response to chemoradiation . Mucosal inflammation , asthenia , odynophagia , and dysphagia were the most commonly reported adverse events with lapatinib . Conclusion : Short-term lapatinib monotherapy did not demonstrate apoptotic changes , but provided evidence of clinical activity in locally advanced SCCHN , and warrants further investigation in this disease BACKGROUND The anti-HER2 monoclonal antibody trastuzumab and the tyrosine kinase inhibitor lapatinib have complementary mechanisms of action and synergistic antitumour activity in models of HER2-overexpressing breast cancer . We argue that the two anti-HER2 agents given together would be better than single-agent therapy . METHODS In this parallel groups , r and omised , open-label , phase 3 study undertaken between Jan 5 , 2008 , and May 27 , 2010 , women from 23 countries with HER2-positive primary breast cancer with tumours greater than 2 cm in diameter were r and omly assigned to oral lapatinib ( 1500 mg ) , intravenous trastuzumab ( loading dose 4 mg/kg [ DOSAGE ERROR CORRECTED ] , subsequent doses 2 mg/kg ) , or lapatinib ( 1000 mg ) plus trastuzumab . Treatment allocation was by stratified , permuted blocks r and omisation , with four stratification factors . Anti-HER2 therapy alone was given for the first 6 weeks ; weekly paclitaxel ( 80 mg/m(2 ) ) was then added to the regimen for a further 12 weeks , before definitive surgery was undertaken . After surgery , patients received adjuvant chemotherapy followed by the same targeted therapy as in the neoadjuvant phase to 52 weeks . The primary endpoint was the rate of pathological complete response ( pCR ) , analysed by intention to treat . This trial is registered with Clinical Trials.gov , NCT00553358 . FINDINGS 154 patients received lapatinib , 149 trastuzumab , and 152 the combination . pCR rate was significantly higher in the group given lapatinib and trastuzumab ( 78 of 152 patients [ 51·3 % ; 95 % CI 43·1 - 59·5 ] ) than in the group given trastuzumab alone ( 44 of 149 patients [ 29·5 % ; 22·4 - 37·5 ] ; difference 21·1 % , 9·1 - 34·2 , p=0·0001 ) . We recorded no significant difference in pCR between the lapatinib ( 38 of 154 patients [ 24·7 % , 18·1 - 32·3 ] ) and the trastuzumab ( difference -4·8 % , -17·6 to 8·2 , p=0·34 ) groups . No major cardiac dysfunctions occurred . Frequency of grade 3 diarrhoea was higher with lapatinib ( 36 patients [ 23·4 % ] ) and lapatinib plus trastuzumab ( 32 [ 21·1 % ] ) than with trastuzumab ( three [ 2·0 % ] ) . Similarly , grade 3 liver-enzyme alterations were more frequent with lapatinib ( 27 [ 17·5 % ] ) and lapatinib plus trastuzumab ( 15 [ 9·9 % ] ) than with trastuzumab ( 11 [ 7·4 % ] ) . INTERPRETATION Dual inhibition of HER2 might be a valid approach to treatment of HER2-positive breast cancer in the neoadjuvant setting . FUNDING GlaxoSmithKline BACKGROUND According to the results of a number of phase 3 r and omized studies , sorafenib is the only approved systemic therapy for advanced HCC ; however the issue of high economic cost remains challenging ; thus we have conducted this retrospective analysis of our HCC patients treated with sorafenib . METHODS HCC patients treated at Ain Shams University Hospitals , in the period between 2010 and 2012 were review ed . Eligible patients were those who had received sorafenib for advanced HCC not eligible for or progressed after surgery or locoregional therapy . We investigated the impact of baseline clinicopathological factors ( age , gender , child status , performance score , BCLC tumor stage , cause of chronic liver disease , median baseline alpha fetoprotein level and previous treatment received for HCC ) on overall survival ( OS ) in an adjusted Cox regression model . RESULTS 41 patients were included in the analysis fulfilling the inclusion criteria . At a median follow up period of 13 months , the median PFS for the whole group was 4 months ; the median OS for the whole group is 6.25 months . Multivariate analysis identified three baseline characteristics that were prognostic indicators for overall survival : ECOG performance status ( median OS for ECOG 1=7.01 months and for ECOG 2=3.03 months ) , Child-Pugh status ( median OS for child A=12.04 months and for child B=5.23 months ) , and median baseline levels of alpha-fetoprotein . CONCLUSIONS In limited re source countries like Egypt , we suggest that the use of sorafenib for the treatment of advanced HCC cases should be restricted to a highly selected subgroup of patients with good performance and child BACKGROUND The safety and efficacy of neratinib monotherapy were compared with that of lapatinib plus capecitabine in patients with human epidermal growth factor receptor-2-positive ( HER2 + ) , locally advanced/metastatic breast cancer and prior trastuzumab treatment . METHODS Patients received neratinib 240 mg/d continuously ( n=117 ) or lapatinib 1250 mg/d continuously plus capecitabine 2000 mg/m(2 ) per day on days 1 - 14 of each 21-d cycle ( n=116 ) . The primary aim was to demonstrate non-inferiority of neratinib for progression-free survival ( PFS ) . FINDINGS The non-inferiority of neratinib was not demonstrated when compared with lapatinib plus capecitabine ( hazard ratio , 1.19 ; 95 % confidence interval , 0.89 - 1.60 ; non-inferiority margin , 1.15 ) . Median PFS for neratinib was 4.5 months versus 6.8 months for lapatinib plus capecitabine and median overall survival was 19.7 months versus 23.6 months . Objective response rate ( neratinib , 29 % versus lapatinib plus capecitabine , 41 % ; P=0.067 ) and clinical benefit rate ( 44 % versus 64 % ; P=0.003 ) were lower for the neratinib arm but consistent with previously reported results . In both treatment arms , diarrhoea was the most frequently reported treatment-related adverse event of any grade ( neratinib , 85 % versus lapatinib plus capecitabine , 68 % ; P=0.002 ) and of grade 3/4 ( 28 % versus 10 % ; P<0.001 ) , but was typically managed with concomitant anti-diarrhoeal medication and /or study treatment modification . Importantly , neratinib had no significant skin toxicity . INTERPRETATION The results are considered as inconclusive since neither inferiority nor non-inferiority of treatment with neratinib versus lapatinib plus capecitabine could be demonstrated . The study confirmed relevant single-agent clinical activity and acceptable overall tolerability of neratinib in patients with recurrent HER2 + advanced breast cancer The only approved systemic therapy for patients with advanced hepatocellular carcinoma ( HCC ) till now is sorafenib . A preliminary study suggested that capecitabine , an oral fluoropyrimidine , may be effective in advanced HCC . We have tested this hypothesis in this phase 2 study . In this single-center , phase 2 , open-label trial , we r and omly assigned 52 patients with advanced HCC who had not received previous systemic treatment to receive either sorafenib ( at a dose of 400 mg twice daily ) or capecitabine ( 1,000 mg/m2 twice daily ) ( day 1–day 14 ) . Primary outcome was progression-free survival . Secondary outcomes included the overall survival and safety . Median overall survival was 7.05 months in the sorafenib group and 5.07 months in the capecitabine group ( hazard ratio in the capecitabine group 2.36 ; 95 % confidence interval 1.174–4.74 ; P < 0.016 ) . The median progression-free survival was 6 months in the sorafenib group and 4 months in the capecitabine group ( P < 0.005 ) . Three patients in the sorafenib group ( 11.5 % ) and one patient in the capecitabine group ( 3 % ) had a partial response ; one patient ( 3 % ) had a complete response in the sorafenib group . H and –foot skin reaction was more frequent in the sorafenib group , hyperbilirubinemia was more common in the capecitabine group , and diarrhea was equivalent between both groups . In patients with advanced HCC , capecitabine is inferior to sorafenib in terms of median progression-free survival and overall survival , and it should not be used alone for the treatment of advanced HCC , but rather , combination therapy with sorafenib should be considered PURPOSE Pazopanib and lapatinib are tyrosine kinase inhibitors that target vascular endothelial growth factor receptor , platelet-derived growth factor receptor , and c-Kit or epidermal growth factor receptor ( EGFR ) and human epidermal growth factor receptor 2 ( HER2/neu ) , respectively . In cervical cancer , EGFR and HER2/neu overexpression and high microvascular density correlate with survival . PATIENTS AND METHODS Patients with measurable stage IVB persistent/recurrent cervical carcinoma not amenable to curative therapy and at least one prior regimen in the metastatic setting were r and omly assigned in a ratio of 1:1:1 to pazopanib at 800 mg once daily , lapatinib at 1,500 mg once daily , or lapatinib plus pazopanib combination therapy ( lapatinib at 1,000 mg plus pazopanib at 400 mg once daily or lapatinib at 1,500 mg plus pazopanib at 800 mg once daily ) . Therapy continued until progression or withdrawal because of adverse events ( AEs ) . Primary end point was progression-free survival ( PFS ) , and secondary end points were overall survival ( OS ) , response rate ( RR ) , and safety . The futility boundary was crossed at the planned interim analysis for combination therapy compared with lapatinib therapy , and the combination was discontinued . RESULTS Of 230 patients enrolled , 152 were r and omly assigned to the monotherapy arms : pazopanib ( n = 74 ) or lapatinib ( n = 78 ) . Most patients ( 62 % ) had recurrent cancer . Pazopanib improved PFS ( hazard ratio [ HR ] , 0.66 ; 90 % CI , 0.48 to 0.91 ; P = .013 ) and OS ( HR , 0.67 ; 90 % CI , 0.46 to 0.99 ; P = .045 ) . Median OS was 50.7 weeks and 39.1 weeks and RRs were 9 % and 5 % for pazopanib and lapatinib , respectively . The only grade 3 AE > 10 % was diarrhea ( 11 % pazopanib and 13 % lapatinib ) . Grade 4 AEs were 9 % ( lapatinib ) and 12 % ( pazopanib ) . CONCLUSION This study confirms the activity of antiangiogenesis agents in advanced and recurrent cervical cancer and demonstrates the benefit of pazopanib based on the prolonged PFS and favorable toxicity profile BACKGROUND Lapatinib , a tyrosine kinase inhibitor of human epidermal growth factor receptor type 2 ( HER2 , also referred to as HER2/neu ) and epidermal growth factor receptor ( EGFR ) , is active in combination with capecitabine in women with HER2-positive metastatic breast cancer that has progressed after trastuzumab-based therapy . In this trial , we compared lapatinib plus capecitabine with capecitabine alone in such patients . METHODS Women with HER2-positive , locally advanced or metastatic breast cancer that had progressed after treatment with regimens that included an anthracycline , a taxane , and trastuzumab were r and omly assigned to receive either combination therapy ( lapatinib at a dose of 1250 mg per day continuously plus capecitabine at a dose of 2000 mg per square meter of body-surface area on days 1 through 14 of a 21-day cycle ) or monotherapy ( capecitabine alone at a dose of 2500 mg per square meter on days 1 through 14 of a 21-day cycle ) . The primary end point was time to progression , based on an evaluation by independent review ers under blinded conditions . RESULTS The interim analysis of time to progression met specified criteria for early reporting on the basis of superiority in the combination-therapy group . The hazard ratio for the independently assessed time to progression was 0.49 ( 95 % confidence interval , 0.34 to 0.71 ; P<0.001 ) , with 49 events in the combination-therapy group and 72 events in the monotherapy group . The median time to progression was 8.4 months in the combination-therapy group as compared with 4.4 months in the monotherapy group . This improvement was achieved without an increase in serious toxic effects or symptomatic cardiac events . CONCLUSIONS Lapatinib plus capecitabine is superior to capecitabine alone in women with HER2-positive advanced breast cancer that has progressed after treatment with regimens that included an anthracycline , a taxane , and trastuzumab . ( Clinical Trials.gov number , NCT00078572 [ Clinical Trials.gov ] . ) BACKGROUND Trastuzumab emtansine ( T-DM1 ) is an antibody-drug conjugate incorporating the human epidermal growth factor receptor 2 (HER2)-targeted antitumor properties of trastuzumab with the cytotoxic activity of the microtubule-inhibitory agent DM1 . The antibody and the cytotoxic agent are conjugated by means of a stable linker . METHODS We r and omly assigned patients with HER2-positive advanced breast cancer , who had previously been treated with trastuzumab and a taxane , to T-DM1 or lapatinib plus capecitabine . The primary end points were progression-free survival ( as assessed by independent review ) , overall survival , and safety . Secondary end points included progression-free survival ( investigator-assessed ) , the objective response rate , and the time to symptom progression . Two interim analyses of overall survival were conducted . RESULTS Among 991 r and omly assigned patients , median progression-free survival as assessed by independent review was 9.6 months with T-DM1 versus 6.4 months with lapatinib plus capecitabine ( hazard ratio for progression or death from any cause , 0.65 ; 95 % confidence interval [ CI ] , 0.55 to 0.77 ; P<0.001 ) , and median overall survival at the second interim analysis crossed the stopping boundary for efficacy ( 30.9 months vs. 25.1 months ; hazard ratio for death from any cause , 0.68 ; 95 % CI , 0.55 to 0.85 ; P<0.001 ) . The objective response rate was higher with T-DM1 ( 43.6 % , vs. 30.8 % with lapatinib plus capecitabine ; P<0.001 ) ; results for all additional secondary end points favored T-DM1 . Rates of grade 3 or 4 adverse events were higher with lapatinib plus capecitabine than with T-DM1 ( 57 % vs. 41 % ) . The incidences of thrombocytopenia and increased serum aminotransferase levels were higher with T-DM1 , whereas the incidences of diarrhea , nausea , vomiting , and palmar-plantar erythrodysesthesia were higher with lapatinib plus capecitabine . CONCLUSIONS T-DM1 significantly prolonged progression-free and overall survival with less toxicity than lapatinib plus capecitabine in patients with HER2-positive advanced breast cancer previously treated with trastuzumab and a taxane . ( Funded by F. Hoffmann-La Roche/Genentech ; EMILIA Clinical Trials.gov number , NCT00829166 . ) BACKGROUND Worldwide , many patients with HER2-positive early stage breast cancer do not receive trastuzumab-the st and ard adjuvant treatment . We investigated the efficacy and safety of adjuvant lapatinib for patients with trastuzumab-naive HER2-positive early-stage breast cancer , started at any time after diagnosis . METHODS This study was a placebo-controlled , multicentre , r and omised phase 3 trial . Women out patients from 405 [ corrected ] centres in 33 countries [ corrected ] with HER2-positive early-breast cancer who had previously received adjuvant chemotherapy but not trastuzumab were r and omly assigned ( 1:1 ) to receive daily lapatinib ( 1500 mg ) or daily placebo for 12 months . R and omisation was done with a computer-generated sequence , stratified by time since diagnosis , lymph node involvement at diagnosis , and tumour hormone-receptor status . Investigators , site staff , and patients were masked to treatment assignment . The primary endpoint was disease-free survival in the intention-to-treat population . This study is registered with Clinical Trials.gov , number NCT00374322 . FINDINGS Between August , 2006 , and May , 2008 , 3161 women were enrolled and 3147 were assigned to lapatinib ( n=1571 ) or placebo ( n=1576 ) . After a median follow-up of 47·4 months ( range 0·4 - 60·0 ) in the lapatinib group and 48·3 ( 0·7 - 61·3 ) in the placebo group , 210 ( 13 % ) disease-free survival events had occurred in the lapatinib group versus 264 ( 17 % ) in the placebo group ( hazard ratio [ HR ] 0·83 , 95 % CI 0·70 - 1·00 ; p=0·053 ) . Central review of HER2 status showed that only 2490 ( 79 % ) of the r and omised women were HER2-positive . 157 ( 13 % ) of 1230 confirmed HER2-positive patients in the lapatinib group and in 208 ( 17 % ) of 1260 in the placebo group had a disease-free survival event ( HR 0·82 , 95 % 0·67 - 1·00 ; p=0·04 ) . Serious adverse events occurred in 99 ( 6 % ) of 1573 patients taking lapatinib and 77 ( 5 % ) of 1574 patients taking placebo , with higher incidences of grade 3 - 4 diarrhoea ( 97 [ 6 % ] vs nine [ < 1 % ] ) , rash ( 72 [ 5 % ] vs three [ < 1 % ] ) , and hepatobiliary disorders ( 36 [ 2 % ] vs one [ < 1 % ] ) . INTERPRETATION Our data show that there was no significant difference in disease-free survival between groups when analysed in the intention-to-treat population . However , exploratory analyses restricted to patients who had HER2-positive disease confirmed by central fluorescence in-situ hybridisation review suggested marginal benefit with lapatinib in terms of disease-free survival . Thus lapatinib might be an option for women with HER2-positive breast cancer who do not or can not receive adjuvant trastuzumab . FUNDING GlaxoSmithKline PURPOSE This phase III trial was performed to assess the potential benefit of adding maintenance erlotinib to bevacizumab after a first-line chemotherapy regimen with bevacizumab for advanced non-small-cell lung cancer ( NSCLC ) . PATIENTS AND METHODS One thous and one hundred forty-five patients with histologically or cytologically confirmed NSCLC ( stage IIIB with malignant pleural effusion , stage IV , or recurrent ) received four cycles of chemotherapy plus bevacizumab . Seven hundred forty-three patients without disease progression or significant toxicity were then r and omly assigned ( 1:1 ) to bevacizumab ( 15 mg/kg , day 1 , 21-day cycle ) plus either placebo or erlotinib ( 150 mg per day ) . The primary end point was progression-free survival ( PFS ) . RESULTS Median PFS from time of r and om assignment was 3.7 months with bevacizumab/placebo and 4.8 months with bevacizumab/erlotinib ( hazard ratio [ HR ] , 0.71 ; 95 % CI , 0.58 to 0.86 ; P < .001 ) . Median overall survival ( OS ) times from r and om assignment were 13.3 and 14.4 months with bevacizumab/placebo and bevacizumab/erlotinib , respectively ( HR , 0.92 ; 95 % CI , 0.70 to 1.21 ; P = .5341 ) . During the postchemotherapy phase , there were more adverse events ( AEs ) overall , more grade 3 and 4 AEs ( mainly rash and diarrhea ) , more serious AEs , and more AEs leading to erlotinib/placebo discontinuation in the bevacizumab/erlotinib arm versus the bevacizumab/placebo arm . The incidence of AEs leading to bevacizumab discontinuation was similar in both treatment arms . CONCLUSION The addition of erlotinib to bevacizumab significantly improved PFS but not OS . Although generally well tolerated , the modest impact on survival and increased toxicity associated with the addition of erlotinib to bevacizumab maintenance mean that this two-drug maintenance regimen will not lead to a new postchemotherapy st and ard of care PURPOSE We investigated the pattern of rash , diarrhea , and hepatic adverse events ( AEs ) secondary to lapatinib and their association with age and pathologic complete response ( pCR ) in the Neoadjuvant Lapatinib and /or Trastuzumab Treatment Optimisation ( NeoALLTO ) phase III trial . PATIENTS AND METHODS Patients with HER2-positive early breast cancer were r and omly assigned to receive lapatinib ( Arm A ) , trastuzumab ( Arm B ) , or their combination ( Arm C ) for 6 weeks followed by the addition of paclitaxel for 12 weeks before surgery . We investigated the frequency and time to developing each AE according to age ( ≤ 50 v > 50 years ) and their association with pCR in a logistic regression model adjusted for age , hormone receptors , tumor size , nodal status , planned breast surgery , completion of lapatinib administration , and treatment arm . RESULTS Only patients r and omly assigned to arms A and C were eligible ( n = 306 ) . Younger patients ( ≤ 50 years ) experienced significantly more rash compared with older patients ( 74.4 % v 47.9 % ; P < .0001 ) . Diarrhea and hepatic AEs were observed in 78.8 % and 41.2 % of patients , respectively , with no differences in rate or severity or time of onset according to age . Early rash ( ie , before starting paclitaxel ) was independently associated with a higher chance of pCR , mainly in patients older than 50 years ( odds ratio [ OR ] = 3.76 ; 95 % CI , 1.69 to 8.34 ) but not in those ≤ 50 years ( OR = 0.92 ; 95 % CI , 0.45 to 1.88 ; P for interaction = .01 ) . No significant association was observed between pCR and diarrhea or hepatic AEs . CONCLUSION Our results indicate that the frequency and clinical relevance of lapatinib-related rash is largely dependent on patient age BACKGROUND This r and omised Phase II study assessed the activity and safety of concurrent chemoradiotherapy ( CRT ) and lapatinib followed by maintenance treatment in locally advanced , unresected stage III/IVA/IVB head and neck cancer . PATIENTS AND METHODS Patients were r and omised 1:1 to concurrent CRT and placebo followed by placebo or concurrent CRT and lapatinib followed by lapatinib . Treatment continued until disease progression or study withdrawal . Primary end-point was complete response rate ( CRR ) by independent review 6 months post-CRT . RESULTS Sixty-seven patients ( median age 56 years ; 97 % Eastern Cooperative Oncology Group performance status ≤1 ; 82 % stage IV ) were recruited . CRT dose intensities were unaffected by lapatinib : median radiation dose 70 Gy ( lapatinib , placebo ) , duration 49 ( lapatinib ) and 50 days ( placebo ) ; median cisplatin dose 260 mg/m(2 ) ( lapatinib ) and 280 mg/m(2 ) ( placebo ) . Lapatinib combined with CRT was well-tolerated . Grade 3/4 toxicities during CRT were balanced between arms , with the exception of an excess of grade 3 diarrhoea ( 6 % versus 0 % ) and rash ( 9 % versus 3 % ) and two grade 4 cardiac events in the lapatinib arm . CRR at 6 months post-CRT was 53 % with lapatinib versus 36 % with placebo in the intent-to-treat population . The progression-free survival ( PFS ) and overall survival rates at 18 months were 55 % versus 41 % and 68 % versus 57 % for the lapatinib and placebo arms , respectively . The difference between study arms was greatest in p16-negative disease ( median PFS > 20.4 months [ lapatinib ] versus 10.9 [ placebo ] ) . CONCLUSION Lapatinib combined with CRT is well-tolerated with numeric increases in CRR at 6 months post-CRT and median PFS in p16-negative disease |
14,043 | 28,749,700 | Diagnostic odds ratio values revealed a wide range of results across the studies and determined a higher heterogeneity for PR compared with CBCT .
CBCT was the imaging exam that rendered a higher diagnostic accuracy for root fractures | OBJECTIVES Many studies to evaluate the accuracy of root fracture diagnosis have been conducted .
However , there is a scarcity of studies to assess the quality and the sources of heterogeneity in the literature .
For this reason , the aim of this study was to conduct systematic review s and meta-analyses to summarize the available evidence on detection of root fractures by cone beam CT ( CBCT ) and periapical radiograph ( PR ) images and the interference of artefact by investigating possible sources of heterogeneity . | OBJECTIVES The aim of this study was to assess the accuracy of cone beam CT ( CBCT ) in detecting vertical root fractures and to compare the accuracy with images from an intraoral sensor and from conventional intraoral film . METHODS 60 extracted , single-rooted human teeth were divided equally into two groups : a control group of 30 teeth and an induced fracture group of 30 teeth . All teeth were r and omly placed into sockets in six dry m and ibles . Each tooth was imaged by three modalities : CBCT , intraoral digital radiography and intraoral F-speed film . Three beam angulations ( an orthogonal projection and additional projections with ± 20 ° horizontal shifts of the central ray ) were used when radiographs were made using film and a digital sensor . Three oral and maxillofacial radiologists evaluated the presence of root fractures twice in each image modality using a five-point confidence rating scale . Areas under receiver operating characteristic curves ( A(z ) ) were computed for each observer and modality and were tested for statistical differences using the Kruskal-Wallis test . RESULTS There was no statistical difference in the performance of the three modalities ( mean of A(z ) values : CBCT = 0.811 , film = 0.797 and sensor = 0.775 ; p = 0.771 ) . CONCLUSIONS There was no significant difference between intraoral film , a high-resolution complementary metal oxide semiconductor digital imaging system and CBCT in detecting vertical root fractures in m and ibular single-rooted teeth INTRODUCTION The purpose of this study was to evaluate the influence of cone-beam computed tomography ( CBCT ) imaging modes in the diagnosis of vertical root fractures with different intracanal material s. METHODS The sample consisted of 30 single-rooted teeth divided into 3 groups ( n = 10 ) , control and complete and incomplete root fracture . In each tooth , different material s were used ( gutta-percha , metal post , and fiber post ) as well as no filling material . Each tooth/root was scanned in a 3D Accuitomo 170 CBCT device by using 4 different imaging modes ( high-resolution , high-fidelity , high-speed , and st and ard ) . In addition , the dose-area product was calculated for each CBCT imaging mode . The images were r and omly evaluated by 5 dentomaxillofacial radiologists . RESULTS Complete root fractures were visualized more easily than incomplete fractures . The presence of metal post and gutta-percha negatively influenced the diagnosis of root fracture . Regarding the CBCT imaging modes , there was no influence for complete root fracture diagnosis . In cases of incomplete root fractures , high-fidelity , high-resolution , and st and ard had a higher diagnostic accuracy , especially in the fiber post and no filling groups . CONCLUSIONS The CBCT imaging modes had little influence in the diagnosis of complete and incomplete root fractures , whereas the presence of intracanal material had greater impact on the diagnostic ability , demonstrating that CBCT is not beneficial for the diagnosis of root fractures when metal posts are present OBJECTIVES Two-dimensional intraoral radiography is the most common tool for diagnosing root fractures ( RFs ) . Cone beam CT ( CBCT ) is widely used to depict RFs in endodontically treated teeth . Beam hardening and other artefacts caused by gutta percha may result in an incorrect diagnosis when using CBCT only . A comparison of two CBCT machines with photostimulated phosphor ( PSP ) plate images enhanced with the equalization tool was carried out to detect RFs in endodontically treated teeth . METHODS 66 roots were collected , decoronated and treated endodontically using the same technique with gutta percha . 33 of these roots were r and omly selected and fractured ; the 2 root fragments were glued together with 1 layer of methyl methacrylate and placed r and omly in 8 prepared beef rib fragments . Large fields of view ( FOVs ) were acquired with one CBCT unit and small FOVs with the second CBCT unit . Periapical radiographs ( using intraoral PSP plates ) were also acquired . A contrast enhancement tool was used when evaluating the PSP plate images . RESULTS Small FOV images had significantly higher accuracy ( area under the receiver operating characteristic curve ) and sensitivity in detecting RFs than PSP plates and large FOV images . The specificity of the enhanced PSP images was higher than , although not significantly higher than , the small FOV images and was significantly higher than the large FOV images . CONCLUSIONS CBCT small FOVs should be acquired for depicting RFs of endodontically treated teeth . Images obtained using PSP plates had the lowest rate of false-positive results and their use can save the patient a radiation dose Objectives This study aim ed to compare the diagnostic accuracy of two different cone-beam computed tomography ( CBCT ) units with several intraoral radiography techniques for detecting horizontal root fractures . Methods The study material comprised 82 extracted human maxillary incisors without root fractures that had not undergone any root canal treatment . Root fractures were created in the horizontal plane in 31 teeth by a mechanical force using a hammer with the tooth placed on a soft foundation as described in a previous study . The teeth were divided into two groups : a control group with no fractures and a test group with fractures . These were r and omized to the empty maxillary anterior sockets of a dry human maxilla . Each tooth was imaged at various vertical angles using each of the following modalities : a 3D Accuitomo 170 CBCT , a NewTom 3 G CBCT , a VistaScan PSP , a CCD sensor , and conventional film . Specificity and sensitivity for assessing horizontal root fracture by each radiographic technique were calculated . Chi-square statistics were used to evaluate differences between modalities . Kappa statistics assessed the agreement between observers . Results were considered significant at P < 0.05 . Results The kappa values for inter-observer agreement between observers ranged between 0.88 and 0.98 for the 3D Accuitomo 170 , 0.82 and 0.91 for the NewTom 3 G , and 0.61 and 0.72 for the different types of intraoral images . The diagnostic accuracy for detecting fracture lines in 3D Accuitomo 170 ( 0.93 ) was significantly higher than NewTom 3 G ( 0.87 ) , VistaScan ( 0.71 ) , CCD ( 0.70 ) , and CF ( 0.68 ) . Conclusions 3D Accuitomo 170 has the highest sensitivity and diagnostic accuracy for detecting horizontal root fracture among the 5 radiographic modalities examined . CBCT should be considered as the most reliable imaging modality of choice for the diagnosis of horizontal root fracture . Clinical relevance CBCT imaging offers the clear advantage over conventional imaging that traumatized teeth can be visualized in all three dimensions — especially the oro-facial AIM To compare the accuracy of digital radiography ( DR ) , multidetector computed tomography ( MDCT ) and cone beam computed tomography ( CBCT ) in detecting vertical root fractures ( VRF ) in the absence and presence of gutta-percha root filling . METHODOLOGY The root canals of 100 extracted human single-rooted teeth were prepared and r and omly divided into four groups : two experimental groups with artificially fractured root and two intact groups as controls . In one experimental and one control group , a size 40 , 0.04 taper gutta-percha cone was inserted in the root canals . Then DR , MDCT and CBCT were performed and the images evaluated . Statistical analyses of sensitivity , specificity and accuracy of each imaging technique in the presence and absence of gutta-percha were calculated and compared . RESULTS In the absence of gutta-percha , the specificity of DR , MDCT and CBCT was similar . CBCT was the most accurate and sensitive imaging technique ( P < 0 .05 ) . In the presence of gutta-percha , the accuracy of MDCT was higher than the other imaging techniques ( P < 0.05 ) . The sensitivity of CBCT and MDCT was significantly higher than that of DR ( P < 0.05 ) , whereas CBCT was the least specific technique . CONCLUSIONS Under the conditions of this ex vivo study , CBCT was the most sensitive imaging technique in detecting vertical root fracture . The presence of gutta-percha reduced the accuracy , sensitivity and specificity of CBCT but not MDCT . The sensitivity of DR was reduced in the presence of gutta-percha . The use of MDCT as an alternative technique may be recommended when VRF are suspected in root filled teeth . However , as the radiation dose of MDCT is higher than CBCT , the technique could be considered at variance with the principles of ALARA AIM To assess the failure and bone-to-implant contact rate of dental implants placed on osteoporotic subjects . METHODS Extensive examination strategies were created to classify studies for this systematic review . MEDLINE ( via PubMed ) and EMBASE data base were examined for studies in English up to and including May 2014 . The examination presented a combination of the MeSH words described as follow : " osteoporosis " or " osteopenia " or " estrogen deficiency " AND " implant " or " dental implant " or " osseointegration " . Assessment of clinical and /or histological peri-implant conditions in osteoporosis subjects treated with titanium dental implants . The examination included a combination of the MeSH terms described as follow : " osteoporosis " or " osteopenia " or " estrogen deficiency " AND " implant " or " dental implant " or " osseointegration " . RESULTS Of 943 potentially eligible articles , 12 were included in the study . A total of 133 subjects with osteoporosis , 73 subjects diagnosed with osteopenia and 708 healthy subjects were assessed in this systematic review . In these subjects were installed 367 , 205 , 2981 dental implants in osteoporotic , osteopenic and healthy subjects , respectively . The failure rate of dental implant was 10.9 % in osteoporotic subjects , 8.29 % in osteopenic and 11.43 % in healthy ones . Bone-to-implant contact obtained from retrieved implants ranged between 49.96 % to 47.84 % , for osteoporosis and non-osteoporotic subjects . CONCLUSION Osteoporotic subjects presented higher rates of implant loss , however , there is a lower evidence to strengthen or refute the hypothesis that osteoporosis may have detrimental effects on bone healing . Consequently , final conclusions regarding the effect of osteoporosis in dental implant therapy can not be made at this time . There are no r and omized clinical trial accessible for evaluation and the retrospective nature of the evaluated studies shall be taken in account when interpreting this study This is the second in a series of five articles Considerable effort has been expended at the interface between clinical medicine and scientific methods to achieve the maximum validity and usefulness of diagnostic tests . This article focuses on the specific kinds of questions that arise in diagnostic research and the study architectures ( the conversions of these clinical questions into appropriate research design s ) used to answer them . As an example we shall take shall take assessment of the value of the plasma concentration of B-type natriuretic peptide ( BNP ) in the diagnosis of left ventricular dysfunction.1 R and omised controlled trials are dealt with elsewhere . As in other forms of clinical research , there are several different ways study ing the potential or real diagnostic value of a physical sign or laboratory test , and each is appropriate to one kind of question and inappropriate for others . Among the possible questions about the relation between a putative diagnostic test and a target disorder ( for example , the concentration of BNP and left ventricular dysfunction ) , four are most relevant . # # # # Summary points Diagnostic studies should match methods to diagnostic questions The keys to validity in diagnostic test studies are Both specificity and sensitivity may change as the same diagnostic test is applied in primary , |
14,044 | 31,726,676 | The relative risk of piglet mortality was 14 % higher in farrowing pens than farrowing crates , which indicated that non-confinement of sows compromises post-natal piglet survival .
Overall , the type of farrowing accommodation did not affect the number of stillborn piglets .
However , the rate of stillborn piglets was lower in farrowing pens that were not enriched when compared with farrowing crates , also with no enrichment .
There was no effect of housing type on the number of piglets born alive or the number of piglets weaned , although the sample size for the later was much smaller .
Producers should anticipate an increase in mortality when piglets are reared by sows that are unconfined in the pen design s that are currently available , which supports the wider belief that crates are successful for reducing pre-weaning piglet mortality .
Abstract There are conflicting reports regarding the effect of farrowing house accommodation on piglet performance .
There was no overall effect on piglets that were born alive or number weaned .
This was the first systematic review and meta- analysis conducted on the performance of farrowing accommodation and identified that farrowing pens do compromise post-natal piglet survival . | Simple Summary The aim of this project was to review previously published research with a focus on the effects of farrowing accommodation on piglet performance .
The specific design features were analysed to determine whether animals in loose housed farrowing pens or crates from loading to weaning contribute to differences in litter performance obtained from different farrowing house accommodation types .
The aim of this investigation was to use a systematic review and meta-analyses to summarise the results of publications that focused on direct comparisons between full confinement conventional crates and various design s of loose-housed farrowing pens from loading until weaning . | The limited space in farrowing crate imposes many challenges , such as prolonged farrowing duration and high piglet stillbirth rate . Although the features of farrowing pens compensate for the drawbacks of farrowing crates , they are associated with high piglet crushing mortality caused by the greater space afforded to sows and their rolling-over behaviour . Therefore , a freedom farrowing pen was design ed to overcome the drawbacks of both farrowing crates and farrowing pens . The main features of the freedom farrowing pen are its left anti-crushing bar and detachable right anti-crushing bar on the sides of the sow lying area . It also has a 10 cm-high anti-crushing bar in the non-lying area . Eighteen healthy , multiparous Yorkshire sows ( 3 - 7 parity ) were averaged and r and omly assigned to farrowing crates , farrowing pens , and freedom farrowing pens to compare the effects of the farrowing systems on sow behaviour and performance . Results showed that the farrowing duration and the mean piglet birth intervals were longer for the sows in farrowing crates than for those in farrowing pens and freedom farrowing pens ( P<0.05 ) , but there was no difference between the sows in farrowing pens and those in freedom farrowing pens ( P>0.05 ) . The piglet stillbirth rate was higher for the sows in farrowing crates than for those in farrowing pens and freedom farrowing pens ( P<0.001 ) . Crushing mortality was higher among piglets in farrowing pens ( P<0.001 ) , but there was no difference between piglets in freedom farrowing pens and those in farrowing crates ( P>0.05 ) . The freedom farrowing pen and the farrowing pen allowed sows to turn around and move freely , but because of the different structures of their anti-crushing bars , the increase in sow movement did not cause higher piglet crushing mortality ( P>0.05 ) . Sows in freedom farrowing pens were found to be more protective of their piglets Alternatives to farrowing crates with continuous confinement of the sow are urgently needed because the animal welfare is negatively impacted . Given the increase of herd sizes , practical experience with loose-housing is needed to force the implementation of these systems in the field . Next to aspects of labour efficiency , detrimental piglet mortality rates that may occur during the first days postpartum ( pp ) is a major criticism . Therefore , loose-housing after a crating period limited to the first days pp might be a feasible alternative to improve welfare under intensive production conditions . The aim was to investigate the effect of crating sows during lactation for different periods on their behaviour and integument alterations and on piglets ' performance . Gilts from a commercial herd were observed from 5 to 26 days pp and housed in farrowing crates ( 1.85 × 2.50 m ) that could be altered between confinement crates and loose-housing pens . Animals were divided into three groups , that were either crated continuously from birth until weaning ( Group A , n=55 ) , until 14 days pp ( Group B ; n=54 ) or 7 days pp ( Group C , n=59 ) . The behaviour of six r and omly selected gilts per group was video recorded from 5 to 26 days pp and analysed by time sampling technique . Lesions on the legs , shoulder and lumbar vertebra were scored on days 7 , 14 and 25 pp . Piglets were weighed weekly , causes of losses recorded and weight losses of gilts measured . Not different between groups ( P>0.05 ) , animals spent 72 to 76 % lying laterally , 14 to 17 % lying in abdominal or semi-abdominal position , 9 to 10 % st and ing and 1 to 3 % sitting . B-sows were lying longer in week 3 and 4 of lactation compared to A- and C-sows ( P0.05 ) , whereas almost 90 % of the losses occurred in the first week pp . In conclusion , loose-housing of lactating gilts after a reduced postnatal crating period of 7 days affected neither the activity level of the gilts and lesions on the integument nor pre-weaning mortality . Therefore , it is recommended to allow sows to move around to some extent during the later lactation period In the 24-h period prior to parturition , sows are active and motivated to perform nest-building behavior . The aim of this study was to investigate whether prepartum activity ( nesting and postural changes ) could predict maternal behavior 24 h postpartum , piglet mortality , and BW gain 24 h postpartum in farrowing pens and crates . Sows were r and omly moved either to a farrowing pen ( = 20 ) or a farrowing crate ( = 18 ) . Prepartum nest-building behavior ( PRE-nesting ) and prepartum postural changes ( prepartum postural changes ) were analyzed 24 h before the birth of the first piglet ( BFP ) and were divided into twelve 2-h intervals . Latency of the first suckling from the litter was observed after the birth of the last piglet . Udder accesses and piglet suckling were noted at 5-min intervals , using 1/0 sampling , during the first 24 h after BFP were counted . Piglet trapping , crushing , and total live-born mortality were measured during the first 72 h after BFP . Piglet BW gain was estimated 24 h after BFP . Increased PRE-nesting observed 2 h before BFP were associated with fewer suckling intervals in crates but not in pens ( < 0.01 ) as well as an increase in postural changes during parturition ( < 0.001 ) in both housings . A link between housing and PRE-postural changes was evident . An increase in the number of PRE-postural changes 2 h prior to BFP was associated with lower incidences of udder access in crates but not in pens ( < 0.05 ) . A higher probability of piglet trapping was associated with increased PRE-nesting in the 2 to 4 h before BFP . No significant relationship between either PRE-nesting and postural changes and piglet BW gain and mortality was detected . Our results suggest that increased prepartum activity 2 h before parturition is associated with less suckling and less udder access in farrowing crates but not in farrowing pens . This suggests that the same sow behavior can have different consequences in pens vs. in crates . Future research should focus on nest-building activity , its relationship to endocrine indicators ( e.g. , oxytocin , cortisol ) before parturition , and its potential long-lasting effects on subsequent maternal behaviors and piglet production Free farrowing pens ( pens ) improve the welfare of sows but may increase sow activity and negatively influence piglet production . The aim of this study was to assess the effect of pens and crates on sow postural changes , piglet trapping , sow responses to piglet screams , piglet mortality , and piglet BW gain . It was predicted that provision of greater space ( in pens ) would increase not only the frequency of sow postural changes and the probability of trappisng but also sow responses to the screams of piglets ; thus , the outcome would be no differences in fatal piglet crushing or overall mortality between the housing systems . Sows were r and omly moved to either a farrowing pen ( n = 20 ) or farrowing crate ( n = 18 ) . Sow behavior was recorded and analyzed for 72 h from the birth of the first piglet ( BFP ) . Sow postural changes included rolling from a ventral to lateral position and vice versa and going from st and ing to sitting , st and ing to lying , and sitting to lying . Occurrences of piglet trapping and sow responsiveness to real crushing situations were analyzed . Sow responsiveness was assessed in response to audio playbacks ( PB ) of piglet screams on d 3 postpartum ( 48 to 72 h after BFP ; PB crush calls ) and real piglet crushing during the first 72 h after BFP ( real crush calls ) . Piglet BW gain was estimated 24 h after BFP , piglet BW was recorded at weaning , and piglet crushing and piglet mortality were recorded during the 72 h after BFP . Data were analyzed using PROC MIXED and PROC GENMOD of SAS . Sows in pens showed more postural changes ( P = 0.04 ) and tended to have greater incidences of piglet trapping ( P = 0.07 ) than those in crates . Sow response to PB crush calls was greater in pens ( P = 0.04 ) but did not differ for real crush calls between pens and crates ( P = 0.62 ) . There was no effect on the probability of piglet crushing ( P = 0.38 ) and mortality ( P = 0.41 ) during the 72 h after BFP nor in piglet mortality at weaning ( P = 0.81 ) between pens and crates . Piglet BW gain at 24 h after BFP ( P = 0.01 ) and piglet BW at weaning ( P = 0.02 ) were greater in pens . Sows in pens showed more postural changes and tended to trap more piglets ; however , the response to real crush calls did not differ between the two housing systems . Despite this , there was no increase in piglet crushing or mortality in pens , which might be influenced by the better piglet body condition observed in pens , which in turn could influence their ability to avoid crushing by the sow |
14,045 | 19,724,046 | In Bell palsy , corticosteroids are associated with a reduced risk of unsatisfactory recovery .
Antiviral agents , when administered with corticosteroids , may be associated with additional benefit | CONTEXT New evidence has emerged regarding the use of corticosteroids and antiviral agents in Bell palsy .
OBJECTIVE To estimate the association of corticosteroids and antiviral agents with the risk of unsatisfactory facial recovery in patients with Bell palsy . | In a double-blind study , we compared the final outcome of 99 Bell 's palsy patients treated with either acyclovir-prednisone ( 53 patients ) or placebo-prednisone ( 46 patients ) . For patients receiving acyclovir , the dosage was 2,000 mg ( 400 mg 5 times daily ) for 10 days . Electrical tests included electroneurography and the maximal stimulation test . Univariate comparisons of outcome and electrical tests between the two groups were made with χ2 analysis , Fisher 's exact test , and t-tests . The outcome in acyclovir-prednisone-treated patients was superior to that in placebo-prednisone-treated patients . Treatment with acyclovir-prednisone was statistically more effective in returning volitional muscle motion ( recovery profile of 10 ; p = .02 ) and in preventing partial nerve degeneration ( p = .05 ) than placebo-prednisone treatment . The t-tests indicated that the recovery profile and index means were significantly better for the acyclovir-treated group ( recovery profile t = 1.99 , p = .051 ; recovery index t = 2.10 , p = .040 ) . We conclude that acyclovir-prednisone is superior to prednisone alone in treating Bell 's palsy patients and suggest that herpes simplex is the probable cause of Bell 's palsy The therapeutic effect of corticosteroids in acute idiopathic peripheral nerve paralysis ( Bell 's palsy ) in children is controversial . The authors evaluated the effect of steroids on the early and late outcome of children with Bell 's palsy in a prospect i ve r and omized controlled setting . Forty-two patients ( 21 females , 21 males ) with complete paralysis were enrolled in the study . Group 1 ( n = 21 ) received methylprednisolone ( 1 mg/kg daily for 10 days orally ) ; Group 2 ( n = 21 ) did not . All patients were observed in the first 3 days of the disease and at 4 , 6 , and 12 months of follow-up . The mean age of Group 1 was 52.4 + /- 4.3 months , not significantly different from that of Group 2 . In Group 1 , 86 % and 100 % exhibited normal nerve function at 4 and 6 months of follow-up , respectively ; in Group 2 , 72 % and 86 % demonstrated complete recovery at 4 and 6 months , respectively , with improvement in all patients by 12 months . The improvement rates between the treated and untreated groups did not differ significantly . No side effects necessitated steroid withdrawal . The results of this study indicate that steroid therapy initiated at an early stage of childhood Bell 's palsy does not significantly improve the outcome OBJECTIVES Bell 's palsy ( BP ) , which causes facial paralysis , affects 11 - 40 people per 100 000 per annum in the UK . Its cause is unknown but as many as 30 % of patients have continuing facial disfigurement , psychological difficulties and occasionally facial pain . We present an r and omised controlled trial ( RCT ) -based economic evaluation of the early administration of steroids ( prednisolone ) and /or antivirals ( acyclovir ) compared to placebo , for treatment of BP . METHODS The RCT was not powered to detect differences in the cost-effectiveness ; therefore , we adopted a decision analytic model approach as a way of gaining precision in our cost-effectiveness comparisons [ e.g. prednisolone only ( PO ) versus acyclovir only versus prednisolone and acyclovir versus placebo , prednisolone versus no prednisolone ( NP ) and acyclovir versus no acyclovir ] . We assumed that trial interventions affect the probability of being cured/not cured but their consequences are independent of the initial therapy . We used the percentage of individuals with a complete recovery ( based on House-Brackmann grade = 1 ) at 9 months and Quality Adjusted Life Years ( e.g. derived on responses to the Health Utilities Index III ) as measures of effectiveness . Other parameter estimates were obtained from trial data . RESULTS PO dominated-i.e . was less costly and more effective-all other therapy strategies in the four arms model [ 77 % probability of cost-effective ( CE ) ] . Moreover , Prednisolone dominated NP ( 77 % probability of being CE at 30 000 UK pounds threshold ) while no acyclovir dominated aciclovir ( 85 % chance of CE ) , in the two arms models , respectively . CONCLUSIONS Treatment of BP with prednisolone is likely to be considered CE while treatment with acyclovir is highly unlikely to be considered CE . Further data on costs and utilities would be useful to confirm findings Abstract . The objective of this double-blind , r and omized , placebo-controlled study was to test the efficacy of high-dose prednisone , administered as early as possible , in modifying the natural progression of Bell 's palsy . Sixty-two consecutive patients , enrolled within 72 hours of facial palsy onset , were assigned to high dose intravenous prednisone in combination with intramuscular polyvitaminic therapy ( group A ) or polyvitaminic therapy alone ( group B ) . Clinical grading of facial muscle strength and length of absence from work were evaluated . An early worsening of facial muscle strength was observed in controls , leading to the divergence in the trends of the grading scores in the two groups ; this result was not confirmed in the long-term follow-up . Treated patients returned to work earlier than controls . In conclusion , early treatment based on high-dose corticosteroids slightly accelerates spontaneous improvement in Bell 's palsy Objective : To assess the agreement between the Sunnybrook facial nerve grading system and the House-Brackmann and Yanagihara systems . Study Design : Prospect i ve clinical facial nerve grading . Setting : Tertiary referral center . Patients : One-hundred assessment s , 94 in patients with Bell ’s palsy and 6 with herpes zoster . Intervention : Diagnostic . Main Outcome Measures : Evaluation according to the weighted regional Sunnybrook system , the gross House-Brackmann system , and the unweighted regional Yanagihara system . Weighted κ statistics was used to measure agreement between the grading systems . Results : The average weighted κ value between the Sunny-brook , House-Brackmann , and Yanagihara grading systems was 0.65 ; κ values increased temporally ( but not statistically significantly ) up to day 180 . The highest agreement value , 0.72 , was found between the Sunnybrook and Yanagihara grading systems . The weighted κ value between the Sunnybrook and House-Brackmann systems was 0.59 . In Sunnybrook gradings less than 63 , there was an overlap between House-Brackmann scores of III to VI . Reliable conversion tables between the gross House-Brackmann system and the regional Sunnybrook and Yanagihara systems could not be established . Conclusion : The Sunnybrook system scores at the same agreement level as the House-Brackmann and Yanagihara grading systems . There is an evaluative difference between the weighted regional Sunnybrook and the gross House-Brackmann systems . Substantial agreement was found between the regional Sunnybrook and Yanagihara scales . Sunnybrook grading is easy and quick . By adding objective measurements and additional secondary defects , the Sunnybrook system can be an alternative to the other predominating grading systems Objective : To investigate the effects of valacyclovir and prednisolone in comparison with those of placebo and prednisolone for the treatment of Bell 's palsy , excluding zoster sine herpete . Study Design : Prospect i ve , multicenter , r and omized placebo-controlled study . Setting : Six academic tertiary referral centers . Patients : Ultimately , 221 patients with Bell 's palsy who were treated within 7 days of the onset . Serological and polymerase chain reaction examinations were performed to distinguish Bell 's palsy from zoster sine herpete . Intervention : The patients were treated with either valacyclovir ( dosage , 1,000 mg/d for 5 days ) plus prednisolone ( VP [ n = 114 ] ) or placebo plus prednisolone ( PP [ n = 107 ] ) administered orally . Main Outcome Measure : Recovery from the palsy was defined as a score higher than 36 using Yanagihara 40-point scoring system without facial contracture or synkinesis . The patients were followed up until complete recovery occurred or for more than 6 months in cases with a poor prognosis . Results : The overall rate of patient recovery among those treated with VP ( 96.5 % ) was significantly better ( p < 0.05 ) than the rate among those treated with PP ( 89.7 % ) . The rate of patient recovery was also analyzed by classifying the initial severity of facial palsy . In cases of complete or severe palsy , the rates of patients treated with VP and PP who recovered were 95.7 % ( n = 92 ) and 86.6 % ( n = 82 ) , respectively ; the recovery rate for treatment with VP was significantly better than that with PP ( p < 0.05 ) . Conclusion : The valacyclovir and prednisolone therapy was more effective in treating Bell 's palsy , excluding zoster sine herpete , than the conventional prednisolone therapy . To our knowledge , this is the first controlled study of an antiviral agent in the treatment of a sufficient number of Bell 's palsy cases based on an etiologic background Idiopathic facial nerve paralysis ( IFNP ) is a common malady . Because its etiology is unclear , there are a variety of treatment options . Studies to date have not clearly established the benefits of treatment with oral steroids ( prednisone ) . The authors performed a r and omized double-blind controlled study comparing the use of placebo versus prednisone which shows that prednisone-treated patients benefit from early treatment . Seventy-six patients met inclusion criteria and completed follow-up until recovery ; 35 patients received prednisone and 41 received placebo . Their mean age was 36.8 years . Facial nerve function was assessed using the House-Brackmann facial nerve grading scale , as well as a variety of other measures . Patients were evaluated pretreatment , regularly post-treatment until judged recovered ( return of facial function to a grade III or better ) , and at 6 months after recovery . Difference in mean time to resolution for the prednisone ( 51.4 days ) and placebo ( 69.3 days ) groups was not statistically significant . There was a significant difference in grade at recovery , with the placebo group having a higher proportion of grade III results ( P < .03 ) . Eight of 10 patients with electroneurography ( ENOG ) evidence of denervation were in the placebo group and accounted for 6 of the 7 grade III results . However , the difference in proportion of patients with evidence of denervation for the prednisone ( 5.7 % ) and placebo ( 19.5 % ) groups did not achieve statistical significance . This study shows that patients treated with prednisone have less denervation than placebo-treated patients . They also have a significant improvement in facial grade at recovery compared to placebo-treated patients . Therefore , the authors recommend that all patients at risk for developing denervation receive prednisone treatment A prospect i ve , controlled , double-blind study was design ed to evaluate the effect of steroid treatment on the natural history of Bell 's palsy . Fifty-one patients were included in the study between 1972 and 1974 . The patients were evaluated and started on treatment within two days of onset of Bell 's palsy and followed for six months . Treatment was given in r and omized double-blind fashion and consisted of either vitamins or a total of 410 mg of prednisone plus vitamins in descending doses over 10 days . The recovery of facial motor function was determined by three physicians who had no knowledge of the treatment received by the patients . They examined photographs of the patients taken six months after onset of paralysis in eight positions of facial function and categorized them as to complete fair , or poor recovery of facial function . These results of this evaluation were su bmi tted to the biostatistician who broke the treatment code . The results of this study demonstrate no statistically significant beneficial effect of steroid therapy upon recovery from Bell 's palsy . Factors considered included the patients ' age , sex , the presence of pain , ageusia , hyperacusis , diabetes , hypertension , the progression and degree of palsy , the results of nerve excitability and salivary flow tests , and the time at which recovery was first noted or became complete . Bell 's palsy remains without a proven efficacious treatment Idiopathic facial palsy ( Bell ’s palsy ) was first described by Charles Bell in 1883 [ 1 ] . Since then , the treatments employed have been empirical in some way , as no etiological cause has been well established . Some theories are widely accepted such as viral , ischemic , and autoimmune origin [ 2–4 ] . All of them are based on vascular changes causing edema with neural compression and then neuropraxia . The drug most commonly used is cortisone , with the finality of aging on the edema . In the literature we have found no citations about the use of dexamethasone , although it is known to have an excellent effect in acute processes of the central nervous system because of its fast efficacy and aggregation on neuronal membrane . We observed that many patients treated with different drugs had a good evolution too . The aim of this study is to find out the real advantage of treating patients with dexamethasone by analyzing the final evolution of the paralysis and the recuperation time OBJECTIVES To determine whether reactivation of herpes simplex virus ( HSV ) type 1 or varicella-zoster virus ( VZV ) is the main cause of Bell 's palsy and whether antiviral drugs bring about recovery from Bell 's palsy . STUDY DESIGN R and omized , multicenter , controlled study . METHODS One hundred fifty patients with Bell 's palsy were enrolled in this study . The patients were r and omly assigned to a prednisolone group or a prednisolone-valacyclovir group , in whom virologic examinations for HSV-1 and VZV were performed by simple r and omization scheme in sealed envelopes . The recovery rates among various groups were analyzed using the Kaplan-Meier method and the Cox proportional hazards model . RESULTS Reactivation of HSV-1 , VZV , and both viruses was detected in 15.3 % , 14.7 % , and 4.0 % of patients , respectively . There was no significant difference in recovery rates between the prednisolone group and the prednisolone-valacyclovir group , although recovery in the patients with HSV-1 reactivation tended to be higher in the prednisolone-valacyclovir group than in the prednisolone group . There was a significant difference in recovery among age groups and between individuals with complete and incomplete paralysis . CONCLUSIONS Reactivation of HSV-1 or VZV was observed in 34 % of the patients with Bell 's palsy . The effect of combination therapy with prednisolone and valacyclovir on recovery was not significantly higher than that with prednisolone alone PURPOSE The pathogenetic mechanism of Bell 's palsy is thought to involve herpes simplex virus reactivation within the geniculate ganglion , followed by inflammation and entrapment of the nerve at the meatal foramen . We therefore compared the therapeutic effect of acyclovir plus steroid vs steroid alone , in combination with physical therapy , in patients with Bell 's palsy . MATERIAL S AND METHODS In a double-blind , r and omized , prospect i ve trial , 91 patients were r and omized to treatment with acyclovir and prednisone ( 44 patients ) or prednisone alone ( 47 patients ) . All patients underwent physical therapy . The follow-up period was greater than 6 months or encompassed the period of complete recovery from paralysis . House-Brackmann grade was evaluated 2 and 6 months after onset , with complete and satisfactory recovery defined as House-Brackmann grade s I and II , respectively . RESULTS The overall recovery rate of patients treated with steroid and acyclovir ( 93.1 % ) was greater than that of patients treated with steroid alone ( 85.1 % ) , but the difference was not statistically significant . CONCLUSION The benefit of acyclovir in Bell 's palsy has not been definitively established |
14,046 | 26,224,322 | NSAIDs versus other NSAIDsWhen NSAIDs were compared with each other there was little evidence of the superiority of any individual NSAID for either pain relief or safety .
There was no evidence that COX-2-specific inhibitors were more effective or tolerable for the treatment of dysmenorrhoea than traditional NSAIDs ; however data were very scanty .
There was no evidence of a difference with regard to adverse effects , though data were very scanty .
NSAIDs appear to be a very effective treatment for dysmenorrhoea , though women using them need to be aware of the substantial risk of adverse effects .
There is insufficient evidence to determine which ( if any ) individual NSAID is the safest and most effective for the treatment of dysmenorrhoea . | BACKGROUND Dysmenorrhoea is a common gynaecological problem consisting of painful cramps accompanying menstruation , which in the absence of any underlying abnormality is known as primary dysmenorrhoea .
Research has shown that women with dysmenorrhoea have high levels of prostagl and ins , hormones known to cause cramping abdominal pain .
Nonsteroidal anti-inflammatory drugs ( NSAIDs ) are drugs that act by blocking prostagl and in production .
They inhibit the action of cyclooxygenase ( COX ) , an enzyme responsible for the formation of prostagl and ins .
The COX enzyme exists in two forms , COX-1 and COX-2 .
Traditional NSAIDs are considered ' non-selective ' because they inhibit both COX-1 and COX-2 enzymes .
More selective NSAIDs that solely target COX-2 enzymes ( COX-2-specific inhibitors ) were launched in 1999 with the aim of reducing side effects commonly reported in association with NSAIDs , such as indigestion , headaches and drowsiness .
OBJECTIVES To determine the effectiveness and safety of NSAIDs in the treatment of primary dysmenorrhoea . | The clinical efficacy of tolfenamic acid and mefenamic acid in the treatment of primary dysmenorrhoea was studied in a prospect i ve , controlled , double-blind , cross-over study comprising 73 patients aged 13 - 39 with an average body weight of 56 kilos . The patients were r and omized to receive either tolfenamic acid ( 200 mg t.i.d . ) or mefenamic acid ( 500 mg t.i.d . ) for 3 days , during 3 consecutive menstrual cycles each , in a sequential design A-B or B-A. At the beginning and at the end of each treatment period , 13 dysmenorrhoeic symptoms were evaluated on a visual analogue scale ( lower back pain , interference with daily activities , nausea , vomiting , diarrhoea , headache , dizziness , fatigue , sweating , chills , hot flashes , depressant states , and mood swings ) . The data were analyzed by using two statistical models . The first one , for the 73 patients , by making paired comparisons regardless of treatment sequence . With respect to the initial values , the results showed that both drugs were statistically significant ( P < 0.05 ) in reducing the intensity of the evaluated symptoms . When comparing both treatments , tolfenamic acid showed a significant difference as to interference with daily activities ( P < 0.025 ) and hot flashes ( P < 0.005 ) . In the result analysis with the second model , the groups were divided according to the first assigned treatment and paired comparisons were made . It was observed that the group receiving tolfenamic acid in the last sequence reached a higher level of response and statistical significance was demonstrated in 8 of 13 evaluated symptoms . ( ABSTRACT TRUNCATED AT 250 WORDS In 12 dysmenorrheic patients we examined the therapeutic action of the Prostagl and in- synthesis inhibitor : Ibuprofen , a non-steroidal analgesic agent . Ibuprofen highly significantly reduced the resting pressure ( P less than 0.001 ) , active pressure ( P less than 0.001 ) and frequency ( P less than 0.05 ) of cyclic activity of the uterus , as well as menstrual pain ( P less than 0.001 ) . Since these effects occurred after a single oral dose of 800 mg Ibuprofen , without side effects or complications , extensive field trials are recommended with this and other PG- synthesis inhibitors , to assess their therapeutic benefits Following the demonstration that increased prostagl and in F2 alpha production causes pain similar to dysmenorrhea , and the finding that prostagl and in synthetase inhibitors are capable of relieving menstrual pain , the early theory of uterine ischemia has once again gained support as the most likely explanation for this condition . In a double-blind , placebo-controlled , crossover study , 30 of 43 women with moderate to severe dysmenorrhea who completed the trial preferred flurbiprofen ( Ansaid , Upjohn ) , a potent new analgesic/anti-inflammatory agent ( 50 mg four times daily ) , to aspirin ( 650 mg four times daily ) and placebo . Flurbiprofen was also rated superior to aspirin and placebo in the degree of pain relief . An algorithm for the diagnosis and treatment of 90 percent of women with primary dysmenorrhea is presented A multicenter open crossover study compared piroxicam and mefenamic acid and piroxicam and diclofenac in the treatment of primary dysmenorrhea in 91 patients . Piroxicam 40 mg/day for two days followed by 20 mg/day was compared with mefenamic acid 500 mg t.i.d . and diclofenac 50 mg b.i.d . for two menstrual cycles on each drug . Assessment of efficacy found that piroxicam was more effective than either comparative drug . All three agents were well tolerated . It is concluded that piroxicam is a safe and effective drug for the treatment of primary dysmenorrhea Prostagl and ins E2 and F2a in the menstrual fluid from 12 patients with primary dysmenorrhea were measured by radioimmunoassay ( RIA ) . Each patient was studied for 3 cycles , using vaginal tampons issued for this study . All tampons were collected individually for prostagl and in extraction and RIA . Severity of dysmenorrhea and clinical response to treatment were evaluated by a scoring method and by the patients ' self- assessment . Each patient in this double-blind cross-over study had a control cycle and 2 treatment cycles with naproxen sodium tablets ( 275 mg ) or placebo in r and om order . The treatment regimen was 2 tablets at the first sign of menses followed by one tablet 4 times daily for 3 days . Nine patients obtained good to excellent relief from naproxen sodium , but no relief from the placebo . Two patients had moderate to good response to both naproxen and placebo , and one patient showed no response . Naproxen therapy but not placebo therapy sharply reduced menstrual prostagl and in F2a and prostagl and in E2 release . There was a positive correlation between menstrual prostagl and in levels and the severity of dysmenorrhea . Symptomatically , naproxen sodium was most effective in alleviating severe menstrual cramps but had little effect on mild cramps . It was also effective in ameliorating many but not all of the subjective symptoms such as dizziness , nausea , and vomiting . Relief of dysmenorrhea was apparent within one hour after the initial dose , attained maximum level in 2 hours , and was maintained throughout therapy Background : Dysmenorrhea has negative effects on women 's life . Due to side-effects of chemical drugs , there is growing trend toward herbal medicine . The aim of this study was to assess the effect of Dill compared to mefenamic acid on primary dysmenorrhea . Material s and Methods : This double-blind , r and omized , clinical trial study was conducted on 75 single female students between 18 and 28 years old educating in Nursing and Midwifery School and Paramedical Faculty of Qom University of Medical Sciences of Iran in 2011 . They were allocated r and omly into one of the three groups : In Dill group , they took 1000 mg of Dill powder q12h for 5 days from 2 days before the beginning of menstruation for two cycles . Other groups received 250 mg mefenamic acid or 500 mg starch capsule as placebo , respectively . Dysmenorrhea severity was determined by a verbal multidimensional scoring system and a visual analog scale ( VAS ) . Students with mild dysmenorrhea were excluded . Data were analyzed by SPSS using the descriptive statistic , paired- sample s t-test , Wilcoxon signed-rank test , Mann-Whitney test , and Kruskal-Wallis test . Results : There were no significant differences between three groups for demographic or descriptive variables . Comprising the VAS showed that the participants of Dill and mefenamic acid groups had lower significant pain in the 1st and the 2nd months after treatment , whereas in the placebo group this was only significant in the 2nd month ( P < 0.05 ) . Conclusion : Dill was as effective as mefenamic acid in reducing the pain severity in primary dysmenorrhea . Further studies regarding side-effects of Dill and its interactivity are recommended & NA ; The paradoxical improvement of many subjective phenomena during placebo therapy is both well established and notorious for confounding many well design ed studies . Consistently high placebo response rates of as much as 44 % have been reported in subjective studies of dysmenorrhea . In an effort to evaluate the discordant role of objective uterine activity known to be associated with primary dysmenorrhea and the subjective sensation of discomfort , data from 18 patients undergoing meclofenamate therapy for primary dysmenorrhea were evaluated . In this study both the sum of pain intensity differences ( SPID ) and the total pain relief scores at each study time ( TOTPAR ) showed increases during both drug and placebo therapy with statistically significant differences favoring drug therapy . Ten percent of patients eventually reported ‘ complete relief ’ during placebo therapy . In contrast to this subjective placebo response , objective measures of intrauterine pressure showed consistent worsening in 13 out of 14 pressure parameters with 25 % of patients experiencing a 2‐fold or greater increase in the number of contractions while on placebo therapy . The ability to document unchanged or worsening objective parameters associated with the development of ‘ pain ’ in the face of reported subjective improvements may provide new insight into the mechanisms by which the ‘ placebo effect ’ occurs Forty-two women with primary dysmenorrhea were successfully enrolled in a double-blind , three-way crossover study in which each patient received either ibuprofen ( Motrin ) , indomethacin ( Indocin ) , or a placebo during each of three successive painful menstrual cycles . Thirty-one patients successfully completed the study . The results showed that ibuprofen and indomethacin were superior to the placebo in their ability to relieve pain and that patients preferred ibuprofen to indomethacin . Ibuprofen was significantly superior to the placebo regarding the number of patients who could pursue normal daily function , whereas indomethacin was not . Four patients reported side effects , all during the indomethacin cycle 90 women participated in a 4-month study . During the first 2 periods , they took no pain relievers whatsoever ; during their last 2 periods they took 2 X 325 mg aspirin , acetaminophen or an identically packaged placebo every 4 h to total 8 tablets during the first 24 h of their periods beginning with spotting . For statistical analysis , periods 1 and 2 were combined and averaged , then compared with periods 3 and 4 combined and averaged . Total menstrual loss in grams , number of days of flow , and pain of cramps and headaches were analyzed by MANOVA for each of the three treatment groups . An ANOVA for each of these variables as well as for daily menstrual loss for the first 3 menstrual days was also performed . The MANOVA for all variables by the three treatment groups failed to show any significant differences . Similarly , ANOVAs for the individual variables failed to indicate significant differences except for the variable pain of cramps ( p = 0.0072 ) . The Duncan 's Multiple Range Test for pain of cramps showed that the average pain for the placebo group was higher than for either the aspirin or the acetaminophen group , although the means for these two groups were not significantly different . These results indicate that neither aspirin nor acetaminophen in the doses given alter either total menstrual loss or the pattern of loss during the first 3 menstrual days . However , both preparations were found to be more effective than placebo in reducing pain of cramps BACKGROUND Dysmenorrhea is the most common menstrual complaint in young women , with a prevalence as high as 90 % . It is responsible for substantial repeated short-term absenteeism from school and work in young women . Effective treatments are available , including nonsteroidal anti-inflammatory drugs ( NSAIDs ) . In many countries , a variety of NSAIDs have become available as over-the-counter ( OTC ) drugs . OBJECTIVE The goal of this study was to compare the efficacy and safety of OTC doses of naproxen ( 400 mg ) and naproxen/naproxen sodium ( 200/220 mg ) with acetaminophen ( 1000 mg ) , ibuprofen ( 200 mg ) , and placebo in the treatment of primary dysmenorrhea . METHODS A pooled analysis of 5 trials was performed . Efficacy was assessed by pain relief , relief of other dysmenorrheic symptoms , time to backup medication or remedication , and treatment preference . Tolerability was assessed by recording adverse events ( AEs ) . RESULTS A total of 443 women were enrolled in the combined studies . Naproxen 400 mg provided greater pain relief than acetaminophen and placebo within 30 minutes of administration ( P < 0.01 and P < 0.05 , respectively ) . Furthermore , naproxen 400 mg and 200 mg provided greater pain relief than both acetaminophen ( P < 0.01 and P < 0.05 , respectively ) and ibuprofen ( P < 0.001 and P < 0.01 , respectively ) at 6 hours after administration . Both doses of naproxen had higher scores than placebo for symptom relief and drug preference ( all P < 0.001 ) . The AEs and their frequency were similar among the treatment groups . No serious AEs were reported . CONCLUSION When administered at OTC doses , naproxen was effective in the relief of pain and other symptoms of primary dysmenorrhea and had a good safety profile in the population studied Our objective was to examine the effect of an Iranian herbal drug in the treatment of primary dysmenorrhea . A r and omized , double-blind , placebo-controlled pilot trial among 180 female students at Isfahan University dormitory aged 18 to 27 who suffered from primary dysmenorrhea was undertaken . The participants were r and omly divided into three groups : herbal drug , mefenamic acid , and placebo . The herbal drug group was given 500 mg of highly purified saffron , celery seed , and anise ( SCA ) extracts three times a day for three days , starting from the onset of bleeding or pain . Participants were followed for two to three cycles from the beginning of menstruation through the three days of bleeding . Main outcome measures were the severity and duration of pain at 2 and 3 months . A visual analogue scale was used to record pain . There were statistically significant reductions in pain scores and pain duration scores in the groups that took SCA ( P < . 001 ) and mefenamic acid ( P < . 01 ) . The decrease in pain score was reflected by a significant reduction in other drug use among the treatment groups compared with the women in the placebo group . The magnitude of the reduction was significantly greater in the SCA group than in the mefenamic acid and placebo groups . Both drugs effectively relieved menstrual pain as compared with the placebo . More clinical trials are needed to establish the efficacy of this herbal drug Background This paper examines the association between use of protective devices , frequency of acute health problems and health-protection information received by participants engaged in the Prestige oil spill clean-up in Asturias and Cantabria , Spain . Methods We studied 133 seamen , 135 bird cleaners , 266 volunteers and 265 paid workers selected by r and om sampling , stratified by type of worker and number of working days . Information was collected by telephone interview conducted in June 2003 . The association of interest was summarized , using odds ratios ( OR ) obtained from logistic regression . Results Health-protection briefing was associated with use of protective devices and clothing . Uninformed subjects registered a significant excess risk of itchy eyes ( OR:2.89 ; 95%CI:1.21–6.90 ) , nausea/vomiting/dizziness ( OR:2.25 ; 95%CI:1.17–4.32 ) and throat and respiratory problems ( OR:2.30 ; 95%CI:1.15–4.61 ) . There was a noteworthy significant excess risk of headaches ( OR:3.86 : 95%CI:1.74–8.54 ) and respiratory problems ( OR:2.43 ; 95%CI:1.02–5.79 ) among uninformed paid workers . Seamen , the group most exposed to the fuel-oil , were the worst informed and registered the highest frequency of toxicological problems . Conclusion Proper health-protection briefing was associated with greater use of protective devices and lower frequency of health problems . Among seamen , however , the results indicate poorer dissemination of information and the need of specific guidelines for removing fuel-oil at sea Abstract . The analgesic effect of paracetamol , acetyl‐salicylic acid , and placebo on dysmenorrhea were compared in a double‐blind cross‐over study of 30 women . There was a moderate placebo effect , but no significant difference was found between the three treatments . Blood loss was also measured and it did not vary , with the type of drug ingested . It is concluded that paracetamol and acetylsalicylic acid in the doses used ( 0.5 g x 4 for 3 days ) were not effective against heavy dysmenorrhea , and that none of the drugs influenced the amount of blood lost Summary : The efficiency and side‐effects of tiaprofenic acid , mefenamic acid and placebo were compared in the treatment of primary dysmenorrhoea . The trial was a double‐blind prospect i ve r and omized 3‐way crossover study during 6 successive menstrual cycles following a 2‐cycle run‐in period and involved 50 women with primary dysmenorrhoea selected from 96 volunteers between 16 and 35 years of age . Overall pain was significantly less ( p < 0.05 ) on treatment with tiaprofenic acid than on treatment with mefanemic acid , placebo , or the women 's usual treatments . Both active treatments were well tolerated but more side‐effects were reported during treatment with mefenamic acid Objective To determine the effect of 3 different cyclo-oxygenase ( COX ) inhibitors on primary dysmenorrheic pain . Method Eleven female patients self-medicated with either placebo ( sugar ) , 25 mg of the COX-2 specific inhibitor rofecoxib , 50 mg of the nonselective COX inhibitor diclofenac potassium , or 7.5 mg of the COX-2 selective inhibitor meloxicam , over 4 menstrual cycles . Pain was assessed using the McGill Pain Question naire and a visual analog scale . Results The pain response index , present pain index , and visual analog scale were highly correlated as measures of intensity of pain ( r=0.81 to 0.96 , P<0.0001 ) . Rofecoxib and diclofenac potassium both decreased the duration of dysmenorrheic pain compared with placebo ( P<0.001 ) and with meloxicam ( P<0.01 ) , and were equally effective in improving pain , compared with placebo , after each capsule ( P<0.001 ) . When compared with placebo , both drugs also provided 50 % or more pain relief , after each capsule ( P<0.0048 ) . Meloxicam , although superior to placebo , was not as effective as rofecoxib and diclofenac potassium in reducing pain , and when compared with placebo , was associated with providing 50 % or more of pain relief only after the third and fourth capsules ( P=0.016 ) . Conclusions Rofecoxib and diclofenac potassium , when taken in recommended doses , were equally effective in alleviating pain associated with primary dysmenorrhea Thirty‐two patients were treated with placebo tablets or indomethacin ( 25 mg three times daily ) in a six‐month , double‐blind , cross‐over trial . During indomethacin therapy , 75 per cent of patients experienced significant pain relief while associated vomiting and diarrhoea were relieved in 44 per cent and 64 per cent of patients respectively . The efficacy of indomethacin was comparable to that of other prostagl and in synthetase inhibitors OBJECTIVES To investigate the efficacy of single daily doses of rofecoxib , a selective inhibitor of cyclooxygenase-2 , in dysmenorrhea . METHODS Fifty-five patients were included in this r and omized , placebo-controlled , cross-over study . Patients were r and omized to use placebo , naproxen sodium ( 550 mg ) , 25 and 50 mg doses of rofecoxib in various orders . Pain intensity , analgesic efficacy of drugs , total number of pills used and side effects were evaluated . RESULTS Rofecoxib with daily single doses of 25 and 50 mg decreased the pain intensity in a manner similar to naproxen sodium . Most of the patients ( 85.45 % and 96.46 % ) evaluated the analgesic efficacy of rofecoxib as ' perfectly effective ' . Rofecoxib was found to be effective for pain relief both in primary and secondary dysmenorrhea . Gastrointestinal adverse effects were less than those with naproxen sodium . CONCLUSIONS A ' one a day ' dose of 25 mg rofecoxib is an effective choice with lower gastrointestinal adverse effects than naproxen sodium BACKGROUND Nonsteroidal anti-inflammatory drugs ( NSAIDs ) are established as treatment for managing pain associated with primary dysmenorrhea . However , the efficacy and tolerability of lumiracoxib 200 mg once daily ( q.d . ) has not previously been examined in primary dysmenorrhea . METHODS Two r and omized , multicenter , double-blind , placebo-controlled , crossover studies of similar design have assessed the efficacy and tolerability of two regimens of lumiracoxib compared with placebo ( Study 1 ) or naproxen and placebo ( Study 2 ) in women ( aged 18 - 45 years ) with moderate to severe primary dysmenorrhea . In Study 1 ( n = 132 ) , patients received lumiracoxib 200 mg q.d . , lumiracoxib 200 mg with a 200 mg redose ( p.r.n . ) on day 1 , or placebo . In Study 2 ( n = 144 ) , patients received lumiracoxib 200 mg q.d . , lumiracoxib 200 mg with a 200 mg redose p.r.n . on day 1 , naproxen 500 mg twice daily ( b.i.d . ) , or placebo . Patients recorded study medication use , efficacy assessment s , and rescue medication use . RESULTS The primary efficacy variable , summed ( time-weighted ) pain intensity difference ( categorical scale ) over the first 8 hours ( SPID-8 ) , was similar between all active treatments ( e.g. , p = 0.939 for naproxen 500 mg b.i.d . vs. lumiracoxib 200 mg q.d . in Study 2 ) , and all active treatments were superior to placebo ( p < 0.001 ) . Median time-to-onset of analgesia was similar between lumiracoxib 200 mg q.d . and naproxen 500 mg b.i.d . Similar trends were observed for all other secondary efficacy variables . All treatments were well tolerated . CONCLUSIONS Short-term administration of lumiracoxib 200 mg q.d . is effective and well tolerated and provides an alternative treatment option for the management of moderate to severe pain associated with primary dysmenorrhea Fifty-five women with primary dysmenorrhea were enrolled in a study in which each took ibuprofen ( 400 mg ) , propoxyphene hydrochloride ( 64 mg ) , or a placebo alternately in consecutive menstrual cycles for relief of pain . Fifty-one completed the study during three successive cycles in this triple-blind , crossover , r and omized investigation . Ibuprofen was clearly superior to propoxyphene and the placebo in patient preference , degree of relief , and need for supplementary analgesics . In addition , a significantly greater number of patients were able to pursue their normal daily functions during the ibuprofen cycle . Propoxyphene was superior to the placebo but not to the same extent as ibuprofen . Only three side effects were reported during the study , two relative to propoxyphene and one recorded during a placebo cycle . These data show that ibuprofen is an effective agent when used for treatment of dysmenorrhea without organic etiology The prostagl and in synthetase inhibitor ibuprofen was evaluated for relief of severe primary dysmenorrhea in a controlled , double-blind , cross-over study in seven patients for a total of 23 menstrual cycles . In eight untreated cycles , the amount of prostagl and in ( PG ) in the menstrual fluid was higher than in nondysmenorrheic subjects . There was good to excellent relief of dysmenorrhea in seven ibuprofen-treated cycles , which was associated with a threefold to fourfold reduction in menstrual PG released . When a placebo was given in five cycles , only poor or minimal relief of dysmenorrhea was obtained and the menstrual PG released was similar to that in control cycles . In individual patients , there was a remarkable correlation between the severity of menstrual pain as assessed daily by the patient and the level of menstrual PG released during the corresponding period . The effect of ibuprofen therapy on menstrual fluid volume was inconsistent . The study shows that in severe primary dysmenorrhea there is increased release of PG in the menstrual fluid ; this can be effectively suppressed with ibuprofen , which provides excellent relief from the symptoms of dysmenorrhea Abstract . Three groups of patients with primary dysmenorrhea were treated with prostagl and in synthetase inhibitors . Thirty‐one women received indomethacin at a dose of 25 mg × 3‐4 per day usually starting one to two days before the onset of menstruation and 38 women received naproxen 250 mg × 3–4 per day usually starting on the first day of bleeding ( open studies ) . Seventy‐one per cent of the patients experienced moderate or good relief of pain following indomethacin and 67 % following naproxen . In a third series a double‐blind crossover study using the sodium salt of naproxen versus placebo in 26 patients showed that naproxen‐sodium was significantly more effective than the placebo ( p<0.05 ) . At the doses employed , the prostagl and in synthetase inhibitors were not associated with any side effects of major concern . The study indicates that this form of therapy offers an effective alternative in patients who for some reasons do not accept hormonal treatment Painful menses , one of the most frequent gynecologic complaints , is incapacitating for many women . It has recently been proposed that increased endometrial prostagl and in production and prostagl and in-induced myometrial contractility may be responsible for dysmenorrhea . In this prospect i ve , double-blind , 3-way , crossover study , relief of pain by an antiprostagl and in drug , ibuprofen ( 400 mg ) , was compared with propoxyphene ( 64 mg ) and placebo in 22 women with severe primary dysmenorrhea . Ibuprofen was significantly more effective in 18 patients when compared to the other 2 treatment regimens ( P < 0.001 ) , while propoxyphene was superior to placebo in 13 patients ( P < 0.05 ) . Prostagl and in E and F synthesis rates in endometrial biopsy specimens taken on the second day of treatment in 2 patients during each treatment cycle were lowest during ibuprofen in one case but showed no definite pattern in the second This communication reports the results of a double-blind , cross-over study to determine the efficacy of the prostagl and in ( PG ) synthetase inhibitor ibuprofen ( MotrinB , Upjohn ) in relieving primary dysmenorrhea , and in suppressing the release of PG in menstrual fluid . A total of 7 patients and 23 menstrual cycles were studied , following a double-blind cross-over protocol . All subjects recruited for the study were 23 - 25 years of age , nulliparous , weighed 50 - 70 kg , had a history of primary dysmenorrhea starting within a year of their menarche , had no clinical evidence of pelvic pathology on repeated bimanual pelvic examination , and were not on any form of hormonal contraception or intrauterine device . One or more control cycles , during which no medication was taken , were studied in each patient . In the study cycles , 400 mg ibuprofen or a placebo of identical appearance were taken four times a day , beginning 3 days before through 3 days after the expected onset of menses , with a total duration not exceeding 7 consecutive days in any cycle . The patients abstained from sexual intercourse in the last week of their cycle and did not take any other medications . All cycles studied were ovulatory as documented by biphasic basal body temperature and plasma progesterone Under double-blind , crossover conditions , 43 women with primary dysmenorrhea received ketoprofen , ibuprofen , and placebo during three consecutive menstrual cycles . Pain intensity and pain relief were determined before and for 6 hours after the loading dose ( ketoprofen 150 mg , ibuprofen 800 mg ) and before and 2 hours after the maintenance dose ( ketoprofen 75 mg , ibuprofen 400 mg ) . Mean pain intensity difference and pain relief scores consistently indicated greater pain relief after the loading doses of ketoprofen and ibuprofen than after placebo . Significant ( P less than 0.05 ) mean changes that were measured by 13 indices of analgesia after the loading doses of both ketoprofen and ibuprofen indicated greater efficacy for the active treatments than for placebo . The patients ' global evaluations after the loading doses were significantly ( P less than 0.05 ) better for the active treatments than for placebo . The efficacy results were similar after the maintenance doses . The rates of a " good " to " excellent " response were 77 % for ketoprofen , 73 % for ibuprofen , and 35 % for placebo . Ketoprofen and ibuprofen were equally well tolerated , the most frequent adverse experiences being gastrointestinal symptoms for ketoprofen and central nervous system side effects for ibuprofen Abstract Objective : Assess the efficacy and safety of etoricoxib 120 mg compared with ibuprofen 600 mg qid in the treatment of moderate to severe primary dysmenorrhea in Chinese women . Methods : This multicenter , double-blind , two-period , cross-over study r and omized healthy , Chinese women ≥18 years of age to etoricoxib 120 mg qd or ibuprofen up to 2400 mg ( 600 mg qid ) upon onset of moderate or severe primary dysmenorrhea symptoms during two menstrual cycles . The primary efficacy endpoint was Total Pain Relief score over the first 6 hours ( TOPAR6 ) . Secondary endpoints included Sum of Pain Intensity Difference scores over the first 6 hours ( SPID6 ) and Patient ’s Global Evaluation ( GLOBAL ) of pain at 6 and 24 hours post initial dose . The primary hypothesis was that etoricoxib would be non-inferior to ibuprofen . Adverse experiences ( AE ) were monitored and evaluated . Results : A total of 139 patients were included in this study . Difference in least squares ( LS ) mean ( 95 % CI ) TOPAR6 score for etoricoxib vs. ibuprofen was 0.89 ( 0.03 , 1.76 ) ( p = 0.043 ) . LS mean ( 95 % CI ) difference for etoricoxib vs. ibuprofen SPID6 , GLOBAL6 , and GLOBAL24 were 0.20 ( −1.16 , 1.57 ) ( p = 0.768 ) , 0.26 ( 0.07 , 0.45 ) ( p = 0.007 ) , and 0.36 ( 0.17 , 0.54 ) ( p < 0.001 ) , respectively . AEs were rare , with the following AEs determined to be drug-related : hypomenorrhea ( two patients on etoricoxib ) and allergic dermatitis ( one patient on ibuprofen ) . Limitations of the study design include a sample size that is not adequate for evaluation of rare adverse effects , an evaluation period that was limited to 24 hours , and inconsistent frequency of active treatment doses between etoricoxib ( once daily ) and ibuprofen ( up to four times daily ) . Conclusions : The primary objective of the study was met , demonstrating that etoricoxib 120 mg qd was non-inferior to ibuprofen 600 mg qid ; further , etoricoxib was statistically superior to ibuprofen 600 mg qid according to the primary endpoint ( TOPAR6 ) and patient global assessment s of study medication . Etoricoxib and ibuprofen were generally well tolerated Background : Dysmenorrhea is one of the most common medical problems in gynecology causing several problems in the personal and social life of women . This study was conducted to compare the effect of thymus vulgaris and ibuprofen on the treatment of primary dysmenorrhea Methods : This clinical study was conducted on 84 students of Babol University of Medical Sciences with primary dysmenorrhea . The students were r and omly assigned to three groups receiving thymus vulgaris , ibuprofen and placebo . In all three groups , with the beginning of pain , 200 mg capsules and 25 drops of essential oil were given every 6 hours for two consecutive cycles . Pain intensity used the visual scale before and one hour after each dose for 48 hour after starting medication . The data were collected and analyzed . This study was registered in the Iranian Registry of Clinical Trial ( www.i rct .ir ) with registration number ID : I RCT 201101245683N1 Results : The mean age of participants was 20.5±1.8 years . Both thymus vulgaris and ibuprofen were effective to reduce the pain severity of dysmenorrhea . Before treatment , the mean pain intensity in thymus vulgaris , ibuprofen and placebo groups were 6.57±2.02 , 5.30±2.23 and 6.18±1.78 , respectively and after treatment decreased to 1.21±1.06 , 1.48±1.62 and 3.54±2.26 , respectively . Reduction of pain severity was not statistically significant between the two medications , however it was significant for each drug compared with placebo ( p<0.001 ) . Conclusion : The results suggest that thymus vulgaris as well as ibuprofen can be effective in reducing the severity of pain and spasm in primary dysmenorrhea 41 women under 30 years of age took part in a prospect i ve , double-blind study to determine whether indomethacin is effective in treating dysmenorrhea . Indomethacin capsules ( 35 mg x 3/day ) or suppositories ( 100 mg ) or placebos were administered for 2 consecutive days in 2 consecutive menstrual cycles , after which the other type of preparation ( indomethacin or placebo ) was used . 13 said that indomethacin and placebo use were equally effective in relieving dysmenorrhea . 28 preferred indomethicin ( P .00025 ) . Days of sick leave and days of bed rest ( P .0005 ) , use of thermotherapy ( P .0025 ) , and duration of uterine cramping and use of supplemental medicine ( P .00025 ) were all significantly reduced among indomethicin users . Gastrointestinal symptoms were significantly more frequent among indomethicin users ( P .05 ) OBJECTIVES Study was planned to evaluate the efficacy and safety of lornoxicam in moderate to severe menstrual pain due to primary dysmenorrhea . STUDY DESIGN This doubled blind , double dummy , r and omized , comparable study of lornoxicam versus ibuprofen was conducted at Sir Takhtsinghji General Hospital , Bhavnagar , Gujarat , India . Total 57 primary dysmenorrhea participants having mean age±st and ard deviation ( SD ) of 19.2±2.08 were analyzed . The participants were r and omly allocated to either lornoxicam 8 mg or ibuprofen 400 mg two times a day for maximum of three days on two consecutive menstrual periods . The different medication was taken on each cycle . The analgesic efficacy was compared by a total area under pain relief score to 4 and 8h , pain intensity difference , sum of pain intensity difference to 4 and 8h , peak pain intensity difference to 4 and 8h , peak pain relief to 4 and 8h , total medication consumption , rescue medication and participant global evaluation . Adverse effects were recorded in both groups . RESULTS In both treatments , efficacy parameters were significantly reduced at measured time points as compared to baseline . No significant difference was observed between lornoxicam and ibuprofen in terms of efficacy parameters : total area under pain relief to 4h ( 8.0±2.6 vs 8.3±2.7 ) , total area under pain relief to 8h ( 22.4±4.6 vs 23.0±4.4 ) , sum of pain intensity difference to 4h ( -5.7±1.9 vs -6.0±2.0 ) , sum of pain intensity difference to 8h ( -17.5±3.3 vs -17.8±3.5 ) , peak pain relief to 4h ( 3.4±0.8 vs 3.5±0.8 ) , peak pain relief to 8h ( 3.9±0.5 vs 3.9±0.4 ) , peak pain intensity difference to 4h ( -2.6±0.7 vs -2.7±0.7 ) , peak pain intensity difference to 8h ( -3.3±0.6 vs -3.3±0.6 ) . Total medication consumption , a requirement of rescue medication and global evaluation of efficacy were comparable in both groups . The incidence of adverse effect was also similar in both groups . CONCLUSIONS Lornoxicam appears to be a new therapeutic agent for the treatment of primary dysmenorrhea Sixty-four women with primary dysmenorrhea participated in a double-blind , parallel trial of naproxen sodium versus placebo during three menstrual cycles . Comparative measures employed to assess the efficacy of the medications included changes in pain intensity during each dysmenorrheic episode , the degree of pain relief afforded , the necessity of using a supplementary analgesic , and the extent to which medication enabled the patients to continue their daily activities unimpeded . By these measures , naproxen sodium was significantly superior as compared to the placebo . Particularly striking was the fact that of 22 naproxen sodium treated women who historically had to stay at home from work and /or in bed , only 5 remained incapacitated compared with 21 of 26 patients of the placebo group . Only 1 patient experienced side effects ( nausea and hypomenorrhea ) from naproxen sodium The efficacy of diclofenac sodium was investigated in the painful symptoms of primary dysmenorrhea and in reducing menstrual bleeding . Thirty-five nulliparous women ( 17 - 28 yr of age ) were included in a double-blind cross-over study for four menstrual periods , two periods with diclofenac sodium and two periods with placebo . The diclofenac sodium treatment ( total of 58 periods ) reduced the pain significantly in comparison with placebo ( 57 periods ) , as evaluated by subjective rating ( P less than 0.001 ) and by a 6-point scale of pain intensity ( P less than 0.05 ) . Also the amount of menstrual bleeding was significantly reduced as measured by subjective rating ( P less than 0.001 ) and by counting the number of sanitary pads used ( P less than 0.05 ) . The results indicate that diclofenac sodium in low dose ( about 75 mg daily ) is effective not only in reducing the pain at menstruation , but also the bleeding In a double-blind between-patient clinical trial , 82 patients were admitted to the study and after a preliminary period with placebo administered in single-blindness , they were divided into two groups : " placebo-responders " and " placebo non-responders " . Responders were treated with pirprofen capsules ( 400 mg , b.i.d . ) or placebo capsules b.i.d . ; non-responders were treated with pirprofen capsules ( 400 mg , b.i.d . ) or naproxen capsules ( 250 mg , b.i.d . ) according to two different r and omisation lists , for four menstrual cycles . A complete medical examination , including evaluation of associated symptomatology , menstrual flow entity and global efficacy , was performed after each cycle . In the responders group results were significantly better with pirprofen than with placebo after only the second cycle of treatment ( p less than 0.01 ) . In the non-responders group both treatments showed " good " or " excellent " results in more than 80 % of patients in all cycles . In all patients there were no significant differences in the evaluation of the menstrual flow entity , of the associated symptomatology and of the number of side-effects Two prostagl and in synthesis inhibitors , fluproquazone ( 100 mg ) and indomethacin ( 25 mg ) , were compared in a double-blind , crossover study for treatment of primary dysmenorrhoea in 31 patients . Each drug was used during two consecutive menstruations in r and omized order . Both treatments significantly relieved spasmodic pains and other dysmenorrhoeic symptoms . No significant differences were found between the treatments in regard to the overall efficacy assessed at the end of each treated cycle . However , 20 patients preferred indomethacin and 7 patients fluproquazone . Three patients reported mild side-effects with fluproquazone as compared to five patients wih indomethacin . It is concluded that both treatments can be used for treatment of primary dysmenorrhoea The efficacy of oral contraceptives ( OC ) in the treatment of primary dysmenorrhea in controlled studies varies from 50 to 80 % . The addition of a prostagl and in synthetase inhibitor , naproxen , was found to afford pain relief to a further 70 % of women with OC-resistant dysmenorrhea in a double-blind cross-over study comprising 39 patients . This effect was shown to be statistically significant at p = 0.0005 . Our recommendation is that low-dose OCs should be the first choice as contraceptive agents for women with dysmenorrhea and that a prostagl and in synthetase inhibitor should be given when OCs are ineffective OBJECTIVE : To compare the analgesic efficacy of valdecoxib with placebo and naproxen sodium for relieving menstrual cramping and pain due to primary dysmenorrhea . DESIGN : Single-center , double-blind study with a 4-period , 4-sequence crossover design . Patients assessed pain intensity and pain relief at regular intervals up to 12 hours following the initial dose . SETTING : Privately owned outpatient clinic . PATIENTS / PARTICIPANTS : One hundred twenty patient with moderate to severe menstrual cramping were r and omized . Eighty-seven patients completed all treatment cycles . INTERVENTIONS : Valdecoxib 20 mg or 40 mg , naproxen sodium 550 mg , or placebo twice a day as required for ≤ 3 days in a single menstrual cycle . MEASUREMENTS AND MAIN RESULTS : Both doses of valdecoxib ( 20 and 40 mg ) were comparable to naproxen sodium and superior to placebo at all time points assessed for each of the primary end points . Valdecoxib and naproxen sodium had comparable onset and duration of action . Although the study design allowed patients 2 doses per day , only 15 % and 20 % of patients in the valdecoxib 20 mg and valdecoxib 40 mg groups , respectively , required remedication within the first 12 hours . The incidence of adverse events was similar between active and placebo groups . CONCLUSION : Valdecoxib provided a fast onset of analgesic action , a level of efficacy similar to naproxen sodium , and a high level of patient satisfaction in the relief of menstrual pain due to primary dysmenorrhea . Valdecoxib was effective and well tolerated and thus appears to be a viable treatment for menstrual pain due to primary dysmenorrhea The efficacy of different regimens of naproxen sodium for relief of dysmenorrhea in female adolescents was compared and the effect of other social/psychologic factors on the response to treatment tested . Following pretesting , 45 female adolescents were r and omly assigned in a double-blind fashion to one of five treatment regimens and were followed up after 1 , 2 , and 3 months of treatment . There was a dose-related response to naproxen sodium therapy , with subjects receiving loading doses of 550 mg reporting better symptom relief than subjects receiving loading doses of 275 mg . During the first month of treatment , adolescents who reported increased life crisis events experienced greater symptom severity following naproxen therapy . Also , adolescents who reported more severe dysmenorrhea symptoms following three months of naproxen therapy had significantly lower self-concepts than adolescents who reported less symptoms following treatment Forty women with moderate to severe primary dysmenorrhea participated in a two-month , double-blind , crossover trial comparing ketoprofen with mefenamic acid . Treatment with ketoprofen provided rapid and marked pain relief similar to that afforded by mefenamic acid . This improvement in symptoms was accompanied by an amelioration of the disability score , which was equivalent for both drugs . There were no differences between the two treatments with respect to duration of menses or amount of menstrual flow . Patients rated both drugs as equally effective and had no preference for one treatment over the other . One patient dropped out because of a mild allergic reaction to ketoprofen . All other side effects were not severe , although slightly more gastrointestinal reactions were observed with ketoprofen . It is concluded that ketoprofen is as safe and effective as mefenamic acid in the treatment of primary dysmenorrhea OBJECTIVES To compare the effects of ginger , mefenamic acid , and ibuprofen on pain in women with primary dysmenorrhea . METHODS This was a double-blind comparative clinical trial conducted from September 2006 to February 2007 . Participants were 150 students ( 18 years old and over ) with primary dysmenorrhea from the dormitories of two medical universities who were alternately divided into three equal groups . Students in the ginger group took 250 mg capsules of ginger rhizome powder four times a day for three days from the start of their menstrual period . Members of the other groups received 250 mg mefenamic acid or 400 mg ibuprofen capsules , respectively , on the same protocol . A verbal multidimensional scoring system was used for assessing the severity of primary dysmenorrhea . Severity of disease , pain relief , and satisfaction with the treatment were compared between the groups after one menstruation . RESULTS There were not significant differences between groups in baseline characteristics , p > 0.05 . At the end of treatment , severity of dysmenorrhea decreased in all groups and no differences were found between the groups in severity of dysmenorrhea , pain relief , or satisfaction with the treatment , p > 0.05 . No severe side effects occurred . CONCLUSION Ginger was as effective as mefenamic acid and ibuprofen in relieving pain in women with primary dysmenorrhea . Further studies regarding the effects of ginger on other symptoms associated with dysmenorrhea and efficacy and safety of various doses and treatment duration s of ginger are warranted This study assessed the influence of internal health locus of control ( IHLC ) and anxiety on the adolescent 's response to the treatment of mild and moderate pain . Fifty-four adolescents ( ages 16 - 22 years ) from two adolescent clinics presenting with mild to moderate pain caused by dysmenorrhea , muscle sprain or strain , headache , or backache were studied . Following a physical examination and a pretest assessment of pain , IHLC , and the Spielberger State-Trait Anxiety Inventory , subjects were r and omly assigned in a double-blind fashion to groups receiving placebo ( n = 16 ) , 100 mg of naproxen sodium ( n = 19 ) , or 200 mg naproxen sodium ( n = 19 ) and assessed at 1 , 2 , 3 , and 4 hours . Based on a repeated-measure analysis of covariance test , there were no differences between groups in the pretest measurements . All treatment groups had a decrease in pain over the 4 hours ( p less than 0.0001 ) . Patients from one institution had more pain reduction than at the other ( p less than 0.0001 ) , and females had more pain reduction than males ( p less than 0.034 ) . Subjects receiving 200 mg of naproxen sodium had more pain relief ( p less than 0.034 ) than subjects taking placebo at hour 2 . Baseline anxiety was positively associated with pain after receiving placebo , but inversely associated with pain after taking naproxen sodium . The IHLC appeared to have a positive effect on the response to naproxen sodium , but no effect on the response to placebo Two r and omised , multicentre , double-blind , placebo- and active-controlled , 3-way crossover studies were performed to evaluate the efficacy and tolerability of the novel COX-2 selective inhibitor lumiracoxib in the treatment of primary dysmenorrhoea . Subjects with moderate-to-severe dysmenorrhoea received lumiracoxib 400 mg once daily ( od ) , rofecoxib 50 mg od and placebo ( Study 1 ; n = 84 ) or lumiracoxib 400 mg od , naproxen 500 mg twice daily and placebo ( Study 2 ; n = 99 ) . For the primary variable , summed pain intensity difference from 0 to 8 h on day 1 ( SPID-8 ) , all active treatments were superior to placebo in each study ( p < 0.001 ) ; lumiracoxib was comparable to rofecoxib and naproxen . For PID ( categorical scale ) , all active treatments were significantly better than placebo from 2 to 12 h ; lumiracoxib was generally comparable to rofecoxib and naproxen . All treatments were well tolerated . Lumiracoxib 400 mg is effective and well tolerated in the treatment of primary dysmenorrhoea , with efficacy comparable to rofecoxib and naproxen The prostagl and in bio synthesis inhibitors ketoprofen and indomethacin were compared in the treatment of primary dysmenorrhea in a double-blind , cross-over trial involving 23 patients . Each drug was used for 2 - 4 days during 3 consecutive menstruations in r and omized order . Good or moderate overall relief was obtained in 60 of the 68 ketoprofen-treated menstruations ( 88 % ) . A dysmenorrhea score , based on subjective estimations of 8 symptoms , similarly decreased from a mean ( + /- S.E.M. ) basal level of 9.6 + /- 0.6 to 3.6 + /- 0.3 during ketoprofen treatment and to 4.0 + /- 0.3 during indomethacin . Both drugs relieved pelvic and lower back pains and eliminated vomiting and diarrhea in 82 - 97 % of the cycles whereas headache , fatigue and nervousness were less frequently alleviated ( 40 - 67 % ) . Eighteen of the 23 women ( 78 % ) had been unable to work during the first day of menstruation , the rate of working days lost was reduced to 4 % with ketoprofen and 9 with indomethacin . Mild side-effects occurred during 12 ketoprofen and 14 indomethacin therapies . Ketoprofen thus seems to be as effective and tolerable as indomethacin in the treatment of primary dysmenorrhea 1 In a double-blind crossover study , flurbiprofen produced marked relief of pain which was significantly more than with aspirin and placebo in patients suffering from primary dysmenorrhoea . In contrast , there was no significant difference between the relief of pain obtained with aspirin and placebo . 2 The clinician 's overall assessment of efficacy also indicated that flurbiprofen produced better response as compared to aspirin and placebo in these patients with dysmenorrhoea . 3 Both flurbiprofen and aspirin did not produce any apparent adverse effects on blood loss during the menstrual period . 4 In conclusion , the analgesic effect of flurbiprofen seen in this trial establishes the therapeutic usefulness of the drug in the treatment of primary dysmenorrhoea 26 women aged 15 - 45 with severe , primary dysmenorrhea were treated with naproxen ( NAPROSYN , SYNTEX ) and placebo during 2 x 2 consecutive menstrual cycles in a r and omized , double-blind crossover study . The dosage of naproxen was 500 mg ( 2 tablets ) initially , followed by 250 mg as needed , with a maximum of 1250 mg daily . In most cases medication started at the first sign of menstrual distress . 80 per cent of the women preferred naproxen to placebo . The number of tablets taken during each menstruation fell from a mean of 17.8 in the placebo period to 5.1 in the naproxen period . Likewise , additional analgesics fell from 7.1 to 1.6 and hours of bed rest from 16.4 to 1.2 . Total number of days of sick leave per two menstruations decreased from 40 to 7 . These differences are statistically significant ( P < 0.001 ) . The side effects were mild . CNS or gastrointestinal side effects were not seen . Naproxen changed the amount of bleeding in 12 and delayed bleeding in three . Two developed acne , which however gradually diminished during the next five bleeding periods treated with naproxen . The influence of prostagl and in synthetase inhibitors on the ovarian production of steroids is discussed OBJECTIVE To determine the analgesic efficacy and safety of a single oral dose of aceclofenac 100 mg and compare that with placebo and naproxen 500 mg in women with primary dysmenorrhoea . STUDY DESIGN In this double-blind , prospect i ve , multicentre , r and omised , three-way , crossover study , women were r and omly assigned to receive one of six treatment sequences , comprising single oral doses of aceclofenac 100 mg , naproxen 500 mg or placebo , when menstrual pain reached a predetermined level of severity . A single dose of the assigned study medication was taken on three menstrual periods ; a different medication was taken on each treatment day . Analgesic efficacy was determined by self-reported analgesia scoring and participants ' and investigators ' global evaluation of treatment effectiveness . Measurements also included physical examination and adverse events . RESULTS Total pain relief scores were not statistically significantly different for aceclofenac and naproxen , and both were statistically significantly more effective than placebo ( p = 0.019 and 0.002 , respectively ) . This finding was supported by secondary endpoints including sum of pain intensity differences ( SPID/8 ) , peak analgesia ( peak pain intensity and peak pain relief ) , and participants ' and investigators ' overall evaluation of effectiveness . Both aceclofenac and naproxen were well tolerated . CONCLUSIONS Aceclofenac ( 100 mg ) and naproxen ( 500 mg ) effectively treated the pain associated with primary dysmenorrhoea , and both were more effective than placebo at easing menstrual pain assessed by various pain relief criteria UNLABELLED We assessed the efficacy of diclofenac potassium , a nonsteroidal anti-inflammatory drug , in alleviating menstrual pain and restoring exercise performance to that measured in the late-follicular phase of the menstrual cycle . Twelve healthy young women with a history of primary dysmenorrhea completed , in a r and om order , laboratory exercise-testing sessions when they were in the late-follicular ( no menstruation , no pain ) phase of the menstrual cycle and when they were experiencing dysmenorrhea and receiving , in a double-blinded fashion , either 100 mg of diclofenac potassium or placebo . We assessed the women 's leg strength ( 1-repetition maximum test ) , aerobic capacity ( treadmill walking test ) , and ability to perform a functional test ( task-specific test ) . Compared with placebo , diclofenac potassium significantly decreased dysmenorrhea on the day of administration ( Visual Analog Scale , P < .001 at all times ) . When receiving placebo for menstrual pain , the women 's performance in the tests was decreased significantly , compared with when they were receiving diclofenac potassium for menstrual pain ( P < .05 ) and compared with when they were in the late-follicular phase of the menstrual cycle ( P < .05 for treadmill test , P < .01 for task-specific test and 1-repetition maximum test ) . Administration of diclofenac potassium for menstrual pain restored exercise performance to a level not different from that achieved in the late-follicular phase of the cycle . PERSPECTIVE In women with primary dysmenorrhea , menstrual pain , if untreated , decreases laboratory-assessed exercise performance . A recommended daily dose of a readily available nonsteroidal anti-inflammatory drug , diclofenac potassium , is effective in relieving menstrual pain and restoring physical performance to levels achieved when the women were in the late-follicular ( no menstruation , no pain ) phase of the menstrual cycle With approximately 25 % of dysmenorrheic patients reporting no improvement with nonsteroidal anti-inflammatory drugs , a study was devised to evaluate the effectiveness of a laparoscopic technique for the interruption of the uterosacral nerves . In a double-blind study of 21 patients with primary dysmenorrhea , 81 % ( 9 of 11 ) reported significant relief from menstrual pain after the surgery . Performed as an outpatient procedure , laparoscopic uterine nerve ablation may alleviate dysmenorrheic complaints when other modalities have failed . Half the treated women reported continued relief of menstrual pain at 12 months . These results suggest that uterosacral nerve interruption may prove an effective alternative treatment for this menstrual disorder Abstract Objective : To compare the efficacy and acceptability of ethamsylate , mefenamic acid , and tranexamic acid for treating menorrhagia . Design : R and omised controlled trial . Setting : A university department of obstetrics and gynaecology . Subjects : 76 women with dysfunctional uterine bleeding . Interventions : Treatment for five days from day 1 of menses during three consecutive menstrual periods . 27 patients were r and omised to take ethamsylate 500 mg six hourly , 23 patients to take mefenamic acid 500 mg eight hourly , and 26 patients to take tranexamic acid 1 g six hourly . Main outcome measures : Menstrual loss measured by the alkaline haematin method in three control menstrual periods and three menstrual periods during treatment ; duration of bleeding ; patient 's estimation of blood loss ; sanitary towel usage ; the occurrence of dysmenorrhoea ; and unwanted events . Results : Ethamsylate did not reduce mean menstrual blood loss whereas mefenamic acid reduced blood loss by 20 % ( mean blood loss 186 ml before treatment , 148 ml during treatment ) and tranexamic acid reduced blood loss by 54 % ( mean blood loss 164 ml before treatment , 75 ml during treatment ) . Sanitary towel usage was significantly reduced in patients treated with mefenamic acid and tranexamic acid . Conclusions : Tranexamic acid given during menstruation is a safe and highly effective treatment for excessive bleeding . Patients with dysfunctional uterine bleeding should be offered medical treatment with tranexamic acid before a decision is made about surgery . Key messages In any year around 5 % of women aged 30 - 49 years visit their general practitioners with menor-rhagia Every year in the United Kingdom around 45 000 hysterectomies and a further 10 000 endometrial ablations are performed for menorrhagia The commonest drug prescribed in the British Isles for menorrhagia ( norethisterone ) has little or no effect in reducing menstrual bleeding Tranexamic acid ( an antifibrinolytic ) 1 g six to eight hourly reduces menstrual blood loss by over half and should be offered to women with dysfunctional bleeding before a decision is made about Prostagl and in synthetase inhibitors have been used in clinical trials for the treatment of primary dysmenorrhea on the theory that the disorder may be caused by a high level of prostagl and ins . However , a causal role of prostagl and in in dysmenorrhea has not been established , and there is only indirect evidence that the amelioration of dysmenorrhea by prostagl and in synthetase inhibitors is related to their inhibition of prostagl and in synthesis in the uterus . We , therefore , monitored menstrual prostagl and in release in 14 dysmenorrheic patients in a controlled , double-blind , cross-over trial of ibuprofen ( Motrin ) and in two dysmenorrheic subjects while they were receiving oral contraceptive therapy and while they were not . A total of 89 menstrual cycles were studied . We found that ibuprofen therapy reduced menstrual prostagl and in release and relieved dysmenorrhea but that placebo therapy did not . Oral contraceptives decreased menstrual flow , reduced prostagl and in release and also alleviated dysmenorrhea . We conclude that primary dysmenorrhea is related to a high level of menstrual prostagl and in release . Ibuprofen inhibits prostagl and in synthesis whereas oral contraceptives inhibit ovulation and cyclic endometrial development . Thus , the two drugs suppress endometrial prostagl and in through different mechanisms . Reduction of menstrual prostagl and in release leads to alleviation of dysmenorrhea Summary : A double‐blind crossover placebo‐controlled trial over 6 cycles in 38 Australian women has confirmed that ibuprofen is a valuable drug for the treatment of primary spasmodic dysmenorrhoea . This drug was highly effective when given in a dosage of one 400 mg tablet at the first sign of pain or bleeding followed by further 400 mg tablets every 4 to 6 hours for the duration of expected symptoms . Side‐effects were mild and noted with equal low frequency during placebo treatment Sixty female out- patients suffering from moderate to severe primary dysmenorrhea , aged 14 - 40 years ( mean 27 years ) , entered this r and omized , double-blind , 3-period , within-patient study , evaluating the efficacy and tolerability of diclofenac dispersible 46.5 mg ( equivalent to 50 mg of diclofenac sodium ) , ibuprofen 400 mg and placebo taken up to 4 times daily for a maximum of 3 days . Pain relief was evaluated on a verbal rating scale ( 0 = none , 1 = slight , 2 = moderate , 3 = considerable , 4 = complete ) at 0.5 , 1,2,3,4,5 and 6 hours after the first dose ; the weighted sum of pain relief scores over the 6-hour observation period was also investigated ( TOTPAR-6 ) . Pain intensity was assessed on a verbal rating scale ( 0 = nil , 1 = mild , 2 = moderate , 3 = severe ) at baseline and at the above mentioned time points ; the weighted sum of pain intensity differences at each time point was also analyzed ( SPID-6 ) . A rescue medication was permitted 1 hour or more after the intake of the test drug : in such cases the last value of pain intensity/relief scores was carried forward and used for the analysis . A global evaluation of efficacy and of trial medication as compared to her usual medication was performed by the patient at the end of each treatment period . Finally , adverse experiences were recorded throughout the study period . Analysis of covariance and Koch 's adaptation of the Wilcoxon-Mann-Whitney rank sum test were used , where appropriate , for statistical analysis . Mean TOTPAR-6 values for diclofenac dispersible , ibuprofen and placebo were 16.5 , 17.8 and 14.7 , respectively . ( ABSTRACT TRUNCATED AT 250 WORDS OBJECTIVE To identify the prevalence and correlates of three types of pelvic pain ( dysmenorrhoea , dyspareunia , and other chronic pelvic pain [ CPP ] ) in a nationally representative sample of Australian women . DESIGN AND SETTING The CPP survey was part of a broader national study of health and relationships . Computer-assisted telephone interviews were administered to a r and om sample of 8656 Australian households ; 4366 women aged between 16 and 64 years were interviewed in 2004 and 2005 . Eighteen of the more than 200 potential survey questions related to pelvic pain . MAIN OUTCOME MEASURES Self-reports of dysmenorrhoea , dyspareunia , and any other CPP not associated with sexual intercourse or menstruation . RESULTS Data on 1983 women aged 16 - 49 years who were still menstruating and sexually active were analysed . Prevalences were 71.7 % for dysmenorrhoea , 14.1 % for dyspareunia and 21.5 % for other CPP ; 23.3 % of women reported no pelvic pain of any kind . Severe pain was reported by 15.0 % ( 95 % CI , 13.0%-17.1 % ) of women with dysmenorrhoea , 7.8 % ( 95 % CI , 5.0%-11.9 % ) of women with dyspareunia and 20.0 % ( 95 % CI , 16.1%-24.6 % ) of women with other CPP . Just over a third ( 34.2 % ) of women who reported any pain had sought advice from a health professional . Women reporting CPP were also likely to report other health conditions , most notably depression and anxiety . There were clear associations between CPP and sexual difficulties , pregnancy and pregnancy outcomes . CONCLUSIONS Rates of pelvic pain in Australian women are high . General practitioners need to be ready to discuss these issues with patients , particularly in relation to underlying anxiety and depression Abstract . Ninety‐two patients with primary dysmenorrhea were included in a double‐blind r and omized crossover trial to study the efficacy of piroxicam on menstrual pain and associated symptoms , with placebo as control Abstract . A survey of earlier published studies on treatment of dysmenorrhea with prostagl and in synthetase inhibitors is given and personal clinical experiences are presented . The time when treatment should start in relation to the onset of bleeding is also discussed In a double-blind , crossover study in 39 women with dysmenorrhoea , the effects of oral treatment with single doses of 100 mg ketoprofen and 500 mg naproxen were compared with regard to time for onset of pain relief and overall effect on symptoms . Assessment s of pain severity using a visual analogue scale and an activity-related scale were made at 15-minute intervals for 2.5 hours . The results showed that ketoprofen was significantly more effective at 60 and 45 minutes , respectively , after intake of medicine and the differences remained significant until 120 and 105 minutes , respectively . Reduction in original pain by 50 % , the patient 's view on the overall effect after each treatment as well as a comparison of effects at the end of the study all differed significantly in favour of ketoprofen . No significant differences were found between treatments in the need for additional analgesic therapy after the 2-hour observation period or in the incidence of side-effects , which was low with both medications . It is suggested that ketoprofen could have a therapeutic advantage over naproxen , particularly in patients in whom menstrual pain develops rapidly Sixty-eight women with primary dysmenorrhea were r and omly assigned to one of five four-times-daily treatment groups for a minimum of three days and a maximum of five days . Three of the groups received different initial single-daily doses of piroxicam , which were followed on each treatment day with placebo for the second through fourth doses , namely , piroxicam 20 mg daily for five days ( piroxicam 20 mg for five days ) ; piroxicam 40 mg on Day 1 , followed by piroxicam 20 mg on Days 2 through 5 ( piroxicam 40 mg for one day ) ; and piroxicam 40 mg on Days 1 and 2 , followed by piroxicam 20 mg on Days 3 through 5 ( piroxicam 40 mg for two days ) . The fourth group received ibuprofen 400 mg four times per day , and the fifth group received placebo four times per day . Patients determined the severity of overall discomfort and pelvic-abdominal pain at baseline and prior to each dose using a four-point numerical scale . Supplemental ibuprofen , 400 mg four times per day , was provided for those patients requiring additional pain relief . Patients also made a global determination of overall relief at the end of the study . At 24 hours , the results revealed that piroxicam 40 mg for two days , piroxicam 20 mg for five days , and ibuprofen provided significantly more relief of overall discomfort compared with placebo ( p = 0.003 , p = 0.018 , and p = 0.026 , respectively ) . All four active treatment groups also experienced significantly more relief of pelvic-abdominal pain compared with placebo : piroxicam 40 mg for two days followed by three days of 20 mg ( p = 0.002 ) , piroxicam 40 mg for one day followed by four days of 20 mg ( p = 0.023 ) , piroxicam 20 mg for five days ( p = 0.012 ) , and ibuprofen ( p = 0.011 ) . A significantly smaller percentage of patients treated with piroxicam 40 mg for two days required supplemental medication as compared with those treated with piroxicam 20 mg for five days ( p = 0.035 ) and patients treated with placebo ( p = 0.010 ) . A greater amount of overall relief was obtained by patients treated with piroxicam 40 mg for two days compared with patients treated with piroxicam 40 mg for one day ( p = 0.041 ) and placebo-treated patients ( p = 0.001 ) . It was concluded that single daily doses of piroxicam 20 mg and 40 mg were as effective as ibuprofen , 400 mg four times per day , for the relief of primary dysmenorrhea Twenty-one women with intrauterine contraceptive devices ( IUCD ) and severe dysmenorrhea were studied . All the women who participated in the study had primary dysmenorrhea of varying intensities . The insertion of IUCD increased the intensity of dysmenorrheic pain . The effect of naproxen ( Naprosyn ) on pain alleviation was studied in a double-blind cross-over trial using naproxen and placebo . The effect of naproxen was significantly better than that of placebo ( P less than 0.01 ) . No severe side effects occurred during the treatment . There was no difference in the duration and amount of the menstrual blood flow during naproxen treatment compared to placebo according to the women 's own judgement The prostagl and in-synthetase inhibitors , mefenamic acid and flufenamic acid , were compared with the analgesic , dextropropoxyphene/paracetamol , in the treatment of primary dysmenorrhoea in a double-blind crossover trial . Results were assessed in 30 patients who took each drug during menstruation for three consecutive cycles . The patients ' assessment of each drug suggests that both mefenamic acid and flufenamic acid are more effective than the other analgesic for general relief of symptoms and for most of nine individual symptoms subjectively assessed by the patient . There was less absenteeism from work or school during mefenamic-acid treatment and fewer capsules of mefenamic acid were taken compared with the other two drugs . Patients took significantly fewer additional analgesics during mefenamic-acid therapy than during treatment with the other two drugs . 5 patients had possible side-effects--3 patients on mefenamic acid and 2 on dextropropoxyphene/paracetamol The analgesic efficacy and tolerance of lysine clonixinate ( LC ) as well as LC-induced changes in menstrual prostagl and in levels were studied according to a prospect i ve double-blind r and omized crossover design , controlled with ibuprofen ( I ) and placebo ( P ) . Treatment consisted in 4 consecutive phases : in the first phase , patients refrained from taking medication and during the remaining three phases , they received double-blind fixed doses of 1 tablet of lysine clonixinate 125 mg , I 400 mg or P , q.6 h. at r and om , three days before onset of menses and during 8 days thereafter . Controls were carried out at each menstrual cycle , assessing pain according to a scale from 0 to 4 , onset of premenstrual and intramenstrual symptoms , relief of pain and occurrence of side-effects . During menstruation , patients recorded their assessment s of pain in a diary and collected the whole menstrual bleeding during the first three days . The intensity of menstrual pain remained unchanged in controls upon admission ( 3.16 ) and during the phase with no treatment ( 3.04 ) , but was significantly reduced with P ( 2.4 ) , LC ( 1.79 ) and I ( 1.54 ) . Significantly lower pain intensities compared with placebo were seen with active treatment phases . Forty-two percent of patients treated with P reported premenstrual pain which was significantly reduced to 17 % with LC and to 12.5 % with I. Active treatment phases revealed 21 % of asymptomatic patients during premenstrual and menstrual periods and 71 % ( LC ) and 75 % ( I ) of cases with partial relief of pain . Patients ' diaries showed significant pain reductions with LC and I , during the 1st and 2nd days compared with P ; such differences were gradually reduced to nil by the 4th day . Levels of menstrual PGs changed according to pain intensity reductions from baseline ( P : 29 % , ( NS ) ; LC : 58 % and I : 61 % ; both were statistically significant , p < 0.01 ) Zomepirac sodium was compared with placebo for relief of primary dysmenorrhea syndrome in a double-blind , crossover study of 47 patients . The agents were taken in three separate crossovers during six menstrual periods . Abdominal cramping and 25 other symptoms of dysmenorrhea syndrome were evaluated daily . Zomepirac was significantly more effective than placebo in relieving 12 of 13 primary symptoms and 6 of 13 associated symptoms ( P less than or equal to 0.05 ) . While taking zomepirac , patients were able to continue normal activities on a significantly higher proportion of days ( P less than 0.001 ) and required supplemental analgesics significantly less often ( P less than 0.001 ) . Zomepirac was well tolerated by these patients . Gastrointestinal disturbances accounted for the largest proportion of adverse effects from either agent . These results indicate that zomepirac gave excellent relief of the symptoms of dysmenorrhea in this study population A r and omized double-blind cross-over study was carried out in 19 young female undergraduates with severe primary dysmenorrhea to compare the efficacy and tolerance of treatment with diflunisal and naproxen . All patients received both substances twice during four consecutive cycles . The first tablet was taken at the onset of dysmenorrheic symptoms and continued according to the individual need , maximally four tablets daily . The overall relieving effect was good or moderate in 73.7 % of the diflunisal cycles and in 92.1 % of the naproxen cycles . The difference was not statistically significant . One third of the women estimated decreased menstrual blood loss during treatment with both the drugs . Side effects were mild and did not cause discontinuation of the therapy . Diflunisal seems to be as equally effective in the treatment of primary dysmenorrhea as naproxen , which is a well-documented and widely used prostagl and in synthetase inhibitor & NA ; A total of 55 patients with primary dysmenorrhea who had shown a favorable response to a preliminary treatment cycle with placebo were admitted to a double‐blind study on placebo versus antiprostagl and in agents ( naproxen and pirprofen ) . To evaluate the placebo effect and its duration , the treatment was given for 4 successive cycles . Whereas the antiprostagl and in agents were effective in most of the patients ( in 80 % of the pirprofen group and 85.7 % of the naproxen group ) and this efficacy was maintained throughout the study , a favorable response to placebo was observed in 84 % in the first cycle , 29 % in the second , 16 % in the third and 10 % in the fourth . The incidence of side effects was similar in the placebo and the active treatment groups ( 35.4 % vs. 37.5 % ) . It is postulated that a placebo effect in dysmenorrhea is due to a central analgesic mechanism mediated by endorphin release or possibly to psychological dynamics ( mental or conditioning theories ) . However , this effect loses efficacy with time possibly due to a decreased susceptibility to the opioid action of the central nervous circuits responsible for menstrual pain perception or to deconditioning mechanisms Past attempts to obtain objective evaluation of dysmenorrhea therapy have been severly limited by the lack of accurate , reliable intrauterine pressure data . The development of the catheter-tip microtransducer has made accurate , error- and artifact-free intrauterine pressure recording a reality . This information has made assessment of uterine effects of drug therapy feasible . The combination of this type of information with the use of mathematical processing of data has finally made truly objective assessment attainable . A description of the current technique and the findings made possible by its use are presented Mefenamic acid ( Ponstel ) , 250 mg four times a day , and placebo were compared in a double-blind , crossover study conducted in 46 women with primary spasmodic dysmenorrhea . When compared with placebo , treatment with mefenamic acid result ed in significant decreases in the frequency and severity of the symptoms , and significantly reduced the need for additional analgesic medication . Mefenamic acid was well tolerated . No changes in clinical laboratory values were associated with its use . ( JAMA 241:2713 - 2716 , 1979 Abstract . In double‐blind , crossover studies , piroxicam was compared with naproxen sodium and with placebo . The different parameters studied were pain intensity , patient 's opinion of the drugs tested , complementary pharmacological treatment , ability to work , overall effect , treatment preference , and side effects . It was concluded that piroxicam was comparable to naproxen sodium and that piroxicam was significantly better than placebo , as regards these parameters . It was also concluded that piroxicam has an effect equivalent to that of naproxen sodium , an accepted treatment for dysmenorrhea OBJECTIVE To compare the efficacy of the cyclooxygenase (COX)‐2‐specific inhibitor valdecoxib with naproxen sodium in treating menstrual pain associated with primary dysmenorrhea . METHOD This single‐center , double‐blind , placebo‐controlled , r and omized , crossover study compared the efficacy and safety of single oral doses of valdecoxib 20 mg and 40 mg with naproxen sodium 550 mg , or placebo , with an option of treatment for up to 3 days , twice daily . Efficacy was assessed by time‐weighted sum of total pain relief , sum of pain intensity difference , time‐specific pain relief , and pain intensity difference over 12 hours , time to rescue medication or first re‐medication , the percentage of patients taking rescue medication , and patient 's global evaluation of study medication . RESULTS Mean time‐weighted sum of total pain relief and sum of pain intensity difference were significantly superior to placebo for the first 8 and 12 hours after the initial dose of valdecoxib 20 mg ( P < .01 ) and 40 mg ( P < .001 ) . Valdecoxib 20 mg and 40 mg were comparable to naproxen sodium 550 mg for all efficacy measures . Other differences in efficacy measures favoring the higher dose of valdecoxib did not achieve statistical significance , with the exception of sum of pain intensity difference‐12 . Both doses of valdecoxib were well tolerated . CONCLUSIONS Both valdecoxib 20‐ and 40‐mg doses were effective and well tolerated for the treatment of primary dysmenorrhea . Valdecoxib 20 mg and 40 mg demonstrate analgesic efficacy , based on onset , magnitude , and duration of analgesia that is similar to naproxen sodium , making it a potential choice for treating women with primary dysmenorrhea Abstract . “ In vitro ” experimentation has shown that naproxen inhibits prostagl and in synthetase generated by uterine microsomes of pregnant rats . In another in vitro system , naproxen inhibited electrically induced contractions of an isolated myometrial strip and abolished the sensitivity of the myometrium to oxytocin Thirty-five patients ( 16 - -23 years old ) who had severe primary dysmenorrhea were each treated with 500 mg of mefenamic acid every eight hours for a maximum of three days during menstruation for three consecutive cycles . A total of 194 treated cycles could be evaluated , 110 cycles with mefenamic acid and 84 with placebo . Mefenamic acid produced complete relief of all the symptoms of dysmenorrhea in 31 ( 88.6 % ) patients in all 98 treated cycles and , in another two patients , moderate relief in five of the six cycles . While on placebo , only five patients ( 13 % ) experienced moderate to slight relief in 11 of the 15 cycles . It is concluded that the mefenamic acid is safe and effective in most patients for the relief of primary dysmenorrhea and represents a rational short-term therapy for this syndrome This prospect i ve , double-blind , parallel , two clinic study compared fenoprofen calcium , 200 mg ; ibuprofen , 400 mg ; and placebo in the treatment of pain due to primary dysmenorrhea . By various criteria , the treatment groups , prior to treatment , were not significantly different ( P greater than 0.05 ) in paired comparisons . However , after oral administration of the study medications , the pain scores were significantly greater ( P less than 0.05 ) for the placebo group than for either other group . The posttreatment pain scores for the fenoprofen and ibuprofen treated groups were not significantly different ( P greater than 0.05 ) Summary . Eighty patients with premenstrual tension were treated prospect ively with mefenamic acid for a mean period of 13 months . Most of them ( 86 % ) reported significant relief of premenstrual tension . Symptoms of dysfunctional menorrhagia or primary dysmenorrhoea were also alleviated . In 19 patients , the plasma concentrations of prostagl and in ( PG ) E2 , PGF2α and 13,14‐dihydro‐15‐keto‐prostagl and in F2α ( PGFM ) were measured at intervals throughout three menstrual cycles . During the first cycle the patients received no treatment ; in the subsequent two cycles they received either mefenamic acid or placebo in a r and omized double‐blind crossover manner . Similar measurements were made in 22 matched control subjects . The plasma concentrations of PGE2 , PGF2α and PGFM were significantly lower in the 19 patients in all three menstrual cycles compared with the values in the control subjects . Excess synthesis of prostagl and ins of the 1 series may occur in premenstrual tension and , by precursor depletion , result in decreased synthesis of the 2‐series prostagl and ins Single and multiple oral doses of bromfenac sodium ( 10 or 50 mg ) were compared with naproxen sodium ( 550 mg loading/275 mg repeat doses ) for the relief of pain from primary dysmenorrhea in 54 women using a crossover design . Pain intensity and pain relief were assessed over 6 h after the first dose , and global ratings were made at the end of day 1 and on day 2 . A single dose of bromfenac 10 or 50 mg was as effective as the loading dose of naproxen sodium ( 550 mg ) in relieving the pain from dysmenorrhea through a 6-h period . All three active treatments were statistically superior ( p < 0.001 ) to placebo for the primary efficacy variables , 3-h and 6-h total pain relief and 3-h and 6-h summed pain intensity difference . All active treatments were statistically superior ( p < 0.05 ) to placebo for the first dose and day 1 global assessment s. One or more adverse study events were reported by 13 patients ( 25 % ) who received bromfenac 50 mg , 15 ( 29 % ) who received bromfenac 10 mg , 20 ( 38 % ) who received naproxen sodium , and 19 ( 37 % ) who received placebo . There were no clinical ly significant differences among the treatments in the types of adverse study events . No serious or unexpected adverse study events were reported , and no women withdrew from the study because of an adverse event . Bromfenac sodium ( 10 mg or 50 mg ) is as effective as naproxen sodium ( 550 mg loading dose/275 mg repeat doses ) for relief of pain from dysmenorrhea Women who experienced severe primary dysmenorrhea had 90 to 120 minutes of continuous uterine pressure monitoring during their peak period of discomfort . During the initial screening cycle , they were given 40 mg of piroxicam , a nonsteroidal anti-inflammatory drug which inhibits prostagl and in synthesis . The pressure tracings were analyzed by a newly proposed ratio , the contractility index . During the painful period , the contractility index averaged approximately 3 . When relief was experienced , the contractility index fell to approximately 1.5 . Women who experienced uncertain or slight relief had a contractility index of approximately 2 . Relief was experienced by 69 % of the women screened . A small double-blind , crossover study was carried out on seven of the women . This revealed different responses to the drug in consecutive cycles and suggests that increased prostagl and ins are an expression of an underlying process , not consistent with a primary cause of dysmenorrhea The effects of flurbiprofen ( 100 mg ) and naproxen sodium ( 500 mg ) on intrauterine pressure and menstrual pain were assessed in 8 women with primary dysmenorrhea using a double‐blind parallel study technique . Intrauterine pressure was recorded with a microtransducer catheter for 4 h and resting pressure , active pressure , frequency of pressure cycles , and the area under the curve were analysed in 30 min periods . Prior to medication all the patients displayed signs of uterine hyperactivity as judged by a high resting pressure 55.3±3.8 mm Hg , high active pressure 175.0±6.1 mm Hg and a high frequency of pressure cycles 12.3±0.7 contractions per 0.5 h. Oral administration of flurbiprofen and naproxen sodium significantly suppressed uterine activity and was associated with a significant reduction in pain intensity . However no significant differences were recorded between the two drugs regarding their effects on intrauterine pressure and pain intensity The purpose of this study was to determine whether adolescents with " spasmodic " dysmenorrhea ( SD ) versus " congestive " dysmenorrhea ( CD ) respond differently to naproxen sodium therapy . Forty-five females ages 12 - 18 years were pretested and r and omly assigned in a double-blind fashion to one of five treatment regimens of various dosages of naproxen sodium and placebo . Subjects were posttested at one , two , and three months . Subjects with initial Menstrual Symptom Question naire ( MSQ ) scores of greater than or equal to 76 were classified as SD ( n = 28 ) and those with scores of less than or equal to 75 were classified as CD ( n = 17 ) . Subjects with SD had a significant ( p less than or equal to 0.05 ) reduction in MSQ scores after the first month of naproxen sodium therapy . By the second month , the degree of reduction was associated with a loading dose of 550 mg of naproxen sodium . Subjects with CD had a dose-related ( p less than or equal to 0.05 ) response to naproxen sodium therapy that appeared to be influenced by other factors . At the first month follow-up , greater post menarchal age and parents ' education were associated with increased symptom relief following naproxen sodium therapy ( p less than or equal to 0.05 ) . At the second month , CD subjects with increased life crisis events and lower self-concepts had more severe symptoms following naproxen sodium therapy ( p less than 0.05 ) . Our subjects with SD symptoms had a greater response to naproxen sodium therapy than those with CD symptoms In a r and omized crossover study 15 dysmenorrheic women were treated during two consecutive menstrual period , once with the potent prostagl and in- synthesis inhibitor : ibuprofen and once with an identical looking placebo . Each patient was medicated for 12 hours during the first day of her menstrual flow and was subsequently fitted with a cervical cup for the collection of menstrual blood during three hours . In these sample s the concentrations of prostagl and in (PG)F and PGE were measured by radioimmunoassay . The patients receiving placebo had high PGF levels 135 + /- 27 ng/ml ( Mean + /- S.E. ) which were significnatly reduced by Ibuprofen to 24 + /- 5 ng/ml ( P less than 0.001 ) . The PGE concentrations decreased from 5 + /- 1 ng/ml to 2 + /- 1 ng/ml ( P less than 0.05 ) . Ibuprofen also reduced the menstrual pain significantly ( P less than 0.001 ) . These results substantiate the earlier conclusion that a causal relationship exists between effective treatment with PG- synthesis inhibitors and decrease in menstrual blood PG levels , intrauterine pressure and dysmenorrheic pain Objective . Assessment of efficacy and safety of meloxicam 7.5 mg and 15 mg once a day ( o.a.d . ) compared with mefenamic acid 500 mg three times a day ( t.i.d . ) , over a treatment period of 3–5 days , during three menstrual cycles , for primary dysmenorrhea Summary The efficacy of indomethacin , a prostagl and in synthetase inhibitor , in severe dysmenorrhoea was established in a double-blind crossover study using aspirin and placebo as the control drugs . Forty-seven female undergraduates were treated twice with each of the three substances during six consecutive menstrual cycles . Good or moderate relief was achieved in 71 % of the cycles treated with indomethacin , in 40 % of those treated with aspirin and in 21 % of those treated with the placebo . Dizziness and drowsiness were cited by 14 patients ( 30 % ) as side-effects of indomethacin , none of these patients discontinued the therapy because all obtained good or moderate relief from dysmenorrhoea . Indomethacin proved to be a valuable agent , and significantly better than aspirin in the treatment of dysmenorrhoea . It allowed many dysmenorrhoeic women to carry out their normal activities and work during the menstrual period Abstract Objectives : Efficacy of pain relief may potentially be enhanced by combining two or more analgesics with different mechanisms of action . The objective of this study was to assess the efficacy and tolerability of a novel single-tablet combination of ibuprofen and paracetamol compared with placebo in females experiencing moderate-to-severe pain due to primary dysmenorrhoea , a prevalent , recurrent condition characterised by pain at the time of menses . Methods : This was a phase II/III , double-blind , r and omised , cross-over , single-dose study in 94 women with moderate-to-severe dysmenorrhoea , examining the efficacy and tolerability of one or two tablets of a single-tablet combination of ibuprofen 200 mg/paracetamol 500 mg compared with placebo . Clinical trial registration : IS RCT N42521357 Results : Total pain relief over 6 hours post-dose ( TOTPAR0–6h ) was significantly greater following administration of two tablets of the single-tablet combination of ibuprofen 200 mg/paracetamol 500 mg compared with placebo ( LS means : 2.35 , 1.85 , respectively ; p = 0.0001 ) and approached significance for one tablet ( LS mean : 2.10 ; p = 0.054 ) . Statistically superior pain relief and reductions in pain intensity were achieved from 2 hours and 90 minutes post-dose , respectively , with the higher dose combination , and from 4 hours with the lower dose combination compared with placebo . Overall effectiveness ( sum of pain intensity difference and pain relief score [ SPRID ] over 6 hours ) were statistically superior to placebo for both one and two tablets of the ibuprofen/paracetamol combination ( p = 0.0011 and p = 0.03 , respectively ) . Both dose combinations were well-tolerated . Adverse events were minor and their frequency and nature did not differ with either treatment compared with placebo . Conclusions : One or two tablets of a single-tablet combination of ibuprofen 200 mg/paracetamol 500 mg is well-tolerated and provides superior analgesic efficacy to placebo in patients with primary dysmenorrhoea Background . To measure the effect of oral naproxen and nimesulide treatments on the uterine and ovarian arterial blood flow velocity in both eumenorrheic and dysmenorrheic women OBJECTIVE : To evaluate the efficacy and tolerability of sumatriptan – naproxen during the mild pain phase of a single menstrual migraine attack associated with dysmenorrhea . METHODS : Two replicate r and omized , multicenter , double-blind , placebo-controlled , trials of adults with menstrual migraine and dysmenorrhea were conducted . Participants treated their menstrual migraine attack during the mild pain phase ( within 1 hour of onset ) with sumatriptan 85 mg and naproxen sodium 500 mg in a single fixed-dose formulation ( sumatriptan – naproxen ) or placebo . The primary endpoint was 2-hour pain-free response . RESULTS : Sumatriptan – naproxen was statistically superior to placebo in both studies ( n=311 , Study 1 ; n=310 , Study 2 ) for 2-hour and , 2- to 24-hour sustained pain-free response , use of headache and menstrual rescue medications , and several nonpain menstrual symptom categories . Two-hour pain-free rates were Study 1 , 42 % compared with 23 % , and Study 2 , 52 % compared with 22 % , P<.001 . Two- to 24-hour sustained pain-free rates were Study 1 , 29 % compared with 18 % , P=.022 ; Study 2 , 38 % compared with 10 % , P<.001 . Headache and menstrual medication rates were Study 1 , 37 % compared with 53 % , P=.005 ; Study 2 , 31 % compared with 69 % , P<.001 . Women treated with sumatriptan – naproxen continued to be pain free through 48 hours compared with placebo : Study 1 , 26 % compared with 17 % , P=.040 ; Study 2 , 28 % compared with 8 % , P<.001 . No serious adverse events were reported in either study ; nausea and dizziness were the most frequently reported adverse events . CONCLUSION : Sumatriptan – naproxen provided an effective pain-free response at 2 hours , which was maintained up to 48 hours in menstrual migraineurs with dysmenorrhea . Sumatriptan – naproxen was well-tolerated and result ed in decreased rescue medication use and relief of nonpainful menstrual symptoms . CLINICAL TRIAL REGISTRATION : Clinical Trials.gov , www . clinical trials.gov , NCT00329459 and NCT00329355 LEVEL OF EVIDENCE : Sixteen young women ( 18–35 years old ) suffering from severe primary dysmenorrhea were treated with the anti-inflammatory drug Flunalgan [ flufenamic acid ; N-(α , α , α-trifluorom-tolyl ) anthranilic acid ] , 125 mg tid or qid , during one to three menstrual periods . In all patients ( a total of 31 treated cycles ) the drug afforded symptomatic relief . Treatment with other analgesic spasmolytic or tranquilizing drugs , or with placebos , was ineffective in these patients ( 72 control cycles ) . Flufenamic acid inhhibits prostagl and in synthetase and the biologic action of prostagl and in F2α on smooth muscle in laboratory animal preparations . The hypothesis is discussed that excessive amounts of prostagl and in originating from breakdown of the “ pseudodecidual ” tissue of the premenstrual endometrium during cyclic progesterone withdrawal may be the cause of painful myometrial contractures and of the accompanying gastrointestinal symptoms that characterize this syndrome . Further study of the efficacy and safety of drugs that antagonize prostagl and in synthesis and /or action in the treatment of primary dysmenorrhea seems indicated A double-blind cross-over trial of flufenamic acid three times a day ( 200 mg ) was carried out in forty-four patients with primary dysmenorrhoea . While on flufenamic for 3 months 82 % of patients experienced significant pain relief . Associated gastrointestinal symptoms , i.e -- vomiting and diarrhoea -- were relieved in 66 % and 52 % patients respectively while on flufenamic acid . It is concluded that the fenamates are useful and safe drugs in the treatment of primary dysmenorrhoea Summary . The effects of ibuprofen ( 400 mg ) , naproxen sodium ( 250 mg ) and paracetamol ( 500 mg ) on intrauterine pressure and menstrual pain was assessed in 12 women with dysmenorrhoea in a double – blind parallel study . Intrauterine pressure was recorded with a microtransducer catheter for 4 h and resting pressure , active pressure , frequency of pressure cycles and the area under the curve were analysed in 30–min periods . Ibuprofen , in a single oral dose of 400 mg , significantly reduced resting pressure , active pressure , the frequency of pressure cycles and the area under the curve and this was associated with a significant reduction in pain intensity . Neither paracetamol nor naproxen sodium effected significant changes in intrauterine pressure or pain score In a double-blind parallel trial , 24 dysmenorrheic women received a single dose of Anaprox ( 1,100 mg ) or placebo . Over the next 2 hours , pain intensity was scored and intrauterine pressure was measured using an immobilized microballoon . At the end of 2 hours , all 11 patients given Anaprox ( but only three of the 13 given placebo ) experienced complete pain relief ( p = 0.0004 ) . The resting intrauterine pressure ( IUP ) decreased from a mean of 51.4 to 26.8 mm Hg in the Anaprox-treated group , while in the placebo group the mean resting IUP values remained essentially unchanged ( drop from 55.4 to 51.9 mm Hg was observed ) . This difference between the two treatment groups was statistically significant in favor of Anaprox ( p = 0.03 ) . Several patients from each group were given 0.2 mg of ergonovine by intramuscular injection following the 2 hour trial . In both groups , the resting IUP increased within 30 minutes ; the corresponding increase in pain intensity was more pronounced , however , in the placebo group . These results support the premise that a decrease in resting IUP is directly linked to the pain-relieving effects of Anaprox Background : Primary dysmenorrhea is estimated to affect 40–50 % of menstruating young women . Methods : R and omized , double-blind , 3-cycle crossover , active-controlled clinical trial conducted in 102 out patients . Results : 102 patients entered the study and 77 were eligible for analyses . The mean ( SD ) age was 31.1 ( 7.0 ) years , and the mean cycle duration was 28.1 days ( 1.89 ) with a mean menstrual phase of 5.3 days ( 1.28 ) . 40.26 % of patients reported moderate pain from dysmenorrhea , and the remaining 59.74 % reported severe pain . Compared to ibuprofen 400 mg , both dexibuprofen doses ( 200 and 300 mg ) showed a trend towards superiority for sum of pain intensity difference ( sum of PID ) , PID and total pain relief . Furthermore , dexibuprofen 200 mg had a faster onset of action compared to the double dose of ibuprofen ( p = 0.035 ) . A dose-effect relationship could be demonstrated for dexibuprofen in this visceral pain model . Tolerability was similar across all treatments . Conclusions : In patients experiencing acute visceral pain as a result of primary dysmenorrhea , dexibuprofen was associated with a dose-dependent effective analgesia ; this effect was at least equivalent to that of the double dose of ibuprofen . With its lower body-loading dose , dexibuprofen exp and s the alternatives available to treat this condition Thirty-one patients with primary dysmenorrhoea were treated in a double-blind , six-period , cross-over clinical trial with tiaprofenic acid , naproxen sodium and a placebo in r and omized order , each for 2 consecutive cycles . Complete disappearance of the symptoms or pronounced therapeutic effects were obtained with tiaprofenic acid , naproxen sodium and the placebo in 74 % , 65 % and 35 % of cases , respectively , while these treatments were ineffective in 3 % , 6 % and 38 % of cases , respectively . Tiaprofenic acid was superior to the placebo for relieving pelvic pain and overall discomfort and for reducing the need for bed-rest . Naproxen sodium compared favourably with the placebo with respect to pelvic pain and overall discomfort . The effects of tiaprofenic acid and naproxen sodium were not significantly different . Tiaprofenic acid had no side-effects , whereas tiredness was experienced in 3 cases of naproxen sodium treatment . The results indicate that tiaprofenic acid is a useful alternative for the treatment of primary dysmenorrhoea The analgesic effect of flurbiprofen , aspirin and placebo in the treatment of primary dysmenorrhoea was compared in 41 patients using a double blind triple crossover study . No statistically significant differences were found between any pair of treatments and the control for pain relief . Thirty patients had assessment s for all three treatment months , 11 preferred flurbiprofen , 9 preferred placebo , 6 preferred aspirin and 4 had no preference between any of the treatments . Side effects were reported by 14 of the 41 patients : 3 during the control month , 6 during the flurbiprofen month , 4 during the aspirin month and 7 during the placebo month Abstract The efficacy of naproxen sodium ( naproxen-Na ) ∗ ∗Naproxen-sodium is the sodium salt of a-2-(6′-methoxy-2′ naphthyl)-propionic acid . in dysmenorrhea has been established in two independent double-blind ( placebo-controlled ) studies . An initial dose of 550 mg . of naproxen-Na was followed by 275 mg . every six hours for a maximum of five days . Twenty patients were included in Study I ( 10 treated with naproxen-Na ) and 23 patients in Study II ( 12 treated with naproxen-Na ) . Each patient received the medication during four dysmenorrheic episodes . Thus , a total of 172 treatment courses could be evaluated . A variety of efficacy criteria were measured : frequency of pill intake , changes in pain intensity , the degree of relief achieved by the medication , and need for additional analgesics . In both studies naproxen-Na was demonstrated to be superior to the placebo treatment with high statistical significance in each of these parameters Naproxen tablets and suppositories were compared , in the treatment of primary dysmenorrhea , in a double-blind cross-over trial . The results on 32 patients treated during 128 menstruations with either tablets and suppositories were analysed . Both naproxen tablets and suppositories produced a significant but similar overall relief of dysmenorrhea , although the tablets had a better effect in relieving spasmodic pain than the suppositories ( p < 0.05 ) . Occasions of failure to obtain relief were not related to the occurrence of vomiting or diarrhea during the trial . Vomiting seems not to be responsible for the therapeutic failures of oral treatments with prostagl and in-synthetase inhibitors in primary dysmenorrhea A double-blind crossover study was carried out to evaluate the therapeutic efficacy of nimesulide and its effects on uterine activity , menstrual fluid prostagl and in F , and pain in women suffering from primary dysmenorrhea . Twenty-three women entered the clinical pharmacologic study . Intrauterine pressure was monitored with a microballoon-tipped catheter on the first day of menstruation . During the maximal pain period ( based on monitoring in six patients ) , nimesulide significantly decreased intrauterine pressure ; the measure of pain relief was consistent with decrease of uterine activity . In another six patients , the registration of intrauterine pressure during the submaximal pain period demonstrated that both in the nimesulide- and placebo-treated cycles , the uterine activity was at a lower mean level than that registered during maximal pain . Furthermore , when two 100-mg oral doses of nimesulide were administered to 11 dysmenorrheic women , in double-blind , crossover conditions with placebo as a blank reference , it brought about a reduction of menstrual fluid prostagl and in F2 levels from 382 to 94 ng/mL , ( P less than .001 ) . Fourteen women entered a four-cycle , double-blind , crossover therapeutic trial . Each patient was r and omly assigned to one of two treatment sequences with nimesulide 200 mg/d PO or placebo . The therapy was judged very effective or good in 22 of 28 cycles treated with nimesulide compared with nine of 27 cycles treated with placebo ( P less than .01 ) . The amount of bleeding during the treated cycles did not change , and there were no complaints of untoward signs or symptoms related to the therapies Abstract Purpose Primary dysmenorrhea , which refers to painful , spasmodic cramping in the lower abdomen just before/or during menstruation , is the most common gynecological complaint in women of reproductive age . Non-steroidal anti-inflammatory drugs have been prescribed as the first-line therapy for pain relief from dysmenorrhea . We aim ed to investigate the efficacy of the daily recommended dose ( 150 mg ) of diclofenac potassium , administered at set intervals across the first 24 h of menstruation , in treating severe menstrual pain in 24 women with severe primary dysmenorrhea . Methods In a r and omized , placebo-controlled , double-blind cross-over study , women rated their menstrual pain intensity on a 100-mm visual analog scale across set time intervals over a 24-h period . Results Menstrual pain intensity was significantly reduced after taking the first capsule of diclofenac , and remained consistently lower ( P < 0.0001 ) , compared with initial pain intensity , in the morning ( before treatment ) , throughout the day , evening , and into the next morning . Also , women rated their pain intensity as significantly lower ( P < 0.001 ) at each time point across the 24-h time interval of the cycle when receiving diclofenac compared with the cycle when they received placebo . No woman required rescue medication when taking diclofenac potassium compared with six women taking rescue medications during the placebo trial . When taking only placebo , women rated their menstrual pain intensity as persistently severe across the first 24 h of menstruation . Conclusion These results show that the recommended daily dose of diclofenac potassium , in three 50 mg doses across the day and evening , offers effective menstrual pain relief across 24 h , compared with placebo , in women with severe primary dysmenorrhea Dexketoprofen , the pure S(+)-enantiomer of ketoprofen , is a promising new analgesic , but few clinical trials have yet examined its efficacy and tolerability . In this study , patients with a history of primary dysmenorrhea were treated with dexketoprofen doses of 12.5 and 25 mg , ketoprofen 50 mg , and placebo using a r and omized , four-way crossover design . Efficacy analyses showed that dexketoprofen 12.5 and 25 mg and racemic ketoprofen 50 mg significantly reduced pain intensity compared with placebo from 1 h after dose to 4 - 6 h after dose . Interestingly , dexketoprofen at 12.5 mg was significantly superior to placebo at 30 min after dose . Mean pain relief scores also demonstrated that both doses of dexketoprofen and racemic ketoprofen were significantly superior to placebo at 1 - 6 h after the first dose . No indices of analgesic efficacy showed any significant differences between the two doses of dexketoprofen or between dexketoprofen and ketoprofen . After repeated dose administration , similar results were obtained . There were no significant effects of any treatment on activities of daily living , menstrual flow , or associated symptoms . Dexketoprofen was effective , well tolerated , and had no difference in the incidence of adverse events compared to ketoprofen or placebo Abstract . The effect of naproxen , Naprosyn ® , Syntex , in treatment of primary dysmenorrhea was studied in a double‐blind , r and omized , placebo controlled multicenter study OBJECTIVE To assess the efficacy of two different doses of a Psidii guajavae folium extract in the management of primary dysmenorrhea . METHODOLOGY A double-blinded r and omized clinical trial was conducted in 197 women with primary dysmenorrhea . Four intervention groups were defined : two extract doses ( 3 and 6 mg/day ) ; ibuprofen ( 1200 mg/day ) ; placebo ( 3mg/day ) . Participants were followed-up individually for 4 months . The main outcome variable was abdominal pain intensity measured according to a visual analogue scale ( VAS ) . RESULTS The average age of participants was 19 years ; menarche occurred around age 12 years . Participants had menstrual cycles of 28 or 29 days , with menstruation lasting 5 days and mean of pain intensity of 8.2 on the VAS . During each successive treatment cycle , participants experienced a lower pain intensity score . Multiple regression analysis , after adjusting each cycle for baseline pain , treatment compliance and other variables , showed that the group receiving 6 mg/day extract had significantly reduced pain intensity ( p<0.001 ) . This effect was maintained in cycles 2 and 3 , although the reduction in the mean of pain intensity was lower . The group receiving the 3mg/day extract did not show a consistent effect throughout the three cycles . CONCLUSION At a dose of 6 mg/day , the st and ardized phyto-drug ( Psidii guajavae folium extract ) reduced menstrual pain significantly compared with conventional treatment and placebo The efficacy of ibuprofen and naproxen-sodium for the treatment of primary dysmenorrhea was evaluated in a double-blind cross-over study in 57 otherwise healthy women . The severity of pain reported by the patients was significantly ( P less than 0.01 ) reduced during treatment with both ibuprofen and naproxen-sodium compared to the severity of pain before the first dose . The mean pain relief during treatment with ibuprofen was significantly ( P less than 0.05 ) greater than during treatment with naproxen-sodium in the dosages indicated In a double-blind parallel trial , repeated doses of naproxen sodium ( 550 mg initially , followed by 275 mg every 6 hours as needed ) and placebo were administered to a group of intrauterine contraceptive device ( IUD ) users in whom dysmenorrhea and premenstrual uterine pain developed or increased following the insertion of the IUD . Seventeen subjects were treated with naproxen sodium and 16 received placebo . The study covered three episodes of uterine pain and /or cramping . Efficacy of pain relief was judged by : ( 1 ) the overall relief which the patients experienced during the treatment and ( 2 ) the changes in the pain intensity ( measured on a 6 point scale ) . By both these criteria , naproxen sodium was statistically significantly superior to placebo ( p = 0.02 ) ; consequently , naproxen sodium appears to offer a new treatment modality for pain associated with IUD usage Reports on the efficacy of flurbiprofen for dysmenorrhea conflict . We gave 59 dysmenorrheic patients flurbiprofen ( 50 mg ) , aspirin ( 650 mg ) , or placebo . Paired drug comparisons showed that patients preferred flurbiprofen and that it was more effective in relief of pain , in allowing patients to pursue normal daily function , and in reducing the need for additional analgesics . Except in patient preference , aspirin was only marginally superior to placebo . There was an increase in minor side effects in the flurbiprofen group , but our results indicate therapeutic utility for flurbiprofen in dysmenorrhea Prostagl and ins ( PGs ) may be involved in the development of the symptoms of endometriosis . Therefore 18 patients with pelvic endometriosis were treated in placebo controlled double-blind trial with different prostagl and in bio synthesis inhibitors . These drugs were : acetylsalicylic acid ( 0.5 g x 3 ) exerting a weak PG-synthetase inhibition , indomethacin ( 25 mg x 3 ) inhibiting PG-synthetase , and as a representative of fenamates , tolfenamic acid ( 200 mg x 3 ) , which both inhibits PG-synthetase and antagonizes PGs at the target level . The therapeutic effect was evaluated using a specific endometriosis score separately during menstruation and in premenstrum . Prostagl and in bio synthesis inhibitors did not alleviate premenstrual complaints better than placebo . During menstruation tolfenamic acid relieved endometriotic symptoms more effectively than placebo while indomethacin and acetylsalicylic acid did not differ from placebo . A drug which inhibit both the synthesis and action of PGs can thus be used in the alleviation of secondary dysmenorrhea due to endometriosis Abstract . The technique called hysterometry has been used for the quantitative evaluation of effect of naproxen sodium and naproxen on myometrial tension in vivo during dysmenorrhea . It was observed that “ uterine tonicity ” ‐ the datum arrived at after hysterometric recording ‐ decreased significantly during naproxen medication in comparison with placebo treatment . Decrease in uterine tonicity was well correlated with relief of pain Summary . Abnormal production of uterine prostagl and ins ( PG ) causes primary dysmenorrhoea and excessive menstrual blood loss ( MBL ) . We measured here MBL in primary dysmenorrhoea and found it to be normal during treatment with opiate analgesics ( 33.5±1.6 ml ; mean±D , n=13 ) , placebo ( 33.4±18.6 ml ; n=8 ) , proquazone ( 31.8±18.0ml ; n=8 ) and indomethacin ( 26.4±18.7 ml ; n=8 ) . Proquazone and indomethacin relieved pain and other dysmenorrhoeic symptoms similarly in 33 women Objective : To determine the efficacy of etoricoxib in the treatment of primary dysmenorrhea . Methods : Seventy-three women were r and omly assigned to receive single oral doses of etoricoxib 120 mg , placebo , or naproxen sodium 550 mg at the onset of moderate to severe pain associated with menses . During 3 consecutive menstrual cycles in this double-blind , 3-period , crossover study , pain intensity and pain relief were assessed over the 24-hour period following dosing , and global ratings of therapy were made at 8 and 24 h after dosing . Tolerability was assessed by spontaneous reports of adverse experiences . Results : Etoricoxib 120 mg provided analgesic efficacy superior to placebo for the primary endpoint , total pain relief over 8 h ( TOPAR8 , p < 0.001 ) , and for all secondary endpoints ( p < 0.050 ) . The analgesic effect of etoricoxib 120 mg over the first 8 h was similar to that of naproxen sodium 550 mg . All treatments were well tolerated . Conclusions : Etoricoxib 120 mg provided rapid and sustained analgesia that was superior to placebo and similar to that of naproxen sodium 550 mg Eleven women with primary dysmenorrhea completed a r and omized , double-blind , placebo-controlled , three-way cross-over study comparing 200 and 400 mg suprofen . Menstrual fluid volume did not change . Mean+/-S.E.M. menstrual fluid PGF2a was significantly suppressed from 18.9+/-1.9 microg ( placebo ) to 10.9+/-1.7 and 9.3+/-2.1 microg with 200 and 400 mg suprofen , respectively ( p=<0.005 ) . PGE2 dropped from 7.8+/-0.9 to 4.6+/-0.8 and 4.6+/-1.1 microg ( p=<0.05 ) and TxB2 from 17.5+/-4.3 to 7.5+/-2.9 and 3.6+/-1.3 microg ( p=<0.01 ) , respectively . 6-Keto PGF1a was significantly suppressed ( 2.7+/-0.4 to 1.9+/-0.5 microg , p=<0.025 ) with only 400 mg suprofen . Six subjects rated placebo poor and five fair to very good . In contrast , nine rated suprofen excellent to fair while two rated poor . Thus , suprofen was clinical ly effective but the differential suppression of prostanoids favors 200 mg which spares 6-keto PGF1a Primary dysmenorrhea and secondary dysmenorrhea induced by an intrauterine device are associated with increased production and release of endometrial prostagl and ins . The condition may be treated by oral contraceptives , which reduce overall menstrual fluid volume , or by a prostagl and in synthetase inhibitor , such as ibuprofen . Unless the patient wishes to use oral contraceptives for birth control , ibuprofen ( Motrin ) is the drug of choice because it need only be given for two to three days each cycle , does not suppress the pituitary ovarian axis , and does not cause metabolic alterations . Clinical trials have shown ibuprofen to be highly efficacious , and more effective than indomethacin , aspirin , or propoxyphene , with no or few side effects Summary The analgesic effect of paracetamol , acetylsalicylic acid , and placebo on dysmenorrhoea were compared in a double-blind crossover study of 30 women . There was a moderate placebo effect , but no significant difference was found between the three treatments . Blood loss was also measured and it did not vary with the type of drug ingested . It is concluded that paracetamol and acetylsalicylic acid in the doses used ( 0.5 g × 4 for 3 days ) were not effective against heavy dysmenorrhoea , and that none of the drugs influenced the amount of blood lost 1 . Montgomery TL : Adolescent sexuality and para marriage , Am J Obstet Gynecol 124:818 , 1976 . 2 . Feldman M J , Linzey EM , Srebnik E , et al : Abnormal cervical cytology in the teen-ager : A continuing problem , Am J Obstet Crynecol 126:418 , 1976 . 3 . Feldman M J , Kent DR , and Pennington RL : lntraepithelial neoplasia of the uterine cervix in the teenager , Cancer 41:1405 , 1978 . 4 . Pollack RS , and Taylor HC Jr : Carcinoma of the cervix during the two decades of life , Am J Obstet Gyneco153:135 , 1947 . 5 . Walton Report : Can Med Assoc J 114:1003 , 1976 . 6 . Ferguson JH : Positive cancer smears in ieenage girls , JAMA 178:365 , 1961 . 7 . Kaufman RH , Burmeister RE , and Spjut HJ : Cervical cytology in the teen-age patient , Am J Obstet Gynecol 108:515 , 1970 _ 8 . Johnson LD , Nickerson RJ , Easterday CL , et al : Epidemiological evidence for the spectrum of change from dysplasia through carcinoma in situ to invasive cancer , Cancer 22:901 , 1968 . 9 . Koss LG : Concept of genesis development of carcinoma of the cervix , Obstet Gynecol Sur 24:850 , 1969 . 10 . Sedlis A , Cohen A , and Sall S : The fate of cervical dysplasia , Am J Obstet Gynecol 107:1065 , 1970 . 11 . Richart RM : Cervical intraepithelial neoplasia , in Sommers , SC , editor : Pathology annual 1973 . New York , 1973 , Appleton-Century-Crofts , pp 301 - 328 . 12 . Christopherson WM , and Parker JE : Relation of cervical cancer to early marriage and childbearing , N Engl J Med 273:235 , 1965 . 13 . Rotkin ID : A comparison review of key epidemiological studies in cervical cancer related to current search es for transmissible agents , Cancer Res 33:1353 , 1973 . 14 . Creasman WT , Weed JC , Curry SL , et al : Efficacy of cryosurgical treatment of severe cervical intraepithelial neoplasia , Obstet Gynecol 41:501 , 1973 OBJECTIVE To determine whether rofecoxib is effective for treating primary dysmenorrhea and whether cyclooxygenase-2 is involved in the pathophysiology of primary dysmenorrhea . METHODS A double-masked , r and omized , placebo and active-comparator-controlled clinical trial including 127 subjects with histories of primary dysmenorrhea was conducted in an outpatient clinical research center . Subjects were r and omly assigned to placebo , rofecoxib 25 or 50 mg followed by 25 mg every 24 hours as needed , or naproxen sodium 550 mg every 12 hours as needed for up to 3 days . Subjects took all four treatments in a balanced , complete-block , crossover design . Measurements included self-administered question naires of analgesic efficacy , spontaneous reports of adverse experiences , physical examinations , and laboratory safety tests . RESULTS Rofecoxib 25 and 50 mg provided analgesic efficacy greater than placebo ( P < or = .006 ) for the primary endpoint of total pain relief over the first 8 hours . For other efficacy endpoints ( sum of the pain intensity difference over the first 8 hours , subject 's global evaluation , peak pain relief , peak pain intensity difference , and time to remedication ) both doses of rofecoxib were better than placebo ( P < or = .006 ) and were not distinguishable from naproxen sodium for all efficacy endpoints . All treatments were well tolerated . CONCLUSION Rofecoxib effectively treated primary dysmenorrhea , and cyclooxygenase-2-derived prostanoids play a role in the pathophysiology of primary dysmenorrhea Eighteen patients participated in a double-blind , placebo-controlled , single-dose , crossover study of meclofenamate sodium in women with primary dysmenorrhea . Simultaneous evaluations of pain intensity and pain relief , sampling of continuous intrauterine pressure recording , and monitoring of blood meclofenamate levels were carried out . Improvements in pain intensity and pain relief were observed at 45 minutes and reached statistical significance at and beyond 1 hour 45 minutes after meclofenamate therapy . Ten of 14 uterine pressure parameters showed statistically significant responses after drug therapy and 12 of the 14 parameters showed statistically significant differences in time-response patterns . Statistically significant changes were noted as early as 45 minutes after meclofenamate therapy . Statistically significant correlations were found between and among the parameters of blood drug level and the subjective and objective measures . No drug-related adverse effects were found Abstract A group of dysmenorrheic women was treated during two consecutive menstrual bleedings , once with placebo and once with naproxen-sodium ( naproxen-Na ) , a potent inhibitor of prostagl and in synthesis . Concentrations of prostagl and ins F and E ( PGF , PGE ) were assayed in the menstrual blood collected into cervical cups , and in uterine “ jet-wash ” specimens . In the menstrual blood the high PGF concentrations of patients receiving placebo were significantly reduced following treatment with naproxen-Na ( from ± S.E. 227±78.9 ng/ml to 42±19.5 ng/ml ; p=0.03 ) . A significant decrease of PGE concentrations was also observed during naproxen-Na treatment ( from 10.8±2.1 ng/ml to 3.4±1.7 ng/ml ; p=0.03 ) . In the uterine “ jet washings ” naproxen-Na significantly reduced PGE concentrations ( p=0.03 ) while the decrease of PGF concentrations was close to statistical signficance ( p=0.06 ) . These results strenthened the premise of causal relationships between naproxen-Na treatment , decreased uterine prostagl and ins , reduction of intrauterine pressure , and relief from dysmenorrehic pain Summary Dysmenorrhoea is painful menstruation that occurs in 45–72 % of all women . This was a prospect i ve r and omised study of the efficacy of etoricoxib ( Arcoxia ® ) compared with mefenamic acid ( Ponstan ® ) in treating primary dysmenorrhoea . All single , sexually inactive women with primary dysmenorrhoea were r and omised into two groups ( mefenamic acid and etoricoxib ) of pain relief and underwent a cross-over study . The success of treatment as evidence d by pain relief , the side-effects and complications were observed and analysed . Some 80 % ( 20 women ) had significantly better pain relief with etoricoxib , compared with only 20 per cent in the mefenamic acid group ( p = 0.007 ) . Etoricoxib has significantly fewer side-effects compared with mefenamic acid ( p = 0.005 ) with significantly reduced menstrual blood loss ( p = 0.025 ) . In conclusion , etoricoxib is a better treatment for primary dysmenorrhoea with better pain relief , less menstrual blood loss and fewer side-effects compared with mefenamic acid A 6-month double-blind crossover trial compared ketoprofen with placebo in the treatment of primary dysmenorrhea in 27 women who satisfied explicit inclusion and exclusion criteria . The response to treatment was assessed with a pain scale and a disability scale and by noting amelioration of associated symptoms , such as nausea , vomiting , diarrhea , fatigue , dizziness and headache . Ketoprofen was significantly superior to placebo in relieving the pain ( p less than 0.001 ) , disability ( p less than 0.001 ) and headache ( p less than 0.01 ) associated with menstruation . No order effect of treatment was observed . Adverse effects were few and minimal The Prostagl and in- synthesis inhibitor : Naproxen-Sodium ( NS ) ( an analgesic agent ) very significantly ( P less than 0.001 ) reduced the " resting " and " active " pressures and the frequency of cyclic uterine activity of 10 dysmenorrheic patients . It also highly significantly reduced ( P less than 0.001 ) menstrual pain . Since these effects were observed after a single oral dose of 1100 mg NS , without side effects or complications , extensive field trials are recommended for assessing therapeutic benefits of this treatment The effect of flurbiprofen ( 100 mg × 2 for 5 days ) was compared with tranexamic acid ( 1.5 g × 3 for 3 days , 1 g × 2 days 4 and 5 ) in the treatment of 15 women with idiopathic menorrhagia . The mean blood loss during two medication‐free periods was 295 ± 52 ml . A significant ( p < 0.01 ) reduction in menstrual blood loss was recorded during treatment with both flurbiprofen and tranexamic acid . The menstrual blood loss was significantly ( p < 0.01 ) lower during treatment with tranexamic acid ( 155 ± 33 ml ) than with flurbiprofen ( 223 ± 44 ml ) . Various side effects were recorded by 7 of 15 women during treatment with tranexamic acid and by 4 women of 15 during treatment with flurbiprofen . Many women with menorrhagia suffer simultaneously from dysmenorrhea . Thus although tranexamic acid was generally more effective in reducing menstrual blood loss , flurbiprofen provides an important therapeutic alternative to antifibrinolytic agents , especially in patients with concomitant dysmenorrhea Background Dysmenorrhoea refers to the occurrence of painful menstrual cramps of uterine origin and is a common gynaecological complaint . Common treatment for dysmenorrhoea is medical therapy such as nonsteroidal anti-inflammatories ( NSAIDs ) or oral contraceptive pills ( OCPs ) which both work by reducing myometrial activity ( contractions of the uterus ) . The efficacy of conventional treatments such as nonsteroidals is considerable , however the failure rate is still often 20 - 25 % . Many consumers are now seeking alternatives to conventional medicine and research into the menstrual cycle suggests that nutritional intake and metabolism may play an important role in the cause and treatment of menstrual disorders . Herbal and dietary therapies number among the more popular complementary medicines yet there is a lack of taxonomy to assist in classifying them . In the US , herbs and other phytomedicinal products ( medicine from plants ) have been legally classified as dietary supplements since 1994 . Included in this category are vitamins , minerals , herbs or other botanicals , amino acids and other dietary substances . For the purpose of this review we use the wider term herbal and dietary therapies to include the assorted herbal or dietary treatments that are classified in the US as supplements and also the phytomedicines that may be classified as drugs in the European Union . Objectives To determine the efficacy and safety of herbal and dietary therapies for the treatment of primary and secondary dysmenorrhoea when compared to each other , placebo , no treatment or other conventional treatments ( e.g. NSAIDS ) . Search methods Electronic search es of the Cochrane Menstrual Disorders and Subfertility Group Register of controlled trials , CCTR , MEDLINE , EMBASE , CINAHL , Bio extracts , and PsycLIT were performed to identify relevant r and omised controlled trials ( RCTs ) . The Cochrane Complementary Medicine Field 's Register of controlled trials ( CISCOM ) was also search ed . Attempts were also made to identify trials from the National Research Register , the Clinical Trial Register and the citation lists of review articles and included trials . In most cases , the first or corresponding author of each included trial was contacted for additional information . Selection criteria The inclusion criteria were RCTs of herbal or dietary therapies as treatment for primary or secondary dysmenorrhoea vs each other , placebo , no treatment or conventional treatment . Interventions could include , but were not limited to , the following ; vitamins , essential minerals , proteins , herbs , and fatty acids . Exclusion criteria were : mild or infrequent dysmenorrhoea or dysmenorrhoea from an IUD . Data collection and analysis Seven trials were included in the review . Quality assessment and data extraction were performed independently by two review ers . The main outcomes were pain intensity or pain relief and the number of adverse effects . Data on absence from work and the use of additional medication was also collected if available . Data was combined for meta- analysis using Peto odds ratios for dichotomous data or weighted mean difference for continuous data . A fixed effects statistical model was used . If data suitable for meta- analysis could not be extracted , any available data from the trial was extracted and presented as descriptive data . Main results MAGNESIUM : Three small trials were included that compared magnesium and placebo . Overall magnesium was more effective than placebo for pain relief and the need for additional medication was less . There was no significant difference in the number of adverse effects experienced . VITAMIN B6 : One small trial of vitamin B6 showed it was more effective at reducing pain than both placebo and a combination of magnesium and vitamin B6 . MAGNESIUM AND VITAMIN B6 : Magnesium was shown to be no different in pain outcomes from both vitamin B6 and a combination of vitamin B6 and magnesium by one small trial . The same trial also showed that a combination of magnesium and vitamin B6 was no different from placebo in reducing pain . VITAMIN B1 : One large trial showed vitamin B1 to be more effective than placebo in reducing pain . VITAMIN E : One small trial comparing a combination of vitamin E ( taken daily ) and ibuprofen ( taken during menses ) versus ibuprofen ( taken during menses ) alone showed no difference in pain relief between the two treatments . OMEGA-3 FATTY ACIDS : One small trial showed fish oil ( omega-3 fatty acids ) to be more effective than placebo for pain relief . JAPANESE HERBAL COMBINATION : One small trial showed the herbal combination to be more effective for pain relief than placebo , and less additional pain medication was taken by the treatment group . Authors ' conclusions Vitamin B1 is shown to be an effective treatment for dysmenorrhoea taken at 100 mg daily , although this conclusion is tempered slightly by its basis on only one large RCT . Results suggest that magnesium is a promising treatment for dysmenorrhoea . It is unclear what dose or regime of treatment should be used for magnesium therapy , due to variations in the included trials , therefore no strong recommendation can be made until further evaluation is carried out . Overall there is insufficient evidence to recommend the use of any of the other herbal and dietary therapies considered in this review for the treatment of primary or secondary dysmenorrhoea Twenty patients with moderate to very severe painful menstrual periods secondary to endometriosis were treated in a double-blind , four-period , crossover clinical trial with naproxen sodium and placebo . Complete or substantial pain relief was obtained in 83 % of the cases of painful menstruation with naproxen sodium and in 41 % with placebo ( P=.008 ) . Only 5 % of the naproxen sodium-treated women needed supplemental analgesics compared with 36 % of the placebo-treated women ( P=.002 ) . There was a trend towards diminished interference of dysmenorrhea with normal patient activities during naproxen sodium treatment compared with placebo ( P=.069 ) . No significant side effects occurred with either treatment . These results indicated that naproxen sodium is efficacious and safe for the treatment of menstrual distress in patients with endometriosis . ( Obstet Gynecol 65:379 , 1985 Thirty-two dysmenorrheic patients participated in a double-blind trial of naproxen sodium for three consecutive menstrual cycles . The women were divided into two groups : 15 women were given naproxen sodium ( the sodium salt of d-2-(6-methoxy-2-naphthyl ) propionic acid ) and 17 women received placebo tablets . The women were prescribed two tablets ( 550 mg ) at the first sign of menstrual pain and one tablet ( 275 mg ) thereafter every six hours , as required . There were no significant differences between the two groups in physical characteristics , obstetric and gynecologic histories , including the character of dysmenorrhea and pretreatment pain intensity scores ( p = 0.7 ) . Following intake of the drug or placebo , the participants rated the relief provided by the medication with a six-point scoring system . When the scores for pain relief were tallied for the three treatment cycles , the naproxen sodium group averaged 13.7 + /- 0.65 st and ard error , while the placebo group averaged 8.8 + /- 0.95 st and ard error out of a possible maximum relief score of 18 . The difference between the two groups was statistically significant at p = 0.0004 . Few patients reported side effects Abstract . The efficacy of naproxen and indomethacin in the treatment of dysmenorrhea was compared in a double‐blind , cross‐over study . Both drugs were given to 24 female undergraduates with severe primary dysmenorrhea in four consecutive cycles in a r and omized schedule . Both drugs were equally effective . Good or moderate overall relief was achieved in 73 % of 48 cycles treated with indomethacin and in 61 % of the 48 cycles treated with naproxen . The difference was not statistically significant We compared fenoprofen calcium , 200 mg ; fenoprofen calcium , 400 mg ; aspirin , 650 mg ; and a placebo in 85 women for the relief of primary dysmenorrhea in a double-blind , clinical trial . The usefulness of these drugs was judged from data obtained over four consecutive menstrual periods on : restriction of daily activity , pain intensity scores , need for rescue analgesics , withdrawal due to lack of efficacy , and adverse events . Both fenoprofen , 200 mg , and fenoprofen , 400 mg , offered significant ( P less than .01 ) pain relief when compared to placebo and aspirin . Analyses of data on 1 , 2 and 3 indicated that aspirin was not significantly different from placebo . The aspirin-treated group reported the greatest number of adverse reactions , but the differences between the four groups were not statistically significant . Our study lends support to the concept of a " plateau analgesic effect " of nonsteroidal antiinflammatory drugs ( NSAIDs ) : fenoprofen , 200 mg , appears to be as effective as fenoprofen , 400 mg . When this type of drug fails to provide relief for a woman suffering from primary dysmenorrhea , switching to another NSAID may be more appropriate than increasing the dosage and the probability of dosage-related side effects BACKGROUND Celecoxib , a cyclooxygenase-2 inhibitor , has established analgesic efficacy for the treatment of acute pain result ing from a variety of causes . OBJECTIVE This article describes 2 studies design ed to assess the efficacy and tolerability of celecoxib in patients with primary dysmenorrhea . METHODS Two identical , 3-day , multiple-dose , r and omized , double-blind , active- and placebo-controlled , crossover studies were carried out in women aged 18 to 44 years with primary dysmenorrhea ( studies 1 and 2 ) . The studies employed a 6-sequence , 3-period , complete-block crossover design over 3 menstrual cycles . Patients received celecoxib 400 mg , followed by celecoxib 200 mg no sooner than 12 hours after first dose ( day 1 ) , then celecoxib 200 mg q12h as necessary ( days 2 and 3 ) ; naproxen sodium 550 mg followed by naproxen sodium 550 mg no sooner than 12 hours after first dose ( day 1 ) , then naproxen sodium 550 mg q12h as necessary ( days 2 and 3 ) ; or placebo . Primary efficacy measures were time-weighted sum of total pain relief and time-weighted sum of pain intensity difference at 8 hours after administration of the first dose of study medication ( TOTPAR[8 ] and SPID[8 ] , respectively ) . Tolerability was assessed using routine physical examination , including vital sign measurements , and clinical laboratory analyses at screening and end of study . RESULTS In total , 149 and 154 patients were r and omized to 1 of the 6 treatment sequences in studies 1 and 2 , respectively . Across treatment sequences , mean age ranges were 23.4 to 26.9 years ( study 1 ) and 28.3 to 34.1 years ( study 2 ) . Mean weight ranges were 62.7 to 74.5 kg ( study 1 ) and 69.2 to 86.7 kg ( study 2 ) . Most patients ( 96.6 % in study 1 , 80.5 % in study 2 ) were white . Mean TOTPAR[8 ] values with celecoxib ( study 1/ study 2 , 18.28/17.98 ) and naproxen sodium ( 20.59/21.27 ) were significantly greater than with placebo ( 12.82/12.98 ) ( all , P < 0.001 ) . Mean SPID[8 ] values were significantly greater with celecoxib ( 10.06/9.60 ) and naproxen sodium ( 11.48/11.71 ) than with placebo ( 5.96/6.41 ) ( all , P < 0.001 ) . Naproxen sodium was significantly different from celecoxib in TOTPAR[8 ] ( study 2 only ) and SPID[8 ] ( both studies ) ( all , P < 0.001 ) . In both studies , the adverse-events ( AEs ) profile was not significantly different between treatments , with the majority of AEs being related to primary dysmenorrhea and not medication . Less than 10 % of patients experienced severe AEs in any treatment period . CONCLUSIONS In these 2 identically design ed studies in women aged 18 to 44 years , celecoxib 400 mg ( followed by 200 mg q12h ) was more effective , as measured using pain scores , in the treatment of primary dysmenorrhea compared with placebo . In each study , the primary efficacy measures -TOTPAR[8 ] and SPID[8 ] scores-were significantly improved with celecoxib and naproxen sodium compared with placebo . SPID[8 ] in both studies and TOTPAR[8 ] in study 2 were significantly improved with naproxen sodium compared with celecoxib . Both celecoxib and naproxen sodium were well tolerated and provided relief from menstrual pain within 1 hour of administration BACKGROUND Dysmenorrhea produces painful abdominal cramps that can disrupt the personal lives and productivity of women . OBJECTIVE The aim of this study was to compare the analgesic efficacy , including onset and duration of pain relief , peak effect , and total effect , and tolerability of ibuprofen arginate with those of conventional ibuprofen in patients with moderate to severe pain associated with primary dysmenorrhea . METHODS Patients were administered a single dose of ibuprofen arginate ( 200 or 400 mg ) , conventional ibuprofen ( 200 or 400 mg ) , or placebo during each of 5 menstrual cycles in a single-center , double-blind , r and omized , double-dummy , 5-cycle , crossover study . Patients recorded their pain intensity and pain relief at regularly scheduled intervals ( 10 , 20 , 30 , 40 , 50 , 60 , and 90 minutes and 2 , 3 , 4 , 5 , and 6 hours ) after taking the study medication , and all study observations were recorded in a patient diary . Pain intensity was rated using the following 4-point categoric rating scale : 0 = none , 1 = mild , 2 = moderate , and 3 = severe . Pain relief was rated on a 5-point scale as 0 = none , 1 = a little , 2 = some , 3 = a lot , and 4 = complete relief . Tolerability of ibuprofen arginate was based on a comparison of the incidence of spontaneously reported adverse events in each of the treatment groups . RESULTS One hundred four patients entered the study . Of these , 81.7 % were white ; the mean ( SD ) age was 27.5 ( 5.0 ) years . A total of 65.4 % of patients reported moderate pain from dysmenorrhea , and the remaining 34.6 % reported severe pain ; 20.2 % of patients did not complete the study . The median time to achieve meaningful pain relief was ∼30 minutes faster with ibuprofen arginate 400 mg than with either dose of conventional ibuprofen . Tolerability was similar across all treatments . CONCLUSIONS In this study population of patients experiencing acute pain as a result of primary dysmenorrhea , ibuprofen arginate was associated with effective , tolerable analgesia and a more rapid onset of action than conventional ibuprofen . The faster onset of analgesia may have a role in clinical practice in treating women with dysmenorrhea . A faster onset of action may be important to women whose personal relationships , productivity , or ability to sleep is being adversely affected by pain |
14,047 | 27,881,170 | Conclusion Non-smokers have a statistically significant lower HbA1c and more favourable lipid profile compared to smokers .
Smoking cessation does not lead to an increase in HbA1c in long-term and may reduce vascular complications in diabetes by its favourable impact on lipid profile | Background Smoking is associated with increased macrovascular and microvascular complications in people with diabetes .
In addition to other concomitant vascular perturbations , it also seems to influence the cardiometabolic parameters , which may partly explain the accelerated rate of vascular complications in smokers with diabetes .
While smoking cessation is advocated as a universal component of the management of diabetes , there is some anecdotal evidence that HbA1c could increase following smoking cessation .
The aim of this review is to explore the relationship between smoking and its cessation on cardiometabolic parameters in diabetes . | OBJECTIVE To assess the relationship between cigarette smoking and mortality among women with type 2 diabetes in the Nurses ' Health Study cohort . RESEARCH DESIGN AND METHODS The Nurses ' Health Study , a prospect i ve cohort of U.S. female registered nurses , included 7,401 women with type 2 diabetes diagnosed at baseline or during follow-up from 1976 to 1996 . Total and cause-specific mortality of these diabetic women were the outcomes of interest . RESULTS We documented 724 deaths during 20 years of follow-up ( 67,420 person-years ) among women with type 2 diabetes . In multivariate analyses , adjusting for age , history of high blood pressure and high cholesterol , and other cardiovascular risk factors , compared with never smokers , the RRs of mortality were 1.31 ( 95 % CI 1.11 - 1.55 ) for past smokers , 1.43 ( 0.96 - 2.14 ) for current smokers of 1 - 14 cigarettes/day , 1.64 ( 1.24 - 2.17 ) for current smokers of 15 - 34 cigarettes/day , and 2.19 ( 1.32 - 3.65 ) for current smokers of > or = 35 cigarettes/day ( P for trend = 0.0002 ) . Women with type 2 diabetes who had stopped smoking for > or = 10 years had a mortality RR of 1.11 ( 0.92 - 1.35 ) compared with diabetic women who were never smokers . CONCLUSIONS Cigarette smoking is associated in a dose-response manner with an increased mortality among women with type 2 diabetes . Furthermore , quitting smoking appears to decrease this excess risk substantially . Diabetes patients should be strongly advised against smoking Cigarette smoking causes acute blood pressure ( BP ) elevation , although some studies have found similar or lower BPs in smokers compared with nonsmokers . Cross-sectional data from 3 years ( 1994 to 1996 ) of the annual Health Survey for Engl and were used to investigate any difference in BP between smokers and nonsmokers in a nationally representative sample of adults ( ≥16 years old ) . R and omly selected adults ( 33 860 ; 47 % men ) with valid body mass index ( BMI ) and BP measurements provided data on smoking status ( never , past , or current ) and were stratified into younger ( 16 to 44 years old ) and older ( ≥45 years old ) age groups . Analyses provided between 89 % and 94 % power to detect a difference of 2 mm Hg systolic BP between smokers and nonsmokers in the 4 age/gender strata ( & agr;=0.05 ) . Older male smokers had higher systolic BP adjusted for age , BMI , social class , and alcohol intake than did nonsmoking men . No such differences were seen among younger men or for diastolic blood pressure in either age group . Among women , light smokers ( 1 to 9 cigarettes/d ) tended to have lower BPs than heavier smokers and never smokers , significantly so for diastolic BP . Among men , a significant interaction between BMI and the BP-smoking association was observed . In women , BP differences between nonsmokers and light smokers were most marked in those who did not drink alcohol . These data show that any independent chronic effect of smoking on BP is small . Differences between men and women in this association are likely to be due to complex interrelations among smoking , alcohol intake , and BMI The influence of cigarette smoking and use of smokeless tobacco on plasma fibrinogen level , fibrinolytic variables , glucose tolerance and serum insulin was studied in a r and omly selected population sample consisting of 604 men and 662 females between 25 and 64 years . Subjects were grouped according to tobacco habits as follows : regular smokers ( > 1 cig/day ) , ex-smokers , snuff dippers , and non-tobacco users . An oral glucose tolerance test was performed on 54 % of the participants . Tissue plasminogen activator ( tPA ) activity and plasminogen activator inhibitor type 1 ( PAI-1 ) activity were used to study fibrinolysis . Men who smoked had 0.34 g/l ( 95 % CI 0.17 to 0.49 ) higher fibrinogen level than non-tobacco users and numbers of cigarettes smoked correlated with plasma fibrinogen levels ( r = 0.21 , P = 0.006 ) . Female smokers had significantly higher fibrinogen levels than ex-smokers but the difference compared with non-smokers was not significant . Snuff dipping did not affect fibrinogen levels . We found no relationship between tPA activity , PAI-1 activity and tobacco use . Post-load plasma glucose was lower in women who smoked , otherwise no influence of tobacco use on glucose levels was seen . Lower post-load insulin levels ( -8.8 mU/ml , 95 % CI -2.4 to -16.3 ) than in non-smokers were also found in women who smoked . This was only partially explained by a lower body mass index in smokers . We conclude that cigarette smoking is associated with increased fibrinogen levels , unaltered fibrinolysis , normal glucose tolerance and insulin levels . The use of smokeless tobacco , as moist oral snuff , does not appear to affect these potential cardiovascular risk factors |
14,048 | 22,575,353 | This study suggests that weight-related health interventions that require parent participation more effectively reduce body mass indexes of child and adolescent participants .
In addition , longer interventions that include parent participation appear to have greater success . | OBJECTIVE To review child and adolescent weight-related health intervention characteristics , with a particular focus on levels of parental participation , and examine differences in intervention effectiveness . | UNLABELLED Obesity in childhood , which is associated with cardiovascular risk factors such as hypertension , is on the increase . Counter measures are necessary . In this paper , we present the baseline and final data from the StEP TWO programme , a prospect i ve study to prevent overweight and obesity in primary schools . METHODS We recorded and calculated , from 1689 children , anthropometric data , including analyses of bioelectric impedance , waist and hip circumferences , body mass index and its st and ard deviation , and the ratio of waist to hip . Blood pressure was measured after 5 minutes at rest . From the three schools involved in a programme of intervention , 121 children were invited to take part , and 40 ( 33.1 per cent ) completed the programme . The effect was compared with 155 overweight and obese children identified at the 4 control schools . RESULTS 830 ( 49.5 per cent ) boys and 848 girls ( 50.5 per cent ) took part . Their mean age was 8.2 plus or minus 1.3 years , their height was 1.31 plus or minus 0.09 metres , they weighed 30.0 plus or minus 8.2 kilograms , and their mean index of body mass was 17.1 plus or minus 2.9 kilograms per metre squared . Of the children , 7.3 per cent were obese , 10.4 per cent were overweight , 75.7 per cent had normal weights , and 6.6 per cent were underweight . Resting hypertension was observed in 2.3 per cent of the children . Increased blood pressure was associated with a higher body weight , body mass index , st and ard deviation score for body mass index , and waist and hip circumferences ( each p < 0.001 ) , but not with the ratio of waist to hip . Hypertension at rest was also found in 11.0 per cent of obese children , 4.4 per cent of those who were overweight , 1.2 per cent of those with normal weight , and 1.0 per cent of underweight children ( p < 0.001 ) . After the intervention , the increase of the body mass index tended to be lower in those in whom we had intervened ( p = 0.069 ) , and in these the decrease of the st and ard deviation score for body mass index was significantly higher ( p = 0.028 ) . Systolic blood pressure was reduced by about 10 millimetres of mercury in those in whom we had intervened ( p = 0.002 ) , while there were no changes in the control group . Diastolic blood pressure was lowered by 3 millimetres of mercury , but this was not significant . CONCLUSION Obese children had the highest values for systolic and diastolic blood pressure . Increased levels of blood pressure are associated with other parameters of obesity , such as the circumference of the waist and hip . Early preventive measurements in childhood are necessary , and appropriate intervention appears to be effective Background Schools are the most frequent target for intervention programs aim ed at preventing child obesity ; however , the overall effectiveness of these programs has been limited . It has therefore been recommended that interventions target multiple ecological levels ( community , family , school and individual ) to have greater success in changing risk behaviors for obesity . This study examined the immediate and short-term , sustained effects of the Switch program , which targeted three behaviors ( decreasing children 's screen time , increasing fruit and vegetable consumption , and increasing physical activity ) at three ecological levels ( the family , school , and community ) . Methods Participants were 1,323 children and their parents from 10 schools in two states . Schools were matched and r and omly assigned to treatment and control . Measures of the key behaviors and body mass index were collected at baseline , immediately post-intervention , and 6 months post-intervention . Results The effect sizes of the differences between treatment and control groups ranged between small ( Cohen 's d = 0.15 for body mass index at 6 months post-intervention ) to large ( 1.38 ; parent report of screen time at 6 months post-intervention ) , controlling for baseline levels . There was a significant difference in parent-reported screen time at post-intervention in the experimental group , and this effect was maintained at 6 months post-intervention ( a difference of about 2 hours/week ) . The experimental group also showed a significant increase in parent-reported fruit and vegetable consumption while child-reported fruit and vegetable consumption was marginally significant . At the 6-month follow-up , parent-reported screen time was significantly lower , and parent and child-reported fruit and vegetable consumption was significantly increased . There were no significant effects on pedometer measures of physical activity or body mass index in the experimental group . The intervention effects were moderated by child sex ( for fruit and vegetable consumption , physical activity , and weight status ) , family involvement ( for fruit and vegetable consumption ) , and child body mass index ( for screen time ) . The perception of change among the experimental group was generally positive with 23 % to 62 % indicating positive changes in behaviors . Conclusion The results indicate that the Switch program yielded small-to-modest treatment effects for promoting children 's fruit and vegetable consumption and minimizing screen time . The Switch program offers promise for use in youth obesity prevention OBJECTIVE The High 5 for Preschool Kids ( H5-KIDS ) program tested the effectiveness of a home based intervention to teach parents how to ensure a positive fruit-vegetable ( FV ) environment for their preschool child , and to examine whether changes in parent behavior were associated with improvements in child intake . METHODS A group r and omized nested cohort design was conducted ( 2001 to 2006 ) in rural , southeast Missouri with 1306 parents and their children participating in Parents As Teachers , a national parent education program . RESULTS When compared to control parents , H5-KIDS parents reported an increase in FV servings ( MN=0.20 , p=0.05 ) , knowledge and availability of FV within the home ( p=0.01 ) , and decreased their use of noncoercive feeding practice s ( p=0.02 ) . Among preschoolers , FV servings increased in normal weight ( MN=0.35 , p=0.02 ) but not overweight children ( MN=-0.10 , p=0.48 ) , relative to controls . The parent 's change in FV servings was a significant predictor of child 's change in FV in the H5-KIDS group ( p=0.001 ) . CONCLUSION H5-KIDS suggests the need for , and promise of , early home intervention for childhood obesity prevention . It demonstrates the importance of participatory approaches in developing externally valid interventions , with the potential for dissemination across national parent education programs as a means for improving the intake of parents and young children OBJECTIVE To test the hypothesis that family dietary coaching would improve nutritional intakes and weight control in free-living ( noninstitutionalized ) children and parents . DESIGN R and omized controlled trial . SETTING Fifty-four elementary schools in Paris , France . PARTICIPANTS One thous and thirteen children ( mean age , 7.7 years ) and 1013 parents ( mean age , 40.5 years ) . INTERVENTION Families were r and omly assigned to group A ( advised to reduce fat and to increase complex carbohydrate intake ) , group B ( advised to reduce both fat and sugar and to increase complex carbohydrate intake ) , or a control group ( given no advice ) . Groups A and B received monthly phone counseling and Internet-based monitoring for 8 months . OUTCOME MEASURES Changes in nutritional intake , body mass index ( calculated as weight in kilograms divided by height in meters squared ) , fat mass , physical activity , blood indicators , and quality of life . RESULTS Compared with controls , participants in the intervention groups achieved their nutritional targets for fat intake and to a smaller extent for sugar and complex carbohydrate intake , leading to a decrease in energy intake ( children , P < .001 ; parents , P = .02 ) . Mean changes in body mass index were similar among children ( group A , + 0.05 , 95 % confidence interval [ CI ] , - 0.06 to 0.16 ; group B , + 0.10 , 95 % CI , - 0.03 to 0.23 ; control group , + 0.13 , 95 % CI , 0.04 - 0.22 ; P = .45 ) , but differed in parents ( group A , + 0.13 , 95 % CI , - 0.01 to 0.27 ; group B , - 0.02 , 95 % CI , - 0.14 to 0.11 ; control group , + 0.24 , 95 % CI , 0.13 - 0.34 ; P = .001 ) , with a significant difference between group B and the control group ( P = .01 ) . CONCLUSIONS Family dietary coaching improves nutritional intake in free-living children and parents , with beneficial effects on weight control in parents . Trial Registration clinical trials.gov Identifier : NCT00456911 OBJECTIVE . This study examined the efficacy of an Internet-facilitated intervention for weight maintenance and binge eating in adolescents . METHODS . A total of 105 adolescent male and female high school students at risk for overweight ( mean age : 15.1 ± 1.0 years ) were r and omly assigned to a 16-week online intervention , StudentBodies2-BED ( n = 52 ) , or the wait-list control group ( n = 53 ) . RESULTS . Participants in the StudentBodies2-BED group had significantly lower BMI z scores and BMI from baseline assessment to follow-up assessment , compared with the wait-list control group . In addition , significant reductions in objective binge episodes and subjective binge episodes from baseline assessment to posttreatment assessment and from baseline assessment to follow-up assessment were observed among StudentBodies2-BED participants . The StudentBodies2-BED group also reported significantly reduced weight and shape concerns from posttreatment assessment to follow-up assessment and from baseline assessment to follow-up assessment . Participants in the StudentBodies2-BED group who engaged in objective overeating or binge eating episodes at baseline assessment experienced a significantly greater reduction in BMI at follow-up assessment , compared with the wait-list control group . CONCLUSIONS . Results suggest that an Internet-facilitated intervention is moderately effective in short-term weight loss and weight maintenance and yields a large reduction in binge eating . This study also demonstrates that weight management and reduction of eating disorder psychopathological features can be achieved simultaneously by using an easily disseminated , Internet-facilitated program To decrease BMI in overweight and obese children , improved dietary intake and increased physical activity are key elements . Our objective was to evaluate the impact of a 1-y food and physical activity intervention on energy and macronutrient intake in overweight and obese children . A r and omized open trial was conducted with 92 overweight or obese 10.4 ± 1.08-y-old children . The intervention included 14 group sessions with different themes regarding food and physical activity . Dietary intake was assessed with diet history interviews covering 14 d at baseline and 4-d food records after 1 y and was evaluated according to national dietary recommendations . The control group participated in the same measurements as the intervention group but did not take part in group sessions . After 1 y , both groups had decreased their energy intake ( EI ) relative to total energy expenditure , but the effect was more pronounced for the intervention group than for the control group . At 1 y follow-up , a larger proportion of children in the intervention group compared with the control group met the recommended intake of refined sugar ( P = 0.019 ) . However , the groups did not differ in the proportion children who met the recommended intake of dietary fiber . Further , SFA intake relative to total EI did not differ between the groups at 1 y follow-up . In conclusion , despite a rather comprehensive intervention , only modest effects were achieved with respect to reduced EI and improved macronutrient intake OBJECTIVE To determine whether a multicomponent health promotion intervention for Dutch adolescents would be successful in influencing body composition and aerobic fitness . DESIGN R and omized controlled trial . SETTING Ten intervention and 8 control prevocational secondary schools . PARTICIPANTS A total of 978 adolescents ( mean age , 12.7 years ) . INTERVENTION An interdisciplinary multicomponent intervention program with an adapted curriculum for 11 biology and physical education lessons and environmental change options , including additional lessons on physical education and advice on the school canteen selection . MAIN OUTCOME MEASURES Body height and weight , hip and waist circumference , 4 skinfold thickness measurements , and aerobic fitness . RESULTS Multilevel analyses showed significant differences in changes after the 8-month intervention period in favor of the intervention group with regard to hip circumference ( mean difference , 0.53 cm ; 95 % confidence interval , 0.07 to 0.98 ) and sum of skinfolds among girls ( mean difference , -2.31 mm ; 95 % confidence interval , -4.34 to -0.28 ) . In boys , the intervention result ed in a significant difference in waist circumference ( mean difference , -0.57 cm ; 95 % confidence interval , -1.10 to -0.05 ) . No significant intervention effects were found related to aerobic fitness . CONCLUSIONS The multicomponent Dutch Obesity Intervention in Teenagers program positively influenced several measures of body composition among both girls and boys . Our results indicate that secondary prevocational school curriculum changes may contribute to excessive weight gain prevention among adolescents OBJECTIVES . Television viewing and physical inactivity increase the risk of obesity in youth . Thus , identifying new interventions that increase physical activity and reduce television viewing would be helpful in the prevention and treatment of pediatric obesity . This study evaluated the effects of open-loop feedback plus reinforcement versus open-loop feedback alone on physical activity , targeted sedentary behavior , body composition , and energy intake in youth . METHODS . Thirty overweight or obese 8- to 12-year-old children were r and omly assigned to an intervention ( n = 14 ) or control group ( n = 16 ) . Participants wore accelerometers every day for 8 weeks and attended biweekly meetings to download the activity monitors . For children in the open-loop feedback plus reinforcement ( intervention ) group , accumulating 400 counts of physical activity on pedometers earned 1 hour of television/VCR/DVD time , which was controlled by a Token TV electronic device . Open-loop feedback control subjects wore activity monitors but had free access to targeted sedentary behavior . RESULTS . Compared with controls , the open-loop feedback plus reinforcement group demonstrated significantly greater increases in daily physical activity counts ( + 65 % vs + 16 % ) and minutes per day of moderate-to-vigorous physical activity ( + 9.4 vs + 0.3 ) and greater reductions in minutes per day spent in television viewing ( −116.1 vs + 14.3 ) . The intervention group also showed more favorable changes in body composition , dietary fat intake , and energy intake from snacks compared with controls . Reductions in sedentary behavior were directly related to reductions in BMI , fat intake , snack intake , and snack intake while watching television . CONCLUSIONS . Providing feedback of physical activity in combination with reinforcing physical activity with sedentary behavior is a simple method of modifying the home environment that may play an important role in treating and preventing child obesity Objective : The aim of the study was to compare the efficacy of group treatment stressing a health-promoting lifestyle with routine counseling in the treatment of childhood obesity . Design and subjects : Seventy obese children ( weight for height 115–182 % ) aged 7–9 years were r and omized either to routine counseling ( two appointments for children ) or to family-based group treatment ( 15 separate sessions for parents and children ) . These sessions included nutrition education , physical activity education and behavioral therapy . Outcome measures : Children 's weights and heights were measured at baseline , after the 6-month intervention and after the 6-month follow-up . The change of weight for height based on Finnish growth charts was used as the primary , and changes in body mass index ( BMI ) and BMI st and ard deviation scores ( BMI -SDS ) as secondary outcome measures . Results : Children attending the group treatment lost more weight for height ( 6.8 % ) than children receiving routine counseling ( 1.8 % ) ( P=0.001 ) . The difference was significant when the data were analyzed in four groups by the cut-off limits of 0 , −5 and −10 % for the change in weight for height . The respective decreases in BMI were 0.8 vs 0.0 ( P=0.003 ) and in BMI -SDS 0.3 vs 0.2 ( P=0.022 ) . The results remained similar in adjusted analyses . Both group and routine programs were feasible with a high , 87–99 % , participation rate in sessions and appointments and very low , 3 % or less , attrition rate from the programs . Six months after the intervention , beneficial effects were partly lost , but for changes in weight for height and BMI , the differences between the two treatment programs still were significant , and for BMI -SDS , there was a trend . Conclusions : Family-based group treatment that stresses a health-promoting lifestyle and is given separately for parents and children , offers an effective mode of therapy to treat obese school-aged children Few r and omized trials attempt to improve insulin sensitivity and associated metabolic risks in overweight Latino youth . The purpose of this study is to examine the effects of a modified carbohydrate nutrition program combined with strength training on insulin sensitivity , adiposity , and other type 2 diabetes risk factors in overweight Latino adolescents . In a 16-week r and omized trial , 54 overweight Latino adolescents ( 15.5 + /- 1.0 years ) were r and omly assigned to : ( i ) Control ( C ; n = 16 ) , ( ii ) Nutrition ( N ; n = 21 ) , or ( iii ) Nutrition + Strength training ( N+ST ; n = 17 ) . The N group received modified carbohydrate nutrition classes ( once per week ) , while the N+ST received the same nutrition classes plus strength training ( twice per week ) . The following were measured at pre- and postintervention : strength by 1-repetition maximum , dietary intake by 3-day records , body composition by dual-energy X-ray absorptiometry , glucose/insulin indices by oral glucose tolerance test ( OGTT ) and intravenous glucose tolerance test with minimal modeling . Across intervention group effects were tested using analysis of covariance with post hoc pairwise comparisons . A significant overall intervention effect was found for improvement in bench press ( P < 0.001 ) and reductions in energy ( P = 0.05 ) , carbohydrate ( P = 0.04 ) and fat intake ( P = 0.03 ) . There were no significant intervention effects on insulin sensitivity , body composition , or most glucose/insulin indices with the exception of glucose incremental area under the curve ( IAUC ) ( P = 0.05 ) , which decreased in the N and N+ST group by 18 and 6.3 % compared to a 32 % increase in the C group . In conclusion , this intense , culturally tailored intervention result ed in no significant intervention effects on measured risk factors with the exception of a beneficial effect on glycemic response to oral glucose OBJECTIVE : We evaluated the efficacy of family-based , behavioral weight control in the management of severe pediatric obesity . METHODS : Participants were 192 children 8.0 to 12.0 years of age ( mean ± SD : 10.2 ± 1.2 years ) . The average BMI percentile for age and gender was 99.18 ( SD : 0.72 ) . Families were assigned r and omly to the intervention or usual care . Assessment s were conducted at baseline , 6 months , 12 months , and 18 months . The primary outcome was percent overweight ( percent over the median BMI for age and gender ) . Changes in blood pressure , body composition , waist circumference , and health-related quality of life also were evaluated . Finally , we examined factors associated with changes in child percent overweight , particularly session attendance . RESULTS : Intervention was associated with significant decreases in child percent overweight , relative to usual care , at 6 months . Intent-to-treat analyses documented that intervention was associated with a 7.58 % decrease in child percent overweight at 6 months , compared with a 0.66 % decrease with usual care , but differences were not significant at 12 or 18 months . Small significant improvements in medical outcomes were observed at 6 and 12 months . Children who attended ≥75 % of intervention sessions maintained decreases in percent overweight through 18 months . Lower baseline percent overweight , better attendance , higher income , and greater parent BMI reduction were associated with significantly greater reductions in child percent overweight at 6 months among intervention participants . CONCLUSIONS : Intervention was associated with significant short-term reductions in obesity and improvements in medical parameters and conferred longer-term weight change benefits for children who attended ≥75 % of sessions Objective To assess whether a physical activity intervention reduces body mass index in young children . Design Cluster r and omised controlled single blinded trial over 12 months . Setting Thirty six nurseries in Glasgow , Scotl and . Participants 545 children in their preschool year , mean age 4.2 years ( SD 0.2 ) at baseline . Intervention Enhanced physical activity programme in nursery ( three 30 minute sessions a week over 24 weeks ) plus home based health education aim ed at increasing physical activity through play and reducing sedentary behaviour . Main outcome measure Body mass index , expressed as a st and ard deviation score relative to UK 1990 reference data . Secondary measures were objective ly measured physical activity and sedentary behaviour ; fundamental movement skills ; and evaluation of the process . Results Group allocation had no significant effect on the primary outcome measure at six and 12 months or on measures of physical activity and sedentary behaviour by accelerometry . Children in the intervention group had significantly higher performance in movement skills tests than control children at six month follow-up ( P=0.0027 ; 95 % confidence interval 0.3 to 1.3 ) after adjustment for sex and baseline performance . Conclusions Physical activity can significantly improve motor skills but did not reduce body mass index in young children in this trial . Trial registration Current Controlled Trials IS RCT N36363490 BACKGROUND Physical Activity Across the Curriculum ( PAAC ) was a three-year cluster r and omized controlled trial to promote physical activity and diminish increases in overweight and obesity in elementary school children . METHODS Twenty-four elementary schools were cluster r and omized to the Physical Activity Across the Curriculum intervention or served as control . All children in grade s two and three were followed to grade s four and five . Physical Activity Across the Curriculum promoted 90 min/wk of moderate to vigorous intensity physically active academic lessons delivered by classroom teachers . Body Mass Index was the primary outcome , daily Physical activity and academic achievement were secondary outcomes . RESULTS The three-year change in Body Mass Index for Physical Activity Across the Curriculum was 2.0+/-1.9 and control 1.9+/-1.9 , respectively ( NS ) . However , change in Body Mass Index from baseline to 3 years was significantly influenced by exposure to Physical Activity Across the Curriculum . Schools with > or = 75 min of Physical Activity Across the Curriculum/wk showed significantly less increase in Body Mass Index at 3 years compared to schools that had < 75 min of Physical Activity Across the Curriculum ( 1.8+/-1.8 vs. 2.4+/-2.0 , p=0.02 ) . Physical Activity Across the Curriculum schools had significantly greater changes in daily Physical activity and academic achievement scores . CONCLUSIONS The Physical Activity Across the Curriculum approach may promote daily Physical activity and academic achievement in elementary school children . Additionally , 75 min of Physical Activity Across the Curriculum activities may attenuate increases in Body Mass Index Objectives : To reduce gain in body mass index ( BMI ) in overweight/mildly obese children in the primary care setting . Design : R and omized controlled trial ( RCT ) nested within a baseline cross-sectional BMI survey . Setting : Twenty nine general practice s , Melbourne , Australia . Participants : ( 1 ) BMI survey : 2112 children visiting their general practitioner ( GP ) April – December 2002 ; ( 2 ) RCT : individually r and omized overweight/mildly obese ( BMI z-score < 3.0 ) children aged 5 years 0 months–9 years 11 months ( 82 intervention , 81 control).Intervention : Four st and ard GP consultations over 12 weeks , targeting change in nutrition , physical activity and sedentary behaviour , supported by purpose - design ed family material s . Main outcome measures : Primary : BMI at 9 and 15 months post-r and omization . Secondary : Parent-reported child nutrition , physical activity and health status ; child-reported health status , body satisfaction and appearance/self-worth . Results : Attrition was 10 % . The adjusted mean difference ( intervention – control ) in BMI was −0.2 kg/m2 ( 95 % CI : −0.6 to 0.1 ; P=0.25 ) at 9 months and −0.0 kg/m2 ( 95 % CI : −0.5 to 0.5 ; P=1.00 ) at 15 months . There was a relative improvement in nutrition scores in the intervention arm at both 9 and 15 months . There was weak evidence of an increase in daily physical activity in the intervention arm . Health status and body image were similar in the trial arms . Conclusions : This intervention did not result in a sustained BMI reduction , despite the improvement in parent-reported nutrition . Brief individualized solution-focused approaches may not be an effective approach to childhood overweight . Alternatively , this intervention may not have been intensive enough or the GP training may have been insufficient ; however , increasing either would have significant cost and re source implication s at a population level Intervention studies in youth with obesity that can be translated into primary care are limited . We compared a lifestyle intervention to a brief intervention applied by primary care physicians ( control group ) for treating pediatric obesity in the primary care setting . Seventy-six youth with obesity ( body mass index [ BMI ] > 95th percentile or > 90th percentile plus waist circumference > 90th percentile , aged 9 to 17 years ) participated in a 12-month , r and omized , controlled trial , conducted at a primary care unit in Northern México from June 2006 through October 2007 . Participants r and omized to lifestyle intervention attended a family-centered program consisting of 12 sessions of behavioral curriculum , dietary advice from a registered dietitian ( weekly for the first 3 months and monthly thereafter ) , and monthly consultations with a primary care physician . Control group participants attended monthly consultations with a primary care physician who received a brief training on obesity . Forty-three ( 57 % ) participants completed the 12 months of study . After 12 months , mean changes ( 95 % confidence interval ) in body weight for the lifestyle group and the control group were -0.8 kg ( -3.2 , 1.5 ) vs + 5.6 kg ( 3 , 8.2 ; P<0.001 ) and mean changes in BMI were -1.8 ( -2.6 , -0.9 ) vs + 0.4 ( -0.5 , 1.3 ; P<0.001 ) , respectively . Intention-to-treat analysis at 12 months confirmed significant differences in primary outcomes ( weight -3.5 kg , P=0.02 ; BMI -1.2 , P=0.03 ) in favor of the lifestyle group . This study provides preliminary evidence that primary care physicians supported by a registered dietitian and a behavioral curriculum can be a successful strategy for treating pediatric obesity in the primary care setting OBJECTIVE : To assess the relationships between diet , body composition , physical activity , parents ’ obesity and adiposity in children at the age of 8 y and four years later . STUDY DESIGN : Prospect i ve observational study of anthropometric measures initiated in 1992 , follow-up examination in 1996 . METHODS : 112 prepubertal ( age : 8.6±1.0 y ) children were studied . Energy and nutrient intakes were assessed by diet history , body composition by anthropometry and physical activity , by a question naire . Obesity was defined as relative body mass index ( BMI ) ( rel BMI ) > 120 % , where rel BMI =( BMI / BMI at 50th centile for age and gender) × 100 . RESULTS : Prevalence of obesity was not statistically different at baseline ( 22.3 % ) than four years later ( 19.8 % ) : rel BMI at the age of 8 y was positively self-related with rel BMI at the age of 12 y ( r=0.73 , P<0.001 ) . After four years , eight ( 32 % ) obese children became non obese and five ( 6 % ) non obese children became obese . Multiple regression analysis ( stepwise procedure ) revealed that , in the final equation , the mother ’s BMI and TV viewing ( independent variables ) accounted for 17 % of the children ’s rel BMI variance at the age of 8 y ( R=0.42 , P<0.001 ) while the parents ’ BMI s accounted for 13.5 % of the children ’s rel BMI variance at the age of 12 y ( r=0.37 , P<0.001 ) . Other variables such as total energy intake , nutrient intake percentage and amount of physical activity , were all rejected . An autoregressive unbalanced measures model regression analysis recognised the mother ’s and father ’s BMI s as the only variables able to predict rel BMI in the children ( mother ’s BMI coeff . 2.53 ( s.e.m . 0.26 ) , P<0.0001 ; father ’s BMI coeff . 2.07 ( s.e.m . 0.23 ) , P<0.0001 ) . A multivariate logistic regression analysis was also performed . The children who participated in the follow-up , were divided into two groups based on the positive or negative change in the rel BMI between final and baseline measurements . Of all the variables considered , only rel BMI at baseline was selected in the final equation . Other variables such as age , gender , energy and nutrient intake , TV viewing and amount of physical activity , as well as the parents ’ BMI , were all removed . CONCLUSIONS : The parents ’ obesity was the main risk factor for obesity in this group of children . Sedentary behaviour ( TV viewing ) was independently associated with overweight at the age of 8 y. Physical activity and energy and nutrient intakes did not significantly affect the change in rel BMI over the four-year period when the parents ’ obesity was taken into account BACKGROUND Obesity and poor physical fitness constitute a health problem affecting an increasing number of children . Causes include a pervasive " toxic " environment that facilitates increased caloric intake and reduced physical activity . An effective strategy for prevention and treatment of childhood obesity likely includes a collaborative effort in the school setting . OBJECTIVE To determine whether a school-based fitness program can improve body composition , cardiovascular fitness level , and insulin sensitivity in overweight children . DESIGN Fifty overweight middle school children with a body mass index ( BMI ) above the 95th percentile for age were r and omized to lifestyle-focused , fitness-oriented gym classes ( treatment group ) or st and ard gym classes ( control group ) for 9 months . Children underwent evaluation of fasting insulin and glucose levels , body composition by means of dual energy absorptiometry , and maximum oxygen consumption ( V0(2)max ) treadmill testing at baseline ( before the school year ) and at end of the school year . SETTING S Rural middle school and an academic children 's hospital . MAIN OUTCOME MEASURES Baseline test results for cardiovascular fitness , body composition , and fasting insulin and glucose levels . RESULTS At baseline , there were no differences between groups before intervention ( values for age , 12 + /- 0.5 years [ all results , mean + /- SD ] ; BMI [ calculated as weight in kilograms divided by the square of height in meters ] , 31.0 + /- 3.7 ; percentage of body fat , 36.5 % + /- 4.6 % ; lean body mass , 41.4 + /- 8.6 kg ; and V0(2)max , 31.5 + /- 5.1 mL/kg per minute ) . Compared with the control group , the treatment group demonstrated a significantly greater loss of body fat ( loss , -4.1 % + /- 3.4 % vs -1.9 % + /- 2.3 % ; P = .04 ) , greater increase in cardiovascular fitness ( V0(2)max , 2.7 + /- 2.6 vs 0.4 + /- 3.3 mL/kg per minute ; P<.001 ) , and greater improvement in fasting insulin level ( insulin level , -5.1 + /- 5.2 vs 3.0 + /- 14.3 microIU/mL [ -35.4 + /- 36.1 vs 20.8 + /- 99.3 pmol/L ] ; P = .02 ) . CONCLUSIONS Children enrolled in fitness-oriented gym classes showed greater loss of body fat , increase in cardiovascular fitness , and improvement in fasting insulin levels than control subjects . The modification to the school physical education curriculum demonstrates that small but consistent changes in the amount of physical activity has beneficial effects on body composition , fitness , and insulin levels in children . Partnering with school districts should be a part of a public health approach to improving the health of overweight children BACKGROUND Childhood obesity has become a health problem in urban areas in China . Intervention to reduce childhood obesity should be of high priority . School-based intervention programmes are needed to deal with the growing prevalence of childhood obesity in China . METHODS Five primary schools were selected r and omly for this study in the Beijing urban area in China ; two were allocated to the intervention group and three to the control group . A total of 2425 children ( 1029 children in intervention schools and 1396 children in control schools ) took part in the study for 3 years . In the intervention group , children and their parents were involved in a programme of nutrition education and physical activity . Control school students followed their usual health and physical education curriculum with no extra intervention . RESULTS After the 3-year intervention , the prevalence of overweight and obesity were significantly lower in the intervention schools than in the control schools ( overweight : 9.8 % vs. 14.4 % , P < 0.01 ; obesity : 7.9 % vs. 13.3 % , P < 0.01 ) . The prevalence of overweight and obesity decreased by 26.3 % and 32.5 % in intervention schools respectively after intervention . The prevalence of overweight and obesity increased in control schools . There was also significant difference in body mass index between intervention and control schools ( 18.2 + /- 2.6 vs. 20.3 + /- 3.4 , P < 0.01 ) after intervention . More non-obese children became obese in the control schools ( 7.0 % ) than in the intervention schools ( 2.4 % ) at end line ( P < 0.01 ) . Among the children who were obese at baseline , 49.2 % remained obese at end line in intervention schools while 61.9 % remained obese in control schools ( P < 0.01 ) . CONCLUSIONS Our study showed that an intervention programme could be feasible in schools in Beijing , China . The prevalence of overweight and obesity was reduced in schoolchildren in Beijing through an intervention focused on nutrition education and physical activity . Overweight and obesity children as well as normal weight children and their parents should be involved in such an intervention programme OBJECTIVES : The objective of this study was to evaluate a 12-session home/community-based health promotion/obesity prevention program ( Challenge ! ) on changes in BMI status , body composition , physical activity , and diet . METHODS : A total of 235 black adolescents ( aged 11–16 years ; 38 % overweight/obese ) were recruited from low-income urban communities . Baseline measures included weight , height , body composition , physical activity ( PA ) , and diet . PA was measured by 7-day play-equivalent physical activity ( ≥1800 activity counts per minute ) . Participants were r and omly assigned to health promotion/obesity prevention that is anchored in social cognitive theory and motivational interviewing and was delivered by college-aged black mentors or to control . Postintervention ( 11 months ) and delayed follow-up ( 24 months ) evaluations were conducted . Longitudinal analyses used multilevel models with r and om intercepts and generalized estimating equations , controlling for baseline age/gender . Stratified analyses examined baseline BMI category . RESULTS : Retention was 76 % over 2 years ; overweight/obese status declined 5 % among intervention adolescents and increased 11 % among control adolescents . Among overweight/obese youth , the intervention reduced total percentage of body fat and fat mass and increased fat-free mass at delayed follow-up and increased play-equivalent physical activity at postintervention but not at delayed follow-up . Intervention adolescents declined significantly more in snack/dessert consumption than control adolescents at both follow-up evaluations . CONCLUSIONS : At postintervention , there were intervention effects on diet and PA but not BMI category or body composition . At delayed follow-up , dietary changes were sustained and the intervention prevented an increase in BMI category . Body composition was improved for overweight/obese youth . Changes in body composition follow changes in diet and PA and may not be detected immediately after intervention Family variables such as cohesion and nurturance have been associated with adolescent weight-related health behaviors . Integrating family variables that improve family functioning into traditional weight-loss programs can provide health-related benefits . The current study evaluated a family-based psychoeducational and behavioral skill-building weight-loss program for adolescent girls that integrated Family Systems and Social Cognitive Theories . Forty-two overweight ( > or = 95th percentile ) female adolescent participants and parents participated in a 16-week r and omized controlled trial comparing three groups : multifamily therapy plus psychoeducation ( n=15 ) , psychoeducation-only ( n=16 ) , or wait list ( control ; n=11 ) group . Body mass index , energy intake , and family measures were assessed at baseline and posttreatment . Adolescents in the psychoeducation-only group demonstrated a greater decrease in energy intake compared to the multifamily therapy plus psychoeducation and control groups ( P<0.01 ) . Positive changes in family nurturance were associated with lower levels of adolescent energy intake ( P<0.05 ) . No significant effects were found for body mass index . Results provide preliminary support for a psychoeducational program that integrates family variables to reduce energy intake in overweight adolescent girls . Results indicate that nurturance can be an important family variable to target in future adolescent weight-loss and dietary programs OBJECTIVE The authors performed a group-based program for obese children and adolescents in Bavaria , Germany to enable them to establish a health-oriented lifestyle and to reduce overweight . The authors compared this program with a control approach based on the patients ' own initiative . DESIGN This is a controlled clinical trial . SETTING A nutrition program for out patients in a German university hospital . PARTICIPANTS Seventy-three obese patients aged 7 to 15 years ( mean 11.2 years ) were recruited by pediatricians and local newspaper reports and r and omized into intervention and control groups . Children and adolescents in each group were divided into 3 groups according to age--7 - 8 years , 9 - 10 years , and 11 - 13 years . Children were classified overweight ( defined as body mass index ( BMI ) > 90th percentile for age and gender ) , obese ( BMI > 97th percentile ) , and extremely obese ( BMI > 99.5th percentile ) , according to the European Childhood Obesity Group and the German Working Group on Pediatric Obesity , congruent with adult st and ards used to assess overweight and obesity . INTERVENTION Thirty-seven patients ( age 7 - 13 years , mean 10.9 years ) for the 1-year intervention . This intervention consisted of modules for physical activity , nutritional education , and coping strategies . The program was performed twice each week and incorporated parental participation and medical supervision , including laboratory tests . The obese controls ( n = 36 , age 8 - 15 years , mean 11.6 years ) received written therapeutic advice during a visit at 0 and 6 months in the outpatient clinic . MAIN OUTCOME MEASURE The primary outcome variable was the body mass index ( BMI ) z score . ANALYSIS Analysis of variance and t test were used , and a P value < .05 was considered significant . RESULTS There was a reduction of BMI z score in the active treatment group ( P < .05 ) , but not for controls . Moreover , the active group showed beneficial effects for body mass index ( BMI ) , fat mass , and systolic blood pressure 12 months after beginning the intervention . CONCLUSIONS AND IMPLICATION S Group-based programs for young , obese patients can be effective tools for establishing a health-oriented lifestyle and reducing the burden of obesity OBJECTIVE Obesity prevalence among Chilean children is 19.4 % . The present study aim ed to assess the effectiveness of a school-based obesity prevention programme . DESIGN Non-r and omized controlled study . The intervention included activities in nutrition and physical activity , fully applied the first year and partially in the second one . Primary outcomes were BMI Z-score ( BMI Z ) and obesity prevalence ; secondary outcomes were waist circumference and triceps skinfold thickness . Time effects were assessed by changes in BMI -related variables by gender and period ( ANOVA and Tukey test ) , while intervention effects were determined by comparing changes in ( i ) obesity prevalence by gender and period ( PROC GENMOD ) and ( ii ) BMI Z according gender , age and period ( PROC MIXED ) . SETTING Primary schools in the Chilean cities of Casablanca ( intervention group ) and Quillota ( control group ) . SUBJECTS One thous and seven hundred and fifty-nine children from three schools ( intervention group ) and 671 from one school ( control group ) . RESULTS Over the two years , obesity prevalence and BMI Z declined significantly in the intervention group ; from 17.0 % to 12.3 % and 14.1 % to 10.3 % in boys and girls , respectively , and from 0.62 to 0.53 and 0.64 to 0.58 , respectively . In the control group , obesity remained stable at about 21 % and 15 % , while BMI Z increased significantly in the second year . BMI Z declined in both genders and all age categories in the intervention group during the first year ( significant only in younger boys ) . No changes occurred during the summer , while during the second year , BMI Z increased in boys and girls from both groups ( significant only in the younger control boys ) . Obesity declined significantly only in boys during the first year . CONCLUSION Effectiveness was greater in the first school year and more evident in younger boys OBJECTIVE To determine whether an exercise intervention using an active video game ( Dance Dance Revolution [ DDR ] ) is effective in improving endothelial dysfunction ( EDF ) and other risk factors in overweight children . DESIGN Thirty-five children ( Body mass index > or = 85(th ) percentile , mean age 10.21+/-1.67 years , 17 females ) with EDF were assessed for flow-mediated dilation ( FMD ) , lipids , insulin , glucose , NO(2)+NO(3 ) , asymmetric dimethylarginine , symmetric dimethylarginine , l-arginine , height , weight , aerobic fitness , and blood pressure . In a sub sample , tumor necrosis factor alpha , interleukin-6 , C-reactive protein , and adiponectin were also assessed . Subjects were r and omly assigned to 12-weeks of aerobic exercise ( EX ) using DDR or to a non-exercising delayed-treatment control group ( DTC ) . RESULTS EX had significant improvements in FMD ( 5.56+/-5.04 % compared with 0.263+/-4.54 % , p=0.008 ) , exercise time on the grade d exercise test ( 53.59+/-91.54 compared with -12.83+/-68.10 seconds , p=0.025 ) , mean arterial pressure ( MAP ) ( -5.62+/-7.03 compared with -1.44+/-2.16 mmHg , p=0.05 ) , weight ( 0.91+/-1.53 compared with 2.43+/-1.80 kg , p=0.017 ) and peak VO(2 ) ( 2.38+/-3.91 compared with -1.23+/-3.18 mg/kg/min , p=0.005 ) compared with the DTC . Thirteen EX subjects achieved normal EDF while ten did not . These groups differed at baseline with regard to total cholesterol ( TC ) and low-density lipoprotein ( LDL ) . CONCLUSION Twelve weeks of DDR-use improved FMD , aerobic fitness , and MAP in overweight children . Improvements occurred without changes in inflammatory markers or nitric oxide production . The results document the need to explore relationships between obesity , endothelial function , inflammation , lipids , exercise intensity , and gender in a larger sample of overweight children The study tested the effect of aerobic exercise training on executive function in overweight children . Ninety-four sedentary , overweight but otherwise healthy children ( mean age = 9.2 years , body mass index 85th percentile ) were r and omized to a low-dose ( 20 min/day exercise ) , high-dose ( 40 min/day exercise ) , or control condition . Exercise sessions met 5 days/week for 15 weeks . The Cognitive Assessment System ( CAS ) , a st and ardized test of cognitive processes , was administered individually before and following intervention . Analysis of covariance on posttest scores revealed effects on executive function . Group differences emerged for the CAS Planning scale ( p = .03 ) . Planning scores for the high-dose group were significantly greater than those of the control group . Exercise may prove to be a simple , yet important , method of enhancing aspects of children 's mental functioning that are central to cognitive and social development BACKGROUND & AIMS R and omized controlled trials ( RCT ) have demonstrated the effectiveness of lifestyle interventions in obese children . However , the effectiveness of interventions for overweight , but no obese children has not been demonstrated yet by RCTs . METHODS A total of 66 overweight ( BMI > 90th < or = 97th percentile ) children ( mean age 11.5+/-1.6 years , 58 % females , mean BMI 23.4+/-1.5kg/m(2 ) ) were r and omized into a control group ( CG ) ( n=32 ; no intervention for a duration of 6 months ) or intervention group ( IG ) ( n=34 ; 6 months intervention " Obeldicks light " based on physical activity , nutrition education , and behaviour counselling ) . BMI , waist circumference , skinfold thickness , bioimpedance analyses , blood pressure , physical activity based on question naires , and three-day-weighed dietary records were determined at baseline ( T0 ) and 6 months ( T1 ) later . Degree of overweight was calculated as BMI -SDS . Comparisons were performed on an intention-to-treat approach . RESULTS The drop-out rate was 3 % in IG and 16 % in CG . At T1 , 94 % of the children in IG decreased their BMI -SDS and 24 % of them were normal weight . The changes between T0 and T1 in BMI -SDS differed significantly ( p<0.001 ) between IG and CG ( CG : + 0.05+/-0.19 BMI -SDS ; IG : -0.26+/-0.22 BMI -SDS ) . Similar findings were observed for blood pressure , waist circumference , skinfold thickness , and fat mass based on bioimpedance analyses . In the IG , energy , fat and sugar intake decreased significantly between T0 and T1 , while no significant changes were observed in the CG . CONCLUSIONS The lifestyle intervention was associated with an improvement of dietary patterns and was effective in reducing degree of overweight , fat mass , waist circumference , and blood pressure OBJECTIVES To assess the impact of a culturally proficient dietary/physical activity intervention on changes in body mass index ( BMI ) ( kg/m 2 ) . STUDY DESIGN R and omized controlled trial ( Hip-Hop to Health Jr. ) conducted between September 1999 and June 2002 in 12 Head Start preschool programs in Chicago , Illinois . RESULTS Intervention children had significantly smaller increases in BMI compared with control children at 1-year follow-up , 0.06 vs 0.59 kg/m 2 ; difference -0.53 kg/m 2 ( 95 % CI -0.91 to -0.14 ) , P = .01 ; and at 2-year follow-up , 0.54 vs 1.08 kg/m 2 ; difference -0.54 kg/m 2 ( 95 % CI -0.98 to -0.10 ) , P = .02 , with adjustment for baseline age and BMI . The only significant difference between intervention and control children in food intake/physical activity was the Year 1 difference in percent of calories from saturated fat , 11.6 % vs 12.8 % ( P = .002 ) . CONCLUSIONS Hip-Hop to Health Jr. was effective in reducing subsequent increases in BMI in preschool children . This represents a promising approach to prevention of overweight among minority children in the preschool years INTRODUCTION There has been a paucity of theory-based interventions to improve health outcomes in overweight adolescents . Therefore , two intervention studies were conducted to : ( a ) determine the feasibility of implementing the Creating Opportunities for Personal Empowerment ( COPE ) Healthy Lifestyles Thinking , Emotions , Exercise , and Nutrition ( TEEN ) program with overweight adolescents ; ( b ) obtain feedback that could be used to refine the program ; and ( c ) examine the preliminary efficacy of the COPE program on the adolescents ' weight and body mass index ( BMI ) . METHOD Phase I and Phase II clinical trials were conducted with 23 overweight teens . The Phase 1 trial used a pre-experimental design with one group of 11 urban adolescents . The Phase 2 trial was conducted with 12 suburban teens using a r and omized controlled pilot study . COPE teens received a 15-session cognitive-behavioral skills building program that included physical activity , while the control group received an attention control program . Weight change and BMI were the key outcomes . RESULTS COPE teens experienced a significantly greater reduction in weight and BMI than did teens in the control group , who gained weight over time . Although the COPE program was well received by all of the teens , retention of subjects across time and parent involvement in the program were challenges in the urban high school . DISCUSSION These studies provide preliminary data to indicate that the implementation of COPE is feasible and may lead to a reduction in weight and BMI in overweight teens . Implementing COPE within the context of the school day may be more successful in sustaining adolescent involvement in the program versus using an after-school format |
14,049 | 26,203,535 | Uninterrupted perioperative warfarin therapy is safe for patients undergoing arterial procedures , but interrupted warfarin may be preferred for those undergoing venous procedures ; no differences in outcome rates were found in the r and omized controlled trials . | PURPOSE To conduct a systematic review and meta- analysis of complication rates and outcomes in patients undergoing endovascular procedures who receive uninterrupted versus interrupted warfarin therapy . | AIMS Current guidelines recommend discontinuation of oral anticoagulation treatment ( OAT ) and switch to heparin 2 - 5 days before catheter ablation of atrial fibrillation ( AF ) . However , increasing evidence leans against the ' bridge therapy ' and support continuation of OAT during the procedure . METHODS AND RESULTS We evaluated the safety of AF ablation among patients with therapeutic OAT . The study population comprised 193 consecutive patients who underwent 228 AF ablation procedures guided by electroanatomical mapping . Periprocedural international normalized ratio was < 2 ( 1.6 ± 0.3 ) in 103 cases ( Group 1 ) and ≥2 ( 2.4 ± 0.4 ) in 125 cases ( Group 2 ) . Heparin ( 5000 IU bolus followed by continuous infusion through an open-irrigated ablation catheter ) was used in both groups . No intracardiac echocardiographic guidance was used and activated clotting time ( ACT ) was not monitored . The incidence of major ( intracranial bleeding , tamponade , bleeding that required surgical intervention , or blood transfusion ) and minor bleeding complications and all thrombo-embolic events were registered during the 3-month follow-up . There was no statistical difference in major ( P = 1.0 ) and minor complications ( P = 0.74 ) between the groups . The bleeding complications included one surgically corrected groin haematoma in both groups ( 0.9 % ) , 25 small haematomas at the puncture site ( 11 in Group 1 ( 10.7 % ) and 14 in Group 2 ( 11.2 % ) , P = 0.90 ) , and two minor pericardial effusions in Group 1 . In Group 2 , one patient had ischaemic stroke 16 days after the procedure . CONCLUSION Transseptal puncture and AF ablation can be performed safely in patients with ongoing OAT without intracardiac echocardiographic guidance and ACT monitoring Background — The best approach to management of anticoagulation before and after atrial fibrillation ablation is not known . Methods and Results — We compared outcomes in consecutive patients undergoing pulmonary vein antrum isolation for persistent atrial fibrillation . Early in our practice , warfarin was stopped 3 days before ablation , and a transesophageal echocardiogram was performed to rule out clot . Enoxaparin , initially 1 mg/kg twice daily ( group 1 ) and then 0.5 mg/kg twice daily ( group 2 ) , was used to “ bridge ” patients after ablation . Subsequently , warfarin was continued to maintain the international normalized ratio between 2 and 3.5 ( group 3 ) . Minor bleeding was defined as hematoma that did not require intervention . Major bleeding was defined as either cardiac tamponade , hematoma that required intervention , or bleeding that required blood transfusion . Pulmonary vein ablation was performed in 355 patients ( group 1=105 , group 2=100 , and group 3=150 ) . More patients had spontaneous echocardiographic contrast in groups 1 and 2 . One patient in group 1 had an ischemic stroke compared with 2 patients in group 2 and no patients in group 3 . In group 1 , 23 patients had minor bleeding , 9 had major bleeding , and 1 had pericardial effusion but no tamponade . In group 2 , 19 patients had minor bleeding , and 2 patients developed symptomatic pericardial effusion with need for pericardiocentesis 1 week after discharge . In group 3 , 8 patients developed minor bleeding , and 1 patient developed pericardial effusion with no tamponade . Conclusions — Continuation of warfarin throughout pulmonary vein ablation without administration of enoxaparin is safe and efficacious . This strategy can be an alternative to bridging with enoxaparin or heparin in the periprocedural period INTRODUCTION Many patients undergoing catheter ablation of atrial flutter ( AFL ) require periprocedural anticoagulation . We compared a strategy of conversion to low molecular weight heparin ( LMWH ) periprocedure to uninterrupted warfarinization in a nonr and omized , case-controlled study . METHODS One hundred and one consecutive patients requiring periprocedural anticoagulation for catheter ablation of typical AFL were studied . The first 51 patients underwent conversion to LMWH ( enoxaparin 1 mg/kg bd ) with a warfarin pause ( LMWH group ) , the subsequent 50 continued with uninterrupted oral anticoagulation ( Warfarin group ) . Primary endpoint was a composite of major and minor bleeding complications and groin symptoms . RESULTS Fewer patients in the Warfarin group reached the primary endpoint ( 36.0 % vs 56.8 % , P = 0.013 ) . Four patients in the LMWH group but no patient in the Warfarin group required hospital admission for bleeding-related complications . Cost analysis showed mean cost per patient of anticoagulation with LMWH to be pounds sterling 100.9 ( 95 % CI 94.46 - 107.30 ) compared to pounds sterling 10.23 ( 4.49 - 15.97 ) in the Warfarin group ( P < 0.0001 ) . Transesophageal echocardiography ( TEE ) was performed prior to ablation in 11 patients in the Warfarin group and in 3 patients in the LMWH ( P = 0.019 ) . When TEE costs were included , costs were pounds sterling 125.00 ( $ 188.25 ) ( 96.80 - 153.60 ) for the LMWH strategy and pounds sterling 108.5 ( $ 163.40 ) ( 54.92 - 162.1 ) for the Warfarin group ( P < 0.0001 ) . CONCLUSIONS Catheter ablation of typical AFL without interruption of warfarin appears safer and more cost-effective than periprocedural conversion to LMWH . It could be used as a routine anticoagulation strategy for the ablation of right-sided arrhythmias Background — Periprocedural thromboembolic and hemorrhagic events are worrisome complications of catheter ablation for atrial fibrillation ( AF ) . The periprocedural anticoagulation management could play a role in the incidence of these complications . Although ablation procedures performed without warfarin discontinuation seem to be associated with lower thromboembolic risk , no r and omized study exists . Methods and Results — This was a prospect i ve , open-label , r and omized , parallel-group , multicenter study assessing the role of continuous warfarin therapy in preventing periprocedural thromboembolic and hemorrhagic events after radiofrequency catheter ablation . Patients with CHADS2 score ≥1 were included . Patients were r and omly assigned in a 1:1 ratio to the off-warfarin or on-warfarin arm . The incidence of thromboembolic events in the 48 hours after ablation was the primary end point of the study . The study enrolled 1584 patients : 790 assigned to discontinue warfarin ( group 1 ) and 794 assigned to continuous warfarin ( group 2 ) . No statistical difference in baseline characteristics was observed . There were 39 thromboembolic events ( 3.7 % strokes [ n=29 ] and 1.3 % transient ischemic attacks [ n=10 ] ) in group 1 : two events ( 0.87 % ) in patients with paroxysmal AF , 4 ( 2.3 % ) in patients with persistent AF , and 33 ( 8.5 % ) in patients with long-st and ing persistent AF . Only 2 strokes ( 0.25 % ) in patients with long-st and ing persistent AF were observed in group 2 ( P<0.001 ) . Warfarin discontinuation emerged as a strong predictor of periprocedural thromboembolism ( odds ratio , 13 ; 95 % confidence interval , 3.1–55.6 ; P<0.001 ) . Conclusion — This is the first r and omized study showing that performing catheter ablation of AF without warfarin discontinuation reduces the occurrence of periprocedural stroke and minor bleeding complications compared with bridging with low-molecular-weight heparin . Clinical Trial Registration — URL : http://www . clinical trials.gov . Unique identifier : NCT01006876 AIMS Pulmonary vein antrum isolation ( PVAI ) plays a pivotal role in the comprehensive treatment of atrial fibrillation ( AF ) . The need for effective anticoagulation bridging following PVAI is associated with significant vascular complication rates and increased costs . We investigated the safety of PVAI in patients with therapeutic international normalized ratios ( INR ) the day of the procedure . METHODS A case-control analysis was performed on patients who underwent PVAI with therapeutic INR ( > 2 ) . Patients with normal preprocedure INR served as controls . The incidence of major and minor hematomas , fistulas , vascular injury , and cardiac perforation or tamponade were catalogued . PVAI was performed under fluoroscopic , electro-anatomical , and intracardiac echocardiographic guidance , with an open irrigation ablation technique . RESULTS A total of 194 patients ( mean age 64 + /- 12 ) were included ; 87 patients underwent PVAI with therapeutic INR ( cases ) and 107 with normal INR ( controls ) . Persistent AF was more prevalent than paroxysmal AF in the therapeutic INR group . The mean INR for cases was 2.8 + /- 0.7 compared to 1.4 + /- 0.3 in the control group ( P < 0.01 ) . All procedures were completed without acute complications . Two major adverse events were observed , one in each arm . No significant difference in terms of minor ( 6.5 % vs. 5.7 % , P = 0.23 ) or major ( 0.93 % vs. 1.15 % , P = 0.49 ) vascular events or bleeding was detected between the therapeutic INR and the control group . The combined endpoint of major and minor complications did not differ among groups ( 9.35 % vs. 8.05 % , P = 0.19 ) . CONCLUSION Atrial fibrillation ablation in patients with therapeutic INR on the day of a procedure appears to be safe and feasible . Expensive outpatient anti-coagulation bridging may be safely avoided in this type of population Aims Current guidelines recommend stopping oral anticoagulation ( OAC ) and starting heparin infusion before implanting/replacing a pacemaker/implantable cardioverter-defibrillator ( ICD ) in patients with high risk for thrombo-embolic events . The aim of this study was to demonstrate that the maintenance of OAC during device implantation/replacement is as safe as bridging to intravenous heparin and shortens in-hospital stay . Methods and results A cohort of 101 consecutive patients with high risk for embolic events and indication for implant/replacement of a pacemaker/ICD were r and omized to two anticoagulant strategies : bridging from OAC to heparin infusion ( n = 51 ) vs. maintenance of OAC to reach an INR = 2 ± 0.3 at the day of the procedure ( n = 50 ) . Haemorrhagic and thrombo-embolic complications were evaluated at discharge , 15 and 45 days after the procedure . A total of 4/51 patients ( 7.8 % ) from heparin group and 4/50 ( 8.0 % ) from the OAC group developed pocket haematoma following the implant ( P = 1.00 ) . One haematoma in each group required evacuation ( 1.9 vs. 2 % , P = 1.00 ) . No other haemorrhagic events or embolic complications developed during the follow-up . Duration of the hospital stay was longer in the heparin group [ median of 5 ( 4–7 ) vs. 2 ( 1–4 ) days ; P < 0.001 ] . Conclusion Implant of devices maintaining OAC is as safe as bridging to heparin infusion and allows a significant reduction of in-hospital stay BACKGROUND The anti-thrombotic strategy during coronary stenting is challenging in patients on long-term oral anticoagulation ( OAC ) because of atrial fibrillation ( AF ) . Uninterrupted OAC ( UAC ) is increasingly used , but bridging therapy ( BT ) is still in common use . METHODS AND RESULTS Management of patients with Atrial Fibrillation undergoing Coronary Artery Stenting ( AFCAS ) is a prospect i ve multicenter European registry that recruited 963 patients with AF undergoing coronary stenting . To compare the safety of UAC and BT , bleeding complications and major adverse cardiac and cerebrovascular events ( MACCE ; death , myocardial infa rct ion , target vessel revascularization , stent thrombosis and stroke ) were assessed in 290 patients treated with UAC and 161 patients with BT during a 30-day follow-up period . In the BT group , OAC was interrupted for a median of 5 days . Overall bleeding complications tended to be more common in the BT group ( 18.6 % vs. 12.1 % , P=0.07 ) , with no significant difference in the rate of major bleeding ( 2.5 % vs. 1.4 % ) or MACCE ( 6.2 % vs. 3.8 % ) . After adjustment for propensity score , BT was not associated with bleeding complications ( odds ratio [ OR ] , 1.38 ; 95 % confidence interval [ CI ] : 0.77 - 2.48 , P=0.28 ) or MACCE ( OR , 1.16 ; 95%CI : 0.44 - 3.05 , P=0.76 ) . Periprocedural international normalized ratio was not associated with bleeding or MACCE . CONCLUSIONS UAC does not increase perioperative complications during coronary stenting and is a simple and cost-effective alternative to conventional heparin bridging BACKGROUND Periprocedural management of oral anticoagulation ( OAC ) in patients undergoing cardiac rhythm management ( CRM ) device implantation is controversial . Prior studies demonstrate that uninterrupted OAC may be safe , but limited data from r and omized trials exist . METHODS We conducted a multicenter , r and omized trial to evaluate the safety of uninterrupted OAC during CRM device implantation . Patients on long-term warfarin ( N=213 ) treatment with contemporary indication for CRM device implantation were r and omized to uninterrupted versus interrupted ( 2 days ) OAC therapy . The primary outcome included major bleeding events necessitating additional intervention and thromboembolic events during 4 weeks follow-up . RESULTS The r and omized groups were well matched in terms of bleeding and thromboembolic risk . Only one ( 1 % ) patient in the uninterrupted OAC group ( N=106 ) needed blood transfusion due to rupture of proximal cephalic vein . Large hematomas were detected in 6 % of patients in both groups , but there was no need for pocket revision in either group . Any pocket hematoma was observed in 35 patients ( 33 % ) in the uninterrupted OAC group and in 43 patients ( 40 % ) with interrupted OAC and uninterrupted OAC strategy was non-inferior to interrupted OAC ( HR 0.86 , 95 % , p=0.001 for non-inferiority ) . One patient with interrupted OAC had stroke 3 days after the procedure . Hospital stay was comparable in all patient groups . CONCLUSION Our r and omized study demonstrates that CRM devices can be safely implanted without discontinuation of warfarin treatment INTRODUCTION Catheter ablation for atrial fibrillation is an effective treatment for symptomatic patients who have failed drug therapy . Recent studies using intracardiac echocardiography have demonstrated that ablation can be performed safely on uninterrupted warfarin and may be superior to bridging low molecular weight heparin ( LMWH ) . We sought to assess the safety of an uninterrupted warfarin protocol using a simplified ablation protocol in a prospect i ve controlled study . METHODS Two anticoagulation regimes for patients undergoing catheter ablation for atrial fibrillation were evaluated -- a bridging LMWH group and an uninterrupted warfarin group . Bleeding complications were compared between the 2 groups . RESULTS In total 198 patients were evaluated ( 109 bridging LMWH , 89 uninterrupted warfarin ) . The preprocedure INR in the LMWH group ( mean age 60.6 years , 72 % male ) was 1.2 ± 0.3 compared to 2.3 ± 0.5 in the uninterrupted warfarin group ( mean age 60.9 years , 69 % male ) . The primary outcome ( a composite of major and minor bleeding complications ) was observed in 78 % in the LMWH group compared to 56 % in the warfarin group ( P = 0.001 ) , mainly due to increased pain at the venous access site ( 41 % vs 16 % , P = 0.001 ) . Two patients undergoing ablation on warfarin required pericardiocentesis for cardiac tamponade . Drug costs were lower in the warfarin group ( $ 64.77 ± 31.86 vs $ 20.76 ± 15.60 , P = 0.005 ) , but the overall cost of treatment per patient ( including bed occupancy costs ) was similar in the LMWH group compared to the warfarin group ( $ 883.96 ± 278.78 vs $ 816.59 ± 182.72 , P = 0.06 ) . CONCLUSION Catheter ablation for atrial fibrillation can be performed safely on uninterrupted warfarin without intracardiac echocardiography , with a reduced risk of bleeding complications BACKGROUND Stopping oral anticoagulants prior to cardiac catheterization is associated with an increased risk of thromboembolism . Performing the procedures via the femoral artery and vein without interruption of anticoagulation is associated with a high rate of major access site complications . The transradial technique for left heart catheterization is safe in fully anticoagulated patients but few data are available on the percutaneous right and left heart catheterization utilizing a combination of the radial artery and antecubital vein in this group of patients . METHODS We report our experience in 28 consecutive patients that underwent left and right heart catheterizations via this percutaneous arm approach without interruption of anticoagulation . These were compared to 31 consecutive non-anticoagulated patients that underwent the procedure via a conventional femoral artery and vein approach . RESULTS Arterial and venous accesses were achieved and complete angiographic and hemodynamic data obtained in all patients . There were no access site complications in the anticoagulated patients despite an International normalized ratio ( INR ) of 2.5 + /- 0.5 . Procedural duration was longer in the anticoagulated group of patients , but fluoroscopy time and patient radiation dose were similar in both groups . CONCLUSION Our experience suggests that left and right heart catheterization can be safely performed in most fully anticoagulated patients using this technique with a low bleeding and thromboembolic risk and no increase in radiation exposure BACKGROUND Nonrheumatic atrial fibrillation is common among the elderly and is associated with an increased risk of stroke . We investigated whether anticoagulation with warfarin would reduce this risk . METHODS We conducted a r and omized , double-blind , placebo-controlled study to evaluate low-intensity anticoagulation with warfarin ( prothrombin-time ratio , 1.2 to 1.5 ) in 571 men with chronic nonrheumatic atrial fibrillation ; 525 patients had not previously had a cerebral infa rct ion , whereas 46 patients had previously had such an event . The primary end point was cerebral infa rct ion ; secondary end points were cerebral hemorrhage and death . RESULTS Among the patients with no history of stroke , cerebral infa rct ion occurred in 19 of the 265 patients in the placebo group during an average follow-up of 1.7 years ( 4.3 percent per year ) and in 4 of the 260 patients in the warfarin group during an average follow-up of 1.8 years ( 0.9 percent per year ) . The reduction in risk with warfarin therapy was 0.79 ( 95 percent confidence interval , 0.52 to 0.90 ; P = 0.001 ) . The annual event rate among the 228 patients over 70 years of age was 4.8 percent in the placebo group and 0.9 percent in the warfarin group ( risk reduction , 0.79 ; P = 0.02 ) . The only cerebral hemorrhage occurred in a 73-year-old patient in the warfarin group . Other major hemorrhages , all gastrointestinal , occurred in 10 patients : 4 in the placebo group , for a rate of 0.9 percent per year , and 6 in the warfarin group , for a rate of 1.3 percent per year . There were 37 deaths that were not preceded by a cerebral end point--22 in the placebo group and 15 in the warfarin group ( risk reduction , 0.31 ; P = 0.19 ) . Cerebral infa rct ion was more common among patients with a history of cerebral infa rct ion ( 9.3 percent per year in the placebo group and 6.1 percent per year in the warfarin group ) than among those without such a history . CONCLUSIONS Low-intensity anticoagulation with warfarin prevented cerebral infa rct ion in patients with nonrheumatic atrial fibrillation without producing an excess risk of major hemorrhage . This benefit extended to patients over 70 years of age |
14,050 | 27,149,547 | In line with treatments for other substance use , abstinence rates were relatively low overall , with approximately one-quarter of participants abstinent at final follow-up .
The rate of abstinence was low and unstable although comparable with treatments for other substance use .
Psychosocial intervention was shown , in comparison with minimal treatment controls , to reduce frequency of use and severity of dependence in a fairly durable manner , at least in the short term .
Among the included intervention types , an intensive intervention provided over more than four sessions based on the combination of MET and CBT with abstinence-based incentives was most consistently supported for treatment of cannabis use disorder | BACKGROUND Cannabis use disorder is the most commonly reported illegal substance use disorder in the general population ; although dem and for assistance from health services is increasing internationally , only a minority of those with the disorder seek professional assistance .
Treatment studies have been published , but pressure to establish public policy requires an up date d systematic review of cannabis-specific treatments for adults .
OBJECTIVES To evaluate the efficacy of psychosocial interventions for cannabis use disorder ( compared with inactive control and /or alternative treatment ) delivered to adults in an out-patient or community setting . | BACKGROUND AND OBJECTIVES Substance use disorder ( SUD ) is a major health issue , especially among military veterans . We previously reported the effects of auricular acupuncture and the relaxation response ( RR ) on reducing craving and anxiety following 10-week interventions among veterans who were in recovery from SUDs . Our current analysis examines effects following each intervention session and RR daily practice . METHODS We conducted a three-arm r and omized controlled trial on residents of a homeless veteran rehabilitation program . Sixty-Seven enroled participants were r and omly assigned to acupuncture ( n=23 ) , RR ( n=23 ) , or usual care ( n=21 ) . Participants in the two intervention groups rated their degree of craving for substance on a scale of 1 - 10 and anxiety levels on a scale of 1 - 4 ( total score 20 - 80 ) before and after each intervention session . Mixed effects regression models were used for analysis . RESULTS Craving and anxiety levels decreased significantly following one session of acupuncture ( -1.04 , p=.0001 ; -8.83 , p<.0001 ) or RR intervention ( -.43 , p=.02 ; -4.64 , p=.03 ) . The level of craving continued to drop with additional intervention sessions ( regression coefficient b=-.10 , p=.01 , and b=-.10 , p=.02 for acupuncture and RR groups , respectively ) . Number of daily practice days of RR-eliciting techniques is also associated with reduction in craving ratings ( b=-.02 , p=.008 ) . CONCLUSIONS Findings demonstrate the value of attending regular acupuncture and RR-eliciting intervention sessions , as well as the daily practice of RR-eliciting techniques . SCIENTIFIC SIGNIFICANCE Substance addiction is a complex disease and effective treatment remains a challenge . Our study findings add to the scientific evidence of these two non-pharmaceutical approaches for SUD Background Research has shown that treatments that solely addressed intimate partner violence ( IPV ) perpetration were not very effective in reducing IPV , possibly due to neglecting individual differences between IPV perpetrators . A large proportion of IPV perpetrators is diagnosed with co-occurring substance use disorders and it has been demonstrated that successful treatment of alcohol dependence among alcohol dependent IPV perpetrators also led to less IPV . The current study investigated the relative effectiveness of Integrated treatment for Substance abuse and Partner violence ( I-StoP ) to cognitive behavioral treatment addressing substance use disorders including only one session addressing partner violence ( CBT-SUD+ ) among patients in substance abuse treatment who repeatedly committed IPV . Substance use and IPV perpetration were primary outcome measures . Method Patients who entered substance abuse treatment were screened for IPV . Patients who disclosed at least 7 acts of physical IPV in the past year ( N = 52 ) were r and omly assigned to either I-StoP or CBT-SUD+ . Patients in both conditions received 16 treatment sessions . Substance use and IPV perpetration were assessed at pretreatment , halfway treatment and posttreatment in blocks of 8 weeks . Both completers and intention-to-treat ( ITT ) analyses were performed . Results Patients ( completers and ITT ) in both conditions significantly improved regarding substance use and IPV perpetration at posttreatment compared with pretreatment . There were no differences in outcome between conditions . Completers in both conditions almost fully abstained from IPV in 8 weeks before the end of treatment . Conclusions Both I-StoP and CBT-SUD+ were effective in reducing substance use and IPV perpetration among patients in substance abuse treatment who repeatedly committed IPV and self-disclosed IPV perpetration . Since it is more cost and time-effective to implement CBT-SUD+ than I-StoP , it is suggested to treat IPV perpetrators in substance abuse treatment with CBT-SUD+.Trial registration Clinical Trials.gov : AIMS The purpose of this study was to examine the influence of personal goals ( abstinence or moderation ) on treatment outcomes for marijuana use . Hypotheses regarding self-efficacy for goal attainment were tested . DESIGN Adult marijuana users seeking treatment were assigned r and omly to three treatment conditions : ( 1 ) cognitive-behavioral relapse prevention support group ; ( 2 ) individualized brief motivational enhancement ; and ( 3 ) delayed treatment control group . Follow-up assessment s were conducted at 4 , 7 , 13 and 16 months . SETTING University research offices . PARTICIPANTS Participants were 291 adult marijuana users . Measurements Marijuana use , personal treatment goals and self-efficacy for achieving one 's goal were assessed across the 16-month follow-up . FINDINGS Greater marijuana related problems and dependence symptoms were associated with an initial goal of abstinence . Participants were more likely to achieve outcomes consistent with their personal goals . Participants with abstinence goals reported greater self-efficacy for goal achievement than those with moderation goals after participating in the abstinence oriented treatment ; self-efficacy for goal success predicted goal achievement for both moderate use and abstinence goals . CONCLUSIONS Marijuana users approaching an abstinence-oriented treatment varied in the extent to which they were actively seeking abstinence as the outcome . Differences in goals were predictable from severity of problems related to use . Goal preference and self-efficacy for achieving goals predicted outcomes . Future research should incorporate personal goals into treatment and assess their effects on outcomes Adult marijuana users ( N = 291 ) seeking treatment were r and omly assigned to an extended 14-session cognitive-behavioral group treatment ( relapse prevention support group ; RPSG ) , a brief 2-session individual treatment using motivational interviewing ( individualized assessment and intervention ; IAI ) , or a 4-month delayed treatment control ( DTC ) condition . Results indicated that marijuana use , dependence symptoms , and negative consequences were reduced significantly in relation to pretreatment levels at 1- , 4- , 7- , 13- , and 16-month follow-ups . Participants in the RPSG and IAI treatments showed significantly and substantially greater improvement than DTC participants at the 4-month follow-up . There were no significant differences between RPSG and IAI outcomes at any follow-up . The relative efficacy of brief versus extended interventions for chronic marijuana-using adults is discussed This pilot study sought to test the feasibility of procedures to screen students for marijuana use in Student Health Services ( SHS ) and test the efficacy of a web-based intervention design ed to reduce marijuana use and consequences . Students were asked to participate in voluntary screening of health behaviors upon arrival at SHS . One hundred and twenty-three students who used marijuana at least monthly completed assessment s and were r and omized to one of four intervention conditions in a 2 ( intervention : Marijuana eCHECKUP TO GO vs. control) × 2 ( site of intervention : on-site vs. off-site ) between-groups design . Follow-up assessment s were conducted online at 3 and 6 months . Latent growth modeling was used to provide effect size estimates for the influence of intervention on outcomes . One thous and and eighty undergraduate students completed screening . The intervention did not influence marijuana use frequency . However , there was evidence of a small overall intervention effect on marijuana-related consequences and a medium effect in stratified analyses in the on-site condition . Analyses of psychological variables showed that the intervention significantly reduced perceived norms regarding peer marijuana use . These findings demonstrate that it is feasible to identify marijuana users in SHS and deliver an automated web-based intervention to these students in different context s. Effect size estimates suggest that the intervention has some promise as a means of correcting misperceptions of marijuana use norms and reducing marijuana-related consequences . Future work should test the efficacy of this intervention in a full scale r and omized controlled trial AIMS To examine the efficacy , 3- and 6-month follow-up effects of a psychological treatment for older adolescents and adults with DSM-IV cannabis use disorders . The program was tailored to the needs of this patient population . EXPERIMENTAL PROCEDURES A r and omized controlled clinical trial of 122 patients aged 16 to 44 years with DSM-IV cannabis dependence as the main substance use diagnosis was conducted . Patients were r and omly assigned to either Active Treatment ( AT , n = 90 ) or a Delayed Treatment Control group ( DTC , n = 32 ) . Treatment consisted of 10 sessions of therapy , detailed in a strictly enforced manual . Assessment s were conducted at baseline , during each therapy session , at post treatment and at follow-up assessment s at 3 and 6 months . RESULTS The treatment retention rate was 88 % . Abstinence was achieved in 49 % of AT patients and in 13 % of those in DTC ( p < 0.001 ; intend-to-treat ( ITT ) analysis ) . Further , AT patients improved significantly ( p < = 0.001 ) in the frequency of cannabis use per week , addiction severity , number of disability days , and overall level of psychopathology . Program effects were maintained over a 3-month- ( abstinence rate : 51 % ) and 6-month follow-up ( 45 % ) period . CONCLUSION The treatment program is effective in obtaining abstinence as well as reducing cannabis use and improves the associated social and mental health burden We sought to characterize attrition-related characteristics of three subgroups of adults ( i.e. early dropouts , late dropouts , treatment completers ) who had participated in a marijuana-dependence treatment outcome study involving two alternative forms of outpatient group counseling . Early dropouts were younger , earned less income , were more likely to rent rather than own their domiciles , were less able to pay bills , and had a higher level of psychological distress than was the case with treatment completers . Late dropouts and completers were quite similar on a number of measures ( e.g. , age , income , home ownership , ability to pay bills , psychological stress level , confidence in being abstinent in the future ) , yet the lower rates of abstinence in the late dropouts largely resembled the treatment outcomes of early dropouts . The findings suggest that attrition prevention in the early phase of counseling ought to focus on motivational ambivalence as well as assisting the client in dealing with schedule conflicts or financial impediments to continued involvement . In the later stage of counseling , attrition reduction is more likely to be accomplished through efforts to better underst and and address the client 's dissatisfaction with treatment components delivered at that stage BACKGROUND R and omized trials targeting cannabis use disorders in patients with psychosis have generally been unsuccessful . One of the largest such trials was the CapOpus trial , which had an impact on the number of monthly joints used , but not on the number of days with cannabis use or positive or negative symptoms . OBJECTIVE To investigate the effects of CapOpus on psychiatric treatment . METHODS Six-month r and omized trial on participants meeting ICD-10 criteria for cannabis use disorder and schizophrenia-spectrum psychosis . Participants were r and omized to treatment as usual ( TAU , n=51 ) alone versus TAU plus CapOpus ( n=52 ) consisting of motivational interviewing and cognitive behavior therapy . Data regarding psychiatric treatment was obtained from complete nationwide registers . Analyses were intention-to-treat . Cox and poisson regression were used as appropriate . RESULTS Compared with treatment as usual , participants in the CapOpus group had an overall higher risk of having a psychiatric emergency room contact ( hazard ratio 2.02 , 95 % confidence interval 1.22 - 3.34 ) . Participants in CapOpus also had more contacts with psychiatric emergency rooms ( incidence rate ratio 3.47 ( 2.64 - 4.57 ) ) and more admissions to psychiatric hospitals ( incidence rate ratio 2.24 ( 1.65 - 3.03 ) ) ; conversely , CapOpus- participants spent fewer days admitted to psychiatric hospitals than treatment-as-usual participants ( incidence rate ratio 0.72 ( 0.68 - 0.75 ) ) . CONCLUSIONS CapOpus led to earlier and more psychiatric emergency room contacts and admissions that , however , were of fewer days . This pattern could indicate that participants receiving treatment as usual were inadequately treated . However , it can not be excluded that the differences might be an adverse reaction to the psychosocial intervention OBJECTIVE Most adolescents relapse within 90 days of discharge from residential substance use treatment . We hypothesized that contingency management ( CM ) , assertive continuing care ( ACC ) , and their combination ( CM + ACC ) would each be more effective than usual continuing care ( UCC ) . METHOD Following residential treatment , 337 adolescents were r and omized to 4 continuing care conditions : UCC alone , CM , ACC , or CM + ACC . UCC was available across all conditions . Outcome measures over 12 months included percentage of days abstinent from alcohol , heavy alcohol , marijuana , and any alcohol or other drugs ( AOD ) using self-reports and toxicology testing and remission status at 12 months . RESULTS CM had significantly higher rates of abstinence than UCC for heavy alcohol use , t(297 ) = 2.50 , p < .01 , d = 0.34 ; any alcohol use , t(297 ) = 2.58 , p < .01 , d = 0.36 ; or any AOD use , t(297 ) = 2.12 , p = .01 , d = 0.41 ; and had a higher rate in remission , odds ratio ( OR ) = 2.45 , 90 % confidence interval ( CI ) [ 1.18 , 5.08 ] , p = .02 . ACC had significantly higher rates of abstinence than UCC from heavy alcohol use , t(297 ) = 2.66 , p < .01 , d = 0.31 ; any alcohol use , t(297 ) = 2.63 , p < .01 , d = 0.30 ; any marijuana use , t(297 ) = 1.95 , p = .02 , d = 0.28 ; or any AOD use , t(297 ) = 1.88 , p = .02 , d = 0.30 ; and had higher rates in remission , OR = 2.31 , 90 % CI [ 1.10 , 4.85 ] , p = .03 . The ACC + CM condition was not significantly different from UCC on any outcomes . CONCLUSIONS CM and ACC are promising continuing care approaches after residential treatment . Future research should seek to further improve their effectiveness The prevalence of alcohol and other drug use is high among college students . Reducing their consumption will likely be beneficial for society as a whole . Computer and web-based interventions are promising for providing behaviorally based information . The present study compared the efficacy of three interventions ( computerized screening and motivational intervention [ ASSIST/MBIc ] , non-computerized screening and motivational intervention [ ASSIST/MBIi ] , and screening only [ control ] ) in college students in Curitiba , Brazil . A convenience sample of 458 students scored moderate and high risk on the ASSIST . They were then r and omized into the three arms of the r and omized controlled trial ( ASSIST/MBIc , ASSIST/MBIi [ interview ] , and assessment -only [ control ] ) and assessed at baseline and 3 months later . The ASSIST involvement scores decreased at follow-up compared with baseline in the three groups , suggesting that any intervention is better than no intervention . For alcohol , the specific involvement scores decreased to a low level of risk in the three groups and the MBIc group showed a positive outcome compared with control , and the scores for each question were reduced in the two intervention groups compared to baseline . For tobacco , involvement scores decreased in the three groups , but they maintained moderate risk . For marijuana , a small positive effect was observed in the ASSIST/MBIi and control groups . The ASSIST/MBIc may be a good alternative to interview interventions because it is easy to administer , students frequently use such computer-based technologies , and individually tailored content can be delivered in the absence of a counselor OBJECTIVES Marijuana was involved in 209,563 emergency department ( ED ) visits in 2006 , according to the Drug Abuse Warning Network . Although screening and brief intervention ( SBI ) has been effective in changing drinking among ED patients in a number of studies , tests of marijuana SBI in a pediatric emergency department ( PED ) have not yet been reported . The aim of this pilot study was to test whether SBI is effective in reducing marijuana consumption among youth and young adults presenting to a PED with a diverse range of clinical entities . METHODS A three-group r and omized controlled preliminary trial was structured to test 1 ) differences between Intervention ( Int ) and st and ard Assessed Control ( AC ) groups in marijuana consumption , from baseline to 12 months , and 2 ) the feasibility of adding a Nonassessed Control ( NAC ) group to evaluate regression to the mean and assessment reactivity . Patients aged 14 - 21 years in an urban , academic PED were screened during 2006 - 2007 , using st and ardized risk factor questions . Subjects were eligible if they used marijuana three or more times in the past 30 days , but were excluded for co-occurring high-risk alcohol use . Consented enrollees were r and omized to NAC , AC , and Int groups in a two-stage process that permitted blinding to status during assessment and follow-up . NACs received a re source h and out , written advice about marijuana use risks , and a 12-month follow-up appointment . ACs were assessed using st and ardized instruments and received re sources , written advice , and 3- and 12-month follow-up appointments . The Int group received assessment , re sources , written advice , 3- and 12-month appointments , a 20-minute structured conversation conducted by older peers , and a 10-day booster telephone call . A peer educator utilized a motivational style interview protocol adapted for adolescents to elicit daily life context and future goals , provide feedback , review pros and cons of marijuana use , assess readiness to change , evaluate strengths and assets , negotiate a contract for change , and make referrals to treatment and /or other re sources . Measurements included demographic information ; 30-day self-report of marijuana use ; attempts to quit , cut back , or change conditions of use ; and risk factor questions repeated at follow-up . RESULTS Among 7,804 PED patients screened , 325 were eligible ; 210 consented and enrolled ( Int , n = 68 ; AC , n = 71 ; NAC , n = 71 ) , with a 12-month follow-up rate of 71 % . For the primary objective , we compared Int to AC . At 12 months , Int participants were more likely to be abstinent for the past 30 days than ACs ( odds ratio [ OR ] for reported abstinence = 2.89 , 95 % confidence interval [ CI ] = 1.22 to 6.84 , p < 0.014 ) . The Int group had greater reduction in days used , baseline to 12 months , controlling for baseline ( Int = -7.1 vs. AC = -1.8 ) , were less likely to have been high among those who smoked ( OR = 0.39 , 95 % CI = 0.17 to 0.89 , p < 0.05 ) , and were more likely to receive referrals . In a linear regression model controlling for baseline use , NACs smoked 4 fewer days per month than ACs , but consumption was not significantly different , suggesting no assessment reactivity effect . CONCLUSIONS A preliminary trial of SBI promoted marijuana abstinence and reduced consumption among PED patients aged 14 - 21 years . A no-contact condition for the NAC group over the year after enrollment was insufficient to capture enrollees for follow-up across a range of baseline acuity This study evaluated the effectiveness and cost-effectiveness of two types of outpatient treatment with and without Assertive Continuing Care ( ACC ) for 320 adolescents with substance use disorders . Study participants were r and omly assigned to one of four conditions : ( a ) Chestnut 's Bloomington Outpatient Treatment ( CBOP ) without ACC ; ( b ) CBOP with ACC ; ( c ) Motivational Enhancement Therapy/Cognitive Behavior Therapy-7 session model ( MET/CBT7 ) without ACC ; and ( d ) MET/CBT7 with ACC . All study conditions attained high rates of participant engagement and retention . Follow-up interviews were completed with over 90 % of the adolescents at three , six , nine , and 12 months after treatment admission . There was a significant time by condition effect over 12 months , with CBOP having a slight advantage for average percentage of days abstinent . Unlike previous findings that ACC provided incremental effectiveness following residential treatment , there were no statistically significant findings with regard to the incremental effectiveness of ACC following outpatient treatment . Analysis of the costs of each intervention combined with its outcomes revealed that the most cost-effective condition was MET/CBT7 without ACC AIMS Our objective was to identify client characteristics and other factors associated with pre-treatment drop-out by people with marijuana dependence . DESIGN AND PARTICIPANTS Data from the Marijuana Treatment Project 's screening assessment were used to examine correlates of pre-treatment drop-out . Information from all eligible study participants ( n = 813 ) ( i.e. those who were interested in receiving treatment for their marijuana dependence and were determined to be eligible for the r and omized treatment efficacy trial ) was used to examine differences between the 450 participants who initiated treatment ( by enrolling in the trial ) and the 363 individuals who declined enrollment . SETTING The study was conducted at three community-based outpatient treatment facilities in Farmington , CT , Seattle , WA and Miami , FL . MEASUREMENTS The information gathered in the screening interview included demographic characteristics , residential stability variables , employment and education history and referral source . Substance use variables included the number of days and the number of times per day marijuana was used , self-perceived dependence on marijuana , alcohol or other drugs , other drug use history and current treatment ( i.e. substance abuse , medical , psychiatric ) situation . FINDINGS Stepwise logistic regression was conducted to confirm variables associated with treatment initiation in bivariate analyses . Pre-treatment drop-out was associated with being younger , unmarried , unemployed , less educated and Asian American or Native American . It was also associated with self-perceived dependence on marijuana and use of other drugs . CONCLUSIONS By recognizing demographic and substance use factors that may serve as barriers for individuals accessing treatment for marijuana dependence , clinicians may target clients with these characteristics proactively to encourage treatment initiation and subsequent attendance Youth substance abuse relapse prevention was examined as a function of patients ' situational self-efficacy ( SE ) , their confidence to abstain from substance use in high-risk situations . An increase in SE has been shown to be enhanced by cognitive behavioral therapy ( CBT ) in adults . Eighty-eight adolescent substance abusers were r and omly assigned to either CBT or psycho-education ( PET ) group therapy . Substance use and SE were assessed at end of treatment , 3- and 9-months after the end of planned treatment . Increased SE predicted subsequent abstinence independently from drug urinalysis and treatment condition only during treatment , while previous substance use predicted subsequent self-efficacy . CBT was not differentially effective than PET in promoting SE . It is recommended that potential mediators and moderators of SE in the treatment of adolescent substance abuse should be further explored BACKGROUND While several r and omized controlled trials evaluating a range of treatments for cannabis use disorders have appeared in recent years , these have been marked by inconsistency in selection of primary outcomes , making it difficult to compare outcomes across studies . METHOD With the aim of identifying meaningful and reliable outcome domains in treatment studies of cannabis use disorders , we evaluated multiple indicators of marijuana use , marijuana problems , and psychosocial functioning from two independent r and omized controlled trials of behavioral treatments for cannabis use disorders ( Ns=450 and 136 ) . RESULTS Confirmatory factor analysis indicated that the best-fitting model of outcomes in both trials encompassed three distinct factors : frequency of marijuana use , severity of marijuana use , and psychosocial functioning . In both trials , frequency of marijuana use and longest period of abstinence during treatment were most strongly associated with outcome during follow-up . Using two categorical definitions of " clinical ly significant improvement , " individuals who demonstrated improvement differed on most end-of-treatment and long-term outcomes from those who did not improve . CONCLUSIONS Results may guide future r and omized controlled trials of treatments for cannabis use disorders in the collection of relevant end-of-treatment outcomes and encourage consistency in the reporting of outcomes across trials BACKGROUND More and more adolescents with cannabis problems are seeking treatment at addiction clinics . There is an urgent need for new types of treatment in this field . AIM To evaluate the effectiveness of multidimensional family therapy ( MDFT ) and cognitive behavioral therapy ( CBT ) in adolescents with a cannabis use disorder . METHOD One hundred and nine adolescents were r and omly assigned to outpatient MDFT or CBT . Both types of therapy groups had a planned treatment course lasting 5 to 6 months . After 12 months the two groups were compared in terms of changes in cannabis use and in terms of secondary outcome measures , including delinquency . RESULTS Adolescents in both treatment groups showed significant and relevant reductions in cannabis use and delinquency over 12 months . Although the MDFT treatment lasted longer and was more intensive than the CBT treatment , there was no difference in the key outcome measures of the treatments . Secondary analyses indicated that older adolescents and those without comorbid psychiatric problems derived considerably more benefit from CBT , whereas younger adolescents and those with comorbid psychiatric problems benefited much more from MDFT . CONCLUSION MDFT and CBT are equally effective in reducing cannabis use and delinquent behavior in adolescents with a cannabis use disorder . Age and comorbid psychiatric problems turned out to be important moderators of the treatment results of MDFT and CBT and could therefore be used as a starting point for matching adolescent substance abusers to the most appropriate type of treatment This pilot study tested the efficacy of a brief intervention using motivational interviewing ( MI ) plus mindfulness meditation ( MM ) to reduce marijuana use among young adult females . Thirty-four female marijuana users between the ages of 18 and 29 were r and omized to either the intervention group ( n = 22 ) , consisting of two sessions of MI-MM , or an assessment -only control group ( n = 12 ) . The participants ' marijuana use was assessed at baseline and at 1 , 2 , and 3 months posttreatment . Fixed-effects regression modeling was used to analyze treatment effects . Participants r and omized to the intervention group were found to use marijuana on 6.15 ( z = -2.42 , p = .015 ) , 7.81 ( z = -2.78 , p = .005 ) , and 6.83 ( z = -2.23 , p = .026 ) fewer days at Months 1 , 2 , and 3 , respectively , than controls . Findings from this pilot study provide preliminary evidence for the feasibility and effectiveness of a brief MI-MM for young adult female marijuana users Background A number of studies indicate a link between cannabis-use and psychosis as well as more severe psychosis in those with existing psychotic disorders . There is currently insufficient evidence to decide the optimal way to treat cannabis abuse among patients with psychosis . Objectives The major objective for the CapOpus trial is to evaluate the additional effect on cannabis abuse of a specialized addiction treatment program adding group treatment and motivational interviewing to treatment as usual . Design The trial is design ed as a r and omized , parallel-group , observer-blinded clinical trial . Patients are primarily recruited through early-psychosis detection teams , community mental health centers , and assertive community treatment teams . Patients are r and omized to one of two treatment arms , both lasting six months : 1 ) specialized addiction treatment plus treatment as usual or 2 ) treatment as usual . The specialized addiction treatment is manualized and consists of both individual and group-based motivational interviewing and cognitive behavioral therapy , and incorporates both the family and the case manager of the patient . The primary outcome measure will be changes in amount of cannabis consumption over time . Other outcome measures will be psychosis symptoms , cognitive functioning , quality of life , social functioning , and cost-benefit analyses . Trial registration Clinical Trials.gov NCT00484302 The INCANT pilot study ( International Cannabis Need of Treatment ) is based on the Cannabis Action Research Plan from 2003 , which followed up on the joint Cannabis Conference with the Ministries of Health from Belgium , France , Germany , the Netherl and s , and Switzerl and . It was decided to fund a pilot study into the efficacy of Multidimensional Family Therapy ( MDFT ) in the European context . MDFT has been tested in several U.S.- RCT - studies and is developed by H. Liddle and colleagues at the " Center for Treatment Research on Adolescent Drug Abuse " ( CTRADA ) , University of Miami Medical School . Goal of the INCANT pilot study was to proof the feasibility of a multi-site r and omized controlled trial with MDFT in Europe . The results of the INCANT study confirmed the need of treatment for those young clients in the five countries . The implementation of MDFT in the treatment centers seems to be feasible . The plan is now to start the trans-national multi-site trial ( from 2006 to 2009 ) on behalf of the ministry of health of the five countries Background US-based trials have shown that Multidimensional Family Therapy ( MDFT ) not only reduces substance abuse among adolescents , but also decreases mental and behavioural disorder symptoms , most notably externalising symptoms . In the INCANT trial , MDFT decreased the rate of cannabis dependence among Western European youth . We now focus on other INCANT outcomes , i.e. , lessening of co-morbidity symptoms and improvement of family functioning . Methods INCANT was a r and omised controlled trial comparing MDFT with individual therapy ( IP ) at and across sites in Berlin , Brussels , Geneva , The Hague , and Paris . We recruited 450 boys and girls aged 13 up to 18 years with a cannabis use disorder , and their parent(s ) , and followed them for 12 months . Mental and behavioural characteristics ( classified as ' externalising ’ or ' internalising ’ ) and family conflict and cohesion were assessed . Results From intake through 12 months , MDFT and IP groups improved on all outcome measures . Models including treatment , site , and referral source showed that MDFT outperformed IP in reducing externalising symptoms . Adolescents were either self-referred to treatment ( mostly on the initiative from people close to the teen ) or referred under some measure of coercion by an external authority . These two groups reacted equally well to treatment . Conclusions Both MDFT and IP reduced the rate of externalising and internalising symptoms and improved family functioning among adolescents with a cannabis use disorder . MDFT outperformed IP in decreasing the rate of externalising symptoms . Contrary to common beliefs among therapists in parts of Western Europe , the ' coerced ’ adolescents did at least as well in treatment as the self-referred adolescents . MDFT shows promise as a treatment for both substance use disorders and externalising symptoms . Trial registration ISRNCT : IS RCT IMPORTANCE Although brief intervention is effective for reducing problem alcohol use , few data exist on its effectiveness for reducing problem drug use , a common issue in disadvantaged population s seeking care in safety-net medical setting s ( hospitals and community health clinics serving low-income patients with limited or no insurance ) . OBJECTIVE To determine whether brief intervention improves drug use outcomes compared with enhanced care as usual . DESIGN , SETTING , AND PARTICIPANTS A r and omized clinical trial with blinded assessment s at baseline and at 3 , 6 , 9 , and 12 months conducted in 7 safety-net primary care clinics in Washington State . Of 1621 eligible patients reporting any problem drug use in the past 90 days , 868 consented and were r and omized between April 2009 and September 2012 . Follow-up participation was more than 87 % at all points . INTERVENTIONS Participants received a single brief intervention using motivational interviewing , a h and out and list of substance abuse re sources , and an attempted 10-minute telephone booster within 2 weeks ( n = 435 ) or enhanced care as usual , which included a h and out and list of substance abuse re sources ( n = 433 ) . MAIN OUTCOMES AND MEASURES The primary outcomes were self-reported days of problem drug use in the past 30 days and Addiction Severity Index-Lite ( ASI ) Drug Use composite score . Secondary outcomes were admission to substance abuse treatment ; ASI composite scores for medical , psychiatric , social , and legal domains ; emergency department and inpatient hospital admissions , arrests , mortality , and human immunodeficiency virus risk behavior . RESULTS Mean days used of the most common problem drug at baseline were 14.40 ( SD , 11.29 ) ( brief intervention ) and 13.25 ( SD , 10.69 ) ( enhanced care as usual ) ; at 3 months postintervention , means were 11.87 ( SD , 12.13 ) ( brief intervention ) and 9.84 ( SD , 10.64 ) ( enhanced care as usual ) and not significantly different ( difference in differences , β = 0.89 [ 95 % CI , -0.49 to 2.26 ] ) . Mean ASI Drug Use composite score at baseline was 0.11 ( SD , 0.10 ) ( brief intervention ) and 0.11 ( SD , 0.10 ) ( enhanced care as usual ) and at 3 months was 0.10 ( SD , 0.09 ) ( brief intervention ) and 0.09 ( SD , 0.09 ) ( enhanced care as usual ) and not significantly different ( difference in differences , β = 0.008 [ 95 % CI , -0.006 to 0.021 ] ) . During the 12 months following intervention , no significant treatment differences were found for either variable . No significant differences were found for secondary outcomes . CONCLUSIONS AND RELEVANCE A one-time brief intervention with attempted telephone booster had no effect on drug use in patients seen in safety-net primary care setting s. This finding suggests a need for caution in promoting widespread adoption of this intervention for drug use in primary care . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00877331 AIM To test whether beneficial effects of a single session of Motivational Interviewing ( MI ) on alcohol , tobacco and illicit drug use apparent after 3 months were maintained until 12 months . DESIGN Cluster r and omized trial , allocating 200 young people in the natural groups in which they were recruited to either MI ( n = 105 ) or to an assessment -only control condition ( n = 95 ) . SETTING Ten further education colleges across inner London . PARTICIPANTS Two hundred young people who were current users of illegal drugs ( age range 16 - 20 years ) with whom contact was established through peers trained for the project . INTERVENTION The intervention was adapted from MI in the form of a topic-based 1-hour single-session discussion . MEASUREMENTS Changes in cigarette , alcohol , cannabis and other drug use and perceptions of risk and harm between the time of recruitment and follow-up interviews after 3 and 12 months . FINDINGS A satisfactory follow-up rate ( 81 % ) was achieved . After 12 months , 3-month differences between MI and assessment -only groups have disappeared almost entirely . Unexpected improvements by the assessment -only control group on a number of outcomes suggest the possibility of reactivity to the research assessment at 3-month follow-up . CONCLUSION In the terms of the original experiment , there is little evidence of enduring intervention effectiveness shown by between-group differences after 12 months . Deterioration of effect is the most probable explanation , although reactivity to 3-month assessment , a late Hawthorne effect , can not be ruled out Evidence for negative effects of early-onset cannabis use has led to a need for effective interventions targeting adolescent cannabis users . A r and omized controlled trial of an Australian two-session intervention based on motivational interviewing ( the ACCU , or Weed-Check in Dutch ) was replicated in a larger Dutch sample of 119 non-treatment-seeking adolescent cannabis users . Outcome measures at the 3-month follow-up were quantity and frequency of cannabis use , symptoms of dependence , stage of change , and psychosocial functioning . Changes in all measures were in the expected direction , yet not significant . In moderation analyses , heavier cannabis users at baseline receiving the Weed-Check had greater reductions in cannabis use than those in the control condition . These results suggest that the Weed-Check might be beneficial for heavier cannabis-using adolescents . Further research is needed to confirm these results in a sample of adolescent heavy cannabis users and to examine the relationship between MI skills of prevention workers and outcome Background Cannabis is the most consumed illegal substance in France . General practitioners ( GPs ) are the health professionals who are most consulted by adolescents . Brief intervention ( BI ) is a promising care initiative for the consumption of cannabis , and could be a tool for GPs in caring for adolescents who consume cannabis . The aim of the CANABIC study is to measure the impact of a BI carried out by a GP on the consumption of cannabis by adolescents of 15 to 25 years of age . Methods A r and omized clustered controlled trial , stratified over three areas ( Auvergne , Languedoc-Roussillon , and Rhône - Alpes ) , comparing an intervention group , which carries out the BI in consultation , and a control group , which ensures routine medical care . The main assessment criterion is the consumption of cannabis by amount of joints per month , at 12 months . The amount necessary to highlight a significant difference between the two groups of 30 % of consumption at 12 months is 250 patients ( 50 GPs , 5 patients per GP ; risk α = 5 % ; power = 90 % ; intra-cluster correlation coefficient ρ = 0.2 ; Hawthorne effect = 15 % ; lost to follow-up rates for GPs = 10 % and for patients = 20 % ) . This plan is replicated for the three areas , and therefore a total of 750 patients are expected . The secondary criteria for judgment are the associated consumption of tobacco and alcohol , the perception of the consequences of consumption , and the driving of a vehicle following consumption . Discussion Research about BI for young cannabis users is underway . The aim of the CANABIC study is to vali date a BI suited to adolescents who consume cannabis , which may be performed in the general practice . This would provide a tool for their treatment by a GP , which could be widely distributed during initial or further medical training . Trial registration CANABIC is a r and omized clustered trial ( NCT01433692 , registered 2011 Sept 12 ) , PHRC funded : Clinical Research Hospital Program ( Governmental Fund , Health Ministry ) . Date first patient r and omized : March 2012 Background One in three young people use cannabis in Canada . Cannabis use can be associated with a variety of health problems which occur primarily among intensive/frequent users . Availability and effectiveness of conventional treatment for cannabis use is limited . While Brief Interventions ( BIs ) have been shown to result in short-term reductions of cannabis use risks or problems , few studies have assessed their longer-term effects . The present study examined 12-month follow-up outcomes for BIs in a cohort of young Canadian high-frequency cannabis users where select short-term effects ( 3 months ) had previously been assessed and demonstrated . Findings N = 134 frequent cannabis users were recruited from among university students in Toronto , r and omized to either an oral or a written cannabis BI , or corresponding health controls , and assessed in-person at baseline , 3-months , and 12-months . N = 72 ( 54 % ) of the original sample were retained for follow-up analyses at 12-months where reductions in ‘ deep inhalation/breathholding ’ ( Q = 13.1 ; p < .05 ) and ‘ driving after cannabis use ’ ( Q = 9.3 ; p < .05 ) were observed in the experimental groups . Reductions for these indicators had been shown at 3-months in the experimental groups ; these reductions were maintained over the year . Other indicators assessed remained overall stable in both experimental and control groups . Conclusions The results confirm findings from select other studies indicating the potential for longer-term and sustained risk reduction effects of BIs for cannabis use . While further research is needed on the long-term effects of BIs , these may be a valuable – and efficient – intervention tool in a public health approach to high-risk cannabis use Background Cannabis dependence is a significant public health problem . Because there are no approved medications for this condition , treatment must rely on behavioral approaches empirically complemented by such lifestyle change as exercise . Aims To examine the effects of moderate aerobic exercise on cannabis craving and use in cannabis dependent adults under normal living conditions . Design Participants attended 10 supervised 30-min treadmill exercise sessions st and ardized using heart rate ( HR ) monitoring ( 60–70 % HR reserve ) over 2 weeks . Exercise sessions were conducted by exercise physiologists under medical oversight . Participants Sedentary or minimally active non-treatment seeking cannabis-dependent adults ( n = 12 , age 25±3 years , 8 females ) met criteria for primary cannabis dependence using the Substance Abuse module of the Structured Clinical Interview for DSM-IV ( SCID ) . Measurements Self-reported drug use was assessed for 1-week before , during , and 2-weeks after the study . Participants viewed visual cannabis cues before and after exercise in conjunction with assessment of subjective cannabis craving using the Marijuana Craving Question naire ( MCQ-SF ) . Findings Daily cannabis use within the run-in period was 5.9 joints per day ( SD = 3.1 , range 1.8–10.9 ) . Average cannabis use levels within the exercise ( 2.8 joints , SD = 1.6 , range 0.9–5.4 ) and follow-up ( 4.1 joints , SD = 2.5 , range 1.1–9.5 ) periods were lower than during the run-in period ( both P<.005 ) . Average MCQ factor scores for the pre- and post-exercise craving assessment s were reduced for compulsivity ( P = .006 ) , emotionality ( P = .002 ) , expectancy ( P = .002 ) , and purpose fulness ( P = .002 ) . Conclusions The findings of this pilot study warrant larger , adequately powered controlled trials to test the efficacy of prescribed moderate aerobic exercise as a component of cannabis dependence treatment . The neurobiological mechanisms that account for these beneficial effects on cannabis use may lead to underst and ing of the physical and emotional underpinnings of cannabis dependence and recovery from this disorder . Trial Registration Clinical Trials.gov NCT00838448 Young adults in college have high rates of marijuana use , abuse , and dependence . Web-based interventions are increasingly popular , but their dissemination exceeds empirical support . One popular but understudied program is The Marijuana eCHECKUP TO GO ( e-TOKE ) for Universities & Colleges ( San Diego State University Research Foundation , 2009 ) . The aim of the present study was to evaluate its short-term effectiveness in changing marijuana involvement and perceived norms in undergraduates . Participants were 317 undergraduates ( 52 % female , 78 % White ) who reported marijuana use within the month preceding baseline ; each was r and omly assigned to 1 of 4 conditions formed by crossing e-TOKE versus assessment only , with brief versus extensive baseline assessment ( to assess assessment reactivity ) . Thus , 161 ( 51 % ) received eTOKE ( 77 with extended baseline , 84 with brief baseline ) , and 156 ( 49 % ) received assessment -only control ( 85 with extended baseline , 71 with brief baseline ) . 1 month later , all participants reported on marijuana use , problems , abuse and dependence symptoms , and norms . Assessment reactivity analyses yielded no significant differences by assessment condition . Individuals completing the e-TOKE program reported less extreme descriptive norms ( ps < 0.01 ) but no decrease in marijuana use frequency , problems , abuse or dependence symptoms , or changes in injunctive norms ( ps > 0.10 ) . Thus , e-TOKE reduces perceptions of others ' use , but this study did not provide evidence for its utility in changing personal use and problem indicators in the short-term . More research with longer follow-ups is indicated , given the possibility that descriptive norms could mediate behavior change OBJECTIVE This study evaluated two brief personal feedback substance-use interventions for students m and ated to the Rutgers University Alcohol and Other Drug Assistance Program for Students ( ADAPS ) : ( 1 ) a brief motivational interview ( BMI ) intervention and ( 2 ) a written feedback-only ( WF ) intervention . A key question addressed by this study was whether there is a need for face-to-face feedback in the context of motivational interviewing to affect changes in substance-use behaviors or whether a written personal feedback profile is enough of an intervention to motivate students to change their substance use . METHOD The sample consisted of 222 students who were m and ated to ADAPS , were eligible for the study , and completed the 3-month follow-up assessment . Eligible students completed a baseline assessment from which a personal feedback profile was created . They were then r and omly assigned to the BMI or WF condition . Students were followed 3 months later . RESULTS Students in both interventions reduced their alcohol consumption , prevalence of cigarette and marijuana use , and problems related to alcohol and drug use between baseline and follow-up . There were no differences between the two intervention conditions in terms of any substance-use outcomes . CONCLUSIONS The results suggest that , under these circumstances and with these students , assessment and WF students changed similarly to those who had an assessment and WF within the context of a BMI . Given the fact that the former is less costly in terms of time and personnel , written profiles may be found to be a cost-effective means of reducing alcohol and drug use and related problems among low- to moderate-risk m and ated college students . More research is needed with m and ated students to determine the efficacy of feedback interventions and to isolate the effects of interventions from the effects of being caught and being reprim and ed to treatment One hundred and fifty five drug-dependent women in an urban hospital emergency room in Detroit , Michigan , were the subjects for this 3-year exploratory field study . Subjects were women who told the emergency room staff that while they wanted assistance with their presenting health problems , they wanted no assistance with their drug addiction . The women were r and omly assigned to either the experimental or control study group . Both groups received a pretest in the emergency room , a posttest between 8 and 12 weeks after their emergency room visit , and a follow-up test 6 months after the posttest . In addition , the experimental women were seen by project nurses , primarily in their homes , for a maximum of eight visits on a once-a-week basis . The experimental women were treated using " Personalized Nursing , " a nursing intervention model , which focused on providing assistance for client-identified concerns . It was hypothesized that interaction with the Personalized Nursing Intervention Model would be associated with : a decrease in daily drug cost and a decrease in perceived stress . Results show that while there were no differences between the study groups at the pretest interview , the experimental group reported a lower daily drug cost ( F(1 , 95 ) = 2.90 ; p = 0.09 ) , a lower daily heroin cost ( U = 165 ; p = .01 ) , less perceived stress ( F(1 , 84 ) = 3.00 ; p = .09 ) and emotional distress ( F(1 , 83 ) = 3.70 ; p = .06 ) than control subjects at the 8-week posttest . The experimental subjects also reported less perceived stress ( t(65 ) = -2.35 ; p = .02 ) at 6-month follow-up than control subjects . It was found that results could be improved if members of the experimental clients ' social networks were treated simultaneously and if project nurses were correctly utilizing the model . Implication s for substance abuse treatment programs are discussed . The encouraging results of this exploratory study warrant follow-up and replication Cannabis use adversely affects adolescents and interventions that are attractive to adolescents are needed . This trial compared the effects of a brief motivational intervention for cannabis use with a brief educational feedback control and a no- assessment control . Participants were r and omized into one of three treatment conditions : Motivational Enhancement Therapy ( MET ) , Educational Feedback Control ( EFC ) , or Delayed Feedback Control ( DFC ) . Those who were assigned to MET and EFC were administered a computerized baseline assessment immediately following r and omization and completed assessment s at the 3- and 12-month follow-up periods . Participants in the DFC condition were not assessed until the 3-month follow-up . Following the completion of treatment sessions , all participants were offered up to four optional individual treatment sessions aim ed at cessation of cannabis use . The research was conducted in high schools in Seattle , Washington . The participant s included 310 self-referred adolescents who smoked cannabis regularly . The main outcome measures included days of cannabis use , associated negative consequences , and engagement in additional treatment . At the 3-month follow-up , participants in both the MET and EFC conditions reported significantly fewer days of cannabis use and negative consequences compared to those in the DFC . The frequency of cannabis use was less in MET relative to EFC at 3 months , but it did not translate to differences in negative consequences . Reductions in use and problems were sustained at 12 months , but there were no differences between MET and EFC interventions . Engagement in additional treatment was minimal and did not differ by condition . Brief interventions can attract adolescent cannabis users and have positive impacts on them , but the mechanisms of the effects are yet to be identified Healthy Choices is a motivational interviewing intervention targeting multiple risk behaviors among HIV-positive youth . This study investigated the effects of this intervention program specifically on alcohol and marijuana use . Youth living with HIV ( n = 143 , mean age = 20.7 , 51.5 % male ) were recruited from four sites in the United States , and r and omly assigned to intervention or control conditions . The four-session intervention focused on two of three possible problem behaviors based on entry screening ; this study focused on 143 HIV-positive youth who received the intervention for substance use . At 15-month follow-up past-week alcohol use was significantly lower for intervention youth than control youth ( 39.7 % versus 53.6 % , χ2 = 2.81 , 0.05 < p < 0.01 ) ; developmental trajectory analysis demonstrated significant reductions in alcohol use , but more importantly the intervention was effective over time in significantly reducing the adolescent 's probability of being classified into the high-risk trajectory group . The intervention was less effective in reducing marijuana use This study investigated the efficacy of brief strategic family therapy ( BSFT ) with Hispanic behavior problem and drug using youth , an underrepresented population in the family therapy research literature . One hundred twenty-six Hispanic families with a behavior problem adolescent were r and omly assigned to 1 of 2 conditions : BSFT or group treatment control ( GC ) . Results showed that , compared to GC cases , BSFT cases showed significantly greater pre- to post-intervention improvement in parent reports of adolescent conduct problems and delinquency , adolescent reports of marijuana use , and observer ratings and self reports of family functioning . These results extend prior findings on the efficacy of family interventions to a difficult to treat Hispanic adolescent sample The increasing dem and for cannabis dependence treatment has led to the identification of significant gaps in the knowledge of effective interventions . A r and omized controlled trial of brief cognitive-behavioral interventions ( CBT ) for cannabis dependence was undertaken to address this issue . A total of 229 participants were assessed and allocated to either a 6-session CBT program , a single-session brief intervention , or a delayed-treatment control group . This paper demonstrates that individuals with cannabis use disorder will present for a brief intervention program . While they report similar patterns of cannabis use to nontreatment sample s , they report a range of serious health and psychosocial consequences . While they appear relatively socially stable , they typically demonstrated severe cannabis dependence and significantly elevated levels of psychological distress , with the most commonly cited reason for cannabis use being stress relief . There were clinical ly relevant gender differences among the sample . This study provides more evidence of the dem and for , and nature of issues relevant to , interventions for cannabis use disorders , and supports the need for further research into how best to assist individuals with these disorders We have examined whether practitioner ratings ( immediately post-intervention ) or other recorded characteristics of a single-session 1-hour motivational intervention were predictive of 3-month cannabis use outcome . In the context of a cluster r and omized trial involving 200 non help-seeking illegal drug users ( age range 16 - 20 ) , 105 were r and omized to the intervention , of whom 97 ( 92 % ) were interviewed for followup at 3 months , 96 of whom were current cannabis users at study entry . Six intervention characteristics and seven practitioner ratings as well as patterns of self-motivational statements were investigated in relation to substantial change in use , ( which was defined as cessation or reduction by more than 50 % ) . Both practitioner ratings post-session , and also the subject 's own elicited self-motivational statements , were found to be predictive of outcome 3 months later . The strongest predictor of substantial change , however , was simply whether change had been discussed during the session . On the basis of the above findings , it does indeed appear possible for outcome to be predicted by the motivational interviewing practitioner immediately following delivery of the intervention , on the basis of simple observations and ratings . This area warrants more specific study AIM To test whether a single session of Motivational Interviewing ( MI ) focussing on drinking alcohol , and cigarette and cannabis smoking , would successfully lead to reductions in use or problems . METHODS Naturalistic quasi-experimental study , in 162 young people ( mean age 17 years ) who were daily cigarette smokers , weekly drinkers or weekly cannabis smokers , comparing 59 receiving MI with 103 non-intervention assessment -only controls . MI was delivered in a single session by youth workers or by the first author . Assessment was made of changes in self-reported cigarette , alcohol , cannabis use and related indicators of risk and problems between recruitment and after 3 months by self-completion question naire . RESULTS 87 % of subjects ( 141 of 162 ) were followed up . The most substantial evidence of benefit was achieved in relation to alcohol consumption , with those receiving MI drinking on average two days per month less than controls after 3 months . Weaker evidence s of impact on cigarette smoking , and no evidence of impact on cannabis use , were obtained . CONCLUSIONS Evidence of effectiveness for the delivery of MI by youth workers in routine conditions has been identified . However , the extent of benefit is much more modest than previously identified in efficacy studies CONTEXT Drug abuse by people with severe mental disorder is a significant public health problem for which there is no empirically vali date d treatment . OBJECTIVE To evaluate the efficacy of a new behavioral treatment for drug abuse in this population : Behavioral Treatment for Substance Abuse in Severe and Persistent Mental Illness ( BTSAS ) . DESIGN Participants were r and omly assigned to 6 months of treatment in either BTSAS or a manualized control condition : Supportive Treatment for Addiction Recovery ( STAR ) . SETTING Treatment was conducted in community-based outpatient clinics and a Veterans Affairs medical center in Baltimore , Md. PARTICIPANTS Participants were 129 stabilized out patients meeting DSM criteria for drug dependence ( cocaine , heroin , or cannabis ) and serious mental illness : 39.5 % met DSM-IV criteria for schizophrenia or schizoaffective disorder ; 55.8 % , for major affective disorders ; and the remainder met criteria for severe and persistent mental illness and other Axis I disorders . INTERVENTIONS Both treatments were administered by trained health care professionals in small groups , twice a week for 6 months . The BTSAS program is a social learning intervention that includes motivational interviewing , a urinalysis contingency , and social skills training . The control condition , STAR , is a supportive group discussion treatment . Main Outcome Measure The primary outcome measure was urinalysis results from twice-weekly treatment sessions . RESULTS The BTSAS program was significantly more effective than STAR in percentage of clean urine test results , survival in treatment , and attendance at sessions . The BTSAS program also had significant effects on important community-functioning variables , including hospitalization ; money available for living expenses ; and quality of life . CONCLUSIONS The BTSAS program is an efficacious treatment . Further work needs to be done to increase the proportion of eligible patients who are able to become engaged in treatment AIM To test whether a single session of motivational interviewing ( discussing alcohol , tobacco and illicit drug use ) would lead successfully to reduction in use of these drugs or in perceptions of drug-related risk and harm among young people . DESIGN Cluster r and omized trial , allocating 200 young people in the natural groups in which they were recruited to either motivational interviewing ( n=105 ) or non-intervention education-as-usual control condition ( n=95 ) . SETTING Ten further education colleges across inner London . PARTICIPANTS Two hundred young people ( age range 16 - 20 years ) currently using illegal drugs , with whom contact was established through peers trained for the project . INTERVENTION The intervention was adapted from the literature on motivational interviewing in the form of a 1-hour single-session face-to-face interview structured by a series of topics . MEASUREMENTS Changes in self-reported cigarette , alcohol , cannabis and other drug use and in a range of drug-specific perceptions and other indicators of risk and harm . Measurement at recruitment and follow-up interview 3 months later . FINDINGS A good follow-up rate ( 89.5 % ; 179 of 200 ) was achieved . In comparison to the control group , those r and omized to motivational interviewing reduced their of use of cigarettes , alcohol and cannabis , mainly through moderation of ongoing drug use rather than cessation . Effect sizes were 0.37 ( 0.15 - 0.6 ) , 0.34 ( 0.09 - 0.59 ) and 0.75 ( 0.45 - 1.0 ) for reductions in the use of cigarettes , alcohol and cannabis , respectively . For both alcohol and cannabis , the effect was greater among heavier users of these drugs and among heavier cigarette smokers . The reduced cannabis use effect was also greater among youth usually considered vulnerable or high-risk according to other criteria . Change was also evident in various indicators of risk and harm , but not as widely as the changes in drug consumption . CONCLUSIONS This study provides the first substantial evidence of non-treatment benefit to be derived among young people involved in illegal drug use in receipt of motivational interviewing . The targeting of multiple drug use in a generic fashion among young people has also been supported BACKGROUND AND OBJECTIVES We assessed the feasibility of a new cognitive behavioral therapy ( CBT ) manual , plus transdermal patch nicotine replacement therapy ( NRT ) , to treat co-occurring nicotine and cannabis dependence . METHOD Seven of 12 ( 58.3 % ) adults with DSM-IV diagnoses of both nicotine and cannabis dependence completed 10 weeks of individual CBT and NRT . RESULTS Participants smoked 12.6 ± 4.9 tobacco cigarettes per day at baseline , which was reduced to 2.1 ± 4.2 at the end of treatment ( F[5 ] = 23.5 , p < .0001 ) . The reduction in cannabis use from 10.0 ± 5.3 inhalations per day at baseline to 8.0 ± 5.3 inhalations per day at 10 weeks was not significant ( F[5 ] = 1.12 , p = .37 ) . There was a significant decrease from the mean baseline Fagerstrom Test for Nicotine Dependence scores at weeks 4 , 6 , 8 , and 10 of treatment ( F[4 ] = 19.8 , p < .001 ) and mean Client Satisfaction Question naire scores were uniformly high ( 30.6 ± 1.9 ) . CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE A CBT plus NRT treatment program significantly reduced tobacco smoking but did not significantly reduce cannabis use in individuals with co-occurring nicotine and cannabis dependence . There was no compensatory increase in cannabis use following the reduction in tobacco smoking , suggesting that clinicians can safely pursue simultaneous treatment of co-occurring nicotine and cannabis dependence . The intervention was well-liked by the 7 of the 12 enrollees who completed the study Delay discounting is an index of impulsive decision-making and reflects an individual 's preference for smaller immediate rewards relative to larger delayed rewards . Multiple studies have indicated comparatively high rates of discounting among tobacco , alcohol , cocaine , and other types of drug users , but few studies have examined discounting among marijuana users . This report is a secondary analysis of data from a clinical trial that r and omized adults with marijuana dependence to receive one of four treatments that involved contingency management ( CM ) and cognitive-behavioral therapy interventions . Delay discounting was assessed with the Experiential Discounting Task ( Reynolds & Schiffbauer , 2004 ) at pretreatment in 93 participants and at 12 weeks posttreatment in 61 participants . Results indicated that higher pretreatment delay discounting ( i.e. , more impulsive decision-making ) significantly correlated with lower readiness to change marijuana use ( r = -0.22 , p = .03 ) and greater number of days of cigarette use ( r = .21 , p = .04 ) . Pretreatment discounting was not associated with any marijuana treatment outcomes . CM treatment significantly interacted with time to predict change in delay discounting from pre- to posttreatment ; participants who received CM did not change their discounting over time , whereas those who did not receive CM significantly increased their discounting from pre- to posttreatment . In this sample of court-referred young adults receiving treatment for marijuana dependence , delay discounting was not strongly related to treatment outcomes , but there was some evidence that CM may protect against time-related increases in discounting Sixty individuals seeking outpatient treatment for marijuana dependence were r and omly assigned to 1 of 3 treatments : motivational enhancement ( M ) , M plus behavioral coping skills therapy ( MBT ) , or MBT plus voucher-based incentives ( MBTV ) . In the voucher-based incentive program , participants earned vouchers exchangeable for retail items contingent on them su bmi tting cannabinoid-negative urine specimens . MBTV engendered significantly greater duration s of documented marijuana abstinence during treatment compared with MBT and M , and a greater percentage of participants in the MBTV group compared with the MBT or M groups were abstinent at the end of treatment . No significant differences in marijuana abstinence were observed between the MBT and M groups . The positive effects of the voucher program in this study support the utility of incentive-based interventions for the treatment of substance dependence disorders including marijuana dependence OBJECTIVE To determine whether the addition of cognitive behaviour therapy and motivational interviewing ( CBT/MI ) to st and ard alcohol and other drug ( AOD ) care improves outcomes for young people with comorbid depression and substance misuse . PARTICIPANTS AND SETTING Participants were young people with comorbid depression ( Kessler Psychological Distress Scale score ≥ 17 ) and substance misuse ( mainly alcohol and /or cannabis ) seeking treatment at two youth AOD services in Melbourne , Australia . The study was conducted between September 2006 and September 2008 . Sixty young people received CBT/MI in addition to st and ard care ( SC ) ( the SC+CBT/MI group ) and 28 received SC only ( the SC group ) . MAIN OUTCOME MEASURES Depressive symptoms and AOD use in the previous 30 days , measured at baseline and at 3-month and 6-month follow-up . RESULTS Compared with participants in the SC group , those in the SC+CBT/MI group showed significant reductions in depression and cannabis use and increased social contact and motivation to change substance use at 3-month follow-up . However , at 6-month follow-up , the SC group had achieved similar improvements to the CBT/MI group on these variables . All young people achieved significant improvements in functioning and quality of life variables over time , regardless of treatment group . No changes in AOD use were found in either group at 6-month follow-up . CONCLUSION The delivery of CBT/MI in addition to SC may achieve accelerated treatment gains in the short term BACKGROUND AND AIMS Several studies have found that brief interventions ( BIs ) for drug misuse have superior effectiveness to no-treatment controls . However , many health centers do not provide BIs for drug use consistently due to insufficient behavioral health staff capacity . Computerized BIs for drug use are a promising approach , but their effectiveness compared with in-person BIs has not been established . This study compared the effectiveness of a computerized brief intervention ( CBI ) to an in-person brief intervention ( IBI ) delivered by a behavioral health counselor . METHODS Two-arm r and omized clinical trial , conducted in two health centers in New Mexico , United States . Participants were 360 adult primary care patients with moderate-risk drug scores on the Alcohol , Smoking , and Substance Involvement Screening Test ( ASSIST ) who were r and omly assigned on a 1 : 1 basis to a computerized brief intervention ( CBI ) or to an in-person brief intervention ( IBI ) delivered by a behavioral health counselor . Assessment s were conducted at baseline and 3-month follow-up , and included the ASSIST and drug testing on hair sample s. RESULTS The IBI and CBI conditions did not differ at 3 months on global ASSIST drug scores [ b = -1.79 ; 95 % confidence interval ( CI ) = -4.37 , 0.80 ] or drug-positive hair tests [ odds ratio ( OR ) = 0.97 ; 95 % CI = 0.47 , 2.02 ] . There was a statistically significant advantage of CBI over IBI in substance-specific ASSIST scores for marijuana ( b = -1.73 ; 95 % CI = -2.91 , -0.55 ; Cohen 's d = 0.26 ; P = 0.004 ) and cocaine ( b = -4.48 ; 95 % CI = -8.26 , -0.71 ; Cohen 's d = 0.50 ; P = 0.021 ) at 3 months . CONCLUSIONS Computerized brief intervention can be an effective alternative to in-person brief intervention for addressing moderate drug use in primary care Cannabis is among the most frequently abused substances in the United States . Cognitive control is a contributory factor in the maintenance of substance-use disorders and may relate to treatment response . Therefore , we assessed whether cognitive-control-related neural activity before treatment differs between treatment-seeking cannabis-dependent and healthy individuals and relates to cannabis-abstinence measures during treatment and 1-year follow-up . Cannabis-dependent males ( N=20 ) completed a functional magnetic resonance imaging ( fMRI ) cognitive-control ( Stroop ) task before a 12-week r and omized controlled trial of cognitive – behavioral therapy and /or contingency management . A healthy-comparison group ( N=20 ) also completed the fMRI task . Cannabis use was assessed by urine toxicology and self-report during treatment , and by self-report across a 1-year follow-up period ( N=18 ) . The cannabis-dependent group displayed diminished Stroop-related neural activity relative to the healthy-comparison group in multiple regions , including those strongly implicated in cognitive-control and addiction-related processes ( eg , dorsolateral prefrontal cortex and ventral striatum ) . The groups did not differ significantly in response times ( cannabis-dependent , N=12 ; healthy-comparison , N=14 ) . Within the cannabis-dependent group , greater Stroop-related activity in regions including the dorsal anterior cingulate cortex was associated with less cannabis use during treatment . Greater activity in regions including the ventral striatum was associated with less cannabis use during 1-year posttreatment follow-up . These data suggest that lower cognitive-control-related neural activity in classic ‘ control ’ regions ( eg , dorsolateral prefrontal cortex and dorsal anterior cingulate ) and classic ‘ salience/reward/learning ’ regions ( eg , ventral striatum ) differentiates cannabis-dependent individuals from healthy individuals and relates to less abstinence within-treatment and during long-term follow-up . Clinical ly , results suggest that treatment development efforts that focus on enhancing cognitive control in addition to abstinence may improve treatment outcomes in cannabis dependence Young marijuana abusers rarely seek treatment themselves and are difficult to engage in treatment when referred by social agencies . To evaluate treatment engagement strategies in this population , 65 young probation-referred marijuana abusers were r and omly assigned to either three-session motivational enhancement therapy ( MET alone ) or three-session MET plus contingency management ( MET/CM ) , with vouchers for treatment attendance . A significantly higher number of participants in the MET/CM condition completed the three-session intervention as compared with MET alone . Participants in both conditions reported significant reductions in marijuana use and improvement in legal problems . These findings suggest that young marijuana abusers benefit from scientifically vali date d treatments This study 's aims were ( a ) to investigate the feasibility of a school-based motivational enhancement therapy ( MET ) intervention in voluntarily attracting adolescents who smoke marijuana regularly but who are not seeking formal treatment and ( b ) to evaluate the efficacy of the intervention in reducing marijuana use . Ninety-seven adolescents who had used marijuana at least 9 times in the past month were r and omly assigned to either an immediate 2-session MET intervention or to a 3-month delay condition . Two thirds of the sample characterized themselves as in the precontemplation or contemplation stages of change regarding marijuana use . Participants ' marijuana use and associated negative consequences were assessed at baseline and at a 3-month follow-up . Analyses revealed that both groups significantly reduced marijuana use at the 3-month follow-up ( p = .001 ) ; however , no between-group differences were observed . Despite the absence of a clear effect of MET , this study demonstrated that adolescents could be attracted to participate in a voluntary marijuana intervention that holds promise for reducing problematic levels of marijuana use AIMS Achieving abstinence in the treatment of marijuana dependence has been difficult . To date the most successful treatments have included combinations of motivation enhancement treatment ( MET ) plus cognitive-behavioral coping skills training ( CBT ) and /or contingency management ( ContM ) approaches . Although these treatment approaches are theoretically based , their mechanisms of action have not been explored fully . The purpose of the present study was to explore mechanisms of behavior change from a marijuana treatment trial in which CBT and ContM were evaluated separately and in combination . DESIGN A dismantling design was used in the context of a r and omized clinical trial . SETTING The setting was an out-patient treatment research facility located in a university medical center . PARTICIPANTS Participants were 240 adult marijuana smokers , meeting criteria for cannabis dependence . INTERVENTIONS Participants were assigned to one of four 9-week treatment conditions : a case management control condition , MET/CBT coping skills training , ContM and MET/CBT + ContM. MEASUREMENTS Outcome measures were total 90-day abstinence , recorded every 90 days for 12 months post-treatment . FINDINGS Regardless of treatment condition , abstinence in near-term follow-ups was predicted most clearly by abstinence during treatment , but long-term abstinence was predicted by use of coping skills and especially by post-treatment self-efficacy for abstinence . CONCLUSIONS It was concluded that the most efficacious treatments for marijuana dependence are likely to be those that increase self-efficacy AIMS To evaluate the agreement between adolescent self-reported cannabis use , " on-site " qualitative urine screening , and quantitative laboratory testing . DESIGN A cross-sectional study of intake and follow-up data from 248 adolescents entering substance abuse treatment for cannabis use disorders ( abuse or dependence ) . This is part of the multi-site cooperative agreement Cannabis Youth Treatment study . SETTING Data collected from adolescents r and omly assigned to one of five outpatient treatments at four sites : Operation PAR , Inc. , Florida ; Chestnut Health Systems , Illinois ; University of Connecticut Health Center , Connecticut ; and Children 's Hospital of Philadelphia , Pennsylvania . PARTICIPANTS The data represent 248 unique individuals from a sample of 297 adolescents ranging in age from 12 to 18 years . MEASUREMENTS Prevalence , agreement , kappa , sensitivity , specificity , positive and negative predictive value . FINDINGS The self-report rates were higher at intake than either urine test ( 82.4 % vs. 77.0 % vs. 52.7 % ) , but both lower and higher at the 3-month follow-up ( 55.5 % vs. 70.0 % vs. 47.3 % ) and 6-month follow-up ( 60.2 % vs. 73.5 % vs. 55.8 % ) . The disagreements went in both directions and the kappa coefficients were only in the moderate range ( 0.4 ) . Over two-thirds of these frequent cannabis users tested positive when they said they had not used in 1 week and one-third tested positive even though they said it had been more than 4 weeks since last use . CONCLUSIONS The findings suggest both the advantages of multiple sources of information and the need for further work on the latency of cannabis metabolites in clinical population BACKGROUND Frequent cannabis users are at high risk of dependence , still most ( near ) daily users are not dependent . It is unknown why some frequent users develop dependence , whereas others do not . This study aims to identify predictors of first-incidence DSM-IV cannabis dependence in frequent cannabis users . METHODS A prospect i ve cohort of frequent cannabis users ( aged 18 - 30 , n=600 ) with baseline and two follow-up assessment s ( 18 and 36 months ) was used . Only participants without lifetime diagnosis of DSM-IV cannabis dependence at baseline ( n=269 ) were selected . Incidence of DSM-IV cannabis dependence was established using the Composite International Diagnostic Interview version 3.0 . Variables assessed as potential predictors of the development of cannabis dependence included sociodemographic factors , cannabis use variables ( e.g. , motives , consumption habits , cannabis exposure ) , vulnerability factors ( e.g. , childhood adversity , family history of mental disorders or substance use problems , personality , mental disorders ) , and stress factors ( e.g. , life events , social support ) . RESULTS Three-year cumulative incidence of cannabis dependence was 37.2 % ( 95 % CI=30.7 - 43.8 % ) . Independent predictors of the first incidence of cannabis dependence included : living alone , coping motives for cannabis use , number and type of recent negative life events ( major financial problems ) , and number and type of cannabis use disorder symptoms ( impaired control over use ) . Cannabis exposure variables and stable vulnerability factors did not independently predict first incidence of cannabis dependence . CONCLUSIONS In a high risk population of young adult frequent cannabis users , current problems are more important predictors of first incidence cannabis dependence than the level and type of cannabis exposure and stable vulnerability factors An initial efficacy test of an innovative behavioral outpatient treatment model for adolescents with problematic use of marijuana enrolled 69 adolescents , aged 14 - 18 , and r and omly assigned them to one of two treatment conditions . Both conditions received individualized Motivational Enhancement and Cognitive Behavioral Therapy ( MET/CBT ) and a twice-weekly drug-testing program . The experimental contingency management condition involved a clinic-delivered , abstinence-based incentive program , and weekly behavioral parent training sessions that included a parent-delivered , abstinence-based , substance monitoring contract . The comparison condition included an attendance-based incentive program , and weekly psychoeducational parent sessions . Follow-up assessment s were performed at 3 , 6 , and 9 months post-treatment . The experimental condition showed greater marijuana abstinence during treatment , e.g. , 7.6 vs. 5.1 continuous weeks and 50 % vs. 18 % achieved > or = 10 weeks of abstinence . Improvements were found in parenting and youth psychopathology across treatment conditions , and improvements in negative parenting uniquely predicted post-treatment abstinence . The outcomes observed in the experimental condition are consistent with adult substance-dependence treatment literature , and suggest that integrating CM abstinence-based approaches with other empirically based outpatient interventions provides an alternative and efficacious treatment model for adolescent substance abuse/dependence . Replication and continued development of more potent interventions remain needed to further advance the development of effective substance abuse treatments for adolescents BACKGROUND Patients who experience the onset of psychotic illness with a comorbid diagnosis of cannabis dependence experience poor clinical outcomes . Few studies have identified interventions that reduce cannabis use and improve clinical outcome in this population . AIMS We undertook a multi-center , r and omized controlled trial of a group psychological intervention for psychosis with comorbid cannabis dependence to determine whether there was any impact on cannabis use symptoms , global functioning , insight , attitudes to treatment and subjective quality of life . METHOD Across three centers , we compared a group psychological intervention , based on cognitive behavioral therapy and motivational interviewing , with treatment as usual among patients experiencing their first psychotic episode or early in the course of psychotic illness . Substance misuse and indices of clinical outcome were assessed at baseline , 3months and 1year . RESULTS At 3month and 1year follow-ups , there was no evidence for an intervention effect on cannabis use , symptoms , global functioning insight or attitude to treatment . However , the intervention improved subjective quality of life at 3months and this effect was sustained at 1year . CONCLUSIONS Over the early phase of psychotic illness , group psychological interventions for those with comorbid cannabis dependence improved subjective quality of life . However , this was not associated with reduction in use of cannabis or improvement in clinical outcomes AIM To analyze data from a r and omized clinical trial to determine the cost-effectiveness of using contingency management ( CM ) and motivational/skills building therapy ( motivational enhancement therapy/cognitive-behavioral therapy : MET/CBT ) to treat young adults with marijuana dependence . PARTICIPANTS , DESIGN AND MEASUREMENTS : A total of 136 marijuana-dependent young adults , all referred by the criminal justice system , were r and omized to one of four treatment conditions : MET/CBT with CM , MET/CBT without CM , drug counseling ( DC ) with CM and DC without CM . Patient outcome measures include the longest duration of confirmed marijuana abstinence ( LDA ) during treatment and the total number of marijuana-free urine specimens provided during treatment . Costs were collected retrospectively from the provider and include the costs of therapy , patient drug testing , and those associated with the incentives component ( value of vouchers , time to administer the voucher system ) . SETTING Out-patient substance abuse clinic in New Haven , Connecticut , USA . FINDINGS Which treatment is the most cost-effective depends on the threshold values of an additional week of LDA or an additional marijuana-free urine specimen . For example , the most effective treatment , MET/CBT with CM , was also the most cost-effective treatment at the highest threshold values , while the least effective treatment , DC , was the most cost-effective at the lowest values . Because consensus threshold values for these patient outcomes do not exist , results are presented showing the ranges of values over which each treatment would be considered cost-effective compared to the others . Acceptability curves are presented to show the decision uncertainty associated with these ranges . The results are shown to be robust to ( i ) sensitivity analyses on several key cost parameters and ( ii ) patient outcomes measured during the 6-month follow-up period . CONCLUSIONS This study uses incremental cost-effectiveness ratios and acceptability curves to shed light on the relative cost-effectiveness of four interventions for treating young adults with marijuana dependence . Given the relatively small and specialized nature of our study sample , and the fact that we examined a CM procedure with a single reinforcement schedule , additional studies are warranted to determine the reliability and generalizability of our results both to alternative marijuana-using population s and to CM procedures with alternative incentive parameters . Nevertheless , the relative durability of effects of MET/CBT compared to DC through the 6-month follow-up , and its cost-effectiveness over a comparatively wide range of threshold values , underscores the promise of this approach AIMS Recent findings regarding the prevalence of marijuana dependence and associated consequences indicate the need for empirically vali date d treatments for this population . The Marijuana Treatment Project ( MTP ) was a multi-site study of two treatments for adults with marijuana dependence . DESIGN Participants ( N= 450 ) were r and omly assigned to one of three conditions at each of three sites : 1 ) a 9-session cognitive behavioral treatment ( CBT ) with motivational enhancement therapy ( MET ) and case management ( CM ) components ; 2 ) a 2-session MET intervention ; or 3 ) a delayed treatment control ( DTC ) . SETTING The study was conducted in outpatient drug treatment clinics in three U.S. cities . PARTICIPANTS Participants were individuals aged 18 or over who met diagnostic criteria for cannabis dependence and who voluntarily presented for treatment . MEASUREMENT Study variables included DSM-IV dependence criteria , timeline follow-back assessment of drug use , Addiction Severity Index composite scores , and problems related to marijuana use . FINDINGS Participants were daily users , who smoked marijuana multiple times per day , and had been doing so for more than 15 years . They reported multiple dependence symptoms and negative consequences related to marijuana use . Approximately 32 % of the sample was female , and 30 % of the sample was either Hispanic ( 17 % ) , African American ( 12 % ) , or of mixed racial background s ( 1 % ) . CONCLUSIONS The multi-site nature of the MTP allowed for the recruitment of a more ethnically and gender diverse sample than had been studied previously but there were few differences in the clinical characteristics of participants at the geographically and sociodemographically diverse study sites OBJECTIVE The study examined the association between fidelity of programs to the assertive community treatment model and client outcomes in dual disorders programs . METHODS Assertive community treatment programs in the New Hampshire dual disorders study were classified as low-fidelity programs ( three programs ) or high-fidelity programs ( four programs ) based on extensive longitudinal process data . The study included 87 clients with a dual diagnosis of severe mental illness and a comorbid substance use disorder . Sixty-one clients were in the high-fidelity programs , and 26 were in the low-fidelity programs . Client outcomes were examined in the domains of substance abuse , housing , psychiatric symptoms , functional status , and quality of life , based on interviews conducted every six months for three years . RESULTS Clients in the high-fidelity assertive community treatment programs showed greater reductions in alcohol and drug use and attained higher rates of remission from substance use disorders than clients in the low-fidelity programs . Clients in high-fidelity programs had higher rates of retention in treatment and fewer hospital admissions than those in low-fidelity programs . No differences between groups were found in length of hospital stays and other residential measures , psychiatric symptoms , family and social relations , satisfaction with services , and overall life satisfaction . CONCLUSIONS Faithful implementation of , and adherence to , the assertive community treatment model for persons with dual disorders was associated with superior outcomes in the substance use domain . The findings underscore the value of measures of model fidelity , and they suggest that local modifications of the assertive community treatment model or failure to comply with it may jeopardize program success Ninety cannabis-dependent adults seeking treatment were r and omly assigned to receive cognitive-behavioral therapy , abstinence-based voucher incentives , or their combination . Treatment duration was 14 weeks , and outcomes were assessed for 12 months posttreatment . Findings suggest that ( a ) abstinence-based vouchers were effective for engendering extended periods of continuous marijuana abstinence during treatment , ( b ) cognitive-behavioral therapy did not add to this during-treatment effect , and ( c ) cognitive-behavioral therapy enhanced the posttreatment maintenance of the initial positive effect of vouchers on abstinence . This study extends the literature on cannabis dependence , indicating that a program of abstinence-based vouchers is a potent treatment option . Discussion focuses on the strengths of each intervention , the clinical significance of the findings , and the need to continue efforts toward development of effective interventions STUDY OBJECTIVE Brief interventions ( BI ) for alcohol misuse and recently for marijuana use for emergency department patients have demonstrated effectiveness . We report a 12-month outcome data of a r and omized controlled trial of emergency department ( ED ) patients using a novel model of BI that addresses both alcohol and marijuana use . METHODS ED research assistants recruited adult patients who admitted alcohol use in the last month , and marijuana use in the last year . In the ED , patients received an assessment of alcohol and marijuana use and were r and omized to treatment ( n=249 ) or st and ard care ( n=266 ) . Treatment consisted of two sessions of BI . At 3 and 12months , both groups had an assessment of alcohol and marijuana use and negative consequences of use . RESULTS 515 patients were r and omized . We completed a 12-month follow-up assessment s on 83 % of those r and omized . Measures of binge drinking and conjoint marijuana and alcohol use significantly decreased for the treatment group compared to the st and ard care group . At 12-month binge alcohol use days per month in the treatment group were ( M=0.72:95 % CI=0.36 - 1.12 ) compared to st and ard care group ( M=1.77:95 % CI=1.19 - 1.57 ) Conjoint use days in the treatment group ( M=1.25.1:95 % CI=0.81 - 1.54 ) compared to st and ard care group ( M=2.16:95 % CI=1.56 - 2.86 ) . No differences in negative consequences or injuries were seen between the treatment and st and ard care groups . CONCLUSIONS BI for alcohol and marijuana decreased binge drinking and conjoint use in our treatment group . BI appears to offer a mechanism to reduce risky alcohol and marijuana use among ED patients but expected reductions in consequences of use such as injury were not found 12months after the ED visit BACKGROUND Motives for use have been identified as important predictors of substance use and related problems ; however , little is known about how motives for use change following an intervention and how this change may impact future substance use behaviors . The present study sought to describe change in motives following an intervention for marijuana-dependent adults . Furthermore , investigators examined change in motives as a predictor of treatment outcome . METHOD The study r and omized 74 adults to one of two conditions : both of which received 9-sessions base treatment of cognitive behavioral therapy and motivational enhancement therapy and had access to additional sessions of cognitive behavioral treatment on an as-needed basis . The experimental condition received two additional " check-ups " during the course of follow-up . RESULTS Significant decreases in reported frequency of motives used were observed following treatment . Changes in Expansion and Coping were associated with differential treatment outcomes . Decreases in Expansion were associated with poorer treatment outcome , while decreases in Coping were associated with better treatment outcome . CONCLUSIONS The relationship between expansion motives and outcomes was paradoxical . Although there were some inconsistencies in the findings , the results regarding the coping motive were consistent with hypotheses and may have important implication s for treatment BACKGROUND When excessive cannabis consumption occurs in adolescence , the adverse consequences extend into adulthood . Interventions by GPs are effective in preventing harm associated with alcohol use . Similar interventions have potential in addressing cannabis use . AIM To develop and pilot test a brief intervention targeting excessive cannabis use ( defined as > or = 1x/week ) in young people in primary care . DESIGN OF THE STUDY Pilot intervention trial . SETTING Seven family practice s in Switzerl and . METHOD The team collaborated with GPs and young people to develop the intervention . Seven GPs piloted its use in their consultations . Patients aged 15 to 24 years consulting for any health problem were recruited before the consultation . Cannabis use , other substance use , and their psychosocial correlates were assessed with a short confidential question naire administered before the consultation and 1 month later . GPs , staff , and patients were asked to comment on the study and its feasibility . RESULTS Of 81 young people invited to participate , 78 ( 70 % female ) agreed ( participation rate : 96 % ) . One in seven ( 13.2 % , 95 % confidence interval = 7.5 % to 18.9 % ) used cannabis at least once a week . Data at 1 month were available for 42 % who had provided email contact details and 91 % of those who had provided their mobile phone number ( 63 % overall ) . In most cases , the intervention lasted no more than 5 minutes . Comments from participants added favourable data towards the feasibility of the study . CONCLUSION This pilot study provides a solid base on which to build a r and omised trial of a brief intervention addressing cannabis use in young people consulting in family practice AIMS To assess the effectiveness of a motivational interview among hospitalized psychiatric patients with comorbid substance use disorder in reducing alcohol and other drug ( AOD ) use . DESIGN Subjects were assigned r and omly to receive an individual motivational interview ( n=79 ) or a self-help booklet ( control condition ; n=81 ) . SETTING Subjects were volunteers recruited from a major public psychiatric hospital . PARTICIPANTS Subjects met abuse or dependence criteria on the structured clinical interview for diagnosis ( SCID ) for alcohol , cannabis or amphetamine or they reported hazardous use during the last month of one or more of these drug types on the opiate treatment index ( OTI ) . INTERVENTION Either one 30 - 45-minute motivational interview or brief advice . MEASUREMENTS The SCID and OTI were the main measures . FINDINGS There was a modest short-term effect of the motivational interview on an aggregate index of alcohol and other drug use ( polydrug use on the OTI ) . Cannabis use remained high among the sample over the 12-month follow-up period . CONCLUSION Although motivational interviewing appears feasible among in- patients in psychiatric hospital with comorbid substance use disorders , more extensive interventions are recommended , continuing on an out-patient basis , particularly for cannabis use Men ( n = 161 ) and women ( n = 51 ) seeking treatment for marijuana use were r and omly assigned to either a relapse prevention ( RP ; G.A. Marlatt & J.R. Gordon , 1985 ) or a social support ( SSP ) group discussion intervention . Data collected for 12 months posttreatment revealed substantial reductions in frequency of marijuana use and associated problems . There were no significant differences between the cognitive-behavioral RP intervention and the SSP group discussion conditions on measures of days of marijuana use , related problems , or abstinence rates . Men in the RP condition were more likely than men in the SSP condition to report reduced use without problems at 3-month follow-up . Posttreatment increases in problems associated with alcohol did not appear to relate to reduced marijuana use . Results are discussed in terms of the need for further research with marijuana-dependent adults and the efficacy of RP The increasing dem and for treatment for cannabis dependence in Australia and internationally has led to the identification of significant gaps in knowledge of effective interventions . A r and omized controlled trial of brief cognitive-behavioral interventions ( CBT ) for cannabis dependence was undertaken to address this issue . A total of 229 participants were assessed and r and omly assigned to either a six-session CBT program ( 6CBT ) , a single-session CBT intervention ( 1CBT ) , or a delayed-treatment control ( DTC ) group . Participants were assisted in acquiring skills to promote cannabis cessation and maintenance of abstinence . Participants were followed-up a median of 237 days after last attendance . Participants in the treatment groups reported better treatment outcomes than the DTC group . They were more likely to report abstinence , were significantly less concerned about their control over cannabis use , and reported significantly fewer cannabis-related problems than those in the DTC group . Those in the 6CBT group also reported more significantly reduced levels of cannabis consumption than the DTC group . While the therapist variable had no effect on any outcome , a secondary analysis of the 6CBT and 1CBT groups showed that treatment compliance was significantly associated with decreased dependence and cannabis-related problems . This study supports the attractiveness and effectiveness of individual CBT interventions for cannabis use disorders and the need for multisite replication trials AIMS The Marijuana Treatment Project , a large multi-site r and omized clinical trial , compared a delayed treatment control condition with a brief ( two-session ) and extended ( nine-session ) multi-component treatment among 450 marijuana-dependent participants . In this report we present treatment process data , including the fidelity of treatment delivery in the three community-based treatment setting s as well as the relationships between treatment process and outcome . DESIGN Independent evaluations of clinician adherence and competence ratings were made based on 633 videotaped sessions from 163 participants . Relationships between clinician adherence and competence , ratings of the working alliance and marijuana treatment outcomes were evaluated . FINDINGS Protocol treatments were implemented with strong fidelity to manual specifications and with few significant differences in adherence and competence ratings across sites . In the brief two-session treatment condition , only the working alliance was associated significantly with frequency of marijuana use , but in the extended treatment therapist ratings of working alliance predicted outcomes , as did the interaction of alliance and curvilinear adherence . CONCLUSIONS Behavioral treatments for marijuana use were delivered in community setting s with good fidelity . Participant and therapist working alliance scores were associated significantly with improved marijuana use outcomes in a brief behavioral treatment for adults with marijuana dependence . In extended treatment the therapist ratings of working alliance were associated with more positive outcome . However , in that treatment there was also a significant interaction between alliance and curvilinear adherence Despite emerging evidence of the efficacy of psychotherapies for marijuana dependence , variability in outcome exists . This study examined the role of anxiety on treatment involvement and outcome . Four questions were examined : ( 1 ) Is greater anxiety associated with greater impairment at baseline ? ( 2 ) Is baseline anxiety related to greater marijuana use and problems following treatment ? ( 3 ) Does adding cognitive-behavioral therapy ( CBT ) to motivation enhancement therapy ( MET ) reduce anxiety relative to MET alone ; ( 4 ) Are reductions in anxiety associated with better outcomes ? The sample comprised 450 marijuana-dependent patients in the Marijuana Treatment Project . Marijuana use and anxiety were measured at pretreatment and 4- and 9-month follow-ups . At baseline , anxiety was linked to more marijuana-related problems . CBT was associated with less anxiety at follow-up compared to MET alone . Reductions in anxiety were related to less marijuana use . In fact , reduction in anxiety from baseline to 4-month follow-up was associated with less marijuana use at 9 months , but reduction in marijuana use did not predict subsequent anxiety . Data suggest that anxiety is an important variable that deserves further attention in marijuana-dependence treatment The aim of this study was to evaluate the efficacy of a brief motivational enhancement therapy in reducing cannabis use and cannabis-related problems in a population of non-treatment-seeking adolescent cannabis users . In a r and omized controlled trial , 40 young people ( aged 14 - 19 years ) were r and omly assigned to either a two-session brief intervention or a 3-month delayed-treatment control condition . The intervention consisted of a detailed assessment and a session of motivational enhancement therapy . An additional optional discussion of skills for reducing or quitting cannabis use was offered if a participant was interested in discussing these issues . Primary outcome measures were changes in days of cannabis use , mean quantity of cannabis used weekly , and number of Diagnostic and Statistical Manual of Mental Disorders , Fourth Edition dependence symptoms reported . Significantly greater reductions on these measures were found in the Adolescent Cannabis Check-up group at 3-month follow-up . Between-group effect sizes were moderate . The approach is acceptable to participants and merits further evaluation with this difficult to reach population The present study evaluates the efficacy of a brief intervention for cannabis users . A r and omized controlled trial compared 3 conditions : 4 weekly individual sessions of motivational interviewing and relapse prevention over 1 month ( 1MIRP ) ; the same 4 sessions over 3 months ( 3MIRP ) , and delayed treatment control ( DTC ) . The short term impact of each intervention was followed up 4 months after r and omization . Participants were 160 highly educated adults with a long history of frequent cannabis use . Both treatments showed better results than the DTC , and for primary outcomes ( i.e. , cannabis consumption ) there was no difference between treatments , while the 3MIRP scheme showed greater efficacy in reducing dependence symptoms and other drug use according to the ASI drug subscale . There was a tendency for the longer treatment to have better outcomes , regardless of intensity , although the waiting list did have some positive effect . The cohort needs to be followed up for a longer period in order to ascertain whether changes are maintained over time BACKGROUND To meet the treatment needs of the growing number of adolescents who seek help for cannabis use problems , new or supplementary types of treatment are needed . We investigated whether multidimensional family therapy ( MDFT ) was more effective than cognitive behavioral therapy ( CBT ) in treatment-seeking adolescents with a DSM-IV cannabis use disorder in The Netherl and s. METHODS One hundred and nine adolescents participated in a r and omized controlled trial , with study assessment s at baseline and at 3 , 6 , 9 and 12 months following baseline . They were r and omly assigned to receive either outpatient MDFT or CBT , both with a planned treatment duration of 5 - 6 months . Main outcome measures were cannabis use , delinquent behavior , treatment response and recovery at one-year follow-up , and treatment intensity and retention . RESULTS MDFT was not found to be superior to CBT on any of the outcome measures . Adolescents in both treatments did show significant and clinical ly meaningful reductions in cannabis use and delinquency from baseline to one-year follow-up , with treatment effects in the moderate range . A substantial percentage of adolescents in both groups met the criteria for treatment response at month 12 . Treatment intensity and retention was significantly higher in MDFT than in CBT . Post hoc subgroup analyses suggested that high problem severity subgroups at baseline may benefit more from MDFT than from CBT . CONCLUSIONS The current study indicates that MDFT and CBT are equally effective in reducing cannabis use and delinquent behavior in adolescents with a cannabis use disorder in The Netherl and OBJECTIVE Marijuana is the most frequently reported illicit substance used on college campuses . Despite the prevalence , few published intervention studies have focused specifically on addressing high-risk marijuana use on college campuses . The present study evaluated the efficacy of an in-person brief motivational enhancement intervention for reducing marijuana use and related consequences among frequently using college students . METHOD Participants included 212 college students from 2 campuses who reported frequent marijuana use ( i.e. , using marijuana at least 5 times in the past month ) . Participants completed Web-based screening and baseline assessment s and upon completion of the baseline survey were r and omized to either an in-person brief intervention or an assessment control group . Follow-up assessment s were completed approximately 3 and 6 months post-baseline . Marijuana use was measured by number of days used in the past 30 days , typical number of joints used in a typical week in the last 60 days , and marijuana-related consequences . RESULTS Results indicated significant intervention effects on number of joints smoked in a typical week and a trend toward fewer marijuana-related consequences compared with the control group at 3-month follow-up . CONCLUSION This study provides preliminary data on short-term effects of a focused marijuana intervention for college students at reducing marijuana use during the academic quarter Two manually guided brief interventions were evaluated with a r and omized , controlled trial . Adolescents ( aged 13 - 17 years ) suspected of abusing alcohol and other drugs and their parent were r and omly assigned to receive either a 2-session adolescent only ( BI-A ) , 2-session adolescent and additional parent session ( BI-AP ) , or assessment only control condition ( CON ) . Adolescents were identified in a school setting , and the intervention was delivered by trained counselors . Outcome analyses ( N = 284 ; 90 % of those enrolled ) of relative change ( from intake to 12 months ) and absolute status ( at 12 months ) revealed a general pattern of reductions in drug use behaviors , particularly with the cannabis outcome measures , in both active conditions ( BI-A and BI-AP ) . Students in the control condition showed worse outcome compared with the BI-A and BI-AP groups . Among the 4 mediating variables measured at 6 months , use of additional services , motivation to change , and parenting practice s had significant influences on 12-month outcome ; problem-solving skills approached significance as a mediator . The potential value of a brief intervention for drug abusing adolescents is discussed AIMS To evaluate the construct and predictive validity of six different subtyping classifications selected on the basis of their empirical support in the literature on adolescent substance abuse . METHODS Typological data were collected from a heterogeneous sample of 600 adolescents presenting for marijuana treatment . The classification schemes were gender , onset age , family history , externalizing disorders , internalizing disorders and temperament . Subgroups were compared in terms of substance use frequency , substance abuse problems , social support for substance use , family conflict , school problems and negative peer associations . RESULTS Each of the categorical classification schemes differentiated subtypes significantly on some or all of the construct validation measures after controlling for demographic factors , thereby indicating that each has valuable explanatory power from a theoretical perspective . Externalizing disorders , onset age , difficult temperament and internalizing disorders continued to add unique variance to discrimination after the effects of the other subtypes had been removed . At 12-month follow-up there were no differences between subtypes on substance use frequency , but adolescents with higher levels of externalizing disorders and internalizing disorders continued to experience more substance use problems . CONCLUSION Categorical subtypes may have particular relevance to the development of treatment interventions as well as prevention measures This study tested the ability of sets of demographic , socioeconomic , marijuana use/abuse , psychological distress , and self-efficacy variables to predict posttreatment indices of marijuana intake and problems related to use . Subjects were 167 adults who participated in one of two outpatient treatments for marijuana dependence and completed the 3- , 6- , and 12-month posttreatment follow-ups . Only pretreatment marijuana quantity-frequency of intake and self-efficacy variables made significant and consistent contributions to the regression equations predicting posttreatment frequency of use . In contrast , socioeconomic and severity of abuse indicators predicted posttreatment marijuana-related problems . Contrary to social cognitive theory ( B and ura , 1986 ) , there was no evidence that self-efficacy mediated the effects of other predictors . Results are discussed in terms of the specificity of predictor- outcome relationships and the need for improvements in self-efficacy measurement Substance-dependent patients ( N=29 ) living with a family member other than a spouse were r and omly assigned to equally intensive treatments consisting of either ( a ) Behavioral Family Counseling ( BFC ) plus Individual-Based Treatment ( IBT ) or ( b ) IBT alone . Outcome data were collected at baseline , post-treatment , and at 3- and 6-month follow-up . BFC patients remained in treatment significantly longer than IBT patients . BFC patients improved significantly from baseline at all time periods on all outcomes studied , and had a medium effect size reflecting better primary outcomes of increased abstinence and reduced substance use than IBT patients . For secondary outcomes of reduced negative consequences and improved relationship adjustment , both BFC and IBT patients improved significantly and to an equivalent extent . The present results show BFC is a promising method for retaining patients in treatment , increasing abstinence , and reducing substance use . These results also provide support for larger scale , r and omized trials examining the efficacy of behavioral family counseling for patients living with family members beyond spouses OBJECTIVES This r and omized controlled study compared acceptance and commitment therapy ( ACT ) , cognitive-behavioral therapy ( CBT ) , and a control group . METHOD The participants were 50 incarcerated women diagnosed with current substance use disorder . Two psychologists carried out pre- and posttreatment assessment and a 6-month follow-up assessment using the following instruments : Anxiety Sensitivity Index , Addiction Severity Index-6 , Mini International Neuropsychiatric Interview , and Acceptance and Action Question naire . RESULTS The study shows that the women who received treatment benefited differentially from the interventions . At posttreatment , CBT was more effective than ACT in reducing anxiety sensitivity ; however , at follow-up , ACT was more effective than CBT in reducing drug use ( 43.8 vs. 26.7 % , respectively ) and improving mental health ( 26.4 % vs. 19.4 % , respectively ) . CONCLUSION ACT may be an alternative to CBT for treatment of drug abuse and associated mental disorders . In fact , at long-term , ACT may be more appropriate than CBT for incarcerated women who present serious problems Marijuana-dependent young adults ( N = 136 ) , all referred by the criminal justice system , were r and omized to 1 of 4 treatment conditions : a motivational/skills-building intervention ( motivational enhancement therapy/cognitive-behavioral therapy ; MET/CBT ) plus incentives contingent on session attendance or su bmi ssion of marijuana-free urine specimens ( contingency management ; CM ) , MET/CBT without CM , individual drug counseling ( DC ) plus CM , and DC without CM . There was a significant main effect of CM on treatment retention and marijuana-free urine specimens . Moreover , the combination of MET/CBT plus CM was significantly more effective than MET/CBT without CM or DC plus CM , which were in turn more effective than DC without CM for treatment attendance and percentage of marijuana-free urine specimens . Participants assigned to MET/CBT continued to reduce the frequency of their marijuana use through a 6-month follow-up The purpose of this study was to examine the relationship between psychological distress , self-efficacy , and marijuana use using data from a r and omized controlled trial of treatments for marijuana dependence [ J. Consult . Clin . Psychol . 68 ( 2000 ) 898 - 908 ] . Adult marijuana users seeking treatment ( N=291 ) were r and omly assigned to three treatment conditions : ( 1 ) cognitive-behavioral relapse prevention support group ( RPSG ) , ( 2 ) individualized assessment and advice group ( IAI ) , and ( 3 ) delayed treatment control group ( DTC ) . As predicted , psychologically distressed individuals had lower self-efficacy for avoiding marijuana use in psychologically distressing ( PD ) situations as opposed to nonpsychologically distressing ( NPD ) situations . However , all participants tended to have lower self-efficacy for NPD situations than PD situations . Efficacy increased and marijuana use decreased following treatment but the RPSG treatment did not have greater benefit for psychologically distressed participants Background : Cannabis use has a negative impact on psychosis . Studies are needed to explore the efficacy of psychological interventions to reduce cannabis use in psychosis . Our aim is to study the efficacy of a specific motivational intervention on young cannabis users suffering from psychosis . Methods : Participants ( aged less than 35 years ) were r and omly assigned to treatment as usual ( TAU ) alone , or treatment as usual plus motivational intervention ( MI + TAU ) . TAU was comprehensive and included case management , early intervention and mobile team when needed . Assessment s were completed at baseline and at 3 , 6 and 12 months follow-up . Results : Sixty-two participants ( 32 TAU and 30 MI + TAU ) were included in the study . Cannabis use decreased in both groups at follow-up . Participants who received MI in addition to TAU displayed both a greater reduction in number of joints smoked per week and greater confidence to change cannabis use at 3 and 6 months follow-up , but differences between groups were nonsignificant at 12 months . Conclusions : MI is well accepted by patients suffering from psychosis and has a short-term impact on cannabis use when added to st and ard care . However , the differential effect was not maintained at 1-year follow-up . MI appears to be a useful active component to reduce cannabis use which should be integrated in routine clinical practice BACKGROUND Screening and brief intervention programs related to addictive disorders have proven effective in a variety of environments . Both the feasibility and outcome of brief interventions performed in police custody by forensic physicians are unknown . Our objectives were to characterize addictive behaviors in detainees and to evaluate the feasibility of a brief intervention at the time of the medical examination in police custody . METHODS This prospect i ve study included 1000 detainees in police custody who were examined by a physician for the assessment of fitness for detention . We used a st and ardized question naire and collected data concerning individual characteristics , addictive disorders , and reported assaults or observed injuries . RESULTS 944 men and 56 women ( 94 - 6 % ) were studied . We found an addictive disorder in 708 of 1000 cases ( 71 % ) , with the use of tobacco ( 62 % ) , alcohol ( 36 % ) , cannabis ( 35 % ) , opiates ( 5 % ) , and cocaine ( 4 % ) being the most common . A brief intervention was performed in 544 of these 708 cases ( 77 % ) . A total of 139 of the 708 individuals ( 20 % ) expressed a willingness to change and 14 of 708 ( 2 % ) requested some information on treatment options . The main reasons why brief interventions were not performed were aggressive behaviors , drowsiness , or fanciful statements by the detainee . CONCLUSION Brief interventions and screening for addictive behaviors in police custody are feasible in the majority of cases . The frequent link between addictive behaviors and the suspected crimes highlights the value of such interventions , which could be incorporated into the public health mission of the physician in police custody Background : Few studies have addressed comorbid antisocial personality disorder ( ASPD ) and marijuana dependence in young adults , and results from previous studies are inconsistent . Objectives : This study evaluated differences in pretreatment characteristics and treatment outcomes between marijuana-dependent young adults with and without ASPD . Methods : Data for this study were derived from a r and omized trial , in which marijuana-dependent young adults ( n = 136 ) between 18 and 25 years of age were r and omized to four behavioral conditions : ( 1 ) MET/CBT with CM , ( 2 ) MET/CBT without CM , ( 3 ) DC with CM , and ( 4 ) DC without CM . Results : Forty-four percent of the participants met DSM-IV-TR criteria for ASPD . ASPD clients had significantly more lifetime alcohol dependence disorders , marijuana use in the 28 days pretreatment , arrests , and assault and weapon charges compared to those without ASPD . ASPD clients did not differ in retention or substance use outcomes at 8 weeks posttreatment or the 6-month follow-up . In general , both groups had more attendance in the voucher condition , but there were no significant ASPD by treatment interactions . Conclusions : These data suggest that marijuana-dependent young adults with comorbid ASPD do not necessarily have poorer retention or substance use outcomes compared with marijuana-dependent young adults who do not have ASPD when treated in a well-defined behavioral therapy protocol . Scientific significance : Previous research has shown increased risks for clients with comorbid ASPD and marijuana dependence ; however , our findings suggest that specialized programs for clients with ASPD may not be necessary if they are provided with empirically supported , structured treatments OBJECTIVE To develop and evaluate a culturally adapted brief intervention for Indigenous people with chronic mental illness . DESIGN A mixed methods design in which an exploratory phase of qualitative research was followed by a nested r and omised controlled trial . SETTING Psycho-education re sources and a brief intervention , motivational care planning ( MCP ) , were developed and tested in collaboration with aboriginal mental health workers in three remote communities in northern Australia . PARTICIPANTS A total of 49 patients with mental illness and 37 carers were recruited to a r and omised controlled trial that compared MCP ( n = 24 ) with a clinical control condition ( treatment as usual , n = 25 ) . INTERVENTION The early treatment group received MCP at baseline and the late treatment group received delayed treatment at six months . MAIN OUTCOME MEASURES The primary outcome was mental health problem severity as measured by the health of the nation outcome scales . Secondary measures of well-being ( Kessler 10 ) , life skills , self-management and substance dependence were chosen . Outcome assessment s were performed at baseline , six-month , 12-month and 18-month follow up . RESULTS R and om effects regression analyses showed significant advantage for the treatment condition in terms of well-being with changes in health of the nation outcome scales ( P < 0.001 ) and Kessler 10 ( P = 0.001 ) , which were sustained over time . There was also significant advantage for treatment for alcohol dependence ( P = 0.05 ) , with response also evident in cannabis dependence ( P = 0.064 ) and with changes in substance dependence sustained over time . CONCLUSIONS These results suggest that MCP is an effective treatment for Indigenous people with mental illness and provide insight into the experience of mental illness in remote communities This study examined whether a coping-skills-based treatment for marijuana dependence operated by encouraging the use of coping skills or via other mechanisms . Participants were 450 men and women treated in the multisite Marijuana Treatment Project who were r and omly assigned to motivational enhancement therapy plus cognitive-behavioral ( MET-CB ) treatment , motivational enhancement therapy ( MET ) , or a delayed treatment control group . Marijuana use and coping skills were measured at baseline and at follow-ups through 15 months . Results showed that marijuana outcomes were predicted by treatment type and by coping skills use , but that the coping-skills-oriented MET-CB treatment did not result in greater use of coping skills than did the MET treatment . The results suggest that mechanisms of coping skills treatment may need to be reconceptualized BACKGROUND In a recent paper , we reported the efficacy of a modular cognitive-behavioral intervention for treating adolescents and adults with cannabis use disorders ( CUD ) . In this study , we examine the outcome of this intervention after translating it into clinical practice . METHODS A multi-site , r and omized controlled trial of 279 treatment seekers with ICD-10 cannabis use disorders aged 16- 63 years was conducted in 11 outpatient addiction treatment centers in Germany . Patients were r and omly assigned to an Active Treatment ( AT , n=149 ) or Delayed Treatment Control ( DTC , n=130 ) . Treatment consisted of 10 sessions of fully manualized individual psychotherapy that combined Cognitive-Behavioral Therapy , Motivational EnhancementTherapy and problem-solving training . Assessment s were conducted at baseline , during each therapy session , at post-treatment and at three and six month follow-ups . RESULTS At post assessment 53.3 % of AT patients reported abstinence ( 46.3 % negative urine screenings ) compared to 22 % of DTC patients ( 17.7 % negative drug screenings ) ( p<0.001 , Intention-to-treat analysis ) . AT patients improved in the frequency of cannabis use , number of cannabis dependence criteria , severity of dependence , as well as number and severity of cannabis-related problems . Effect sizes were moderate to high . While abstinence rates in the AT group decreased over the 3-month ( negative urine screenings : 32.4 % ) and 6-month ( negative urine screenings : 35.7 % ) follow-up periods , the effects in secondary outcomes were maintained . CONCLUSIONS The intervention can successfully be translated to and applied in clinical practice . It has the potential to improve access to evidence -based care for chronic CUD patients AIMS To evaluate the efficacy of a two-session assessment and feedback intervention design ed to reach and increase motivation for change in marijuana users who were experiencing negative consequences but were ambivalent about change . DESIGN R and om assignment to one of two types of feedback conditions or a delayed feedback control ( DFC ) with follow-up assessment s at 7 weeks , 6 months and 12 months . Setting University of Washington research center in Seattle , Washington . PARTICIPANTS A total of 188 adult male and female marijuana users who responded to advertisements . Interventions A personalized feedback ( PF ) condition utilizing motivational interviewing was compared to an educational control condition labeled multi-media feedback ( MMF ) . MEASUREMENTS Marijuana use , dependence symptoms , other associated negative consequences and motivational constructs were assessed at all time-points . FINDINGS PF participants reported fewer days of use per week , fewer periods of use per day and fewer dependence symptoms at 7 weeks than those in the MMF and DFC conditions . PF participants also reported fewer days of use per week compared to MMF participants at the 12-month follow-up and fewer dependence symptoms at both the 6- and 12-month follow-ups compared to MMF participants . CONCLUSIONS The PF intervention , delivered in the context of a check-up , shows potential as a way of reaching and motivating change in marijuana users with a diagnosable disorder who otherwise are not ready to approach treatment . Ways of augmenting the modest absolute levels of change are discussed We r and omized 332 women , 18 - 24 years old , who were not explicitly seeking treatment for their marijuana use to either a two-session motivationally focused intervention or an assessment -only condition . Assessed by timeline follow-back methodology , participants reported using marijuana 57 % of days in the 3 months prior to study entry . Intervention effects on the likelihood of marijuana use were not statistically significant at 1 month ( odds ratio [ OR ] = 0.77 , p = .17 ) , significant at 3 months ( OR = 0.53 , p = .01 ) , and no longer significant at 6 months ( OR = 0.74 , p = .20 ) . Among the 61 % of participants endorsing any desire to quit using marijuana at baseline , significant intervention effects on the likelihood of marijuana use days were observed at 1 month ( OR = 0.42 , p = .03 ) , 3 months ( OR = 0.31 , p = .02 ) , and 6 months ( OR = 0.35 , p = .03 ) . A two-session brief motivational intervention reduced marijuana use among young women not seeking treatment . Women with a desire to quit showed a greater and more durable response Cannabis use is prevalent among young people , and frequent users are at an elevated risk for health problems . Availability and effectiveness of conventional treatment are limited , and brief interventions ( BIs ) may present viable alternatives . One hundred thirty-four young high-frequency cannabis users from among university students were r and omized to either an oral ( C-O ; n = 25 ) or a written experimental cannabis BI ( C-W ; n = 47 ) intervention group , or to either an oral ( H-O ; n = 25 ) or written health BI ( H-W ; n = 37 ) control group . Three-month follow-up assessment s based on repeated measures analysis of variance techniques found a decrease in the mean number of cannabis use days in the total sample ( p = 0.024 ) , reduced deep inhalation/breathholding use in the C-O group ( p = 0.003 ) , reduced driving after cannabis use in the C-W group ( p = 0.02 ) , and a significant reduction in deep inhalation/breathholding in the C-O group ( p = 0.011 ) compared with controls . Feasibility and short-term impact of the BIs were demonstrated , yet more research is needed AIMS To evaluate reciprocal enhancement ( combining treatments to offset their relative weaknesses ) as a strategy to improve cannabis treatment outcomes . Contingency management ( CM ) with reinforcement for homework completion and session attendance was used as a strategy to enhance cognitive-behavioral therapy ( CBT ) via greater exposure to skills training ; CBT was used as a strategy to enhance durability of CM with rewards for abstinence . SETTING Community-based out-patient treatment program in New Haven , Connecticut , USA . DESIGN Twelve-week r and omized clinical trial of four treatment conditions : CM for abstinence alone or combined with CBT , CBT alone or combined with CM with rewards for CBT session attendance and homework completion . PARTICIPANTS A total of 127 treatment-seeking young adults ( 84.3 % male , 81.1 % minority , 93.7 % referred by criminal justice system , average age 25.7 years ) . MEASUREMENTS Weekly urine specimens testing positive for cannabis , days of cannabis use via the time-line follow-back method . FINDINGS Within treatment , reinforcing homework and attendance did not significantly improve CBT outcomes , and the addition of CBT worsened outcomes when added to CM for abstinence ( 75.5 versus 57.1 % cannabis-free urine specimens , F = 2.25 , P = 0.02 ) . The CM for abstinence condition had the lowest percentage of cannabis-negative urine specimens and the highest mean number of consecutive cannabis-free urine specimens ( 3.3 , F = 2.33 , P = 0.02 ) . Attrition was higher in the CBT alone condition , but r and om effect regression analyses indicated this condition was associated with the greatest rate of change overall . Cannabis use during the 1-year follow-up increased most rapidly for the two enhanced groups . CONCLUSIONS Combining contingency management and cognitive-behavioural therapy does not appear to improve success rates of treatment for cannabis dependence in clients involved with the criminal justice system OBJECTIVE The purpose of the present study was to develop a treatment for marijuana dependence specifically design ed to enhance self-efficacy . METHOD The participants were 215 marijuana-dependent men and women r and omized to one of three 9-week outpatient treatments : a condition intended to enhance self-efficacy through successful completion of treatment-related tasks ( motivational enhancement plus cognitive-behavioral treatment plus contingency management reinforcing completion of treatment homework ; MET+CBT+CM(Homework ) ) ; a condition that controlled for all elements except for reinforcement of homework ( MET+CBT+contingency management reinforcing drug abstinence ; MET+CBT+CM(Abstinence ) ) ; or a case management control condition ( CaseM ) . Participants in the two MET+CBT conditions were also asked to complete interactive voice recordings three times per week during treatment to confirm homework completion . RESULTS All patients showed modest improvements over time through 14months , with few between-treatment effects on outcomes . Latent Class Growth Models , however , indicated that a sub sample of patients did extremely well over time . This sub sample was more likely to have been treated in the CM(Abstinence ) condition . In turn , this treatment effect appears to have been accounted for by days of continuous abstinence accrued during treatment , and by pre-post increases in self-efficacy . CONCLUSIONS The most effective treatments may be those that elicit abstinence while increasing self-efficacy INTRODUCTION Advice is a widely recommended and practised intervention with young drug users . Study of precisely how advice is given and received in any setting has , however , been limited . DESIGN AND METHODS We qualitatively analysed 106 audio-recordings of advice sessions on cannabis use for young people within a r and omised trial . Inductive data analysis was guided by a focus on practitioner behaviour which served to engage the active participation of the young drug user in the session . RESULTS A cluster of ' Information Management ' activities was identified together with an ' Interactive Orientation ' evident in a series of specific behaviours . Participants were most successfully engaged when both were combined , understood here as ' Personalised Advice-giving ' . DISCUSSION AND CONCLUSIONS These components identified in this exploratory study might assist further research in rectifying the absence of a solid empirical basis for effective practice in advice giving with young drug users and more widely PROBLEM Adolescent substance abuse remains a public health problem , and more effective treatment approaches are needed . PURPOSE The study aims to determine the feasibility and preliminary effectiveness of implementing a cost-effective contingency management ( CM ) intervention in community substance abuse treatment for adolescents with marijuana use disorders . METHODS Thirty-one adolescents with primary marijuana use disorder enrolled in a community treatment were r and omized into either a prize-based CM intervention contingent when su bmi tting negative urine drug screens ( UDS ) or a noncontingent control group . FINDINGS There were no significant group differences in percent negative UDS , sustained negative UDS , or retention in treatment . CONCLUSIONS CM was difficult to integrate into community treatment programs and did not seem to be an effective adjunct to st and ard community substance abuse treatment for adolescents with marijuana use disorders . Modifying the CM procedure for adolescents , changing staff attitudes toward CM , and /or combining CM with other evidence -based psychosocial treatment may improve outcomes BACKGROUND Few studies have examined clinical trial participation rates and treatment outcomes among underserved young adults who are dependent on marijuana , the most commonly abused illicit drug . METHOD The present study was a secondary analysis of a trial of court-referred marijuana-dependent young adults ( ages 18 - 25 ) r and omized to one of four treatment conditions : Motivational Enhancement Therapy/Cognitive Behavioral Therapy ( MET/CBT ) , MET/CBT+Contingency Management ( CM ) , Drug Counseling ( DC ) or DC+CM . African American ( N=81 ) participants were compared to White ( N=31 ) participants with respect to rates of participation in phases of treatment and substance use outcomes . In addition , the interaction of race and treatment condition was examined to ascertain if the interventions yielded different effects based on race . RESULTS Among those who started treatment , African American young adults were significantly less likely to complete the treatment and posttreatment phases of the clinical trial than their White counterparts . Irrespective of treatment type , substance use outcomes ( i.e. , percentage of marijuana-negative specimens and longest duration of continuous abstinence ) did not vary by race . However , there was a significant interaction effect between treatment type and race ; African American young adults did not benefit differentially from any specific type of treatment , but CM was effective in reducing proportion of marijuana positive sample s among White young adults . CONCLUSIONS Findings suggest that clinical trial treatment and posttreatment completion rates vary by race in this population , as does response to specific treatment types . More treatment research focusing specifically on African American marijuana-dependent young adults is warranted |
14,051 | 30,476,259 | Although nearly two thirds of process evaluations cited a theoretical approach , only a quarter were informed by , applied , or tested a theory-despite the potential complementarity of these strategies .
When theory was used , it was primarily applied .
Using theory more substantively in process evaluations may accelerate our underst and ing of how implementation interventions operate | Interventions to implement changes into health care practice ( i.e. , implementation interventions ) are critical to improving care but their effects are poorly understood .
Two strategies to better underst and intervention effects are conducting process evaluations and using theoretical approaches ( i.e. , theories , models , frameworks ) .
The extent to which theoretical approaches have been used in process evaluations conducted alongside trials of implementation interventions is unclear .
In this study context , we review ed ( a ) the proportion of process evaluations citing theoretical approaches , ( b ) which theoretical approaches were cited , and ( c ) whether and how theories were used . | Background Pragmatic trials of implementation interventions focus on evaluating whether an intervention changes professional behaviour under real-world conditions rather than investigating the mechanism through which change occurs . Theory-based process evaluations conducted alongside pragmatic r and omised trials address this by assessing whether the intervention changes theoretical constructs proposed to mediate change . The Ontario Printed Educational Material s ( PEM ) cluster trial was design ed to increase family physicians ’ guideline -recommended prescription of thiazide diuretics . The trial found no intervention effect . Using the theory of planned behaviour ( TPB ) , we hypothesised that changes in thiazide prescribing would be reflected in changes in intention , consistent with changes in attitude and subjective norm , with no change to their perceived behavioural control ( PBC ) , and tested this alongside the RCT . Methods We developed and sent TPB postal question naires to a r and om sub- sample of family physicians in each trial arm 2 months before and 6 months after dissemination of the PEMs . We used analysis of covariance to test for group differences using a 2 × 3 factorial design . We content-analysed an open-ended question about perceived barriers to thiazide prescription . Using control group data , we tested whether baseline measures of TPB constructs predicted self-reported thiazide prescribing at follow-up . Results Four hundred twenty-six physicians completed pre- and post-intervention question naires . Baseline scores on measures of TPB constructs were high : intention mean = 5.9 out of 7 ( SD = 1.4 ) , attitude mean = 5.8 ( SD = 1.1 ) , subjective norm mean = 5.8 ( SD = 1.1 ) and PBC mean = 6.2 ( SD = 1.0 ) . The arms did not significantly differ post-intervention on any of the theory-based constructs , suggesting a possible ceiling effect . Content analysis of perceived barriers suggested post-intentional barriers to prescribing thiazides most often focused on specific patient clinical characteristics and potential side effects . Baseline intention ( β = 0.63 , p < 0.01 ) but not PBC ( β = 0.04 , p = 0.78 ) predicted 42.6 % of the variance in self-reported behaviour at follow-up in the control group . Conclusions Congruent with the Ontario Printed Educational Messages trial results and aligned with the TPB , we saw no impact of the intervention on any TPB constructs . The theoretical basis of this evaluation suggests possible explanations for the failure of the PEM intervention to change professional behaviour , which can directly inform the design and content of future theory-based PEM interventions to change professional behaviour . Trial registration IS RCT N , Canada IS RCT Background : Many patients with or at risk for chronic kidney disease ( CKD ) in the primary care setting are not receiving recommended care . Objective : The objective of this study is to determine whether a multifaceted , low-cost intervention compared with usual care improves the care of patients with or at risk for CKD in the primary care setting . Design : A pragmatic cluster-r and omized trial , with an embedded qualitative process evaluation , will be conducted . Setting : The study population comes from the Electronic Medical Record Administrative data Linked Data base ® , which includes clinical data for more than 140 000 rostered adults cared for by 194 family physicians in 34 clinics across Ontario , Canada . The 34 primary care clinics will be r and omized to the intervention or control group . Intervention : The intervention group will receive re sources from the “ CKD toolkit ” to help improve care including practice audit and feedback , printed educational material s for physicians and patients , electronic decision support and reminders , and implementation support . Measurements : Patients with or at risk for CKD within participating clinics will be identified using laboratory data in the electronic medical records . Outcomes will be assessed after dissemination of the CKD tools and after 2 rounds of feedback on performance on quality indicators have been sent to the physicians using information from the electronic medical records . The primary outcome is the proportion of patients aged 50 to 80 years with nondialysis-dependent CKD who are on a statin . Secondary outcomes include process of care measures such as screening tests , CKD recognition , monitoring tests , angiotensin-converting enzyme inhibitor or angiotensin receptor blocker prescriptions , blood pressure targets met , and nephrologist referral . Hierarchical analytic modeling will be performed to account for clustering . Semistructured interviews will be conducted with a r and om purpose ful sample of physicians in the intervention group to underst and why the intervention achieved the observed effects . Conclusions : If our intervention improves care , then the CKD toolkit can be adapted and scaled for use in other primary care clinics which use electronic medical records . Trial Registration : Clinical Trials.gov Identifier : Introduction As an increasing number of people are living with more than 1 long-term condition , identifying effective interventions for the management of multimorbidity in primary care has become a matter of urgency . Interventions are challenging to evaluate due to intervention complexity and the need for adaptability to different context s. A process evaluation can provide extra information necessary for interpreting trial results and making decisions about whether the intervention is likely to be successful in a wider context . The 3D ( dimensions of health , drugs and depression ) study will recruit 32 UK general practice s to a cluster r and omised controlled trial to evaluate effectiveness of a patient-centred intervention . Practice s will be r and omised to intervention or usual care . Methods and analysis The aim of the process evaluation is to underst and how and why the intervention was effective or ineffective and the effect of context . As part of the intervention , quantitative data will be collected to provide implementation feedback to all intervention practice s and will contribute to evaluation of implementation fidelity , alongside case study data . Data will be collected at the beginning and end of the trial to characterise each practice and how it provides care to patients with multimorbidity . Mixed methods will be used to collect qualitative data from 4 case study practice s , purposively sample d from among intervention practice s. Qualitative data will be analysed using techniques of constant comparison to develop codes integrated within a flexible framework of themes . Quantitative and qualitative data will be integrated to describe case study sites and develop possible explanations for implementation variation . Analysis will take place prior to knowing trial outcomes . Ethics and dissemination Study approved by South West ( Frenchay ) National Health Service ( NHS ) Research Ethics Committee ( 14/SW/0011 ) . Findings will be disseminated via a final report , peer- review ed publications and practical guidance to healthcare professionals , commissioners and policymakers . Trial registration number IS RCT N06180958 Developing more effective behavioural interventions requires an underst and ing of the mechanisms of behaviour change , and methods to rigorously test their theoretical basis . The delivery and theoretical basis of an intervention protocol were assessed in ProActive , a UK trial of an intervention to increase the physical activity of those at risk of Type 2 diabetes ( N = 365 ) . In 108 intervention sessions , behaviours of facilitators were mapped to four theories that informed intervention development and behaviours of participants were mapped to 17 theoretical components of these four theories . The theory base of the intervention specified by the protocol was different than that delivered by facilitators , and that received by participants . Of the intervention techniques delivered , 25 % were associated with theory of planned behaviour ( TPB ) , 42 % with self-regulation theory ( SRT ) , 24 % with operant learning theory ( OLT ) and 9 % with relapse prevention theory ( RPT ) . The theoretical classification of participant talk showed a different pattern , with twice the proportion associated with OLT ( 48 % ) , 21 % associated with TPB , 31 % with SRT and no talk associated with RPT . This study demonstrates one approach to assessing the extent to which the theories used to guide intervention development account for any changes observed Objectives A patient safety intervention was tested in a 33-ward r and omised controlled trial . No statistically significant difference between intervention and control wards was found . We conducted a process evaluation of the trial and our aim in this paper is to underst and staff engagement across the 17 intervention wards . Design Large qualitative process evaluation of the implementation of a patient safety intervention . Setting and participants National Health Service staff based on 17 acute hospital wards located at five hospital sites in the North of Engl and . Data We concentrate on three sources here : ( 1 ) analysis of taped discussion between ward staff during action planning meetings ; ( 2 ) facilitators ’ field notes and ( 3 ) follow-up telephone interviews with staff focusing on whether action plans had been achieved . The analysis involved the use of pen portraits and adaptive theory . Findings First , there were palpable differences in the ways that the 17 ward teams engaged with the key components of the intervention . Five main engagement typologies were evident across the life course of the study : consistent , partial , increasing , decreasing and disengaged . Second , the intensity of support for the intervention at the level of the organisation does not predict the strength of engagement at the level of the individual ward team . Third , the st and ardisation of facilitative processes provided by the research team does not ensure that implementation st and ardisation of the intervention occurs by ward staff . Conclusions A dilution of the intervention occurred during the trial because wards engaged with Patient Reporting and Action for a Safe Environment ( PRASE ) in divergent ways , despite the st and ardisation of key components . Facilitative processes were not sufficiently adequate to enable intervention wards to successfully engage with PRASE components Background To reduce the spread of antibiotic resistance , there is a pressing need for worldwide implementation of effective interventions to promote more prudent prescribing of antibiotics for acute LRTI . This study is a process analysis of the GRACE/INTRO trial of a multifactorial intervention that reduced antibiotic prescribing for acute LRTI in six European countries . The aim was to underst and how the interventions were implemented and to examine effects of the interventions on general practitioners ’ ( GPs ’ ) and patients ’ attitudes . Methods GPs were cluster r and omised to one of three intervention groups or a control group . The intervention groups received web-based training in either use of the C-reactive protein ( CRP ) test , communication skills and use of a patient booklet , or training in both . GP attitudes were measured before and after the intervention using constructs from the Theory of Planned Behaviour and a Website Satisfaction Question naire . Effects of the interventions on patients were assessed by a post-intervention question naire assessing patient enablement , satisfaction with the consultation , and beliefs about the risks and need for antibiotics . Results GPs in all countries and intervention groups had very positive perceptions of the intervention and the web-based training , and felt that taking part had helped them to reduce prescribing . All GPs perceived reducing prescribing as more important and less risky following the intervention , and GPs in the communication groups reported increased confidence to reduce prescribing . Patients in the communication groups who received the booklet reported the highest levels of enablement and satisfaction and had greater awareness that antibiotics could be unnecessary and harmful . Conclusions Our findings suggest that the interventions should be broadly acceptable to both GPs and patients , as well as feasible to roll out more widely across Europe . There are also some indications that they could help to engender changes in GP and patient attitudes that will be helpful in the longer-term , such as increased awareness of the potential disadvantages of antibiotics and increased confidence to manage LRTI without them . Given the positive effects of the booklet on patient beliefs and attitudes , it seems logical to extend the use of the patient booklet to all patients Background R and omised trials of knowledge translation strategies for professional behaviour change can provide robust estimates of effectiveness , but offer little insight into the causal mechanisms by which any change is produced . To illustrate the applicability of causal methods within r and omised trials , we undertook a theory-based process evaluation study within an implementation trial to explore whether the cognitions of primary care doctors ' predicted their test requesting behaviours and , secondly , whether the trial results were mediated by the theoretical constructs . Methods The process evaluation comprised a cross-sectional question naire survey of a r and om 50 % sample of the r and omised groups of primary care practice s in Grampian ( NHS Grampian ) , UK , who took part in a trial of the effect of enhanced feedback and brief educational reminders on test requesting behaviour . The process evaluation was based upon the Theory of Planned Behaviour and focussed on three of the test requesting behaviours that were targeted in the trial -- ferritin , follicle stimulating hormone ( FSH ) , and Helicobacter Pylori serology ( HPS ) . Results The question naire was completed by 131 primary care doctors ( 56 % ) from 42 ( 98 % ) of the sample d practice s. Behavioural intention , attitude , and subjective norm were highly correlated for all the tests . There was no evidence that perceived behavioural control was correlated with any of the other measures . Simple linear regression analysis of the rate of test requests on minimum behavioural intentions had R2 of 11.1 % , 12.5 % , and 0.1 % for ferritin , FSH , and HPS requesting , respectively . Mediational analysis showed that the trial results for ferritin and FSH were partially mediated ( between 23 % and 78 % mediation ) through intentions . The HPS trial result was not mediated through intention . Conclusions This study demonstrated that a theory-based process evaluation can provide useful information on causal mechanisms that aid not only interpretation of the trial but also inform future evaluations and intervention development Background There is a considerable evidence base for ' collaborative care ' as a method to improve quality of care for depression , but an acknowledged gap between efficacy and implementation . This study utilises the Normalisation Process Model ( NPM ) to inform the process of implementation of collaborative care in both a future full-scale trial , and the wider health economy . Methods Application of the NPM to qualitative data collected in both focus groups and one-to-one interviews before and after an exploratory r and omised controlled trial of a collaborative model of care for depression . Results Findings are presented as they relate to the four factors of the NPM ( interactional workability , relational integration , skill-set workability , and context ual integration ) and a number of necessary tasks are identified . Using the model , it was possible to observe that predictions about necessary work to implement collaborative care that could be made from analysis of the pre-trial data relating to the four different factors of the NPM were indeed borne out in the post-trial data . However , additional insights were gained from the post-trial interview participants who , unlike those interviewed before the trial , had direct experience of a novel intervention . The professional freedom enjoyed by more senior mental health workers may work both for and against normalisation of collaborative care as those who wish to adopt new ways of working have the freedom to change their practice but are not obliged to do so . Conclusions The NPM provides a useful structure for both guiding and analysing the process by which an intervention is optimized for testing in a larger scale trial or for subsequent full-scale implementation Clinical and health services research is continually producing new findings that may contribute to effective and efficient patient care . However , the transfer of research findings into practice is unpredictable and can be a slow and haphazard process . Ideally , the choice of implementation strategies would be based upon evidence from r and omised controlled trials or systematic review s of a given implementation strategy . Unfortunately , review s of implementation strategies consistently report effectiveness some , but not all of the time ; possible causes of this variation are seldom reported or measured by the investigators in the original studies . Thus , any attempts to extrapolate from study setting s to the real world are hampered by a lack of underst and ing of the effects of key elements of individuals , interventions , and the setting s in which they were trialled . The explicit use of theory offers a way of addressing these issues and has a number of advantages , such as providing : a generalisable framework within which to represent the dimensions that implementation studies address , a process by which to inform the development and delivery of interventions , a guide when evaluating , and a way to allow for an exploration of potential causal mechanisms . However , the use of theory in design ing implementation interventions is method ologically challenging for a number of reasons , including choosing between theories and faithfully translating theoretical constructs into interventions . The explicit use of theory offers potential advantages in terms of facilitating a better underst and ing of the generalisability and replicability of implementation interventions . However , this is a relatively unexplored method ological area Background There are recognised gaps between evidence and practice in general practice , a setting which provides particular challenges for implementation . We earlier screened clinical guideline recommendations to derive a set of ‘ high impact ’ indicators based upon criteria including potential for significant patient benefit , scope for improved practice and amenability to measurement using routinely collected data . We aim to evaluate the effectiveness and cost-effectiveness of a multifaceted , adaptable intervention package to implement four targeted , high impact recommendations in general practice . Methods / design The research programme Action to Support Practice Implement Research Evidence ( ASPIRE ) includes a pair of pragmatic cluster-r and omised trials which use a balanced incomplete block design . Clusters are general practice s in West Yorkshire , United Kingdom ( UK ) , recruited using an ‘ opt-out ’ recruitment process . The intervention package adapted to each recommendation includes combinations of audit and feedback , educational outreach visits and computerised prompts with embedded behaviour change techniques selected on the basis of identified needs and barriers to change . In trial 1 , practice s are r and omised to adapted interventions targeting either diabetes control or risky prescribing and those in trial 2 to adapted interventions targeting either blood pressure control in patients at risk of cardiovascular events or anticoagulation in atrial fibrillation . The respective primary endpoints comprise achievement of all recommended target levels of haemoglobin A1c ( HbA1c ) , blood pressure and cholesterol in patients with type 2 diabetes , a composite indicator of risky prescribing , achievement of recommended blood pressure targets for specific patient groups and anticoagulation prescribing in patients with atrial fibrillation . We are also r and omising practice s to a fifth , non-intervention control group to further assess Hawthorne effects . Outcomes will be assessed using routinely collected data extracted 1 year after r and omisation . Economic modelling will estimate intervention cost-effectiveness . A process evaluation involving eight non-trial practice s will examine intervention delivery , mechanisms of action and unintended consequences . Discussion ASPIRE will provide ‘ real-world ’ evidence about the effects , cost-effectiveness and delivery of adapted intervention packages targeting high impact recommendations . By implementing our adaptable intervention package across four distinct clinical topics , and using ‘ opt-out ’ recruitment , our findings will provide evidence of wider generalisability . Trial registration IS RCT Background Antipsychotic medications are routinely prescribed in nursing homes to address the behavioral and psychological symptoms of dementia . Unfortunately , inappropriate prescribing of antipsychotic medications is common and associated with increased morbidity , adverse drug events , and hospitalizations . Multifaceted interventions can achieve a 12–20 % reduction in antipsychotic prescribing levels in nursing homes . Effective interventions have featured educational outreach and ongoing performance feedback . Methods / Design This pragmatic , cluster-r and omized control trial and embedded process evaluation seeks to determine the effect of adding academic detailing to audit and feedback on prescribing of antipsychotic medications in nursing homes , compared with audit and feedback alone . Nursing homes within pre-determined regions of Ontario , Canada , are eligible if they express an interest in the intervention . The academic detailing intervention will be delivered by registered health professionals following an intensive training program including relevant clinical issues and techniques to support health professional behavior change . Physicians in both groups will have the opportunity to access confidential reports summarizing their prescribing patterns for antipsychotics in comparison to the local and provincial average . Participating homes will be allocated to one of the two arms of the study ( active/full intervention versus st and ard audit and feedback ) in two waves , with a 2:1 allocation ratio . Homes will be r and omized after stratifying for geography , baseline antipsychotic prescription rates , and size , to ensure a balance of characteristics . The primary outcome is antipsychotic dispensing in nursing homes , measured 6 months after allocation ; secondary outcomes include clinical outcomes and healthcare utilization . Discussion Policy-makers and the public have taken note that antipsychotics are used in nursing homes in Ontario far more than other jurisdictions . Academic detailing can be an effective technique to address challenges in appropriate prescribing in nursing homes , but effect sizes vary widely . This opportunistic , policy-driven evaluation , embedded within a government-initiated demonstration project , was design ed to ensure policy-makers receive the best evidence possible regarding whether and how to scale up the intervention . Trial registration Clinical Trials.gov NLM Identifier : NCT02604056 Background Process evaluations are recommended to open the ‘ black box ’ of complex interventions evaluated in trials , but there is limited guidance to help research ers design process evaluations . Much current literature on process evaluations of complex interventions focuses on qualitative methods , with less attention paid to quantitative methods . This discrepancy led us to develop our own framework for design ing process evaluations of cluster-r and omised controlled trials . Methods We review ed recent theoretical and method ological literature and selected published process evaluations ; these publications identified a need for structure to help design process evaluations . We drew upon this literature to develop a framework through iterative exchanges , and tested this against published evaluations . Results The developed framework presents a range of c and i date approaches to underst and ing trial delivery , intervention implementation and the responses of targeted participants . We believe this framework will be useful to others design ing process evaluations of complex intervention trials . We also propose key information that process evaluations could report to facilitate their identification and enhance their usefulness . Conclusion There is no single best way to design and carry out a process evaluation . Research ers will be faced with choices about what questions to focus on and which methods to use . The most appropriate design depends on the purpose of the process evaluation ; the framework aims to help research ers make explicit their choices of research questions and methods .Trial registration Clinical trials.gov Background The case has been made for more and better theory-informed process evaluations within trials in an effort to facilitate insightful underst and ings of how interventions work . In this paper , we provide an explanation of implementation processes from one of the first national implementation research r and omized controlled trials with embedded process evaluation conducted within acute care , and a proposed extension to the Promoting Action on Research Implementation in Health Services ( PARIHS ) framework . Methods The PARIHS framework was prospect ively applied to guide decisions about intervention design , data collection , and analysis processes in a trial focussed on reducing peri-operative fasting times . In order to capture a holistic picture of implementation processes , the same data were collected across 19 participating hospitals irrespective of allocation to intervention . This paper reports on findings from data collected from a purposive sample of 151 staff and patients pre- and post-intervention . Data were analysed using content analysis within , and then across data sets . Results A robust and uncontested evidence base was a necessary , but not sufficient condition for practice change , in that individual staff and patient responses such as caution influenced decision making . The implementation context was challenging , in which individuals and teams were bounded by professional issues , communication challenges , power and a lack of clarity for the authority and responsibility for practice change . Progress was made in sites where processes were aligned with existing initiatives . Additionally , facilitators reported engaging in many intervention implementation activities , some of which result in practice changes , but not significant improvements to outcomes . Conclusions This study provided an opportunity for reflection on the comprehensiveness of the PARIHS framework . Consistent with the underlying tenant of PARIHS , a multi-faceted and dynamic story of implementation was evident . However , the prominent role that individuals played as part of the interaction between evidence and context is not currently explicit within the framework . We propose that successful implementation of evidence into practice is a planned facilitated process involving an interplay between individuals , evidence , and context to promote evidence -informed practice . This proposal will enhance the potential of the PARIHS framework for explanation , and ensure theoretical development both informs and responds to the evidence base for implementation . Trial registration IS RCT N18046709 - Peri-operative Implementation Study Evaluation ( PoISE ) Background New clinical research findings may require clinicians to change their behaviour to provide high- quality care to people with type 2 diabetes , likely requiring them to change multiple different clinical behaviours . The present study builds on findings from a UK-wide study of theory-based behavioural and organisational factors associated with prescribing , advising , and examining consistent with high- quality diabetes care . Aim To develop and evaluate the effectiveness and cost of an intervention to improve multiple behaviours in clinicians involved in delivering high- quality care for type 2 diabetes . Design / methods We will conduct a two-armed cluster r and omised controlled trial in 44 general practice s in the North East of Engl and to evaluate a theory-based behaviour change intervention . We will target improvement in six underperformed clinical behaviours highlighted in quality st and ards for type 2 diabetes : prescribing for hypertension ; prescribing for glycaemic control ; providing physical activity advice ; providing nutrition advice ; providing on-going education ; and ensuring that feet have been examined . The primary outcome will be the proportion of patients appropriately prescribed and examined ( using anonymised computer records ) , and advised ( using anonymous patient surveys ) at 12 months . We will use behaviour change techniques targeting motivational , volitional , and impulsive factors that we have previously demonstrated to be predictive of multiple health professional behaviours involved in high- quality type 2 diabetes care . We will also investigate whether the intervention was delivered as design ed ( fidelity ) by coding audiotaped workshops and interventionist delivery reports , and operated as hypothesised ( process evaluation ) by analysing responses to theory-based postal question naires . In addition , we will conduct post-trial qualitative interviews with practice teams to further inform the process evaluation , and a post-trial economic analysis to estimate the costs of the intervention and cost of service use . Discussion Consistent with UK Medical Research Council guidance and building on previous development research , this pragmatic cluster r and omised trial will evaluate the effectiveness of a theory-based complex intervention focusing on changing multiple clinical behaviours to improve quality of diabetes care . Trial registration IS RCT N66498413 Background Theory-based process evaluations conducted alongside r and omized controlled trials provide the opportunity to investigate hypothesized mechanisms of action of interventions , helping to build a cumulative knowledge base and to inform the interpretation of individual trial outcomes . Our objective was to identify the underlying causal mechanisms in a cluster r and omized trial of the effectiveness of printed educational material s ( PEMs ) to increase referral for diabetic retinopathy screening . We hypothesized that the PEMs would increase physicians ’ intention to refer patients for retinal screening by strengthening their attitude and subjective norm , but not their perceived behavioral control . Methods Design : A theory based process evaluation alongside the Ontario Printed Educational Material ( OPEM ) cluster r and omized trial . Postal surveys based on the Theory of Planned Behavior were sent to a r and om sample of trial participants two months before and six months after they received the intervention . Setting : Family physicians in Ontario , Canada . Participants : 1,512 family physicians ( 252 per intervention group ) from the OPEM trial were invited to participate , and 31.3 % ( 473/1512 ) responded at time one and time two . The final sample comprised 437 family physicians fully completing question naires at both time points . Main outcome measures : Primary : behavioral intention related to referring patient for retinopathy screening ; secondary : attitude , subjective norm , perceived behavioral control . Results At baseline , family physicians reported positive intention , attitude , subjective norm , and perceived behavioral control to advise patients about retinopathy screening suggesting limited opportunities for improvement in these constructs . There were no significant differences on intention , attitude , subjective norm , and perceived behavioral control following the intervention . Respondents also reported additional physician- and patient-related factors perceived to influence whether patients received retinopathy screening . Conclusions Lack of change in the primary and secondary theory-based outcomes provides an explanation for the lack of observed effect of the main OPEM trial . High baseline levels of intention to advise patients to attend retinopathy screening suggest that post-intentional and other factors may explain gaps in care . Process evaluations based on behavioral theory can provide replicable and generalizable insights to aid interpretation of r and omized controlled trials of complex interventions to change health professional behavior . Trial registration IS RCT N72772651 Background The study aim ed to conduct a process evaluation for a cluster r and omised trial of a computer-delivered , point-of-care intervention to reduce antibiotic prescribing in primary care . The study aim ed to evaluate both the intervention and implementation of the trial . Methods The intervention comprised a set of electronic educational and decision support tools that were remotely installed and activated during consultations with patients with acute respiratory infections over a 12 month intervention period . A mixed method evaluation was conducted with 103 general practitioners ( GPs ) who participated in the trial . Semi-structured telephone interviews were conducted with 20 GPs who had been in the intervention group of the trial and 4 members of the implementation staff . Question naires , consisting of both intervention evaluation and theory-based measures , were self-administered to 83 GPs ( 56 control group and 27 intervention group ) . Results Interviews suggested that a key factor influencing GPs ’ use of the intervention appeared to be their awareness of the implementation of the system into their practice . GPs who were aware of the implementation of the intervention reported feeling confident in using it if they chose to and understood the purpose of the intervention screens . However , GPs who were unaware that the intervention would be appearing often reported feeling confused when they saw the messages appear on the screen and not fully underst and ing what they were for or how they could be used . Intervention evaluation question naires indicated that GPs were satisfied with the usability of the prompts , and theory-based measures revealed that intervention group GPs reported higher levels of self-efficacy in managing RTI patients according to recommended guidelines compared to GPs in the control group . Conclusions Remote installation of a computer-delivered intervention for use at the point-of-care was feasible and acceptable . Additional measures to promote awareness of the intervention may be required to promote health care professionals ’ utilisation of the intervention and these might sometimes compromise the pragmatic intention of a trial . Trial registration IS RCT N47558792 ( registered on 17 March 2010 ) Background Implementation of long-term condition management interventions rests on the notion of whole systems re- design , where incorporating wider elements of health care systems are integral to embedding effective and integrated solutions . However , most self-management support ( SMS ) evaluations still focus on particular elements or outcomes of a sub-system . A r and omised controlled trial of a SMS intervention ( WISE — Whole System Informing Self-management Engagement ) implemented in primary care showed no effect on patient-level outcomes . This paper reports on a parallel process evaluation to ascertain influences affecting WISE implementation at patient , clinical and organisational levels . Normalisation Process Theory ( NPT ) provided a sensitising background and analytical framework . Methods A multi- method approach using surveys and interviews with organisational stakeholders , practice staff and trial participants about impact of training and use of tools developed for WISE . Analysis was sensitised by NPT ( coherence , cognitive participation , collective action and reflective monitoring ) . The aim was to identify what worked and what did not work for who and in what context . Results Interviews with organisation stakeholders emphasised top-down initiation of WISE by managers who supported innovation in self-management . Staff from 31 practice s indicated engagement with training but patchy adoption of WISE tools ; SMS was neither prioritised by practice s nor fitted with a biomedically focussed ethos , so little effort was invested in WISE techniques . Interviews with 24 patients indicated no awareness of any changes following the training of practice staff ; furthermore , they did not view primary care as an appropriate place for SMS . Conclusion The results contribute to underst and ing why SMS is not routinely adopted and implemented in primary care . WISE was not embedded because of the perceived lack of relevance and fit to the ethos and existing work . Enacting SMS within primary care practice was not viewed as a legitimate activity or a professional priority . There was failure to , in principle , engage with and identify patients ' support needs . Policy presumptions concerning SMS appear to be misplaced . Implementation of SMS within the health service does not currently account for patient circumstances . Primary care priorities and support for SMS could be enhanced if they link to patients ' broader systems of implementation networks and re sources Background The results of r and omised controlled trials can be usefully illuminated by studies of the processes by which they achieve their effects . The Theory of Planned Behaviour ( TPB ) offers a framework for conducting such studies . This study used TPB to explore the observed effects in a pragmatic cluster r and omised controlled trial of a structured recall and prompting intervention to increase evidence -based diabetes care that was conducted in three Primary Care Trusts in Engl and . Methods All general practitioners and nurses in practice s involved in the trial were sent a postal question naire at the end of the intervention period , based on the TPB ( predictor variables : attitude ; subjective norm ; perceived behavioural control , or PBC ) . It focussed on three clinical behaviours recommended in diabetes care : measuring blood pressure ; inspecting feet ; and prescribing statins . Multivariate analyses of variance and multiple regression analyses were used to explore changes in cognitions and thereby better underst and trial effects . Results Fifty-nine general medical practitioners and 53 practice nurses ( intervention : n = 55 , 41.98 % of trial participants ; control : n = 57 , 38.26 % of trial participants ) completed the question naire . There were no differences between groups in mean scores for attitudes , subjective norms , PBC or intentions . Control group clinicians had ' normatively-driven ' intentions ( i.e. , related to subjective norm scores ) , whereas intervention group clinicians had ' attitudinally-driven ' intentions ( i.e. , related to attitude scores ) for foot inspection and statin prescription . After controlling for effects of the three predictor variables , this group difference was significant for foot inspection behaviour ( trial group × attitude interaction , beta = 0.72 , p < 0.05 ; trial group × subjective norm interaction , beta = -0.65 , p < 0.05 ) . Conclusion Attitudinally-driven intentions are proposed to be more consistently translated into action than normatively-driven intentions . This proposition was supported by the findings , thus offering an interpretation of the trial effects . This analytic approach demonstrates the potential of the TPB to explain trial effects in terms of different relationships between variables rather than differences in mean scores . This study illustrates the use of theory-based process evaluation to uncover processes underlying change in implementation trials Background Physical activity ( PA ) and nutrition are the cornerstones of diabetes management . Several review s and meta-analyses report that PA independently produces clinical ly important improvements in glucose control in people with Type 2 diabetes . However , it remains unclear what the optimal strategies are to increase PA behaviour in people with Type 2 diabetes in routine primary care . Methods This study will determine whether an evidence -informed multifaceted behaviour change intervention ( Movement as Medicine for Type 2 Diabetes ) targeting both consultation behaviour of primary healthcare professionals and PA behaviour in adults with Type 2 diabetes is both acceptable and feasible in the primary care setting . An open pilot study conducted in two primary care practice s ( phase one ) will assess acceptability , feasibility and fidelity . Ongoing feedback from participating primary healthcare professionals and patients will provide opportunities for systematic adaptation and refinement of the intervention and study procedures . A two-arm parallel group clustered pilot r and omised controlled trial with patients from participating primary care practice s in North East Engl and will assess acceptability , feasibility , and fidelity of the intervention ( versus usual clinical care ) and trial processes over a 12-month period . Consultation behaviour involving fidelity of intervention delivery , diabetes and PA related knowledge , attitudes/beliefs , intentions and self-efficacy for delivering a behaviour change intervention targeting PA behaviour will be assessed in primary healthcare professionals . We will rehearse the collection of outcome data ( with the focus on data yield and quality ) for a future definitive trial , through outcome assessment at baseline , one , six and twelve months . An embedded qualitative process evaluation and treatment fidelity assessment will explore issues around intervention implementation and assess whether intervention components can be reliably and faithfully delivered in routine primary care . Discussion Movement as Medicine for Type 2 Diabetes will address an important gap in the evidence -base , that is , the need for interventions to increase free-living PA behaviour in adults with Type 2 diabetes . The multifaceted intervention incorporates an online accredited training programme for primary healthcare professionals and represents , to the best of our knowledge , the first of its kind in the United Kingdom . This study will establish whether the multifaceted behavioural intervention is acceptable and feasible in routine primary care . Trial registration Movement as Medicine for Type 2 Diabetes ( MaMT2D ) was registered with Current Controlled Trials on the 14th January 2012 : IS RCT N67997502 . The first primary care practice was r and omised on the 5th October 2012 Background Involving service users in planning their care is at the centre of policy initiatives to improve mental health care quality in Engl and . Whilst users value care planning and want to be more involved in their own care , there is substantial empirical evidence that the majority of users are not fully involved in the care planning process . Our aim is to evaluate the effectiveness and cost-effectiveness of training for mental health professionals in improving user involvement with the care planning processes . Methods / Design This is a cluster r and omised controlled trial of community mental health teams in NHS Trusts in Engl and allocated either to a training intervention to improve user and carer involvement in care planning or control ( no training and care planning as usual).We will evaluate the effectiveness of the training intervention using a mixed design , including a ‘ cluster cohort ’ sample , a ‘ cluster cross-sectional ’ sample and process evaluation . Service users will be recruited from the caseloads of care co-ordinators . The primary outcome will be change in self-reported involvement in care planning as measured by the vali date d Health Care Climate Question naire . Secondary outcomes include involvement in care planning , satisfaction with services , medication side-effects , recovery and hope , mental health symptoms , alliance/engagement , well-being and quality of life . Cost- effectiveness will also be measured . A process evaluation informed by implementation theory will be undertaken to assess the extent to which the training was implemented and to gauge sustainability beyond the time-frame of the trial . Discussion It is hoped that the trial will generate data to inform mental health care policy and practice on care planning . Trial Registration NumberIS RCT N16488358 ( 14 May 2014 Background As pressure ulcers contribute to significant patient burden and increased health care costs , their prevention is a clinical priority . Our team developed and tested a complex intervention , a pressure ulcer prevention care bundle promoting patient participation in care , in a cluster-r and omised trial . The UK Medical Research Council recommends process evaluation of complex interventions to provide insight into why they work or fail and how they might be improved . This study aim ed to evaluate processes underpinning implementation of the intervention and explore end-users ’ perceptions of it , in order to give a deeper underst and ing of its effects . Methods A pre-specified , mixed- methods process evaluation was conducted as an adjunct to the main trial , guided by a framework for process evaluation of cluster-r and omised trials . Data was collected across eight Australian hospitals but mainly focused on the four intervention hospitals . Quantitative and qualitative data were collected across the evaluation domains : recruitment , reach , intervention delivery and response to intervention , at both cluster and individual patient level . Quantitative data were analysed using descriptive and inferential statistics . Qualitative data were analysed using thematic analysis . Results In the context of the main trial , which found a 42 % reduction in risk of pressure ulcer with the intervention that was not significant after adjusting for clustering and covariates , this process evaluation provides important insights . Recruitment and reach among clusters and individuals was high , indicating that patients , nurses and hospitals are willing to engage with a pressure ulcer prevention care bundle . Of 799 intervention patients in the trial , 96.7 % received the intervention , which took under 10 min to deliver . Patients and nurses accepted the care bundle , recognising benefits to it and describing how it enabled participation in pressure ulcer prevention ( PUP ) care . Conclusions This process evaluation found no major failures relating to implementation of the intervention . The care bundle was found to be easy to underst and and deliver , and it reached a large proportion of the target population and was found to be acceptable to patients and nurses ; therefore , it may be an effective way of engaging patients in their pressure ulcer prevention care and promoting evidence -based practise Background Women with breast cancer want to participate in treatment decision-making . Guidelines have confirmed the right of informed shared decision-making . However , previous research has shown that the implementation of informed shared decision-making is suboptimal for reasons of limited re sources of physicians , power imbalances between patients and physicians and missing evidence -based patient information . We developed an informed shared decision-making program for women with primary ductal carcinoma in situ ( DCIS ) . The program provides decision coaching for women by specialized nurses and aims at supporting involvement in decision-making and informed choices . In this trial , the informed shared decision-making program will be evaluated in breast care centers . Methods / Design A cluster r and omized controlled trial will be conducted to compare the informed shared decision-making program with st and ard care . The program comprises an evidence -based patient decision aid and training of physicians ( 2 hours ) and specialized breast care and oncology nurses ( 4 days ) in informed shared decision-making . Sixteen certified breast care centers will be included , with 192 women with primary DCIS being recruited . Primary outcome is the extent of patients ’ involvement in shared decision-making as assessed by the MAPPIN-Odyad ( Multifocal approach to the ‘ sharing ’ in shared decision-making : observer instrument dyad ) . Secondary endpoints include the sub- measures of the MAPPIN-inventory ( MAPPIN-Onurse , MAPPIN-Ophysician , MAPPIN-Opatient , MAPPIN-Qnurse , MAPPIN-Qpatient and MAPPIN-Qphysician ) , informed choice , decisional conflict and the duration of encounters . It is expected that decision coaching and the provision of evidence -based patient decision aids will increase patients ’ involvement in decision-making with informed choices and reduce decisional conflicts and duration of physician encounters . Furthermore , an accompanying process evaluation will be conducted . Discussion To our knowledge , this is the first study investigating the implementation of decision coaches in German breast care centers . Trial registration Current Controlled Trials IS RCT N46305518 , date of registration : 5 June 2015 Background Cardiovascular disease ( CVD ) is the leading cause of death and disability worldwide . Despite the widespread availability of evidence -based clinical guidelines and vali date d risk predication equations for prevention and management of CVD , their translation into routine practice is limited . We developed a multifaceted quality improvement intervention for CVD risk management which incorporates electronic decision support , patient risk communication tools , computerised audit and feedback tools , and monthly , peer-ranked performance feedback via a web portal . The intervention was implemented in a cluster r and omised controlled trial in 60 primary healthcare services in Australia . Overall , there were improvements in risk factor recording and in prescribing of recommended treatments among under-treated individuals , but it is unclear how this intervention was used in practice and what factors promoted or hindered its use . This information is necessary to optimise intervention impact and maximally implement it in a post-trial context . In this study protocol , we outline our methods to conduct a theory-based , process evaluation of the intervention . Our aims are to underst and how , why , and for whom the intervention produced the observed outcomes and to develop effective strategies for translation and dissemination . Methods / Design We will conduct four discrete but inter-related studies taking a mixed methods approach . Our quantitative studies will examine ( 1 ) the longer term effectiveness of the intervention post-trial , ( 2 ) patient and health service level correlates with trial outcomes , and ( 3 ) the health economic impact of implementing the intervention at scale . The qualitative studies will ( 1 ) identify healthcare provider perspectives on implementation barriers and enablers and ( 2 ) use video ethnography and patient semi-structured interviews to underst and how cardiovascular risk is communicated in the doctor/patient interaction both with and without the use of intervention . We will also assess the costs of implementing the intervention in Australian primary healthcare setting s which will inform scale-up considerations . Discussion This mixed methods evaluation will provide a detailed underst and ing of the process of implementing a quality improvement intervention and identify the factors that might influence scalability and sustainability . Trials registration 12611000478910 Background In Victoria , Australia , Maternal and Child Health ( MCH ) services deliver primary health care to families with children 0–6 years , focusing on health promotion , parenting support and early intervention . Family violence ( FV ) has been identified as a major public health concern , with increased prevalence in the child-bearing years . Victorian Government policy recommends routine FV screening of all women attending MCH services . Using Normalization Process Theory ( NPT ) , we aim ed to underst and the barriers and facilitators of implementing an enhanced screening model into MCH nurse clinical practice . Methods NPT informed the process evaluation of a pragmatic , cluster r and omised controlled trial in eight MCH nurse teams in metropolitan Melbourne , Victoria , Australia . Using mixed methods ( surveys and interviews ) , we explored the views of MCH nurses , MCH nurse team leaders , FV liaison workers and FV managers on implementation of the model . Quantitative data were analysed by comparing proportionate group differences and change within trial arm over time between interim and impact nurse surveys . Qualitative data were inductively coded , thematically analysed and mapped to NPT constructs ( coherence , cognitive participation , collective action and reflexive monitoring ) to enhance our underst and ing of the outcome evaluation . Results MCH nurse participation rates for interim and impact surveys were 79 % ( 127/160 ) and 71 % ( 114/160 ) , respectively . Twenty-three key stakeholder interviews were completed . FV screening work was meaningful and valued by participants ; however , the implementation coincided with a significant ( government directed ) change in clinical practice which impacted on full engagement with the model ( coherence and cognitive participation ) . The use of MCH nurse- design ed FV screening/management tools in focussed women ’s health consultations and links with FV services enhanced the participants ’ work ( collective action ) . Monitoring of FV work ( reflexive monitoring ) was limited . Conclusions The use of theory-based process evaluation helped identify both what inhibited and enhanced intervention effectiveness . Successful implementation of an enhanced FV screening model for MCH nurses occurred in the context of focussed women ’s health consultations , with the use of a maternal health and wellbeing checklist and greater collaboration with FV services . Improving links with these services and the ongoing appraisal of nurse work would overcome the barriers identified in this study Background In Engl and , NHS Blood and Transplant conducts national audits of transfusion and provides feedback to hospitals to promote evidence -based practice . Audits demonstrate 20 % of transfusions fall outside guidelines . The AFFINITIE programme ( Development & Evaluation of Audit and Feedback INterventions to Increase evidence -based Transfusion practIcE ) involves two linked , 2 × 2 factorial , cluster-r and omised trials , each evaluating two theoretically-enhanced audit and feedback interventions to reduce unnecessary blood transfusions in UK hospitals . The first intervention concerns the content/format of feedback reports . The second aims to support hospital transfusion staff to plan their response to feedback and includes a web-based toolkit and telephone support . Interpretation of trials is enhanced by comprehensively assessing intervention fidelity . However , review s demonstrate fidelity evaluations are often limited , typically only assessing whether interventions were delivered as intended . This protocol presents methods for assessing fidelity across five dimensions proposed by the Behaviour Change Consortium fidelity framework , including intervention design er- , provider- and recipient-levels . Methods ( 1 ) Design : Intervention content will be specified in intervention manuals in terms of component behaviour change techniques ( BCTs ) . Treatment differentiation will be examined by comparing BCTs across intervention/st and ard practice , noting the proportion of unique/convergent BCTs . ( 2 ) Training : draft feedback reports and audio-recorded role-play telephone support scenarios will be content analysed to assess intervention providers ’ competence to deliver manual-specified BCTs . ( 3 ) Delivery : intervention material s ( feedback reports , toolkit ) and audio-recorded telephone support session transcripts will be content analysed to assess actual delivery of manual-specified BCTs during the intervention period . ( 4 ) Receipt and ( 5 ) enactment : question naires , semi-structured interviews based on the Theoretical Domains Framework , and objective web-analytics data ( report downloads , toolkit usage patterns ) will be analysed to assess hospital transfusion staff exposure to , underst and ing and enactment of the interventions , and to identify context ual barriers/enablers to implementation . Associations between observed fidelity and trial outcomes ( % unnecessary transfusions ) will be examined using mediation analyses . Discussion If the interventions have acceptable fidelity , then results of the AFFINITIE trials can be attributed to effectiveness , or lack of effectiveness , of the interventions . Hence , this comprehensive assessment of fidelity will be used to interpret trial findings . These methods may inform fidelity assessment s in future trials . Trial registration IS RCT N 15490813 . Registered Background Mild head injuries commonly present to emergency departments . The challenges facing clinicians in emergency departments include identifying which patients have traumatic brain injury , and which patients can safely be sent home . Traumatic brain injuries may exist with subtle symptoms or signs , but can still lead to adverse outcomes . Despite the existence of several high quality clinical practice guidelines , internationally and in Australia , research shows inconsistent implementation of these recommendations . The aim of this trial is to test the effectiveness of a targeted , theory- and evidence -informed implementation intervention to increase the uptake of three key clinical recommendations regarding the emergency department management of adult patients ( 18 years of age or older ) who present following mild head injuries ( concussion ) , compared with passive dissemination of these recommendations . The primary objective is to establish whether the intervention is effective in increasing the percentage of patients for which appropriate post-traumatic amnesia screening is performed . Methods / design The design of this study is a cluster r and omised trial . We aim to include 34 Australian 24-hour emergency departments , which will be r and omised to an intervention or control group . Control group departments will receive a copy of the most recent Australian evidence -based clinical practice guideline on the acute management of patients with mild head injuries . The intervention group will receive an implementation intervention based on an analysis of influencing factors , which include local stakeholder meetings , identification of nursing and medical opinion leaders in each site , a train-the-trainer day and st and ardised education and interactive workshops delivered by the opinion leaders during a 3 month period of time . Clinical practice outcomes will be collected retrospectively from medical records by independent chart auditors over the 2 month period following intervention delivery ( patient level outcomes ) . In consenting hospitals , eligible patients will be recruited for a follow-up telephone interview conducted by trained research ers . A cost-effectiveness analysis and process evaluation using mixed- methods will be conducted . Sample size calculations are based on including 30 patients on average per department . Outcome assessors will be blinded to group allocation . Trial registration Australian New Zeal and Clinical Trials Registry ACTRN12612001286831 ( date registered 12 December 2012 ) Background : Primary care physicians ( PCPs ) are optimally situated to identify and manage early stage chronic kidney disease ( CKD ) . Nonetheless , studies have documented suboptimal PCP underst and ing , awareness , and management of early CKD . The TRANSLATE CKD study is an ongoing national , mixed- methods , cluster r and omized control trial that examines the implementation of evidence -based guidelines for CKD into primary care practice . Methods : As part of the mixed- methods process evaluation , semistructured interviews were conducted by phone with 27 providers participating in the study . Interviews were audio-taped and transcribed . Thematic content analysis was used to identify themes . Themes were categorized according to the 4 domains of Normalization Process Theory ( NPT ) . Results : Identified themes illuminated the complex work undertaken to manage CKD in primary care practice s. Barriers to guideline implementation were identified in each of the 4 NPT domains , including ( 1 ) lack of knowledge and underst and ing around CKD ( coherence ) , ( 2 ) difficulties engaging providers and patients in CKD management ( cognitive participation ) , ( 3 ) limited time and competing dem and s ( collective action ) , and ( 4 ) challenges obtaining and using data to monitor progress ( reflexive monitoring ) . Conclusions : Addressing the barriers to implementation with concrete interventions at the levels at which they occur , informed by NPT , will ultimately improve the quality of CKD patient care AIM Our objective was to evaluate the effect of training in a patient-centred intervention for GPs and practice nurses on outcomes for patients with Type II diabetes . METHODS We carried out a r and omized controlled trial within general practice s as the basis for r and omization and a before- and -after design for measures of patient outcome . A parallel process study examined the use of the method by professionals . The study was carried out in 29 general practice s in South Glamorgan who had participated for at least 2 years in a local scheme of audit and CME in relation to Type II diabetes care . The subjects were 252 Type II diabetic patients recruited by 15 experimental and 14 control practice s. The main outcome measures were changes in glycosylated haemoglobin , patient satisfaction with care and treatment , functional health status and professional ability to apply the intervention . RESULTS Professionals adopted the innovative method with enthusiasm , but after 2 years only 19 % continued to apply the method systematic ally . The trial was , therefore , unable to demonstrate significant biochemical or functional improvements . This highlights the need to underst and the factors associated with professional uptake and subsequent ability to sustain changes in behaviour . CONCLUSIONS The efficacy of this behavioural intervention remains unproved , despite its acceptability to professional staff . Detailed and prolonged development and testing of behavioural interventions is an essential first step before embarking on r and omized controlled trials which involve complex behavioural changes in professionals or patients Public concern about the prescription of hypnosedative drugs ( mostly benzodiazepines ) led to a controlled trial of an educational intervention to promote rational prescribing by general practitioners ( GPs ) . This paper describes the educational intervention and its process evaluation . In urban and rural New South Wales 137 GPs were visited in office hours by a GP or pharmacist who had undergone communication skills training . Material offered to GPs included relaxation tapes and a booklet of problem-orientated management guidelines . The interview had three stages : rapport was established , then educational material was introduced and finally the visitor sought the doctor 's agreement to review five patients on long-term benzodiazepines . The visits were well received . Several measures were composed to reflect doctors ' motivation and interest in non-drug management ; there was virtually no correlation between any of these process measures and the trial outcome : a change in prescribing behaviour . Self-rating of benzodiazepine prescribing greatly underestimated actual self-reported incidents of prescribing . We interpret this as a reminder that we do not always do what we mean to do , and that we do not always do what we think we do Background The gap between the level of care recommended by evidence -based clinical practice guidelines and the actual care delivered to patients in practice has been well established . The Canadian Diabetes Association ( CDA ) created an implementation strategy to improve the implementation of its 2008 guidelines . This study will evaluate the impact of the strategy to improve cardiovascular disease ( CVD ) screening , prevention and treatment for people with diabetes . Design A pragmatic cluster-r and omized trial will be conducted to evaluate the CDA 's CVD Toolkit . All family physicians in Ontario , Canada were r and omly allocated to receive the Toolkit , which includes several printed educational material s targeting CVD screening , prevention and treatment , either in spring 2009 ( intervention arm ) or in spring 2010 ( control arm ) . R and omization occurred at the level of the practice . Forty family physicians from each arm will be recruited to participate , and the medical records for 20 of their diabetic patients at high risk for CVD will be retrospectively review ed . Outcome measures will be assessed for each patient between July 2009 and March 2010 . The primary outcome will be that the patient is receiving a statin . Secondary outcomes will include 1 ) the receipt of an angiotensin converting enzyme inhibitor or angiotensin receptor blocker , 2 ) various intermediate measures ( A1c , blood pressure , LDL-cholesterol , total-/HDL-cholesterol ratio , body mass index and waist circumference ) , and 3 ) clinical inertia ( the failure to change therapy in response to an abnormal A1c , blood pressure or cholesterol reading ) . The analysis will be carried out using multilevel hierarchical logistic regression models to account for the clustered nature of the data . The group assignment will be a physician-level variable . In addition , a process evaluation study with six focus groups of family physicians will assess the acceptability of the CDA 's Toolkit and will explore factors contributing to any change or lack of change in behaviour , from the perspectives of family physicians . Discussion Printed educational material s for physicians have been shown to exert small-to-moderate changes in patient care . The CDA 's CVD Toolkit is an example of a practice guideline implementation strategy that can be disseminated to a wide audience relatively inexpensively , and so demonstrating its effectiveness at improving diabetes care could have important consequences for guideline developers , policy makers and clinicians . Trial Registration The trial is registered with http://www . clinical trials.gov , ID # BACKGROUND Interventions in health setting s for intimate partner violence ( IPV ) are being increasingly recognised as part of a response to addressing this global public health problem . However , interventions targeting this sensitive social phenomenon are complex and highly susceptible to context . This study aim ed to eluci date factors involved in women 's uptake of a counselling intervention delivered by family doctors in the weave primary care trial ( Victoria , Australia ) . METHODS We analysed associations between women 's and doctors ' baseline characteristics and uptake of the intervention . We interviewed a r and om selection of 20 women from an intervention group women to explore cognitions relating to intervention uptake . Interviews were audio-recorded , transcribed , coded in NVivo 10 and analysed using the theory of planned behaviour ( TPB ) . RESULTS Abuse severity and socio-demographic characteristics ( apart from current relationship status ) were unrelated to uptake of counselling ( 67/137 attended sessions ) . Favourable doctor communication was strongly associated with attendance . Eight themes emerged , including four sets of beliefs that influenced attitudes to uptake : ( i ) awareness of the abuse and readiness for help ; ( ii ) weave as an avenue to help ; ( iii ) doctor 's communication ; and ( iv ) role in providing care for IPV ; and four sets of beliefs regarding women 's control over uptake : ( v ) emotional health , ( vi ) doctors ' time , ( vii ) managing the disclosure process and ( viii ) viewing primary care as a safe option . CONCLUSIONS This study has identified factors that can promote the implementation and evaluation of primary care-based IPV interventions , which are relevant across health research setting s , for example , ensuring fit between implementation strategies and characteristics of the target group ( such as range in readiness for intervention ) . On practice implication s , providers ' communication remains a key issue for engaging women . A key message arising from this work concerns the critical role of primary care and health services more broadly in reaching victims of domestic violence , and providing immediate and ongoing support ( depending on the healthcare context ) BACKGROUND When improving patient safety a positive safety culture is key . As little is known about improving patient safety culture in primary care , this study examined whether administering a culture question naire with or without a complementary workshop could be used as an intervention for improving safety culture . AIM To gain insight into how two interventions affected patient safety culture in everyday practice . DESIGN AND SETTING After conducting a r and omised control trial of two interventions , this was a qualitative study conducted in 30 general practice s to aid interpretation of the previous quantitative findings . METHOD Interviews were conducted at practice locations ( n = 27 ) with 24 GPs and 24 practice nurses . The theory of communities of practice --in particular , its concepts of a domain , a community , and a practice --was used to interpret the findings by examining which elements were or were not present in the participating practice s. RESULTS Communal awareness of the problem was only raised after getting together and discussing patient safety . The combination of a question naire and workshop enhanced the interaction of team members and nourished team feelings . This shared experience also helped them to underst and and develop tools and language for daily practice . CONCLUSION In order for patient safety culture to improve , the safety culture question naire was more successful when accompanied by a practice workshop . Initial discussion and negotiation of shared goals during the workshop fuelled feelings of coherence and belonging to a community wishing to learn about enhancing patient safety . Team meetings and day-to-day interactions enhanced further liaison and sharing , making patient safety a common and conscious goal Background There is only limited underst and ing of why h and hygiene improvement strategies are successful or fail . It is therefore important to look inside the ‘ black box ’ of such strategies , to ascertain which components of a strategy work well or less well . This study examined which components of two h and hygiene improvement strategies were associated with increased nurses ’ h and hygiene compliance . Methods A process evaluation of a cluster r and omised controlled trial was conducted in which part of the nursing wards of three hospitals in the Netherl and s received a state-of-the-art strategy , including education , reminders , feedback , and optimising material s and facilities ; another part received a team and leaders-directed strategy that included all elements of the state-of-the-art strategy , supplemented with activities aim ed at the social and enhancing leadership . This process evaluation used four sets of measures : effects on nurses ’ h and hygiene compliance , adherence to the improvement strategies , context ual factors , and nurses ’ experiences with strategy components . Analyses of variance and multiple regression analyses were used to explore changes in nurses ’ h and hygiene compliance and thereby better underst and trial effects . Results Both strategies were performed with good adherence to protocol . Two context ual factors were associated with changes in h and hygiene compliance : a hospital effect in long term ( p < 0.05 ) , and high h and hygiene baseline scores were associated with smaller effects ( p < 0.01 ) . In short term , changes in nurses ’ h and hygiene compliance were positively correlated with experienced feedback about their h and hygiene performance ( p < 0.05 ) . In the long run , several items of the components ‘ social influence ’ ( i.e. , addressing each other on undesirable h and hygiene behaviour p < 0.01 ) , and ‘ leadership ’ ( i.e. , ward manager holds team members accountable for h and hygiene performance p < 0.01 ) correlated positively with changes in nurses ’ h and hygiene compliance . Conclusion This study illustrates the use of a process evaluation to uncover mechanisms underlying change in h and hygiene improvement strategies . Our study results demonstrate the added value of specific aspects of social influence and leadership in h and hygiene improvement strategies , thus offering an interpretation of the trial effects . Trial registration The study is registered in Clinical Trials.gov , dossier number : NCT00548015 |
14,052 | 30,571,754 | In patients with advanced cancer and a prognosis < 2 years , the addition of statins to st and ard anti-cancer therapy does not appear to improve overall survival or progression-free survival . | BACKGROUND Pre clinical evidence suggests statins may have anti-tumor properties .
Large observational studies are also consistent with improved survival and cancer-specific outcomes among cancer patients on statins .
We sought to evaluate the r and omized controlled trials of statins in addition to usual anti-cancer therapy . | Purpose Treating small-cell lung cancer ( SCLC ) remains a therapeutic challenge . Experimental studies show that statins exert additive effects with agents , such as cisplatin , to impair tumor growth , and observational studies suggest that statins combined with anticancer therapies delay relapse and prolong life in several cancer types . To our knowledge , we report the first large , r and omized , placebo-controlled , double-blind trial of a statin with st and ard-of-care for patients with cancer , specifically SCLC . Patients and Methods Patients with confirmed SCLC ( limited or extensive disease ) and performance status 0 to 3 were r and omly assigned to receive daily pravastatin 40 mg or placebo , combined with up to six cycles of etoposide plus cisplatin or carboplatin every 3 weeks , until disease progression or intolerable toxicity . Primary end point was overall survival ( OS ) , and secondary end points were progression-free survival ( PFS ) , response rate , and toxicity . Results Eight hundred forty-six patients from 91 United Kingdom hospitals were recruited . The median age of recruited patients was 64 years of age , 43 % had limited disease , and 57 % had extensive disease . There were 758 deaths and 787 PFS events . No benefit was found for pravastatin , either in all patients or in several subgroups . For pravastatin versus placebo , the 2-year OS rate was 13.2 % ( 95 % CI , 10.0 to 16.7 ) versus 14.1 % ( 95 % CI , 10.9 to 17.7 ) , respectively , with a hazard ratio of 1.01 ( 95 % CI , 0.88 to 1.16 ; P = .90 . The median OS was 10.7 months v 10.6 months , respectively . The median PFS was 7.7 months v 7.3 months , respectively . The median OS ( pravastatin v placebo ) was 14.6 months in both groups for limited disease and 9.1 months versus 8.8 months , respectively , for extensive disease . Adverse events were similar between groups . Conclusion Pravastatin 40 mg combined with st and ard SCLC therapy , although safe , does not benefit patients . Our conclusions are the same as those found in all four much smaller , r and omized , placebo-controlled trials specifically design ed to evaluate statin therapy in patients with cancer Abstract Background Statins have potential antineoplastic properties via arrest of cell-cycle progression and induction of apoptosis . A previous study demonstrated in vitro and in vivo antineoplastic synergism between statins and gemcitabine . The present r and omized , double-blinded , phase II trial compared the efficacy and safety of gemcitabine plus simvastatin ( GS ) with those of gemcitabine plus placebo ( GP ) in patients with locally advanced and metastatic pancreatic cancer . Methods Patients were r and omly assigned to receive a 3-week regimen with GS ( gemcitabine 1,000 mg/m2 on days 1 , 8 , and 15 plus simvastatin 40 mg once daily ) or GP ( gemcitabine 1,000 mg/m2 on days 1 , 8 , and 15 plus placebo ) . The primary end point was time to progression ( TTP ) . Results Between December 2008 and April 2012 , 114 patients were enrolled . The median TTP was not significantly different between the two arms , being 2.4 months ( 95 % CI 0.7–4.1 months ) and 3.6 months ( 95 % CI 3.1–4.1 months ) in the GS and GP arms , respectively ( P = 0.903 ) . The overall disease control rate was 39.7 % ( 95 % CI 12.2–33.8 % ) and 57.1 % ( 95 % CI 19.8–44.2 % ) in the GS and GP arms , respectively ( P = 0.09 ) . The 1-year expected survival rates were similar ( 27.7 and 31.7 % in the GS and GP arms , respectively ; P = 0.654 ) . Occurrence of grade 3 or 4 adverse events was similar in both arms , and no patients had rhabdomyolysis . Conclusions Adding low-dose simvastatin to gemcitabine in advanced pancreatic cancer does not provide clinical benefit , although it also does not result in increased toxicity . Given the emerging role of statins in overcoming resistance to anti-EGFR treatment , further studies are justified to evaluate the efficacy and safety of combined simvastatin and anti-EGFR agents , such as erlotinib or cetuximab , plus gemcitabine for treating advanced pancreatic cancer Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more Chemotherapy is not effective for hepatocellular carcinoma ( HCC ) . HMG-CoA redutase inhibitors have cytostatic activity for cancer cells , but their clinical usefulness is unknown . To investigate whether pravastatin , a potent HMG-CoA reductase inhibitor , prolongs survival in patients with advanced HCC , this r and omized controlled trial was conducted between February 1990 and February 1998 at Osaka University Hospital . 91 consecutive patients < 71 years old ( mean age 62 ) with unresectable HCC were enroled in this study . 8 patients were withdrawn because of progressive liver dysfunction ; 83 patients were r and omized to st and ard treatment with or without pravastatin . All patients underwent transcatheter arterial embolization ( TAE ) followed by oral 5-FU 200 mg–1d for 2 months . Patients were then r and omly assigned to control ( n = 42 ) and pravastatin ( n = 41 ) groups . Pravastatin was administered at a daily dose of 40 mg . The effect of pravastatin on tumour growth was assessed by ultrasonography . Primary endpoint was death due to progression of HCC . The duration of pravastatin administration was 16.5 ± 9.8 months ( mean ± SD ) . No patients in either group were lost to follow-up . Median survival was 18 months in the pravastatin group versus 9 months in controls ( P = 0.006 ) . The Cox proportional hazards model showed that pravastatin was a significant factor contributing to survival . Pravastatin prolonged the survival of patients with advanced HCC , suggesting its value for adjuvant treatment . © 2001 Cancer Research Purpose : To evaluate the efficacy and safety of gefitinib plus simvastatin ( GS ) versus gefitinib alone ( G ) in previously treated patients with advanced non – small cell lung cancer ( NSCLC ) . Experimental Design : Between May 2006 and September 2008 , 106 patients ( 51 % men , 75 % adenocarcinoma , 50 % never smoker ) were r and omly assigned to G alone ( 250 mg/d , n = 54 ) or GS ( 250 and 40 mg/d , respectively , n = 52 ) . One cycle was 4 weeks of treatment . Therapy was continued until disease progression or intolerable toxicity was observed . The primary endpoint was response rate ( RR ) . Secondary endpoints included toxicity , progression-free survival ( PFS ) , and overall survival ( OS ) . Results : The RR was 38.5 % ( 95 % CI , 25.3–51.7 ) for GS and 31.5 % ( 95 % CI , 19.1–43.9 ) for G. The median PFS was 3.3 months [ M ] ( 95 % CI , 1.4–5.2 M ) for GS and 1.9 M ( 95 % CI , 1.0–2.8 M ) for G. The median OS was 13.6 M ( 95 % CI , 7.1–20.1 M ) for GS and 12.0 M ( 95 % CI , 7.8–16.2 M ) for G. In exploratory subgroup analysis , GS showed higher RR ( 40 % vs. 0 % , P = 0.043 ) and longer PFS ( 3.6 M vs. 1.7 M , P = 0.027 ) compared with G alone in patients with wild-type epidermal growth factor receptor ( EGFR ) nonadenocarcinomas . Adverse events in both arms were generally mild and mainly consisted of skin rashes . Conclusions : Although no superiority of GS to G was demonstrated in this unselected NSCLC population , GS showed higher RR and longer PFS compared with G alone in patients with wild-type EGFR nonadenocarcinomas . Simvastatin may improve the efficacy of gefitinib in that subgroup of gefitinib-resistant NSCLC patients . Clin Cancer Res ; 17(6 ) ; 1553–60 . © 2011 AACR Purpose This phase II study examined whether the addition of simvastatin to afatinib provides a clinical benefit compared with afatinib monotherapy in previously treated patients with nonadenocarcinomatous non-small cell lung cancer ( NA-NSCLC ) . Material s and Methods Patients with advanced NA-NSCLC who progressed after one or two chemotherapy regimens were r and omly assigned to a simvastatin ( 40 mg/day ) plus afatinib ( 40 mg/day ) ( AS ) arm or to an afatinib ( A ) arm . The primary endpoint was response rate ( RR ) . Results Sixty-eight patients were enrolled ( 36 in the AS arm and 32 in the A arm ) . The RR was 5.7 % ( 95 % confidence interval [ CI ] , 0.7 to 19.2 ) for AS and 9.4 % ( 95 % CI , 2.0 to 25.0 ) for A ( p=0.440 ) . In arms AS and A , the median progression-free survival ( PFS ) was 1.0 versus 3.6 months ( p=0.240 ) and the overall survival was 10.0 months versus 7.0 months ( p=0.930 ) , respectively . Skin rash , stomatitis , and diarrhea were the most common adverse events in both arms . More grade 3 or 4 diarrhea was observed in arm A ( 18.8 % vs. 5.6 % in arm AS ) . In all patients , the median PFS for treatment including afatinib was not correlated with the status of epidermal growth factor receptor ( EGFR ) mutation ( p=0.122 ) , EGFR fluorescence in situ hybridization ( p=0.944 ) , or EGFR immunohistochemistry ( p=0.976 ) . However , skin rash severity was significantly related to the risk of progression for afatinib ( hazard ratio for skin rash grade ≥ 2 vs. grade < 2 , 0.44 ; 95 % CI , 0.25 to 0.78 ; p=0.005 ) . Conclusion There were no significant differences in the efficacy between AS and A arms in patients with NA-NSCLC BACKGROUND Previous trials have shown that the use of statins to lower cholesterol reduces the risk of cardiovascular events among persons without cardiovascular disease . Those trials have involved persons with elevated lipid levels or inflammatory markers and involved mainly white persons . It is unclear whether the benefits of statins can be extended to an intermediate-risk , ethnically diverse population without cardiovascular disease . METHODS In one comparison from a 2-by-2 factorial trial , we r and omly assigned 12,705 participants in 21 countries who did not have cardiovascular disease and were at intermediate risk to receive rosuvastatin at a dose of 10 mg per day or placebo . The first co primary outcome was the composite of death from cardiovascular causes , nonfatal myocardial infa rct ion , or nonfatal stroke , and the second co primary outcome additionally included revascularization , heart failure , and resuscitated cardiac arrest . The median follow-up was 5.6 years . RESULTS The overall mean low-density lipoprotein cholesterol level was 26.5 % lower in the rosuvastatin group than in the placebo group . The first co primary outcome occurred in 235 participants ( 3.7 % ) in the rosuvastatin group and in 304 participants ( 4.8 % ) in the placebo group ( hazard ratio , 0.76 ; 95 % confidence interval [ CI ] , 0.64 to 0.91 ; P=0.002 ) . The results for the second co primary outcome were consistent with the results for the first ( occurring in 277 participants [ 4.4 % ] in the rosuvastatin group and in 363 participants [ 5.7 % ] in the placebo group ; hazard ratio , 0.75 ; 95 % CI , 0.64 to 0.88 ; P<0.001 ) . The results were also consistent in subgroups defined according to cardiovascular risk at baseline , lipid level , C-reactive protein level , blood pressure , and race or ethnic group . In the rosuvastatin group , there was no excess of diabetes or cancers , but there was an excess of cataract surgery ( in 3.8 % of the participants , vs. 3.1 % in the placebo group ; P=0.02 ) and muscle symptoms ( in 5.8 % of the participants , vs. 4.7 % in the placebo group ; P=0.005 ) . CONCLUSIONS Treatment with rosuvastatin at a dose of 10 mg per day result ed in a significantly lower risk of cardiovascular events than placebo in an intermediate-risk , ethnically diverse population without cardiovascular disease . ( Funded by the Canadian Institutes of Health Research and AstraZeneca ; HOPE-3 Clinical Trials.gov number , NCT00468923 . ) PURPOSE We aim ed to the addition of synthetic 3-hydroxy-3-methyglutaryl coenzyme A ( HMG-CoA ) reductase inhibitor , simvastatin to capecitabine-cisplatin ( XP ) in patients with previously untreated advanced gastric cancer ( AGC ) . METHODS In this double-blind , placebo-controlled , phase III study , we enrolled patients aged 18 years or older with histological or cytological confirmed metastatic adenocarcinoma of the stomach or gastroesophageal junction ( GEJ ) at nine centres in Korea . Patients , stratified by disease measurability and participating site , were r and omly assigned ( 1:1 ) to receive capecitabine 1000mg/m(2 ) twice daily for 14 days and cisplatin 80 mg/m(2 ) on day 1 every 3 weeks plus either simvastatin 40 mg or placebo , once daily . Cisplatin was given for 8 cycles ; capecitabine and simvastatin were administered until disease progression or unacceptable toxicities . This study is registered with Clinical Trials.gov , number NCT01099085 . RESULTS Between February 2009 and November 2012 , 244 patients were enrolled and assigned to treatment groups ( 120 simvastatin , 124 placebo ) . Median progression free survival ( PFS ) for 120 patients allocated XP plus simvastatin was 5.2 months ( 95 % confidence interval ( CI ) 4.3 - 6.1 ) compared with 4.63 months ( 95 % CI 3.5 - 5.7 ) for 124 patients who were allocated to XP plus placebo ( hazard ratio 0.930 , 95 % CI 0.684 - 1.264 ; p=0.642 ) . 63 ( 52.5 % ) of 120 patients in simvastatin group and 70 ( 56.4 % ) of 124 had grade 3 or higher adverse events . CONCLUSIONS Addition of 40 mg simvastatin to XP does not increase PFS in our trial , although it does not increase toxicity . Low dose of simvastatin ( 40 mg ) to chemotherapy is not recommended in untargeted population with AGC PURPOSE Statins have for long been considered to play a potential role in anticancer treatment based upon their ability to inhibit the mevalonate synthesis pathway . This r and omised phase II trial compared the efficacy and safety of pravastatin added to epirubicin , cisplatin and capecitabine ( ECC versus ECC+P ) in patients with advanced gastric carcinoma . METHODS Patients were r and omised to receive up to six cycles of 3-weekly ECC with or without pravastatin ( 40 mg , once daily from day 1 of the first cycle until day 21 of the last cycle ) . Primary end-point was progression-free rate at 6 months ( PFR(6 months ) ) . Secondary end-points were response rate ( RR ) , progression-free survival ( PFS ) , overall survival ( OS ) and safety . For early termination in case of futility , a two-stage design was applied ( P(0 ) = 50 % ; P(1 ) = 70 % ; α = 0.05 ; β = 0.10 ) . RESULTS Thirty patients were enrolled . PFR(6 months ) was 6/14 patients ( 42.8 % ) in the ECC+P arm , and 7/15 patients ( 46.7 % ) in the control arm , and therefore the study was terminated after the first stage . In the ECC and ECC+P arm , RR was 7/15 ( 46.7 % ) and 5/15 ( 33.3 % ) , median PFS was 5 and 6 months and median OS was 6 and 8 months , respectively . Toxicity data showed no significant differences , although there was a trend towards more gastrointestinal side-effects such as diarrhoea and stomatitis in the ECC+P arm . CONCLUSION In this r and omised phase II trial the addition of pravastatin to ECC did not improve outcome in patients with advanced gastric cancer . Therefore , further testing of this combination in a r and omised phase III trial can not be recommended |
14,053 | 32,161,868 | Conclusion Results of the present systematic review indicate that there is no clear evidence supporting that preoperative ibuprofen is better than other drugs in reducing the risk and intensity of postendodontic pain | Objective This systematic review aims to evaluate the effects of ibuprofen compared to other drugs on the risk and intensity of postoperative pain result ing from endodontic treatment in adult patients . | INTRODUCTION The extrusion of irrigation solutions beyond the apical constriction may result in postoperative pain . Sodium hypochlorite can cause severe tissue irritation and necrosis outside the root canal system if extruded into the periodontal ligament ( PDL ) space . Different delivery techniques were discussed to reduce this potential risk . The aim of this study was to compare the postoperative level of pain after root canal therapy using either endodontic needle irrigation or a negative apical pressure device . MATERIAL AND METHODS In a prospect i ve r and omized clinical trial , 110 asymptomatic single-rooted anterior and premolar teeth were treated endodontically with two different irrigation techniques . The teeth were r and omly assigned to two groups . In the MP group ( n = 55 ) , procedures were performed using an endodontic irrigating syringe ( Max-i-Probe ; Dentsply Rinn , Elgin , IL ) . The EV group ( n = 55 ) used an irrigation device based on negative apical pressure ( EndoVac ; Discus Dental , Culver City , CA ) . Postoperatively , the patients were prescribed ibuprofen 200 mg to take every 8 hours if required . Pain levels were assessed by an analog scale question naire after 4 , 24 , and 48 hours . The amount of ibuprofen taken was recorded at the same time intervals . RESULTS During the 0- to 4- , 4- to 24- , and 24- to 48-hour intervals after treatment , the pain experience with the negative apical pressure device was significantly lower than when using the needle irrigation ( p < 0.0001 [ 4 , 24 , 48 hours ] ) . Between 0 and 4 and 4 and 24 hours , the intake of analgesics was significantly lower in the group treated by the negative apical pressure device ( p < 0.0001 [ 0 - 4 hours ] , p = 0.001 [ 4 - 24 hours ] ) . The difference for the 24- to 48-hour period was not statistically different ( p = 0.08 ) . The Pearson correlation coefficient revealed a strongly positive and significant relationship for the MP group ( r = 0.851 , p < 0.001 ) and the EV group ( r = 0.596 , p < 0.0001 ) between pain intensity and the amount of analgesics . CONCLUSION The outcome of this investigation indicates that the use of a negative apical pressure irrigation device can result in a significant reduction of postoperative pain levels in comparison to conventional needle irrigation OBJECTIVES This prospect i ve study was conducted to determine whether there is any significant difference in the incidence of postobturation pain after single- and multiple-visit root canal treatment ( RCT ) . METHODS The frequency of postobturation pain was recorded and evaluated over an observation period of 30 days in 291 of 300 consecutive patients receiving RCT . The patients were assigned r and omly and consecutively into either single- or multiple-visit groups . The canals of all teeth were prepared and filled by a single operator using the step-back and lateral condensation techniques . The data were analysed statistically to determine the relationship , if any , between the pain experienced and pulpal vitality , tooth type , pre-operative pain , and the sex and age of the patient . RESULTS Nine of the 300 patients were excluded from the analysis as they failed to attend for postoperative review s. A significantly higher incidence ( P < 0.01 ) of postobturation pain was found in the multiple-visit group ( 38 % ) than in the single-visit group ( 27 % ) within 24 h of obturation . The incidence of pain decreased thereafter , with all patients being sysmptom free at the end of the observation period . No significant correlation was found between postobturation pain and any other factor , with the exception that teeth which had nonvital pulp prior to treatment were associated with a significantly greater ( P < 0.005 ) incidence of postobutration pain . CONCLUSIONS Pain was significantly higher in the multiple-visit RCT group and significantly associated with the treatment of the nonvital pulp AIM To investigate the efficacy of using antibiotics in post endodontic treatment as a method to alleviate post-treatment pain . MATERIAL S AND METHODS After completion of endodontic treatment 129 patients were r and omly divided into two groups : Group A ( 65 patients ) received Ibuprofen 400 mg one tablet before procedure and one tablet every 8 hours for the first day , then one tablet once indicated by pain . Group B ( 64 patients ) received the same regimen as group A in addition to amoxicillin , clavulanic acid tablets ( one tablet before the procedure , and then one tablet twice daily for a total of 3 days ) . Intensity of pain at 8 hours interval using visual analog scale ( VAS ) and total number of Ibuprofen tablets used was recorded by patients . RESULTS Peak postoperative pain occurred at 16 hours post-treatment in both groups , there was a significant difference in the pain scale between the two groups in favor for group B over group A ( 3.8 vs 2.1 respectively ) . Pain scale was significantly lower in group B at 24 , 32 , 40 , and 48 hours post-treatment with a p-value of < 0.05 . The pain scale at 56 , 64 and 72 hours were also less in group B , although could not show up as statistical difference . Patients in group A used statistically significant more Ibuprofen than patients in group B ( 486 vs 402 ) . CONCLUSION Antibiotic prescription to manage post endodontic treatment pain results in less pain with less consumption of Ibuprofens . CLINICAL SIGNIFICANCE Pain management in endodontics is a real challenge , nonsteroidal anti-inflammatory drugs ( NSAIDS ) are used effectively in many patients to alleviate post endodontic pain . Nonsteroidal anti-inflammatory drugs may have adverse reactions or may be contraindicated . Short-term use of antibiotics to alleviate pain can be of clinical benefits in these patients INTRODUCTION Profound pulpal anesthesia in posterior m and ibular teeth with irreversible pulpitis usually requires administering an inferior alveolar nerve block ( IANB ) plus other supplemental injections . The purpose of this prospect i ve , r and omized , double-blind study was to compare the anesthetic success rate of buccal infiltration injections of articaine and lidocaine when supplemented with an IANB . METHODS One hundred twenty-five emergency patients who had their first or second m and ibular molar diagnosed with irreversible pulpitis participated in the study and received the IANB by using either 2 % lidocaine with 1:100,000 epinephrine or 4 % articaine with 1:100,000 epinephrine . One hundred two of the patients reported moderate-to-severe pain upon initiation of their endodontic treatment or through filing of their tooth canals and received supplemental buccal infiltration injections by using the same anesthetic that the IANB had been performed . After the block or the supplemental buccal infiltration injections , success was achieved with no or mild pain during instrumentation of the tooth canals . RESULTS The success rate after the administration of the infiltration injections after an incomplete IANB by using lidocaine was 29 % , whereas by using articaine it was 71 % ( P < .001 ) . No statistical differences were detected in the success rates between the 2 anesthetics after the block injections . CONCLUSIONS Supplementing an incomplete articaine IANB with articaine infiltration raises the anesthetic success more effectively compared with lidocaine in m and ibular molars with irreversible pulpitis Introduction Post endodontic pain is often linked to the inflammatory process as well as additional central mechanisms . The purpose of the present double-blind r and omized clinical trial study was to compare the prophylactic effects of a derivative of Zingiber Officinale , Zintoma , and Ibuprofen on post endodontic pain of molars with irreversible pulpitis . Material s and Methods The post endodontic pain of 72 enrolled patients suffering from irreversible pulpitis was assessed after prophylactic use of 400 mg Ibuprofen , 2 gr Zintoma and placebo . Using the Heft-Parker Visual Analogue Scale , the patients recorded their perceived pain before taking the medicament ( baseline ) , immediately after and also at 4 , 8 , 12 , 24 , 48 , and 72 h post one-visit endodontic treatment . The statistical analysis was done using Kruskal-Wallis , Mann-Whitney , and Freedman tests ( P<0.05 ) . Results At all times , there was significant difference between the Ibuprofen and Zintoma ( P<0.05 ) and also between the Ibuprofen and placebo ( P<0.05 ) . However , there was no significant difference between Zintoma and the placebo in any of time intervals ( P>0.05 ) . No side effects were observed . Conclusion The obtained results of the trial revealed that prophylactic use of 2 gr Zintoma is not an effective pain relieving agent OBJECTIVE To evaluate success of pulpal anaesthesia of m and ibular 1st molar by using 4 % articaine in buccal infiltration versus 2 % lidocaine in inferior alveolar nerve block . STUDY DESIGN R and omized control trial . PLACE AND DURATION OF STUDY Department of Operative Dentistry , Sardar Begum Dental College , G and hara University , Peshawar , from March to August 2014 . METHODOLOGY One hundred and fifty-six emergency patients , who had 1st molar diagnosed with irreversible pulpitis , participated in the study . Subjects were divided into two groups by r and om allocation . One group received 4 % articaine buccal infiltration and the other group received inferior alveolar nerve block of 2 % lidocaine . Subjects’self-reported pain response was recorded on Heft Parker Visual Analogue Scale after local anaesthetic administration during access cavity preparation and pulp extirpation . RESULTS Mean age of subjects was 31.46 ±10.994 years . The success rate of 4 % buccal infiltration was 76.9 % ; whereas the success rate of 2 % lidocaine inferior alveolar nerve block was 62.8 % . There was no statistically significant difference between the two groups . CONCLUSION 4 % articaine buccal infiltration can be considered a viable alternative to 2 % lidocaine inferior alveolar nerve block in securing successful pulpal anaesthesia for endodontic therapy OBJECTIVE The purpose of this study was to determine whether premedication with ibuprofen or meloxicam increases the success rate of anaesthesia in teeth with irreversible pulpitis . MATERIAL S AND METHODS In this parallel , double-blind clinical trial , 92 patients diagnosed with irreversible pulpitis were r and omly divided into four groups of 23 patients . The first group ( the no-premedication group ) received no premedication , the second group ( the meloxicam group ) received 7.5 mg of meloxicam , the third group ( the ibuprofen group ) received 600 mg of ibuprofen , and the fourth group ( the placebo group ) received placebo 1 hour before intervention . Before taking the medication , electrical pulp testing ( EPT ) and the Heft-Parker visual analogue scale ( VAS ) were used to evaluate sensitivity and pain at baseline . Then , local anaesthesia was injected , and after 15 minutes , EPT was used again to evaluate tooth sensitivity . The pain during access preparation was also recorded using the Heft-Parker VAS . RESULTS Ninety-two patients were analysed . The success rates of local anaesthesia were 21.7 % , 34.8 % , 78.3 % and 73.9 % in the no-premedication , placebo , ibuprofen and meloxicam groups , respectively , according to the EPT values . Considering the Heft-Parker VAS values , no premedication gave a 21.7 % success rate , placebo gave a 34.8 % success rate , ibuprofen gave an 82.6 % success rate and meloxicam gave a 65.2 % success rate . The ibuprofen and meloxicam groups showed significantly better results than the placebo and no-premedication groups ( P < 0.001 ) . However , the difference between meloxicam and ibuprofen groups was not significant . CONCLUSIONS Premedication with meloxicam and ibuprofen significantly increased the success rates of inferior alveolar nerve block anaesthesia for teeth with irreversible pulpitis ; however , neither drug provided profound anaesthesia OBJECTIVE To comparatively evaluate the amount of apically extruded debris when ProTaper , ProFile , and HERO Shaper were used for the instrumentation of root canals . STUDY DESIGN Sixty human m and ibular central incisor teeth were r and omly assigned to 3 groups , 20 teeth in each . The teeth in the 3 groups were instrumented according to the manufacturers ' instructions until the working length , with ProTaper , ProFile , and HERO Shaper rotary instruments respectively . The debris produced was collected in polyethylene tubes . The liquid inside the tubes was removed by lyophilization and the remaining debris was calculated for each group and compared . RESULTS All instruments tested produced a measurable amount of debris . No statistically significant difference was observed between ProTaper and HERO Shaper in terms of debris extrusion ( P > .05 ) . Similarly , no statistically significant difference was observed between ProFile and HERO Shaper even though HERO Shaper extruded a relatively higher amount of debris ( P > .05 ) . On the other h and , ProTaper extruded significantly more amount of debris compared to ProFile ( P < .001 ) . CONCLUSIONS ProTaper caused a significantly higher amount of debris extrusion compared to ProFile . No statistically significant difference was observed among the other groups tested . As the quantity of debris extrusion is not the only factor responsible for acute exacerbations , future studies can be planned that focus on the types of bacteria causing flare-ups and methods for their elimination OBJECTIVE The purpose of this prospect i ve , r and omized , double-blind study was to compare the anesthetic efficacy of 4 % articaine and 2 % lidocaine ( both with 1:100,000 epinephrine ) for buccal infiltration in patients experiencing irreversible pulpitis in maxillary posterior teeth . STUDY DESIGN Forty patients with irreversible pulpitis in first premolar or first molar were divided into 4 study groups and received buccal infiltration of either 4 % articaine or 2 % lidocaine in a double-blind manner . Endodontic access was begun 5 minutes after solution deposition . Success was defined as no or mild discomfort ( VAS recordings ) during the endodontic procedure . RESULTS The success rate for maxillary buccal infiltration to produce pulpal anesthesia using articaine was 100 % in first premolar and first molar , and for the lidocaine solution , success rate was 80 % in first premolar and 30 % in first molar . There was high significant difference between the articaine and lidocaine solutions ( ANOVA ; P < .001 ) . CONCLUSION The efficacy of 4 % articaine was superior to 2 % lidocaine for maxillary buccal infiltration in posterior teeth Objectives To assess the incidence of postoperative pain after single- and multi-visit endodontic treatment of teeth with vital and non-vital pulp . Methods In total , 306 patients with teeth requiring endodontic treatment were identified and were included in this study . Two experienced clinicians treated the patients , who were r and omly assigned to two groups . While the teeth of patients in group 1 were obturated , group 2 were temporarily sealed and obturated after one week . Three days after the root canal instrumentation of each tooth , the patients were asked whether they experienced any postoperative pain and to rate the level of discomfort as no , mild , moderate , or severe pain . Data were analyzed statistically using the chi-square test . Results No significant difference in postoperative pain was found between vital and non-vital teeth ( P>.01 ) . Mild , moderate , and severe pain occurred in 31.4 , 13.7 , and 4.6 % of vital teeth , respectively . Postoperative pain occurred in 107 ( 69.9 % ) and 106 ( 69.3 % ) teeth in the single- and multi-visit treatment groups , respectively . There was no significant difference in postoperative pain between the two groups ( P>.01 ) . Conclusions The prevalence of postoperative pain did not differ between vital and non-vital teeth . The majority of patients in either groups reported no or only mild pain Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more OBJECTIVES The aim of this prospect i ve study was to investigate the correlation between the intensity of preoperative pain and the presence of postoperative pain , taking into account the variables sex , tooth type , arch , and tooth vitality . METHODS Two hundred and seventy patients with pulpal pathology who were scheduled for routine endodontic treatment were enrolled in this study . Conventional endodontic treatment was carried out in a single visit . The chemomechanical preparation of root canals was performed with ProTaper instruments , and canals were obturated with a warm gutta-percha obturation technique . A structured question naire was used to record data on sex , age , type of tooth , location and pulp diagnosis . Patients were asked to record their preoperative and postoperative pain using a 10-cm visual analogue scale ( VAS ) . Postoperative pain and the need for analgesic consumption were assessed at 4 , 8 , 16 , 24 , 48 and 72h post-treatment . The data were analyzed using the Mann-Whitney U and chi-square test , and the significance was set at P<.05 . RESULTS The mean level of pain after root canal treatment was 2.58±2.80 on a VAS between 0 and 10 . Variables that were associated with a higher preoperative pain intensity ( female , m and ible and molar ) also had a higher value of postoperative pain ( P>.05 ) . CONCLUSIONS Within the limitations of this study , it can be concluded that the presence of preoperative pain is the variable that most influences the prevalence of postoperative pain . CLINICAL SIGNIFICANCE Pain management should be an integral part of dental treatment . The present study analyses the incidence of postoperative pain that should be expected by patients with different intensity of pain before root canal treatment Background : Postendodontic pain ( PEP ) has always been a major problem for patients and dentists and NSAIDs are being used to relieve PEP and it is supposed that some benzodiazepines may potentiate facilitate the analgesic effects of the NSAIDs . This study was conducted to evaluate the effect of alprazolam on the analgesic effect of ibuprofen in PEP treatment . Methods : This r and omized double-blind clinical trial was conducted on 45 patients aged 20 - 45 years who were subjected of root canal treatment . A written informed consent was obtained from each patient . The subjects were r and omly divided into three groups ; placebo , ibuprofen ( 400 mg ) and alprazolam ( 0.5 ) mg + ibuprofen ( 400 mg ) . The intensity of pain was recorded using visual analog scale ( VAS ) at 4 , 6 , 12 , 24 , 48 and 72 hours after drug administration . Results : Of the participants , twenty six ( 57.8 % ) were males and 19 patients ( 42.2 % ) were females . Four hours after starting treatment , the VAS scores in the placebo and ibuprofen -treated groups were significantly higher than ibuprofen and alprazolam+ibuprofen groups ( 4.93±1.16 , 3.67±1.88 and 2.67±1.11 , respectively , p<0.0001 ) . The VAS scores in alprazolam + ibuprofen group ( 2.33±1.05 ) were significantly lower at 6 hours after treatment when compared to the other groups ( Ibuprofen : 3.00±1.36 and placebo : 3.08±1.74 , P=0.002 ) . This decrease in VAS score sustained to 12 hours after the start of alprazolam + ibuprofen treatment when compared to ibuprofen or placebo receiving group alone ( p<0.003 ) . The average pain score in female patients who received alprazolam + ibuprofen was significantly lower than males at 12 hours ( 1.3±0.6 v.s 2.14±0.9 , P=0.002 ) and 24 hours after treatment ( 0.88±0.6 v.s 1.86±0.9 , P=0.003 ) . Conclusion : According to the results , it can conclude that alprazolam may enhance the analgesic efficacy of ibuprofen in postendodontic pain INTRODUCTION Achieving pulp anesthesia with irreversible pulpitis is difficult . This study evaluated whether nonsteroidal anti-inflammatory drugs assist local anesthesia . METHODS In a r and omized double-blinded clinical trial , 150 patients ( 50 per group ) with irreversible pulpitis were given placebo , 600 mg ibuprofen , or 75 mg indomethacin 1 hour before local anesthesia . Each patient recorded their pain score on a visual analog scale before taking the medication , 15 minutes after anesthesia in response to a cold test , during access cavity preparation and during root canal instrumentation . No or mild pain at any stage was considered a success . Data were analyzed by the chi-square and analysis of variance tests . RESULTS Overall success rates for placebo , ibuprofen , and indomethacin were 32 % , 78 % , and 62 % , respectively ( p < 0.001 ) . Ibuprofen and indomethacin were significantly better than placebo ( p < 0.01 ) . There was no difference between ibuprofen and indomethacin ( p = 0.24 ) . CONCLUSIONS Premedication with ibuprofen and indomethacin significantly increased the success rates of inferior alveolar nerve block anesthesia for teeth with irreversible pulpitis AIM To determine the probability of the incidence , intensity , duration and triggering of post-endodontic pain , considering factors related to the patient ( age , gender , medical evaluation ) and to the affected tooth ( group , location , number of canals , pulp vitality , preoperative pain , periapical radiolucencies , previous emergency access , presence of occlusal contacts with antagonist ) . METHODOLOGY A total of 500 one-visit root canal treatments ( RCTs ) were performed on patients referred to an endodontist . Shaping of root canals was performed manually with Gates-Glidden drills and K-Flexofiles , and apical patency was maintained with a size 10 file . A 5 % NaOCl solution was used for irrigation , and canals were filled with lateral compaction and AH-Plus sealer . Independent factors were recorded during the treatment , and characteristics of post-endodontic pain ( incidence , intensity , type and duration ) were later surveyed through question naires . Of the 500 question naires , 374 were properly returned and split in two groups for two different statistical purpose s : 316 cases were used to adjust the logistic regression models to predict each characteristic of post-endodontic pain using predictive factors , and the remaining 58 cases were used to test the validity of each model . RESULTS The predictive models showed that the incidence of post-endodontic pain was significantly lower when the treated tooth was not a molar ( P = 0.003 ) , demonstrated periapical radiolucencies ( P = 0.003 ) , had no history of previous pain ( P = 0.006 ) or emergency endodontic treatment ( P = 0.045 ) and had no occlusal contact ( P < 0.0001 ) . The probability of experiencing moderate or severe pain was higher with increasing age ( P = 0.09 ) and in m and ibular teeth ( P = 0.045 ) . The probability of pain lasting more than 2 days was increased with age ( P = 0.1 ) and decreased in males ( P = 0.007 ) and when a radiolucent lesion was present on radiographs ( P = 0.1 ) . CONCLUSIONS Predictive formulae for the incidence , the intensity and the duration of post-endodontic pain were generated and vali date d taking account of the interrelation of multiple concomitant clinical factors . A predictive model for triggering post-endodontic pain could not be established To determine if prophylactic etodolac would significantly reduce postendodontic pain , when compared with ibuprofen or placebo , 36 patients consented to single blind oral administration of either 400 mg of etodolac , 600 mg of ibuprofen , or a placebo , before conventional one-appointment root canal therapy . Patient-reported visual analog scale ratings of pain intensity were conducted upon initial clinical presentation , immediately postoperative , 4 , 8 , 12 , 24 , 48 , and 72 h after initiation of root canal therapy . Results showed that prophylactic ibuprofen administration significantly reduced postendodontic pain at 4 and 8 h after initiation of root canal therapy , when compared with etodolac and a placebo . Patients with a periapical diagnosis of acute apical periodontitis or with a Phoenix abscess showed a significant increased need for additional medication after completion of root canal therapy , compared with all other periapical diagnoses The purpose of this study was to evaluate and compare the postoperative level of pain after activation of irrigants using EndoActivator with conventional needle irrigation during root canal therapy . In this prospect i ve r and omised clinical trial , 72 symptomatic irreversible pulpitis patients were selected . Based on block r and omisation after routine root canal preparation , patients were assigned to two groups . In group EN , procedures were performed with endodontic irrigating needle ( n = 36 ) while group EA received activation using EndoActivator ( n = 36 ) in the final irrigation protocol . All the participants were called through phone at 8 , 24 and 48 h to analyse pain score using visual analogue scale . Those patients who developed pain were prescribed ibuprofen 200 mg . Pain score and frequency of tablet intake were recorded and statistically analysed . Results showed that group EA result ed in significantly less postoperative pain and analgesics intake than group EN . In conclusion , within the limitations of this study , the activation of irrigants using EndoActivator can be considered an effective method for reducing postoperative pain Aim . To evaluate the incidence and severity of postendodontic treatment pain ( PEP ) subsequent to root canal treatment ( RCT ) in vital and necrotic pulps and after retreatment . Methodology . A prospect i ve study . Participants were all patients ( n = 274 ) who underwent RCT in teeth with vital pulp , necrotic pulp , or vital pulp that had been treated for symptomatic irreversible pulpitis or who received root canal retreatment , by one clinician , during an eight-month period . Exclusion criteria were swelling , purulence , and antibiotic use during initial treatment . A structured question naire accessed age , gender , tooth location , and pulpal diagnosis . Within 24 h of treatment , patients were asked to grade their pain at 6 and 18 hours posttreatment , using a 1–5 point scale . Results . RCT of teeth with vital pulp induced a significantly higher incidence and severity of PEP ( 63.8 % ; 2.46 ± 1.4 , resp . ) than RCT of teeth with necrotic pulp ( 38.5 % ; 1.78 ± 1.2 , resp . ) or of retreated teeth ( 48.8 % ; 1.89 ± 1.1 , resp . ) . No statistical relation was found between type of pain ( spontaneous or stimulated ) and pulp condition . Conclusion . RCT of teeth with vital pulp induced a significantly higher incidence and intensity of PEP compared to teeth with necrotic pulp or retreated teeth CONTEXT Diagrams of the flow of participants through a clinical trial are recommended in the Consoli date d St and ards for Reporting of Trials ( CONSORT ) statement , but it is unclear whether such flow diagrams improve the quality of trial reports . OBJECTIVE To examine the information contributed by flow diagrams and the completeness of reporting overall in reports of r and omized controlled trials ( RCTs ) published in 5 general and internal medicine journals . DESIGN AND SETTING Analysis of 270 reports of RCTs published in 1998 in the Annals of Internal Medicine ( AIM ; n = 19 ) , BMJ ( n = 42 ) , JAMA ( n = 45 ) , The Lancet ( n = 81 ) , and The New Engl and Journal of Medicine ( NEJM ; n = 83 ) . MAIN OUTCOME MEASURES Proportion of reports that included a flow diagram , information provided in flow diagrams , and completeness of reporting about flow of participants overall in flow diagrams or text . RESULTS A total of 139 reports ( 51.5 % ) of RCTs included a flow diagram , but this varied widely among journals ( AIM , 21.0 % ; BMJ , 38.1 % ; JAMA , 80.0 % ; The Lancet , 93.8 % ; and NEJM , 8.4 % ) . Diagrams generally provided useful information , but only 73 ( 52.5 % ) included the number of participants who received allocated interventions and only 32 ( 23.0 % ) included the number of participants included in the analysis . In logistic regression analysis , overall completeness of reporting about flow of study participants was associated with publication of a flow diagram . CONCLUSIONS Flow diagrams are associated with improved quality of reporting of r and omized controlled trials . However , the structure of current flow diagrams is less than ideal . We propose a revised flow diagram that includes all important counts through the stages of parallel group trials AIMS Etoricoxib is a second-generation selective COX-2 inhibitor . There are a few research es investigating analgesic effect of Etoricoxib in dentistry . METHODS This r and omized , double-blind , active-control study included sixty patients with clinical pulpal diagnosis of necrosis of the first m and ibular molar and an associated periapical radiolucency who experienced severe pain ( more than 60 out of 100 in scale of Visual Analog Scale ( VAS ) . The patients were equally r and omized into four groups , who received 60 mg etoricoxib ( group 1 ) , 90 mg etoricoxib ( group 2 ) , 120 mg etoricoxib ( group 3 ) , and 400 mg ibuprofen ( group 4 ) . All patients r and omly received a single dose of the drug after the first session of the root canal therapy . Using VAS , the severity of pain was recorded 2 , 4 , 6 , 12 , 24 , 48 , and 72 hours after the drug was administered . RESULTS Changing trends of pain over the time was significant for all groups ( P=0.003 ) . In addition , there was not a significant difference between various study arms ( P=0.146 ) . CONCLUSION The results showed that ibuprofen had a comparable effect with various dosage of etoricoxib and may remain as the choice analgesic for dental pulpal pain Four common oral analgesics were tested in a single-blind trial to determine their relative efficacy in the management of postsurgical pain in 103 patients who had their impacted third molars surgically removed under general anesthesia . The analgesics tested were acetylsalicylic acid ( 26 patients ) , ibuprofen ( 26 patients ) , a paracetamol/codeine/caffeine combination ( Solpadeine ) ( 25 patients ) , and dihydrocodeine ( 26 patients ) . The paracetamol/codeine/caffeine combination , ibuprofen , and acetylsalicylic acid preparations produced equally effective analgesia . Dihydrocodeine was found to be a poor analgesic in this pain model . There were no adverse reactions to any of the preparations We investigated effects of two doses of Tenoxicam , a type 2 cyclooxygenase inhibitor , administration on lipid peroxidation and antioxidant redox system in cortex of the brain in rats . Twenty-two male Wistar rats were r and omly divided into three groups . First group was used as control . 10 and 20 mg/kg body weight Tenoxicam were intramuscularly administrated to rats constituting the second and third groups for 10 days , respectively . Both dose of Tenoxicam administration result ed in significant increase in the glutathione peroxidase activity , reduced glutathione and vitamins C and E of cortex of the brain . The lipid peroxidation levels in the cortex of the brain were significantly decreased by the administration . Vitamin A and β-carotene concentration was not affected by the administration . There was no statistical difference in all values between 10 and 20 mg Tenoxicam administrated groups . In conclusion , treatment of brain with 10 and 20 mg Tenoxicam has protective effects on the oxidative stress by inhibiting free radical and supporting antioxidant redox system AIM To compare the effects of single doses of three oral medications on postoperative pain following instrumentation of root canals in teeth with irreversible pulpitis . METHODOLOGY In this double-blind clinical trial , 100 patients who had anterior or premolar teeth with irreversible pulpitis without any signs and symptoms of acute or chronic apical periodontitis and moderate to severe pain were divided by balanced block r and om allocation into four groups of 25 each , a control group receiving a placebo medication , and three experimental groups receiving a single dose of either Tramadol ( 100 mg ) , Novafen ( 325 mg of paracetamol , 200 mg ibuprofen and 40 mg caffeine anhydrous ) or Naproxen ( 500 mg ) immediately after the first appointment where the pulp was removed , and the canals were fully prepared . The intensity of pain was scored based on 10-point VAS before and after treatment for up to 24 h postoperatively . Data were su bmi tted to repeated analysis of variance . RESULTS At the 6 , 12 and 24 h postoperative intervals after drug administration , the intensity of pain was significantly lower in the experimental groups than in the placebo group ( P < 0.01 ) . Tramadol was significantly less effective ( P < 0.05 ) than Naproxen , and Novafen that were similar to each other ( P > 0.05 ) . CONCLUSION A single oral dose of Naproxen , Novafen and Tramadol taken immediately after treatment reduced postoperative pain following pulpectomy and root canal preparation of teeth with irreversible pulpitis INTRODUCTION Anesthetic efficacy of inferior alveolar nerve block decreases in patients with irreversible pulpitis . It was hypothesized that premedication with nonsteroidal anti-inflammatory drugs might improve the success rates in patients with inflamed pulps . METHODS Sixty-nine adult volunteers who were actively experiencing pain participated in this prospect i ve , r and omized , double-blind study . The patients were divided into 3 groups on a r and om basis and were r and omly given 1 of the 3 drugs including ibuprofen , ketorolac , and placebo 1 hour before anesthesia . All patients received st and ard inferior alveolar nerve block of 2 % lidocaine with 1:200,000 epinephrine . Endodontic access preparation was initiated after 15 minutes of initial inferior alveolar nerve block . Pain during treatment was recorded by using a Heft Parker visual analog scale . Success was recorded as none or mild pain . RESULTS Statistical analysis with nonparametric chi2 tests showed that placebo gave 29 % success rate . Premedication with ibuprofen gave 27 % , and premedication with ketorolac gave 39 % success rate . There was no significant difference between the 3 groups . CONCLUSIONS Preoperative administration of ibuprofen or ketorolac has no significant effect on success rate of inferior alveolar nerve block in patients with irreversible pulpitis The root canals of 588 consecutive nonsurgical patients with varying levels of pain were completely instrumented in 10 endodontic practice s and 4 endodontic graduate programs . The participants were sequentially assigned to one of nine medications and a placebo . The severity of pain was assessed by the visual analog scale for 72 h following instrumentation . Among all of the parameters studied , three factors ( preoperative pain , apprehension , and types of medication ) were found to be significant in determining postinstrumentation pain . An association was found between the intensity of pre- and postoperative pain . As the intensity of preoperative pain increased , the chances for more severe postoperative pain increased ( p < 0.0001 ) . In addition , an association between the presence of apprehension before any treatment and postoperative pain was also noted ( between 0.012 < p < 0.047 ) . Examination of the time-effect curves for various medications in patients with no mild pain showed no statistical significant difference between the effectiveness of different medications and placebo . However , a multiple comparison of the effectiveness of various medications and placebo on patients in moderate and severe preoperative pain showed that ibuprofen , ketoprofen , erythromycin base , penicillin , and methylprednisolone plus penicillin were more effective than placebo within the first 48 h following complete instrumentation This study compares single-dose ibuprofen pretreatment for postoperative endodontic pain . Thirty-nine emergent patients were r and omly assigned to 3 groups : placebo , ibuprofen tablets , or ibuprofen liquigels . Patients recorded their pain levels before and at the end of treatment , then every 6 hours for 24 hours after administration of the medications and st and ard endodontic treatment . Pain evaluations by using 3 pain scales ( visual analog scale [ VAS ] , category , and Heft-Parker ) were highly correlated , suggesting the rationale for only using one pain scale in pain studies . No significant differences in postoperative pain levels were found between either single-dose ibuprofen formulation or the placebo control group ( P = .84 ) . Patients treated with calcium hydroxide versus obturation did not differ in postoperative pain levels ( P = .44 ) . This study suggests that single-dose pretreatment analgesia alone in endodontic pain patients will not significantly reduce postoperative pain below the reduction in pain from endodontic treatment AIM To compare ibuprofen , to an ibuprofen/acetaminophen combination in managing postoperative pain following root canal treatment . It is hypothesized that the drug combination will provide more postoperative pain relief than the placebo or ibuprofen alone . METHODOLOGY Patients presenting at the Texas A&M Baylor College of Dentistry 's graduate endodontic clinic , experiencing moderate to severe pain , were considered potential c and i date s. Fifty-seven patients were included based on established criteria . Following administration of local anaesthesia , a pulpectomy was performed . The patients were administered a single dose of either : ( i ) placebo ; ( ii ) 600 mg ibuprofen ; or ( iii ) 600 mg ibuprofen and 1000 mg of acetaminophen . Patients recorded pain intensity following treatment on a visual analogue scale and a baseline four-point category pain scale as well as pain relief every hour for the first 4 h then every 2 h thereafter for a total of 8 h. A general linear model ( GLM ) analysis was used to analyse the outcome . RESULTS Based upon the GLM analysis , there was a significant difference between the ibuprofen and the combination drug group , and between placebo and combination drug groups . There was no significant difference between the placebo and the ibuprofen . CONCLUSION The results demonstrate that the combination of ibuprofen with acetaminophen may be more effective than ibuprofen alone for the management of postoperative endodontic pain OBJECTIVE The purpose of this prospect i ve , r and omized , blinded study was to determine the effect of trephination on postoperative pain and swelling in symptomatic necrotic teeth . STUDY DESIGN Fifty emergency patients participated , and each had a clinical diagnosis of a symptomatic necrotic tooth with associated periapical radiolucency . After endodontic treatment , patients r and omly received either a trephination or mock trephination procedure . The trephination procedure used an intraosseous perforator to provide an initial opening in the cortical bone that was enlarged with files ( No. 25 through No. 70 ) and an endodontic spoon . After surgery , each patient received ibuprofen ; acetaminophen with codeine ( 30 mg ) ; and a 7-day diary to record pain , percussion pain , swelling , and number and type of pain medication taken . RESULTS The majority of patients with symptomatic necrotic teeth had significant postoperative pain and required analgesics to manage this pain . The use of a trephination procedure with an intraosseous perforator , files , and a spoon excavator did not significantly reduce pain , percussion pain , swelling , or the number of analgesic medications taken in symptomatic necrotic teeth with periapical radiolucencies ( P > .05 ) . CONCLUSION We can not recommend the routine use of a trephination procedure , as used in this study , for relief of pain in symptomatic necrotic teeth with radiolucencies INTRODUCTION The purpose of this prospect i ve , r and omized , double-blind study was to determine ibuprofen versus ibuprofen/acetaminophen use for postoperative endodontic pain in symptomatic patients with a pulpal diagnosis of necrosis and an associated periapical radiolucency who were experiencing moderate to severe preoperative pain . We also recorded escape medication use . METHODS Seventy-one adult patients presenting for emergency endodontic treatment with a symptomatic maxillary or m and ibular tooth with a pulpal diagnosis of necrosis , periapical radiolucent area , and moderate to severe pain participated in this study . The patients were r and omly divided into 2 groups by r and om assignment and numeric coding . An emergency debridement of the tooth was completed with h and and rotary instrumentation . At the end of the appointment , the patients r and omly received capsules of either 600 mg ibuprofen or 600 mg ibuprofen combined with 1000 mg acetaminophen ( blinded to both operator and patient ) . Patients also received a 6-day diary to be completed after anesthesia wore off and every morning for 5 days . Patients were asked to record pain , symptoms , and the number of capsules taken . Patients received escape medication ( Vicodin ) if the study medication did not control their pain . Postoperative data were analyzed by r and omization test and step-down Bonferroni method of Holm . RESULTS AND CONCLUSIONS There were decreases in pain levels and analgesic use over time for the ibuprofen and ibuprofen/acetaminophen groups . There was no statistically significant difference between the 2 groups for analgesic use or escape medication use . Approximately 20 % of patients in both groups required escape medication to control pain The purpose of this study was to compare the pain-reducing efficacy of dexamethasone and ketorolac tromethamine when used as an intracanal medication , with oral ibuprofen and a placebo . An additional objective was to establish if any relationship exists between the incidence and severity of pretreatment pain and the incidence and severity of postinstrumentation pain . A total of 48 patients who presented to the University of Illinois postgraduate endodontic clinic were invited to participate . Patients were r and omly assigned to 1 of 4 groups : oral ibuprofen , placebo , dexamethasone , or ketorolac tromethamine . Patients were asked to evaluate their pretreatment pain when they presented to the clinic with a Visual Analog Scale . The root canal treatment was performed in two appointments . The first appointment consisted of cleansing and shaping of the canal/s and placement of an intracanal medication . All teeth were closed with a sterile cotton pellet and IRM . Each patient was sent home with a Visual Analog Scale to fill out at 6 , 12 , 24 and 48 h after initiation of therapy . At the 12-h period , both dexamethasone and ketorolac provided statistically significant better pain relief than placebo . At the 24-h period , only ketorolac demonstrated better pain relief than the placebo . There were no statistically significant differences among the groups at 6 and 48 h. Although ibuprofen pain ratings were less than the placebo at all time points , the reduction was not significant . In addition , no significant differences were demonstrated between ibuprofen and either dexamethasone or ketorolac The purpose of this study was to determine if prophylactic rofecoxib would significantly reduce postendodontic pain , when compared with ibuprofen or placebo . An additional objective was to establish if any relationship exists between periapical diagnosis and the need for additional medication after completion of pulpectomy . A total of 45 patients consented to a double-blind , single-dose oral administration of 50 mg of rofecoxib , 600 mg of ibuprofen , or a placebo before conventional root canal therapy . The root canal treatment was performed in two appointments . Patient-reported visual analog scale ratings of pain intensity were conducted upon initial clinical presentation and at 4 , 8 , 12 , 24 , 48 , and 72 h after completion of pulpectomy . Results showed that at the 4- and 8-h periods , both rofecoxib and ibuprofen provided significantly better pain relief than placebo . At the 12- and 24-h periods , rofecoxib demonstrated significantly better pain relief than both ibuprofen and placebo . Patients with a periapical diagnosis of acute apical periodontitis showed a significantly increased need for additional medication after completion of pulpectomy compared with all other periapical diagnoses INTRODUCTION The purpose of this prospect i ve , r and omized , double-blind , placebo-controlled study was to determine the effect of the administration of the combination of preoperative ibuprofen/acetaminophen on the success of the inferior alveolar nerve ( IAN ) block in patients with symptomatic irreversible pulpitis . METHODS One hundred endodontic emergency patients in moderate to severe pain diagnosed with irreversible pulpitis of a m and ibular posterior tooth r and omly received , in a double-blind manner , identical capsules of either a combination of 800 mg ibuprofen and 1000 mg acetaminophen or placebo 45 minutes before the administration of a conventional IAN block . Access was begun 15 minutes after completion of the IAN block , and all patients had profound lip numbness . Success was defined as no or mild pain ( visual analog scale recordings ) on access or initial instrumentation . RESULTS AND CONCLUSIONS The success rate for the IAN block was 32 % for the combination ibuprofen/acetaminophen group and 24 % for the placebo , with no significant difference ( P = .37 ) between the 2 groups . For m and ibular posterior teeth , a combination dose of 800 mg ibuprofen and 1000 mg acetaminophen given 45 minutes before administration of the IAN block did not result in a statistically significant increase in anesthetic success in patients with symptomatic irreversible pulpitis A study was done comparing the effectiveness of ibuprofen ( Motrin ) , Empirin with Codeine # 3 , and Synalgos-DC for the relief of postendodontic treatment pain . Pain levels of 72 patients were evaluated at 0 , 1 , 2 , and 3 h after ingestion of the r and omly assigned test medications . The results showed that all three medications were equally effective in relieving postendodontic pain . There were no significant differences among the three medications concerning reported side effects This prospect i ve study compared the effectiveness of nine medications and a placebo in controlling pain following obturation . A total of 588 patients who required root canal obturation were included . After obturation of root canals , each patient took one of the medications , salicylic acid ( 2 x 250 mg ) , acetaminophen ( 2 x 250 mg ) , ibuprofen ( 2 x 250 mg ) , ketoprofen ( 2 x 250 mg ) , acetaminophen ( 2 x 250 mg ) plus codeine ( 2 x 250 mg ) , penicillin ( 2 x 250 mg ) , erythromycin base ( 2 x 250 mg ) , penicillin plus ibuprofen ( 2 x 250 mg ) , methylprednisolone ( 2 x 250 mg ) plus penicillin ( 2 x 250 mg ) , or a placebo , every 6 h for 72 h. All medications were encapsulated in identical capsules . The patients registered their degree of discomfort on a visual analogue scale of 0 to 9 . Statistical analysis of the data showed that the incidence of postoperative pain after obturation is lower than that following complete cleaning and shaping ( 5.83 % versus 21.76 % ) . In addition , there was no significant difference between the effectiveness of the various medications and placebo tablets in controlling postoperative pain following obturation |
14,054 | 31,470,841 | Conclusions We engaged with service users and professionals to develop an evidence -based website addressing the agreed core information needs of non-professional carers who wish to provide palliative care to a friend or relative | Background Many people receiving palliative care wish to die at home .
Often , support from family or friends is key to ensuring that this wish is fulfilled .
However , carers report feeling underprepared to undertake this role .
This paper describes the process of developing a consensus and evidence based website to provide core information to help people support someone receiving palliative care on the isl and of Irel and . | Background Family caregivers in palliative care have a need for knowledge and support from health professionals , result ing in the need for educational and supportive interventions . However , research has mainly focused on the experiences of family caregivers taking part in interventions . To gain an increased underst and ing of complex interventions , it is necessary to integrate the perspectives of health professionals and family caregivers . Hence , the aim of this study is to explore the perspectives of health professionals and family caregivers of delivering and participating in a psycho-educational intervention in palliative home care . Methods A psycho-educational intervention was design ed for family caregivers based on a theoretical framework describing family caregiver ’s need for knowing , being and doing . The intervention was delivered over three sessions , each of which included a presentation by healthcare professionals from an intervention manual . An interpretive descriptive design was chosen and data were collected through focus group discussion s with health professionals and individual interviews with family caregivers . Data were analysed using framework analysis . Results From the perspectives of both health professionals and family caregivers , the delivering and participating in the intervention was a positive experience . Although the content was not always adjusted to the family caregivers ’ individual situation , it was perceived as valuable . Consistently , the intervention was regarded as something that could make family caregivers better prepared for caregiving . Health professionals found that the work with the intervention dem and ed time and engagement from them and that the manual needed to be adjusted to suit group characteristics , but the experience of delivering the intervention was still something that gave them satisfaction and contributed to them finding insights into their work . Conclusions The theoretical framework used in this study seems appropriate to use for the design of interventions to support family caregivers . In the perspectives of health professionals and family caregivers , the psycho-educational intervention had important benefits and there was congruence between the two groups in that it provided reward and support . In order for health professionals to carry out psycho-educational interventions , they may be in need of support and supervision as well as securing appropriate time and re sources in their everyday work Background Symptom distress in patients toward the end of life can change rapidly . Family caregivers have the potential to help patients manage those symptoms , as well as their own stress , if they are equipped with the proper re sources . Electronic health ( eHealth ) systems may be able to provide those re sources . Very sick patients may not be able to use such systems themselves to report their symptoms but family caregivers could . Objective The aim of this paper was to assess the effects on cancer patient symptom distress of an eHealth system that alerts clinicians to significant changes in the patient ’s symptoms , as reported by a family caregiver . Methods A pooled analysis from two r and omized clinical trials ( NCT00214162 and NCT00365963 ) compared outcomes at 12 months for two unblinded groups : a control group ( Comprehensive Health Enhancement Support System [CHESS]-Only ) that gave caregivers access to CHESS , an online support system , and an experimental group ( CHESS+CR [ Clinician Report ] ) , which also had CHESS but with a CR that automatically alerted clinicians if symptoms exceeded a predetermined threshold of severity . Participants were dyads ( n=235 ) of patients with advanced lung , breast , or prostate cancer and their respective family caregivers from 5 oncology clinics in the United States of America . The proportion of improved patient threshold symptoms was compared between groups using area-under-the-curve analysis and binomial proportion tests . The proportion of threshold symptoms out of all reported symptoms was also examined . Results When severe caregiver-reported symptoms were shared with clinicians , the symptoms were more likely to be subsequently reported as improved than when the symptoms were not shared with clinicians ( P<.001 ) . Fewer symptom reports were completed in the group of caregivers whose reports went to clinicians than in the CHESS-Only group ( P<.001 ) , perhaps because caregivers , knowing their reports might be sent to a doctor , feared they might be bothering the clinician . Conclusions This study suggests that an eHealth system design ed for caregivers that alerts clinicians to worrisome changes in patient health status may lead to reduced patient distress . Trial Registration Clinical trials.gov NCT00214162 ; https:// clinical trials.gov/ct2/show/NCT00214162 ( Archived by WebCite at http://www.webcitation.org/6nmgdGfuD ) and Clinical trials.gov NCT00365963 ; https:// clinical trials.gov/ct2/show/NCT00365963 ( Archived by WebCite at http://www.webcitation.org/6nmh0U8VP Background Being a family carer to a patient nearing the end of their life is a challenging and confronting experience . Studies show that caregiving can have negative consequences on the health of family carers including fatigue , sleep problems , depression , anxiety and burnout . One of the goals of palliative care is to provide psychosocial support to patients and families facing terminal illness . A systematic review of interventions for family carers of cancer and palliative care patients conducted at the start of this millennium demonstrated that there was a dearth of rigorous inquiry on this topic and consequently limited knowledge regarding the types of interventions likely to be effective in meeting the complex needs of family carers . We wanted to discern whether or not the evidence base to support family carers has improved . Furthermore , undertaking this review was acknowledged as one of the priorities for the International Palliative Care Family Carer Research Collaboration http://www.centreforpallcare.org . Methods A systematic review was undertaken in order to identify developments in family carer support that have occurred over the last decade . The focus of the review was on interventions that targeted improvements in the psychosocial support of family carers of palliative care patients . Studies were grade d to assess their quality . Results A total of fourteen studies met the inclusion criteria . The focus of interventions included psycho-education , psychosocial support , carer coping , symptom management , sleep promotion and family meetings . Five studies were r and omised controlled trials , three of which met the criteria for the highest quality evidence . There were two prospect i ve studies , five pre-test/post-test projects and two qualitative studies . Conclusions The systematic review identified a slight increase in the quality and quantity of psychosocial interventions conducted for family carers in the last decade . More rigorous intervention research is required in order to meet the supportive care needs of family carers of palliative care patients Background A key component of palliative care is support for family caregivers . Although some family caregivers identify positive aspects , the impact is typically burdensome ; they are prone to physical and psychological morbidity , financial disadvantage and social isolation . Outcomes of systematic review s have highlighted the importance of investment in family caregiver intervention research . Purpose To provide an overview of the development , evaluation and outcomes arising from of a programme of research ( The Melbourne Family Support Program ( FSP ) ) , which focused on reducing the psychosocial burden of family caregivers . Methods Developmental work involved a systematic literature review ; focus groups with family caregivers and health professionals ; and identification of a conceptual framework . Following a pilot r and omised controlled trial ( RCT ) , a programme of psychoeducational intervention studies was developed and tested ; one via RCT , the others via prepost test . Results Four psychoeducational interventions , incorporating one-to-one and group format delivery , conducted in both the home and inpatient hospital/hospice were evaluated . Statistically significant outcomes included improvements in family caregivers ’ preparedness , competence , positive emotions , more favourable levels of psychological wellbeing and a reduction in unmet needs . Internationally endorsed guidelines for the psychosocial support of family caregivers were produced and several re sources were constructed . Fifteen publications in international peer- review ed journals have arisen from this programme . Conclusions The interventions and re sources from the Melbourne FSP provide several evidence d-based and clinical ly relevant approaches that focus on reducing the psychosocial burden of the caregiving role . In several instances , however , more rigorous method ological testing is advocated OBJECTIVE To evaluate an online disease management system supporting patients with uncontrolled type 2 diabetes . MATERIAL S AND METHODS Engaging and Motivating Patients Online With Enhanced Re sources for Diabetes was a 12-month parallel r and omized controlled trial of 415 patients with type 2 diabetes with baseline glycosylated hemoglobin ( A1C ) values ≥7.5 % from primary care sites sharing an electronic health record . The intervention included : ( 1 ) wirelessly uploaded home glucometer readings with graphical feedback ; ( 2 ) comprehensive patient-specific diabetes summary status report ; ( 3 ) nutrition and exercise logs ; ( 4 ) insulin record ; ( 5 ) online messaging with the patient 's health team ; ( 6 ) nurse care manager and dietitian providing advice and medication management ; and ( 7 ) personalized text and video educational ' nuggets ' dispensed electronically by the care team . A1C was the primary outcome variable . RESULTS Compared with usual care ( UC , n=189 ) , patients in the intervention ( INT , n=193 ) group had significantly reduced A1C at 6 months ( -1.32 % INT vs -0.66 % UC ; p<0.001 ) . At 12 months , the differences were not significant ( -1.14 % INT vs -0.95 % UC ; p=0.133 ) . In post hoc analysis , significantly more INT patients had improved diabetes control ( > 0.5 % reduction in A1C ) than UC patients at 12 months ( 69.9 ( 95 % CI 63.2 to 76.5 ) vs 55.4 ( 95 % CI 48.4 to 62.5 ) ; p=0.006 ) . CONCLUSIONS A nurse-led , multidisciplinary health team can manage a population of diabetic patients in an online disease management program . INT patients achieved greater decreases in A1C at 6 months than UC patients , but the differences were not sustained at 12 months . More INT than UC patients achieved improvement in A1C ( > 0.5 % decrease ) . Trial registered in clinical trials.gov : # NCT00542204 |
14,055 | 25,556,970 | Generally , the better design ed studies showed no improvement in the primary outcome measure of physical activity at a population level .
Some program level effect was observed with more people walking in the intervention community , however this result was not evident in the whole community .
Overall , there was a noticeable absence of reporting of benefit in physical activity for community wide interventions in the included studies .
However , as a group , the interventions undertaken in China appeared to have the greatest possibility of success with high participation rates reported .
The body of evidence in this review does not support the hypothesis that the multi-component community wide interventions studied effectively increased physical activity for the population , although some studies with environmental components observed more people walking | BACKGROUND Multi-strategic community wide interventions for physical activity are increasingly popular but their ability to achieve population level improvements is unknown .
OBJECTIVES To evaluate the effects of community wide , multi-strategic interventions upon population levels of physical activity . | BACKGROUND Pathways , a multisite school-based study aim ed at promoting healthful eating and increasing physical activity , was a r and omized field trial including 1704 American Indian third to fifth grade students from 41 schools ( 21 intervention , 20 controls ) in seven American Indian communities . METHODS The intervention schools received four integrated components : a classroom curriculum , food service , physical activity , and family modules . The curriculum and family components were based on Social Learning Theory , American Indian concepts , and results from formative research . Process evaluation data were collected from teachers ( n=235 ) , students ( n=585 ) , and families . Knowledge , Attitudes , and Behavior Question naire data were collected from 1150 students including both intervention and controls . RESULTS There were significant increases in knowledge and cultural identity in children in intervention compared to control schools with a significant retention of knowledge over the 3 years , based on the results of repeating the third and fourth grade test items in the fifth grade . Family members participated in Family Events and take-home activities , with fewer participating each year . CONCLUSION A culturally appropriate school intervention can promote positive changes in knowledge , cultural identity , and self-reported healthful eating and physical activity in American Indian children and environmental change in school food service OBJECTIVE To assess the effects of a comprehensive , integrated community-based lifestyle intervention on diet , physical activity and smoking in two Iranian communities . METHODS Within the framework of the Isfahan Healthy Heart Program , a community trial was conducted in two intervention counties ( Isfahan and Najaf-Abad ) and a control area ( Arak ) . Lifestyle interventions targeted the urban and rural population s in the intervention counties but were not implemented in Arak . In each community , a r and om sample of adults was selected yearly by multi-stage cluster sampling . Food consumption , physical exercise and smoking behaviours were quantified and scored as 1 ( low-risk ) or 0 ( other ) at baseline ( year 2000 ) and annually for 4 years in the intervention areas and for 3 years in the control area . The scores for all behaviours were then added to derive an overall lifestyle score . FINDINGS After 4 years , changes from baseline in mean dietary score differed significantly between the intervention and control areas ( + 2.1 points versus -1.2 points , respectively ; P < 0.01 ) , as did the change in the percentage of individuals following a healthy diet ( + 14.9 % versus -2.0 % , respectively ; P < 0.001 ) . Daily smoking had decreased by 0.9 % in the intervention areas and by 2.6 % in the control area at the end of the third year , but the difference was not significant . Analysis by gender revealed a significant decreasing trend in smoking among men ( P < 0.05 ) but not among women . Energy expenditure for total daily physical activities showed a decreasing trend in all areas , but the mean drop from baseline was significantly smaller in the intervention areas than in the control area ( -68 metabolic equivalent task ( MET ) minutes per week versus -114 MET minutes per week , respectively ; P < 0.05 ) . Leisure time devoted to physical activities showed an increasing trend in all areas . A significantly different change from baseline was found between the intervention areas and the control area in mean lifestyle score , even after controlling for age , sex and baseline values . CONCLUSION The results suggest that community-based lifestyle intervention programmes can be effective in a developing country setting The primary aim of the Trial of Activity in Adolescent Girls ( TAAG ) is to test an intervention to reduce by half the age-related decline in moderate to vigorous physical activity ( MVPA ) in middle school girls . The intervention will be evaluated using a group-r and omized trial involving 36 middle schools . The primary endpoint is the mean difference in intensity-weighted minutes ( i.e. , MET-minutes ) of MVPA between intervention and comparison schools assessed using accelerometry . The TAAG study design calls for two cross-sectional sample s , one drawn from 6th grade rs at the beginning of the study and the second drawn from 8th grade rs at the end of the study following the 2-year implementation of the intervention . An important strength of this design over a cohort design is the consistency with the goals of TAAG , which focus on environmental-level rather than individual-level interventions to produce change . The study design specifies a recruitment rate of 80 % and a smaller sample of girls at baseline ( n=48 per school ) than at follow-up ( n=96 per school ) . A two-stage model will be used to test the primary hypothesis . In the first stage , MET-weighted minutes of MVPA will be regressed on school , time ( baseline or follow-up ) , their interaction , ethnicity and week of data collection . The second stage analysis will be conducted on the 72 adjusted means from the first stage . In the main-effects model , we will regress the follow-up school mean MET-weighted minutes of MVPA on study condition , adjusting for the baseline school mean . The TAAG study addresses an important health behavior , and also advances the field of group-r and omized trials through the use of a study design and analysis plan tailored to serve the main study hypothesis Background : Population -based studies directed at promoting physical activity in youth have shown limited success in obesity prevention . Objective : To assess whether an intervention integrating environmental changes to induce sustained changes in physical activity , prevents overweight in adolescents . Design : Four-year r and omized trial started in 2002 in eight middle schools of Eastern France . The intervention , r and omized at school level , was design ed to promote physical activity by changing attitudes through debates and attractive activities , and by providing social support and environmental changes encouraging physical activity . Subjects : Nine hundred and fifty four 12-year-old six- grade rs . Measurements : Body mass index ( BMI ) , body composition , physical activity by question naire , plasma lipids and glucose , insulin resistance . Results : Intervention students had a lower increase in BMI ( P=0.01 ) and age- and gender-adjusted BMI ( P<0.02 ) over time than controls . The differences across groups of the age- and gender-adjusted BMI changes ( 95 % confidence interval ( CI ) ) were −0.29 ( −0.51 ; −0.07 ) kg/m2 at 3 years , −0.25 ( −0.51 ; 0.01 ) kg/m2 at 4 years . An interaction with baseline weight status was noted . The intervention had a significant effect throughout the study in initially non-overweight adolescents ( −0.36 ( −0.60;−0.11 ) kg/m2 for adjusted BMI at 4 years ) , corresponding to a lower increase in fat mass index ( P<0.001 ) . In initially overweight adolescents , the differences observed across groups at 2 years ( –0.40 ( −0.94 ; 0.13 ) kg/m2 for adjusted BMI ) did not persist over time . At 4 years , 4.2 % of the initially non-overweight adolescents were overweight in the intervention schools , 9.8 % in the controls ( odds ratio=0.41 ( 0.22 ; 0.75 ) ; P<0.01 ) . Independent of initial weight status , compared with controls , intervention adolescents had an increase in supervised physical activity ( P<0.0001 ) , a decrease of TV/video viewing ( P<0.01 ) and an increase of high-density cholesterol concentrations ( P<0.0001 ) . Conclusion : Enhancing physical activity with a multilevel program prevents excessive weight gain in non-overweight adolescents . Our study provides evidence that prevention of obesity in youth is feasible Background Recent systematic review s have suggested that pedometers may be effective motivational tools to promote walking . However , studies tend to be of a relatively short duration , with small clinical based sample s. Further research is required to demonstrate their effectiveness in adequately powered , community based studies . Objective Using a r and omized controlled trial design , this study assessed the impact of a 12-week graduated pedometer-based walking intervention on daily step-counts , self-reported physical activity and health outcomes in a Scottish community sample not meeting current physical activity recommendations . MethodS ixty-three women and 16 men ( 49.2 years ± 8.8 ) were r and omly assigned to either an intervention ( physical activity consultation and 12-week pedometer-based walking program ) or control ( no action ) group . Measures for step-counts , 7-day physical activity recall , affect , quality of life ( n = 79 ) , body mass , BMI , % body fat , waist and hip circumference ( n = 76 ) , systolic/diastolic blood pressure , total cholesterol and HDL cholesterol ( n = 66 ) were taken at baseline and week 12 . Analyses were performed on an intention to treat basis using 2-way mixed factorial analyses of variance for parametric data and Mann Whitney and Wilcoxon tests for non-parametric data . Results Significant increases were found in the intervention group for step-counts ( p < .001 ) , time spent in leisure walking ( p = .02 ) and positive affect ( p = .027 ) . Significant decreases were found in this group for time spent in weekday ( p = .003 ) , weekend ( p = .001 ) and total sitting ( p = .001 ) with no corresponding changes in the control group . No significant changes in any other health outcomes were found in either group . In comparison with the control group at week 12 , the intervention group reported a significantly greater number of minutes spent in leisure time ( p = .008 ) , occupational ( p = .045 ) and total walking ( p = .03 ) , and significantly fewer minutes in time spent in weekend ( p = .003 ) and total sitting ( p = .022 ) . Conclusion A pedometer-based walking program , incorporating a physical activity consultation , is effective in promoting walking and improving positive affect over 12 weeks in community based individuals . The discussion examines possible explanations for the lack of significant changes in health outcomes . Continued follow-up of this study will examine adherence to the intervention and possible result ing effects on health outcomes Background Ageing is associated with a decrease in physical activity . This decrease particularly occurs during specific transitional life stages . Especially during adolescence and young adulthood a steep decrease in physical activity is observed . Inactive people are often not aware of their inactivity . Providing feedback on the actual physical activity level by an activity monitor can increase awareness and may in combination with an individually tailored physical activity advice stimulate a physically active lifestyle . Methods In a r and omized controlled trial the effectiveness of providing an activity monitor in combination with a personal physical activity advice through the Internet will be examined . Outcome measures are level of physical activity , determinants of physical activity , quality of life , empowerment , aerobic fitness and body composition . Participants are relatively inactive adolescents and young adults who are measured at baseline , after 3 months intervention and 5 months after the end of the intervention . In addition , facilitating and hindering factors for implementation of the intervention will be investigated . Discussion The use of a personal activity monitor in combination with web-based assisted individually tailored health promotion offers a good opportunity to work interactively with large groups of adolescents and young adults and provide them with advice based on their actual activity level . It has great potential to motivate people to change their behaviour and to our knowledge has not been evaluated before Background We report the main results , among adults , of a cluster-r and omised-trial of Well London , a community-engagement programme promoting healthy eating , physical activity and mental well-being in deprived neighbourhoods . The hypothesis was that benefits would be neighbourhood-wide , and not restricted to intervention participants . The trial was part of a multicomponent process/ outcome evaluation which included non-experimental components ( self-reported behaviour change amongst participants , case studies and evaluations of individual projects ) which suggested health , well-being and social benefits to participants . Methods Twenty matched pairs of neighbourhoods in London were r and omised to intervention/control condition . Primary outcomes ( five portions fruit/vegetables/day ; 5 × 30 m of moderate intensity physical activity/week , abnormal General Health Question naire (GHQ)-12 score and Warwick – Edinburgh Mental Well-being Scale ( WEMWBS ) score ) were measured by postintervention question naire survey , among 3986 adults in a r and om sample of households across neighbourhoods . Results There was no evidence of impact on primary outcomes : healthy eating ( relative risk [ RR ] 1.04 , 95 % CI 0.93 to 1.17 ) ; physical activity ( RR:1.01 , 95 % CI 0.88 to 1.16 ) ; abnormal GHQ12 ( RR:1.15 , 95 % CI 0.84 to 1.61 ) ; WEMWBS ( mean difference [ MD ] : −1.52 , 95 % CI −3.93 to 0.88 ) . There was evidence of impact on some secondary outcomes : reducing unhealthy eating-score ( MD : −0.14 , 95 % CI −0.02 to 0.27 ) and increased perception that people in the neighbourhood pulled together ( RR : 1.92 , 95 % CI 1.12 to 3.29 ) . Conclusions The trial findings do not provide evidence supporting the conclusion of non-experimental components of the evaluation that intervention improved health behaviours , well-being and social outcomes . Low participation rates and population churn likely compromised any impact of the intervention . Imprecise estimation of outcomes and sampling bias may also have influenced findings . There is a need for greater investment in refining such programmes before implementation ; new methods to underst and , longitudinally different pathways residents take through such interventions and their outcomes , and new theories of change that apply to each pathway OBJECTIVES We sought to determine the effects of a community-based , culturally tailored diabetes lifestyle intervention on risk factors for diabetes complications among African Americans and Latinos with type 2 diabetes . METHODS One hundred fifty-one African American and Latino adults with diabetes were recruited from 3 health care systems in Detroit , Michigan , to participate in the Racial and Ethnic Approaches to Community Health ( REACH ) Detroit Partnership diabetes lifestyle intervention . The curriculum , delivered by trained community residents , was aim ed at improving dietary , physical activity , and diabetes self-care behaviors . Baseline and postintervention levels of diabetes-specific quality -of-life , diet , physical activity , self-care knowledge and behaviors , and hemoglobin A1C were assessed . RESULTS There were statistically significant improvements in postintervention dietary knowledge and behaviors and physical activity knowledge . A statistically significant improvement in A1C level was achieved among REACH Detroit program participants ( P<.0001 ) compared with a group of patients with diabetes in the same health care system in which no significant changes were observed ( P=.160 ) . CONCLUSIONS A culturally tailored diabetes lifestyle intervention delivered by trained community residents produced significant improvement in dietary and diabetes self-care related knowledge and behaviors as well as important metabolic improvements BACKGROUND Regular exercise is associated with many health benefits . Community-based exercise programs may increase exercise participation , but little is known about cost implication s. METHOD A retrospective , matched cohort study was conducted to determine if changes in healthcare costs for Medicare-eligible adults who choose to participate in a community-based exercise program were different from similar individuals who did not participate . Exercise program participants included 1114 adults aged > or = 65 years , who were continuously enrolled in Group Health Cooperative of Puget Sound ( GHC ) between October 1 , 1997 and December 31 , 2000 and who participated in the Lifetime Fitness ( exercise ) Program Copyright ( LFP ) at least once ; three GHC enrollees who never attended LFP were r and omly selected as controls for each participant by matching on age and gender . Cost and utilization estimates from GHC administrative data for the time from LFP enrollment to December 31 , 2000 were compared using multivariable regression models . RESULTS The average increase in annual total healthcare costs was less in participants compared to controls ( + 642 dollars vs + 1175 dollars ; p=0.05 ) . After adjusting for differences in age , gender , enrollment date , comorbidity index , and pre-exposure cost and utilization levels , total healthcare costs for participants were 94.1 % ( 95 % confidence interval [ CI ] , 85.6%-103.5 % ) of control costs . However , for participants who attended the exercise program at an average rate of > or = 1 visit weekly , total adjusted follow-up costs were 79.3 % ( 95 % CI , 71.3%-88.2 % ) of controls . CONCLUSIONS Including a community exercise program as a health insurance benefit shows promise as a strategy for helping some Medicare-eligible adults to improve their health through exercise The purpose of this paper is to present key points of an intervention programme ( Agita São Paulo Program ) to promote physical activity in a developing country . Agita is a multi-level , community-wide intervention design ed to increase knowledge about the benefits and the level of physical activity in a mega- population of 34 million inhabitants of São Paulo State , Brazil . The main message was taken from the Centers for Disease Control/American College of Sports Medicine ( CDC/ACSM ) recommendation that : ' everyone should accumulate at least 30 minutes of physical activity , on most days of the weeks , of moderate intensity , in one single or in multiple sessions ' . Activities were encouraged in three setting s : home , transport and leisure time . Focus groups were students from elementary schools through to college , white and blue collar workers , and elderly people . Innovative aspects included : ( 1 ) a research centre leading the process , ( 2 ) scientific and institutional partnerships ( over 160 groups ) , ( 3 ) a feasible approach -- the ' one-step-ahead ' model , ( 4 ) empowerment , ( 5 ) inclusion , ( 6 ) non-paid media , ( 7 ) social marketing , and ( 8) culture-linked . Data were obtained from 645 r and om , home-based question naires over four years -- stratified by sex , age , education and socio-economic level . These data show that the Agita message reached 55.7 % of the population , and among these , 23.1 % knew the main message . Recall of Agita and knowledge of its purpose were well distributed among different socioeconomic levels , being known by 67 % of the most educated . The prevalence of people reaching the recommendation was 54.8 % ( men 48.7 % , women 61 % ) ; and risk of being sedentary was quite smaller among those who knew the Agita message ( 7.1 % ) compared with those who did not know ( 13.1 % ) . In conclusion , based upon the Agita São Paulo experience , it appears that a multi-level , community-wide intervention to promote physical activity may obtain good results if the model contains the items listed above Purpose . This study examined the broader use of a print-media intervention , which was previously shown to be effective at promoting physical activity to participants recruited from a regional Australian community , as a strategy suitable for a more diverse statewide population sample . Methods . Participants were r and omly selected adults who responded to a telephone interview conducted by the New South Wales Health Department and consented to participate in a r and omized controlled trial . Consenters were allocated to either intervention ( n = 361 ) or control ( n = 358 ) conditions . The intervention , a personalized letter plus stage-targeted booklets , was sent 1 week postbaseline . Data were collected via telephone interview at baseline and 2 and 8 months and were analyzed using repeated measures analysis of variance ( ANOVA ) and χ2 statistics . Results . The groups were similar at baseline ( mean age 43 ± 3 years ; 64 % women ) . Process evaluation showed high intervention recall ( 76 % at 2 months ) and high follow-up response rates ( > 85 % at 8 months ) were achieved . Nonsignificant increases in physical activity were observed ( F 1,719 = 2.18 , p = .14 ) . Discussion . A single mailing of stage-targeted print material s was not effective in promoting increases in physical activity among participants selected from the statewide population . Future research could examine how the effectiveness of print media might be enhanced , possibly by using supplementary media , community-based prompts , or other incentives Purpose . To present an evaluation of a 5-year , community-based , chronic disease prevention project managed by a state health department to determine whether the department could replicate similar previous projects that had received more funding and other re sources . Design . The evaluation used a matched comparison design and a review of archive and interview data . Setting . Florence , South Carolina ( population : 56,240 ) . Subjects . A r and om sample of 1642 persons in Florence ( and 1551 in the comparison ) who responded to a risk factor question naire and underwent a physical assessment ; 70 . 7 % of baseline subjects participated in the postintervention . Forty key persons were interviewed concerning project effectiveness . Interventions by Project . Walk-a-thons , a speakers ' bureau , media messages , restaurant food labeling , and cooking seminars . More than 31,000 participants were involved in 585 activities . Measures . Question naires focused on hypertension , obesity , high cholesterol , smoking , and exercise . Physical assessment s determined lipid , lipoprotein , apolipoprotein , and blood pressure levels . Analysis of covariance was used for baseline and postintervention comparisons . Content analysis was used on archive and interview data . Results . The project had a slightly favorable intervention effect on cholesterol and smoking , but failed to have an effect on other risk factors for cardiovascular disease . The project influenced community awareness , enlisted influential community members , and fostered linkages among local health services . Conclusions . Health departments can be instrumental in community risk reduction programming ; however , they may not replicate projects having greater re sources Background The “ Positive Action for Today ’s Health ” ( PATH ) trial tested an environmental intervention to increase walking in underserved communities . Methods Three matched communities were r and omized to a police-patrolled walking plus social marketing , a police-patrolled walking-only , or a no-walking intervention . The 24-month intervention addressed safety and access for physical activity ( PA ) and utilized social marketing to enhance environmental supports for PA . African-Americans ( N = 434 ; 62 % females ; aged 51 ± 16 years ) provided accelerometry and psychosocial measures at baseline and 12 , 18 , and 24 months . Walking attendance and trail use were obtained over 24 months . Results There were no significant differences across communities over 24 months for moderate-to-vigorous PA . Walking attendance in the social marketing community showed an increase from 40 to 400 walkers per month at 9 months and sustained ~200 walkers per month through 24 months . No change in attendance was observed in the walking-only community . Conclusions Findings support integrating social marketing strategies to increase walking in underserved African-Americans ( Clinical Trials.gov # NCT01025726 ) Background : Few studies have considered the neighborhood as a context in which to examine the physical activity and quality of life relationship . Purpose : The goal of this study was to evaluate the effects of a neighborhood walking program on quality of life among older adults . It was design ed as a r and omized trial involving a multilevel design with neighborhoods corresponding to primary sampling units and residents to secondary units . Methods : Five hundred eighty-two communitydwelling senior residents ( 65 years of age or older ) in neighborhoods in the northeast metropolitan area of Portl and , Oregon , were recruited through telephone , direct mail , and referrals . The walking intervention was delivered at the neighborhood level . Neighborhoods ( N = 56 ) were r and omly assigned to a 6-month , 3 times per week , leader-led walking group activity ( n = 28 ) or an information-only control group ( n = 28 ) . Primary outcome measures included SF-12 ( Physical , Mental summary scores ) and life satisfaction ( SWLS ) ; the secondary outcome measure was neighborhood walking activity , assessed at baseline , 3 months , and 6 months of the study period . Results : Compared to the control neighborhoods , results from multilevel , longitudinal analyses indicated significant improvements in the primary outcomes of SF-12 Physical ( p < .05 ) , SF-12 Mental ( p < .05 ) summary scores , and SWLS ( p < .05 ) , over the course of the 6-month intervention . A significant increase was also observed in the secondary outcome of walking activity ( p < .05 ) . Conclusions : Implementing a neighborhood-based walking program of low to moderate intensity is feasible and beneficial for promoting quality of life among senior residents at a community level Background Research and practice partnerships have the potential to enhance the translation of research findings into practice . Purpose This paper describes such a partnership in the development of Walk Kansas ( WK ) and highlights individual and organizational level outcomes . Method Phase 1 examined : ( a ) the reach of WK , ( b ) physical activity changes , and ( c ) maintenance of physical activity changes 6 months after the program was completed . Phase 2 explored WK adoption and sustainability over 5 years . Results WK attracted a large number of participants who were more likely to be female , more active , and older than the adult population within the counties where they resided . Inactive or insufficiently active participants at baseline experienced significant increases in both moderate ( p < 0.001 ) and vigorous ( p < 0.001 ) physical activity . A r and om selection of participants who were assessed 6 months post-program did not demonstrate a significant decrease in moderate or vigorous activity between program completion and 6-month follow-up . The number of counties adopting the program increased across years , peaking at 97 in 2006 and demonstrated the sustainability of the WK over 5 years . Conclusions WK is effective , has a broad reach , and enables participants to maintain increased activity . It also shows promise for broad adoption and sustainability The authors studied the effectiveness of community-wide health education on physical activity knowledge , attitudes , self-efficacy , and behavior . R and om sample s of residents aged 18 - 74 years who lived in four central California cities ( baseline , n = 1,056 men and 1,183 women ) were evaluated in 1979 - 1980 and approximately every 2 years thereafter to obtain four independent sample s. Moreover , every subject in the initial independent sample s was asked to return for follow-up every 2 years thereafter ; subjects who completed all four examinations constituted the cohort sample ( n = 408 men and 499 women ) . Two medium-sized cities received health education and two similarly sized cities served as controls . Results indicated little consistent evidence of a treatment effect on physical activity knowledge , attitudes , or self-efficacy in either men or women . Among physical activity measures , there was an indication of a positive treatment effect for men in the independent sample s for estimated daily energy expenditure and percent participation in vigorous activities ( p < 0.01 ) , and for women in the independent ( p = 0.014 ) and cohort ( p < 0.01 ) sample s for engagement in the number of moderate activities . These results underscore the need for development of more effective interventions to change physical activity than is provided by a broad-based , community-wide health education program and for more sensitive and reliable measures of knowledge , attitudes , and behavior with regard to physical activity Introduction Individuals not engaging in recommended amounts of moderate-intensity physical activity are deemed insufficiently active and are at greater risk of chronic disease . Social marketing strategies may promote positive changes in physical activity levels among insufficiently active individuals . Methods A quasi-experimental design was used to determine whether the results of a previous communitywide physical activity social marketing campaign conducted in Wheeling , WVa ( population , 31,420 ) could be replicated in the larger community of Broome County , New York ( population , 200,536 ) . BC Walks promoted 30 minutes or more of moderate-intensity daily walking among insufficiently active residents of Broome County , New York , aged 40 to 65 years . Promotion activities included paid advertising , media relations , and community health activities . Impact was determined by preintervention and postintervention r and om-digit – dial cohort telephone surveys in intervention and comparison counties . We assessed demographics , walking behavior , moderate and vigorous physical activity , and campaign awareness . Results The paid advertising included 4835 television and 3245 radio gross rating points and 10 quarter-page newspaper advertisements . News media relations result ed in 28 television news stories , 5 radio stories , 10 newspaper stories , and 125 television news promotions . Exposure to the campaign was reported by 78 % of Broome County survey respondents . Sixteen percent of Broome County participants changed from nonactive to active walkers ; 11 % changed from nonactive to active walkers in the comparison county ( adjusted odds ratio , 1.71 ; 95 % confidence interval , 0.99–2.95 ) . Forty-seven percent of Broome County respondents reported any increase in total weekly walking time , compared with 36 % for the comparison county ( adjusted odds ratio , 1.66 ; 95 % confidence interval , 1.14–2.44 ) . Conclusion The BC Walks campaign replicated the earlier Wheeling Walks initiative , although increases in walking were smaller in the BC Walks campaign OBJECTIVE To determine whether a multicomponent health promotion intervention for Dutch adolescents ( defined as persons between 12 and 14 years of age ) would be successful in influencing body composition and dietary and physical activity behavior in both the short and long terms . DESIGN R and omized controlled trial . SETTING Ten intervention and 8 control prevocational secondary schools . PARTICIPANTS A total of 1108 adolescents ( mean age , 12.7 years ) . Intervention An interdisciplinary program with an adapted curriculum for 11 lessons in biology and physical education and environmental change options . MAIN OUTCOME MEASURES Body height and weight , waist circumference , 4 skinfold thickness measurements , and dietary and physical activity behavior data . RESULTS Multilevel analyses showed that the intervention remained effective in preventing unfavorable increases in important measures of body composition after 20-month follow-up in girls ( biceps skinfold and sum of 4 skinfolds ) and boys ( triceps , biceps , and subscapular skinfolds ) . Consumption of sugar-containing beverages was significantly lower in intervention schools both after intervention ( boys : -287 mL/d ; 95 % confidence interval [ CI ] , -527 to -47 ; girls : -249 ; -400 to -98 ) and at 12-month follow-up ( boys : -233 ; -371 to -95 ; girls : -271 ; -390 to -153 ) . For boys , screen-viewing behavior was significantly lower in the intervention group after 20 months ( -25 min/d ; 95 % CI , -50 to -0.3 ) . No significant intervention effects on consumption of snacks or active commuting to school were found . CONCLUSION The Dutch Obesity Intervention in Teenagers program result ed in beneficial effects on the sum of skinfold thickness measurements in girls and consumption of sugar-containing beverages in both boys and girls in both the short and long terms Background This paper examines the association between use of protective devices , frequency of acute health problems and health-protection information received by participants engaged in the Prestige oil spill clean-up in Asturias and Cantabria , Spain . Methods We studied 133 seamen , 135 bird cleaners , 266 volunteers and 265 paid workers selected by r and om sampling , stratified by type of worker and number of working days . Information was collected by telephone interview conducted in June 2003 . The association of interest was summarized , using odds ratios ( OR ) obtained from logistic regression . Results Health-protection briefing was associated with use of protective devices and clothing . Uninformed subjects registered a significant excess risk of itchy eyes ( OR:2.89 ; 95%CI:1.21–6.90 ) , nausea/vomiting/dizziness ( OR:2.25 ; 95%CI:1.17–4.32 ) and throat and respiratory problems ( OR:2.30 ; 95%CI:1.15–4.61 ) . There was a noteworthy significant excess risk of headaches ( OR:3.86 : 95%CI:1.74–8.54 ) and respiratory problems ( OR:2.43 ; 95%CI:1.02–5.79 ) among uninformed paid workers . Seamen , the group most exposed to the fuel-oil , were the worst informed and registered the highest frequency of toxicological problems . Conclusion Proper health-protection briefing was associated with greater use of protective devices and lower frequency of health problems . Among seamen , however , the results indicate poorer dissemination of information and the need of specific guidelines for removing fuel-oil at sea OBJECTIVE To evaluate the cost-effectiveness of non-face-to-face interventions for increasing physical activity in sedentary adults . The study took place in Providence , Rhode Isl and between the years 2000 and 2004 . METHODS Two hundred and thirty-nine participants were r and omized to Phone , Print or a contact control . Phone and Print groups were mailed regular surveys regarding their level of physical activity , motivational readiness and self-efficacy . Surveys were scanned by a computer expert system to generate feedback reports . Phone group participants received feedback by telephone . Print group participants received feedback by mail . The contact control group received mailings unrelated to physical activity . Intervention costs were assessed prospect ively , from a payer perspective . Physical activity was measured using the 7-day Physical Activity Recall . Ambulatory health service use was assessed via monthly surveys . RESULTS The Print intervention was more economically efficient than the Phone intervention in engaging participants in a more active lifestyle . CONCLUSION The Print intervention provides an efficient approach to increasing physical activity . Research is needed to determine the cost-effectiveness of the intervention in a more diverse population , within the context of the health service delivery system and over a longer period of time BACKGROUND AND OBJECTIVE R and omized clinical trials have documented that lifestyle changes through physical activity can prevent diabetes . However there is no data whether such strategies are applicable at community level , that is , in a real life setting . This study demonstrates the first attempt in India , to our knowledge , of increasing physical activity through community empowerment in an attempt at primary prevention of non communicable diseases . METHODS The Chennai Urban Population Study [ CUPS ] was conducted in the year 1996 in two residential areas : a middle income group the Asiad colony at Tirumangalam , and a low income group at Bharathi Nagar in T. Nagar . The Asiad colony was selected for this study . Of the 524 eligible individuals available at baseline in 1998 [ age > or = 20 years ] , 479 individuals consented for the study ( response rate : 91.4 % ) . After seven years , in 2004 , the number of eligible individuals increased to 712 of whom 705 consented for the study ( response rate:99 % ) . Education regarding the benefits of physical activity was provided by mass awareness programmes like public lectures and video clippings . Both at baseline and during follow-up , details about the physical activity were collected using a vali date d question naire , which included job related and leisure time activities , and specific questions on exercise . Study individuals were then grade d as having light , moderate and heavy physical activity using a scoring system . RESULTS In response to the awareness programmes given by our research team , the colony residents constructed a unique public park with their own funds . Though the occupation grade s did not change , there was a significant change in the pattern of physical activity . At baseline , only 14.2 % of the residents did some form of exercise . more than three times a week , which presently increased to 58.7 % [ p < 0.001 ] . The number of subjects who walked more than three times a week increased from 13.8 % at baseline to 52.1 % during follow-up [ p < 0.001 ] . CONCLUSION This study is a demonstration of how community empowerment with increased physical activity could possibly lead to prevention of diabetes and other non communicable diseases at the community level . This study also highlights the importance of sharing the results of research studies with the community Background People over the age of 70 carry the greatest burden of chronic disease , disability and health care use . Participation in physical activity is crucial for health , and walking accounts for much of the physical activity undertaken by sedentary individuals . Pedometers are a useful motivational tool to encourage increased walking and they are cheap and easy to use . The aim of this pilot study was to evaluate the feasibility of the use of pedometers plus a theory-based intervention to assist sedentary older women to accumulate increasing amounts of physical activity , mainly through walking . Methods Female participants over the age of 70 were recruited from primary care and r and omised to receive either pedometer plus a theory-based intervention or a theory-based intervention alone . The theory-based intervention consisted of motivational techniques , goal - setting , barrier identification and self-monitoring with pedometers and daily diaries . The pedometer group were further r and omised to one of three target groups : a 10 % , 15 % or 20 % monthly increase in step count to assess the achievability and acceptability of a range of targets . The primary outcome was change in daily activity levels measured by accelerometry . Secondary outcome measures were lower limb function , health related quality of life , anxiety and depression . Results 54 participants were recruited into the study , with an average age of 76 . There were 9 drop outs , 45 completing the study . All participants in the pedometer group found the pedometers easy to use and there was good compliance with diary keeping ( 96 % in the pedometer group and 83 % in the theory-based intervention alone group ) . There was a strong correlation ( 0.78 ) between accelerometry and pedometer step counts i.e. indicating that walking was the main physical activity amongst participants . There was a greater increase in activity ( accelerometry ) amongst those in the 20 % target pedometer group compared to the other groups , although not reaching statistical significance ( p = 0.192 ) . Conclusion We have demonstrated that it is feasible to use pedometers and provide theory-based advice to community dwelling sedentary older women to increase physical activity levels and a larger study is planned to investigate this further Background Health promotion is a key component for primary prevention of cardiovascular disease ( CVD ) . This study evaluated the impact of healthy lifestyle promotion campaigns on CVD risk factors ( CVDRF ) in the general population in the context of a community-based programme on hypertension management . Methods A quasi-experimental intervention study was carried out in two rural communes of Vietnam from 2006 to 2009 . In the intervention commune , a hypertensive-targeted management programme integrated with a community-targeted health promotion was initiated , while no new programme , apart from conventional healthcare services , was provided in the reference commune . Health promotion campaigns focused on smoking cessation , reducing alcohol consumption , encouraging physical activity and reducing salty diets . Repeated cross-sectional surveys in local adult population aged 25 years and over were undertaken to assess changes in blood pressure ( BP ) and behavioural CVDRFs ( smoking , alcohol consumption , physical inactivity and salty diet ) in both communes before and after the 3-year intervention . Results Overall 4,650 adults above 25 years old were surveyed , in four r and omly independent sample s covering both communes at baseline and after the 3-year intervention . Although physical inactivity and obesity increased over time in the intervention commune , there was a significant reduction in systolic and diastolic BP ( 3.3 and 4.7 mmHg in women versus 3.0 and 4.6 mmHg in men respectively ) in the general population at the intervention commune . Health promotion reduced levels of salty diets but had insignificant impact on the prevalence of daily smoking or heavy alcohol consumption . Conclusion Community-targeted healthy lifestyle promotion can significantly improve some CVDRFs in the general population in a rural area over a relatively short time span . Limited effects on a context -bound CVDRF like smoking suggested that higher intensity of intervention , a supportive environment or a gender approach are required to maximize the effectiveness and maintain the sustainability of the health intervention Background Although school-based interventions to promote physical activity in adolescents have been suggested in several recent review s , questions have been raised regarding the effects of the strategies and the methodology applied and for whom the interventions are effective . The aim of the present study was to investigate effects of a school-based intervention program : the HEalth in Adolescents ( HEIA ) study , on change in physical activity , and furthermore , to explore whether potential effects varied by gender , weight status , initial physical activity level and parental education level . Methods This was a cluster r and omized controlled 20 month intervention study which included 700 11-year-olds . Main outcome -variable was mean count per minute ( cpm ) derived from ActiGraph accelerometers ( Model 7164/GT1 M ) . Weight and height were measured objective ly . Adolescents reported their pubertal status in a question naire and parents reported their education level on the consent form . Linear mixed models were used to test intervention effects and to account for the clustering effect of sampling by school . Results The present study showed an intervention effect on overall physical activity at the level of p = 0.05 with a net effect of 50 cpm increase from baseline to post intervention in favour of the intervention group ( 95 % CI −0.4 , 100 ) . Subgroup analyses showed that the effect appeared to be more profound among girls ( Est 65 cpm , CI 5 , 124 , p = 0.03 ) and among participants in the low-activity group ( Est 92 cpm , CI 41 , 142 , p < 0.001 ) , as compared to boys and participants in the high-activity group , respectively . Furthermore , the intervention affected physical activity among the normal weight group more positively than among the overweight , and participants with parents having 13–16 years of education more positively than participants with parents having either a lower or higher number of years of education . The intervention seemed to succeed in reducing time spent sedentary among girls but not among boys . Conclusions A comprehensive but feasible , multi-component school-based intervention can affect physical activity patterns in adolescents by increasing overall physical activity . This intervention effect seemed to be more profound in girls than boys , low-active adolescents compared to high-active adolescents , participants with normal weight compared to the overweight , and for participants with parents of middle education level as opposed to those with high and low education levels , respectively . An implementation of the HEIA intervention components in the school system may have a beneficial effect on public health by increasing overall physical activity among adolescents and possibly among girls and low-active adolescents in particular Background Childhood obesity and physical inactivity are increasing dramatically worldwide . Children of low socioeconomic status and /or children of migrant background are especially at risk . In general , the overall effectiveness of school-based programs on health-related outcomes has been disappointing . A special gap exists for younger children and in high risk groups . Methods / Design This paper describes the rationale , design , curriculum , and evaluation of a multicenter preschool r and omized intervention study conducted in areas with a high migrant population in two out of 26 Swiss cantons . Twenty preschool classes in the German ( canton St. Gallen ) and another 20 in the French ( canton Vaud ) part of Switzerl and were separately selected and r and omized to an intervention and a control arm by the use of opaque envelopes . The multidisciplinary lifestyle intervention aim ed to increase physical activity and sleep duration , to reinforce healthy nutrition and eating behaviour , and to reduce media use . According to the ecological model , it included children , their parents and the teachers . The regular teachers performed the majority of the intervention and were supported by a local health promoter . The intervention included physical activity lessons , adaptation of the built infrastructure ; promotion of regional extracurricular physical activity ; playful lessons about nutrition , media use and sleep , funny homework cards and information material s for teachers and parents . It lasted one school year . Baseline and post-intervention evaluations were performed in both arms . Primary outcome measures included BMI and aerobic fitness ( 20 m shuttle run test ) . Secondary outcomes included total ( skinfolds , bioelectrical impedance ) and central ( waist circumference ) body fat , motor abilities ( obstacle course , static and dynamic balance ) , physical activity and sleep duration ( accelerometry and question naires ) , nutritional behaviour and food intake , media use , quality of life and signs of hyperactivity ( question naires ) , attention and spatial working memory ability ( two vali date d tests ) . Research ers were blinded to group allocation . Discussion The purpose of this paper is to outline the design of a school-based multicenter cluster r and omized , controlled trial aim ing to reduce body mass index and to increase aerobic fitness in preschool children in culturally different parts of Switzerl and with a high migrant population .Trial Registration Trial Registration : clinical trials.gov Background Although physical inactivity has been linked with numerous chronic health conditions and overall mortality , the majority of English adults report doing insufficient physical activity . To increase population physical activity levels , research ers have called for more community-level interventions . To evaluate these complex public health interventions , innovative study design s are required . This study protocol describes Devon Active Villages , a community-level intervention providing physical activity opportunities to 128 rural villages in southwest Engl and , and the methods used to evaluate its effectiveness in increasing physical activity levels . Methods / Design A stepped wedge cluster r and omised trial will be used to evaluate whether Devon Active Villages leads to increased physical activity levels in rural communities . Community engagement will help tailor activity programmes for each village ; communities will then be supported for a further twelve months . The intervention will be delivered over four periods , each lasting twelve weeks . Data collection consists of a postal survey of a r and om sample of adults aged 18 years and over , at baseline and after each of the four intervention periods . The question naire includes questions on participant demographics , physical activity behaviour , local environment characteristics , awareness of local activity programmes , and psychosocial factors . Based on detecting an increase in the proportion of people who meet physical activity guidelines ( from 25 % to 30 % ) , at least ten respondents are needed from each of the 128 villages at each stage ( 80 % power at the 5 % level of significance ) . Anticipating a 20 % response rate , 6,400 question naires will be sent out at each stage ( i.e. , 50 surveys to each village ) . Using data from all five periods , a comparison of study outcomes between intervention and control arms will be performed , allowing for time period ( as a fixed effect ) and the r and om effect induced by correlation of outcomes ( clustering ) within villages . Discussion This paper describes the use of a stepped wedge cluster r and omised trial to evaluate a complex , community-level physical activity intervention in an under-studied population of adults in rural communities in southwest Engl and . The study addresses gaps in the current literature by providing new insights into physical activity levels in this population .Trial Registration NumberCurrent Controlled Trials IS RCT OBJECTIVE The progression from impaired glucose tolerance (IGT)/impaired fasting glucose ( IFG ) to type 2 diabetes can be prevented or delayed through intensive lifestyle changes . How to translate this to implementation across whole communities remains unclear . We now describe the results to a pilot of a personal trainer ( Maori Community Health Worker , MCHW ) approach among Maori in New Zeal and . DESIGN , SETTING AND SUBJECTS A r and omised cluster-controlled trial of intensive lifestyle change was commenced among 5,240 non-pregnant Maori family members without diabetes from 106 rural and 106 urban geographical clusters . Baseline assessment s included lifestyle question naires , anthropometric measurements and venesection . A pilot study ( Vanguard Study ) cohort of 160 participants were weighed before and during MCHW intervention , and compared with fifty-two participants weighed immediately before intervention and with 1,143 participants from the same geographical area . Interactions between participants and the MCHW were reported using personal digital assistants with a programmed detailed structured approach to each interview . RESULTS During the Vanguard Study , participants and MCHW found the messages , toolkit and delivery approach acceptable . Those with IGT/IFG diagnosed ( n 27 ) experienced significant weight loss after screening and during the Vanguard Study ( 5.2 ( sd 6.6 ) kg , paired t test P < 0.01 ) . Significant weight loss occurred during the Vanguard Study among all participants ( -1.3 ( sd 3.6 ) kg , P < 0.001 ) . CONCLUSIONS Comparable initial weight loss was shown among those with IGT/IFG and those from existing trials . Community-wide prevention programmes are feasible among Maori and are likely to result in significant reductions in the incidence of diabetes Background The majority of adults are not meeting the guidelines for physical activity despite activity being linked with numerous improvements to long-term health . In light of this , research ers have called for more community-level interventions . The main objective of the present study was to evaluate whether a community-level physical activity intervention increased the activity levels of rural communities . Methods 128 rural villages ( clusters ) were r and omised to receive the intervention in one of four time periods between April 2011 and December 2012 . The Devon Active Villages intervention provided villages with 12 weeks of physical activity opportunities for all age groups , including at least three different types of activities per village . Each village received an individually tailored intervention , incorporating a local needs-led approach . Support was provided for a further 12 months following the intervention . The evaluation study used a stepped wedge cluster r and omised controlled trial design . All 128 villages were measured at each of five data collection periods using a postal survey . The primary outcome of interest was the proportion of adults reporting sufficient physical activity to meet internationally recognised guidelines . Minutes spent in moderate- and -vigorous activity per week was analysed as a secondary outcome . To compare between intervention and control modes , r and om effects linear regression and marginal logistic regression models were implemented for continuous and binary outcomes respectively . Results 10,412 adults ( 4693 intervention , 5719 control ) completed the postal survey ( response rate 32.2 % ) . The intervention did not increase the odds of adults meeting the physical activity guideline ( adjusted OR 1.02 , 95 % CI : 0.88 to 1.17 ; P = 0.80 ) , although there was weak evidence of an increase in minutes of moderate- and -vigorous-intensity activity per week ( adjusted mean difference = 171 , 95 % CI : -16 to 358 ; P = 0.07 ) . The ineffectiveness of the intervention may have been due to its low penetration — only 16 % of intervention mode participants reported awareness of the intervention and just 4 % reported participating in intervention events . Conclusions A community-level physical activity intervention providing tailored physical activity opportunities to rural villages did not improve physical activity levels in adults . Greater penetration of such interventions must be achieved if they are to increase physical activity prevalence at the community level . Trial Registration Current Controlled Trials http://www.controlled-trials.com/IS RCT N37321160 BACKGROUND Food intake amongst Canadian Inuit is currently in transition with a concurrent increase in diet-related chronic disease . There is a lack of current data on nutrient intake and dietary adequacy in this population . The present study aim ed to assess dietary intake and adequacy amongst Inuit adults in a community in Nunavut , Canada . METHODS R and om sampling of 130 households in a remote Inuit community in the Kitikmeot region of Nunavut , Canada , was used for this cross-sectional study . Up to three 24-h dietary recalls were collected on nonconsecutive days , capturing weekday and weekend consumption . Data were analysed to estimate energy and nutrient intake , to determine dietary adequacy , and to summarise the most commonly reported foods and the top food contributors to selected nutrients . RESULTS The response rate was 69 % , with 75 Inuit adults participating ( mean ( st and ard deviation ( SD ) ) age 44 ( SD=17 ) years ) . Mean ( SD ) daily energy intake was 9.3 ( 4.4 ) MJ and 8.7 ( 3.5 ) MJ for men and women , respectively . Intakes of dietary fibre , calcium , total folate and vitamins A , D and E were below the Dietary Reference Intakes ( Estimated Average Requirements where available ) for 60 - 100 % of all men and women . Traditional foods contributed substantially to protein and iron intake , whilst shop-bought foods were primary contributors to total fat , carbohydrate and sugar intake . CONCLUSIONS The present study reports an in-depth assessment of total dietary quality amongst Inuit adults in Nunavut , Canada . The results obtained indicate inadequate intakes of several essential nutrients , as well as a reliance on a nontraditional diet . A nutrition intervention is needed to prevent a continued rise in diet-related chronic disease incidence BACKGROUND Ethnic minorities and lower-income adults have among the highest rates of obesity and lowest levels of regular physical activity ( PA ) . The Positive Action for Today 's Health ( PATH ) trial compares three communities that are r and omly assigned to different levels of an environmental intervention to improve safety and access for walking in low income communities . DESIGN AND SETTING Three communities matched on census tract information ( crime , PA , ethnic minorities , and income ) were r and omized to receive either : an intervention that combines a police-patrolled-walking program with social marketing strategies to promote PA , a police-patrolled-walking only intervention , or no-walking intervention ( general health education only ) . Measures include PA ( 7-day accelerometer estimates ) , body composition , blood pressure , psychosocial measures , and perceptions of safety and access for PA at baseline , 6 , 12 , 18 , and 24 months . INTERVENTION The police-patrolled walking plus social marketing intervention targets increasing safety ( training community leaders as walking captains , hiring off-duty police officers to patrol the walking trail , and containing stray dogs ) , increasing access for PA ( marking a walking route ) , and utilizes a social marketing campaign that targets psychosocial and environmental mediators for increasing PA . MAIN HYPOTHESES/ OUTCOMES : It is hypothesized that the police-patrolled walking plus social marketing intervention will result in greater increases in moderate-to-vigorous PA as compared to the police-patrolled-walking only or the general health intervention after 12 months and that this effect will be maintained at 18 and 24 months . CONCLUSIONS Implication s of this community-based trial are discussed Background The Well London program used community engagement , complemented by changes to the physical and social neighborhood environment , to improve physical activity levels , healthy eating , and mental wellbeing in the most deprived communities in London . The effectiveness of Well London is being evaluated in a pair-matched cluster r and omized trial ( CRT ) . The baseline survey data are reported here . Methods The CRT involved 20 matched pairs of intervention and control communities ( defined as UK census lower super output areas ( LSOAs ) ; ranked in the 11 % most deprived LSOAs in London by the English Indices of Multiple Deprivation ) across 20 London boroughs . The primary trial outcomes , sociodemographic information , and environmental neighbourhood characteristics were assessed in three quantitative components within the Well London CRT at baseline : a cross-sectional , interviewer-administered adult household survey ; a self-completed , school-based adolescent question naire ; a fieldworker completed neighborhood environmental audit . Baseline data collection occurred in 2008 . Physical activity , healthy eating , and mental wellbeing were assessed using st and ardized , vali date d question naire tools . Multiple imputation was used to account for missing data in the outcomes and other variables in the adult and adolescent surveys . Results There were 4,107 adults and 1,214 adolescent respondents in the baseline surveys . The intervention and control areas were broadly comparable with respect to the primary outcomes and key sociodemographic characteristics . The environmental characteristics of the intervention and control neighborhoods were broadly similar . There was greater between-cluster variation in the primary outcomes in the adult population compared to the adolescent population . Levels of healthy eating , smoking , and self-reported anxiety/depression were similar in the Well London adult population and the national Health Survey for Engl and . Levels of physical activity were higher in the Well London adult population but this is likely to be due to the different measurement tools used in the two surveys . Conclusions R and omization of social interventions such as Well London is acceptable and feasible and in this study the intervention and control arms are well-balanced with respect to the primary outcomes and key sociodemographic characteristics . The matched design has improved the statistical efficiency of the study amongst adults but less so amongst adolescents . Follow-up data collection will be completed 2012.Trial registration Current Controlled Trials IS RCT Background Consumption of the recommended amounts of fruits and vegetables is associated with several health benefits . Currently less than 25 % of the American population meets the minimum recommendation of five servings a day . In order to change this health behaviour , interventions should be based on theory and include community-wide social support . Methods A low intensity intervention was developed in which participants ( n = 86 ) were r and omly assigned to either the fruit and vegetable intervention ( FVI ) or st and ard control condition . The intervention was integrated into an ongoing community physical activity program and study participants were drawn from the sample of community members enrolled in the program . The FVI consisted of brief social cognitive theory-based messages delivered in nine weekly newsletters design ed to improve participant outcome and self-efficacy expectations related to fruit and vegetable consumption . Results Participants in the FVI condition increased in their fruit and vegetable consumption by approximately one to one and one-third servings per day . The control condition showed no change in consumption . The effect of the intervention was enhanced when examined by the extent to which it was adopted by participants ( i.e. , the number of newsletters read ) . Those participants who read seven or more newsletters showed an increase of two servings per day . Conclusion This intervention was effective at improving fruit and vegetable consumption among adults . Minimal interventions , such as newsletters , have the ability to reach large audiences and can be integrated into ongoing health promotion programs . As such , they have potential for a strong public health impact OBJECTIVE Low-cost ( e.g. , computer-tailored ) interventions with sustained effects are needed to increase and maintain physical activity in older adults . This study examined the long-term efficacy of 2 computer-tailored physical activity interventions for older adults and its psychosocial and environmental mediators . METHODS A clustered r and omized controlled trial ( N = 1,971 ) was conducted that included 3 research arms : ( a ) basic computer-tailored print intervention , targeting psychosocial mediators ; ( b ) environmentally computer-tailored print intervention , targeting psychosocial and environmental mediators ; and ( c ) no-intervention control group . Interventions were developed using the intervention mapping approach and consisted of 3 computer-tailored letters delivered over 4 months . Question naires assessed the study outcomes ( i.e. , total weekly days and total weekly minutes of physical activity ) at baseline and 12 months . Potential mediators ( i.e. , awareness , attitude , self-efficacy , intention , social influence , intrinsic motivation , self-regulation , and perceived environment ) were assessed at baseline and at 3 or 6 months . RESULTS Multilevel regression analyses revealed that both interventions significantly changed total weekly days of physical activity compared with the control group , but only the environmentally computer-tailored print intervention significantly changed weekly minutes of physical activity . Multiple mediation models showed that the effects of both interventions on weekly days of physical activity were mediated by changes in awareness and intention . CONCLUSIONS Computer-tailored interventions were effective in inducing long-term behavioral changes in physical activity behavior of older adults . Awareness and intention were found to be important mediators of changing daily physical activity and should be included in future computer-tailored intervention studies OBJECTIVE The objective was to test the hypothesis that a community-based environmental change intervention could prevent weight gain in young children ( 7.6 + /- 1.0 years ) . RESEARCH METHODS AND PROCEDURES A non-r and omized controlled trial was conducted in three culturally diverse urban cities in Massachusetts . Somerville was the intervention community ; two socio-demographically-matched cities were control communities . Children ( n = 1178 ) in grade s 1 to 3 attending public elementary schools participated in an intervention design ed to bring the energy equation into balance by increasing physical activity options and availability of healthful foods within the before- , during- , after-school , home , and community environments . Many groups and individuals within the community ( including children , parents , teachers , school food service providers , city departments , policy makers , healthcare providers , before- and after-school programs , restaurants , and the media ) were engaged in the intervention . The main outcome measure was change in BMI z-score . RESULTS At baseline , 44 % ( n = 385 ) , 36 % ( n = 561 ) , and 43 % ( n = 232 ) of children were above the 85th percentile for BMI z-score in the intervention and the two control communities , respectively . In the intervention community , BMI z-score decreased by -0.1005 ( p = 0.001 , 95 % confidence interval , -0.1151 to -0.0859 ) compared with children in the control communities after controlling for baseline covariates . DISCUSSION A community-based environmental change intervention decreased BMI z-score in children at high risk for obesity . These results are significant given the obesigenic environmental backdrop against which the intervention occurred . This model demonstrates promise for communities throughout the country confronted with escalating childhood obesity rates Background Social marketing campaigns offer a promising approach to the prevention of childhood obesity . Change4Life ( C4L ) is a national obesity prevention campaign in Engl and . It included mass media coverage aim ing to reframe obesity into a health issue relevant to all and provided the opportunity for parents to complete a brief question naire ( ‘ How are the Kids ’ ) and receive personalised feedback about their children ’s eating and activity . Print and online C4L re sources were available with guidance about healthy eating and physical activity . The study aims were to examine the impact of personalised feedback and print material from the C4L campaign on parents ’ attitudes and behaviours about their children ’s eating and activity in a community-based cluster-r and omised controlled trial . Methods Parents of 5–11 year old children were recruited from 40 primary schools across Engl and . Schools were r and omised to intervention or control ( ‘ usual care ’ ) . Basic demographic data and brief information about their attitudes to their children ’s health were collected . Families in intervention schools were mailed the C4L print material s and the ‘ How are the Kids ’ question naire ; those returning the question naire were sent personalised feedback and others received generic material s. Outcomes included awareness of C4L , attitudes to the behaviours recommended in C4L , parenting behaviours ( monitoring and modelling ) , and child health behaviours ( diet , physical activity and television viewing ) . Follow-up data were collected from parents by postal question naire after six months . Qualitative interviews were carried out with a subset of parents ( n = 12 ) . Results 3,774 families completed baseline question naires and follow-up data were obtained from 1,419 families ( 37.6 % ) . Awareness was high in both groups at baseline ( 75 % ) , but increased significantly in the intervention group by follow-up ( 96 % vs. 87 % ) . Few parents ( 5.2 % of the intervention group ) returned the question naire to get personalised feedback . There were few significant group differences in parental attitudes or parenting and child health behaviours at follow-up . Physical activity was rated as less important in the intervention group , but a significant group-by-socioeconomic status ( SES ) interaction indicated that this effect was confined to higher SES families . Similar interactions were also seen for physical activity monitoring and child television time ; with adverse effects in higher SES families and no change in the lower SES families . Effects were little better in families that completed the question naire and received personalised feedback . At interview , acceptability of the intervention was modest , although higher in lower SES families . Conclusions The C4L campaign material s achieved increases in awareness of the campaign , but in this sample had little impact on attitudes or behaviour . Low engagement with the intervention appeared a key issue . Trial registration numberCurrent Controlled Trials IS RCT N00791709 OBJECTIVES Whether community-wide education changed cardiovascular risk factors and disease risk in Pawtucket , RI , relative to a comparison community was assessed . METHODS R and om- sample , cross-sectional surveys were done of people aged 18 through 64 years at baseline , during , and after education . Baseline cohorts were reexamined . Pawtucket citizens of all ages participated in multilevel education , screening , and counseling programs . RESULTS The downward trend in smoking was slightly greater in the comparison city . Small , insignificant differences favored Pawtucket in blood cholesterol and blood pressure . In the cross-sectional surveys , body mass index increased significantly in the comparison community ; a similar change was not seen in cohort surveys . Projected cardiovascular disease rates were significantly ( 16 % ) less in Pawtucket during the education program . This difference lessened to 8 % posteducation . CONCLUSIONS The hypothesis that projected cardiovascular disease risk can be altered by community-based education gains limited support from these data . Achieving cardiovascular risk reduction at the community level was feasible , but maintaining statistically significant differences between cities was not . Accelerating risk factor changes will likely require a sustained community effort with reinforcement from state , regional , and national policies and programs OBJECTIVES ICAPS ( Intervention Centred on Adolescents ' Physical activity and Sedentary behaviour ) is aim ed at preventing excessive weight gain and cardiovascular risk in adolescents by promoting physical activity ( PA ) with an emphasis on recreational and daily-life PA , with a lifelong perspective . DESIGN R and omized study design ed to last for four years . Study cohort constituted of 954 first-level students ( 91 % of eligible pupils ) , aged 11.7 + /- 0.6 y ( mean + /- SD ) from four pairs of schools r and omly selected in eastern France , after sociogeographical stratification . In each pair , intervention status was r and omised at school-level . The program , not limited to school setting s , involves multiple partners with three objectives : 1 ) changing attitudes through debates and access to attractive activities during breaks and after-school hours , 2 ) encouraging social support , 3 ) providing environmental conditions that enable PA . Adapted times and places , open participation , emphasis on fun , meeting with others and absence of competitive aspects are used to reduce usual barriers to PA . Accessibility and safety are permanent concerns . RESULTS Prevalence of overweight was 23.7 % . High participation rates were attained ( 50 % participated in at least one weekly activity ) . At six-month , the proportion of intervention adolescents not performing supervised PA out of academic PA was reduced by half ( 36 % to 17 % vs 42 % to 42 % in controls P < 10 - 4 ) ; the proportion of those spending > 3 h/day in sedentary occupations decreased ( 34 % to 28 % vs 27 % to 36 % ; P < 10 - 4 ) . CONCLUSION These data demonstrate the feasibility of implementing a multilevel PA intervention program in adolescents . Six-month results document increased PA and decreased sedentary behaviour Background Physical activity ( PA ) is associated with positive cardio-metabolic health and emerging evidence suggests sedentary behavior ( SB ) may be detrimental to children 's health independent of PA . The primary aim of the Transform-Us ! study is to determine whether an 18-month , behavioral and environmental intervention in the school and family setting s results in higher levels of PA and lower rates of SB among 8 - 9 year old children compared with usual practice ( post-intervention and 12-months follow-up ) . The secondary aims are to determine the independent and combined effects of PA and SB on children 's cardio-metabolic health risk factors ; identify the factors that mediate the success of the intervention ; and determine whether the intervention is cost-effective . Methods / design A four-arm cluster-r and omized controlled trial ( RCT ) with a 2 × 2 factorial design , with schools as the unit of r and omization . Twenty schools will be allocated to one of four intervention groups , sedentary behavior ( SB-I ) , physical activity ( PA-I ) , combined SB and PA ( SB+PA-I ) or current practice control ( C ) , which will be evaluated among approximately 600 children aged 8 - 9 years in school year 3 living in Melbourne , Australia . All children in year 3 at intervention schools in 2010 ( 8 - 9 years ) will receive the intervention over an 18-month period with a maintenance ' booster ' delivered in 2012 and children at all schools will be invited to participate in the evaluation assessment s. To maximize the sample and to capture new students arriving at intervention and control schools , recruitment will be on-going up to the post-intervention time point . Primary outcomes are time spent sitting and in PA assessed via accelerometers and inclinometers and survey . Discussion To our knowledge , Transform-Us ! is the first RCT to examine the effectiveness of intervention strategies for reducing children 's overall sedentary time , promoting PA and optimizing health outcomes . The integration of consistent strategies and messages to children from teachers and parents in both school and family setting s is a critical component of this study , and if shown to be effective , may have a significant impact on educational policies as well as on pedagogical and parenting practice s . Trial registration ACTRN12609000715279 ; Current Controlled Trials IS RCT OBJECTIVES We examined the efficacy of a cancer prevention intervention design ed to improve health behaviors among working-class , multiethnic population s employed in small manufacturing businesses . METHODS Worksites were r and omly assigned to an intervention or minimal-intervention control condition . The intervention targeted fruit and vegetable consumption , red meat consumption , multivitamin use , and physical activity . RESULTS Employees in the intervention group showed greater improvements for every outcome compared with employees in the control group . Differences in improvement were statistically significant for multivitamin use and physical activity . Intervention effects were larger among workers than among managers for fruit and vegetable consumption and for physical activity . CONCLUSIONS The social- context model holds promise for reducing disparities in health behaviors . Further research is needed to improve the effectiveness of the intervention This report describes the proposed intervention and outcome measurement procedures for the Pathways study . Pathways is a multicenter school-based study aim ed at reducing the alanning increase in the prevalence of obesity in American Indian children . It is design ed as a r and omized clinical trial , involving approximately 2,00 third grade children in 40 schools in seven diferent American Indian communities . During a 3-year feasibility phase , which was just completed , the major components of the intervention ( school food service , classroom curriculum , physical education program , and family involvement ) were developed and pilot-tested . The measurement instruments for body composition ; physical activity ; dietary intake ; and knowledge , attitudes , and behavior were also developed and vali date d. Comprehensive process evaluation procedures also were defined . As of this writing , thefull-scale intervention program is being initiated and is scheduled to be completed in the spring of 200 . The primary aim of the Pathways intervention is to reduce average percent body fat in intervention-school children by at least 3 % compared with control-school children by the end of the 3-year intervention . This goal is to be achieved primarily by an increase in physical activity and a reduction in the perceni of dietary fat intake . The program does not seek to reduce dietary energy intake . Rather , it is based on the assumption that a healthier ; lower-fat diet , combined with an increase in energy expenditure by increased physical activity , will result in fewer excess calories deposited as body fat To assess the effectiveness of the ' Green Prescription ' ( GRx ) program in promoting self-reported health benefits in previously inactive individuals , between 2001 and 2002 , a retrospective survey was administered to 124 GRx patients throughout New Zeal and . Participants were a non-r and omized subset of a larger GRx population . Logistic regression was used to calculate odds ratios ( OR ) and 95 % confidence intervals ( CI ) for differences in health outcomes between participants who had increased physical activity levels compared to participants who had decreased or not altered activity levels since first being prescribed the GRx . Completed surveys were obtained from 124 of 263 eligible participants ; a response rate of 47 % . Fifty-six percent of participants reported increases in physical activity levels after the GRx program , with 70 % still undertaking some form of physical activity . Participants accumulated at least 30 minutes of physical activity per day on 3.4 + /- 2.5 days ( mean + /- SD ) per week . Participants who reported increased physical activity levels after the GRx reported substantially higher energy levels and improved breathing when compared to participants who reported less or about the same physical activity after the GRx intervention . Increased physical activity in GRx patients was associated with greater perceived health benefits . Effective and ongoing support networks were seen as important for behavior change BACKGROUND Increasing regular physical activity in adults at elevated risk of cardiovascular disease is an important target for preventive medicine . This study evaluated demographic , social and cognitive predictors of self-reported changes in physical activity after 4 and 12 months in a r and omized trial of behavioral counseling in primary care . METHOD Data were analyzed from 234 male and 271 female sedentary patients with a body mass index of 25 - 35 ( age 49.1 years , SD 11.2 years ) , who had been counseled by nurses in general practice using stage-matched behavioral methods or st and ard health promotion and who were reassessed after 4 months . A total of 187 men and 231 women were reassessed after 12 months . RESULTS Physical activity at baseline was associated with educational status , having a partner who exercised , perceived barriers , and self-efficacy . Changes over 4 months were greater with behavioral counseling , in non-smokers and in patients with higher ratings of motivation to change and self-efficacy at baseline . Changes over 12 months were greater with behavioral counseling and were predicted in the behavioral group by social support variables , perceived benefits , and barriers . Stage of readiness to change predicted increased activity at 4 but not 12 months . CONCLUSIONS Social support and cognitive variables predict increased physical activity following counseling in primary care of sedentary overweight adults . Different factors are relevant to short- and long-term modifications in behavior BACKGROUND National and state organizations have called upon afterschool programs ( 3 - 6 PM , ASP ) to promote physical activity ( PA ) . Few strategies exist that ASPs can use to increase the PA of children enrolled . This study evaluated a policy-level intervention ( Movin ' Afterschool , MAS ) design ed to increase PA through staff implemented policy-level changes and ongoing technical support . METHODS Twelve preexisting community-based ASPs serving 580 children ( 5 - 12 yrs , 57 % girls ) were invited to take part in MAS . Evaluation of children 's PA , staff behaviors ( engaged or promote PA , other ASP tasks , general supervising ) , and environmental features ( equipment , organized PA ) at baseline ( Fall 2010 ) and post assessment ( Spring 2011 ) were collected using SOPLAY ( System for Observing Play and Leisure Activity in Youth ) for boys and girls , separately . R and om effects models evaluated changes in PA categories ( sedentary , walking , vigorous ) . RESULTS The percentage of boys and girls sedentary decreased by 11.8 % and 11.4 % , respectively . Girls ' walking increased by 6.9 % while boys ' vigorous PA increased by 6.5 % . Greater increases in vigorous activity were observed as post assessment in organized activities for boys and during indoor activities for girls . CONCLUSIONS Findings indicate a policy-level approach targeting staff training and ongoing technical support can produce notable increases in PA within the ASP setting Background The fastest growing age group globally is older adults , and preventing the need for long-term nursing care in this group is important for social and financial reasons . A population approach to diet and physical activity through the use of social services can play an important role in prevention . This study examined the effectiveness of a social health program for community-dwelling older adults aim ed at introducing and promoting physical activity in the home at each individual ’s pace , helping participants maintain good dietary habits by keeping self-check sheets , and determining whether long-st and ing unhealthy or less-than-ideal physical and dietary habits can be changed . Method This cluster r and omized trial conducted at 6 community centers in an urban community involved 92 community-dwelling older adults aged 65–90 years . The intervention group ( 3 community centers ; n = 57 ) participated in the social health program “ Sumida TAKE10 ! ” which is an educational program incorporating the “ TAKE10 ! ® for Older Adults ” program , once every 2 weeks for 3 months . The control group ( 3 community centers ; n=35 ) was subsequently provided with the same program as a crossover intervention group . The main outcome measures were changes in food intake frequency , food frequency score ( FFS ) , dietary variety score ( DVS ) , and frequency of walking and exercise . The secondary outcome measures were changes in self-rated health , appetite , and the Tokyo Metropolitan Institute of Gerontology ( TMIG ) Index of Competence score . Results Compared to baseline , post-intervention food intake frequency for 6 of 10 food groups ( meat , fish/shellfish , eggs , potatoes , fruits , and seaweed ) , FFS , and DVS were significantly increased in the intervention group , and interaction effects of FFS and DVS were seen between the two groups . No significant differences were observed between baseline and post-intervention in the control group . Frequency of walking and exercise remained unchanged in both groups , and no significant difference in improvement rate was seen between the groups . Self-rated health was significantly increased in the intervention group . Appetite and TMIG Index of Competence score were unchanged in both groups . Conclusions The social health program result ed in improved dietary habits , as measured by food intake frequency , FFS , and DVS , and may improve self-rated health among community-dwelling older adults . Trial registration Background The prevalence of childhood obesity among adolescents has been rapidly rising in Mainl and China in recent decades , especially in urban and rich areas . There is an urgent need to develop effective interventions to prevent childhood obesity . Limited data regarding adolescent overweight prevention in China are available . Thus , we developed a school-based intervention with the aim of reducing excess body weight in children . This report described the study design . Methods / design We design ed a cluster r and omized controlled trial in 8 r and omly selected urban primary schools between May 2010 and December 2013 . Each school was r and omly assigned to either the intervention or control group ( four schools in each group ) . Participants were the 4th grade rs in each participating school . The multi-component program was implemented within the intervention group , while students in the control group followed their usual health and physical education curriculum with no additional intervention program . The intervention consisted of four components : a ) classroom curriculum , ( including physical education and healthy diet education ) , b ) school environment support , c ) family involvement , and d ) fun programs/events . The primary study outcome was body composition , and secondary outcomes were behaviour and behavioural determinants . Discussion The intervention was design ed with due consideration of Chinese cultural and familial tradition , social convention , and current primary education and exam system in Mainl and China . We did our best to gain good support from educational authorities , school administrators , teachers and parents , and to integrate intervention components into schools ’ regular academic programs . The results of and lesson learned from this study will help guide future school-based childhood obesity prevention programs in Mainl and China . Trial registration Registration number : PURPOSE The study evaluated whether targeted changes in factors influencing enjoyment of physical education ( PE ) , physical activity enjoyment , and self-efficacy beliefs about participating in physical activity mediated the effect of the Lifestyle Education for Activity Program ( LEAP ) intervention on participation in physical activity . METHODS High schools ( N=24 ) paired on enrollment size , racial composition , urban or rural location , and class structure were r and omized into control ( N=12 ) or experimental ( N=12 ) groups . Of the 4044 girls enrolled and eligible , 2087 ( 51.6 % ) participated in the measurement component of the study . There were 1038 girls in the control group and 1049 girls in the experimental group . INTERVENTION LEAP was a comprehensive school-based intervention emphasizing changes in instruction and school environment design ed to increase physical activity among black and white adolescent girls . It was organized according to the Coordinated School Health Program and included a PE component with core objectives of promoting enjoyment of PE , physical activity enjoyment , and self-efficacy . RESULTS Latent variable structural equation modeling indicated that : 1 ) the intervention had direct , positive effects on physical activity and factors influencing enjoyment of PE , which subsequently explained the effects of increased physical activity enjoyment and self-efficacy on increased physical activity ; and 2 ) an additional , indirect effect of physical activity enjoyment on physical activity operated by an influence on self-efficacy . CONCLUSIONS Increases in enjoyment partially mediated the positive effect of the LEAP intervention . To our knowledge , we have provided the first experimental evidence from a r and omized controlled trial linking increased enjoyment with increased physical activity among black and white adolescent girls To evaluate the efficacy of a community-based adult obesity intervention in Angang . The intervention included health education activities among residents in a community in Anyang . 2400 and 1200 individual were r and omly selected as intervention group and control group respectively from a community in Anyang . The question nairing survey and body weight measuring were conducted and repeated at the end of the study for one year . The results showed that the awareness on the prevention of obesity was enhanced(P < 0.05 ) and mean weight of target population decreased . The community-based intervention for obesity was effective as well as feasible BACKGROUND Our objective was to evaluate the effects of environmental , policy , and social marketing interventions on physical activity and fat intake of middle school students on campus . DESIGN Twenty-four middle schools were r and omly assigned to intervention or control conditions . Baseline measures were collected in spring 1997 , and interventions were conducted during the 1997 - 1998 and 1998 - 1999 school years SETTING /PARTICIPATION : The schools had mean enrollments of 1109 , with 44.5 % nonwhite students . Over 2 years , physical activity interventions were design ed to increase physical activity in physical education classes and throughout the school day . Nutrition interventions were design ed to provide and market low-fat foods at all school food sources , including cafeteria breakfasts and lunches , a la carte sources , school stores , and bag lunches . School staff and students were engaged in policy change efforts , but there was no classroom health education . MAIN OUTCOMES MEASURES Primary outcomes were measured by direct observation and existing records . RESULTS R and omized regression models ( N = 24 schools ) revealed a significant intervention effect for physical activity for the total group ( p < 0.009 ) and boys ( p < 0.001 ) , but not girls ( p < 0.40 ) . The intervention was not effective for total fat ( p < 0.91 ) or saturated fat ( p < 0.79 ) . Survey data indicated that the interventions reduced reported body mass index for boys ( p < 0.05 ) . CONCLUSIONS Environmental and policy interventions were effective in increasing physical activity at school among boys but not girls . The interventions were not effective in reducing fat intake at school . School environmental and policy interventions have the potential to improve health behavior of the student population , but barriers to full implementation need to be better understood and overcome OBJECTIVE To describe the 1 ) lifestyle intervention used in the Finnish Diabetes Prevention Study , 2 ) short- and long-term changes in diet and exercise behavior , and 3 ) effect of the intervention on glucose and lipid metabolism . RESEARCH DESIGN AND METHODS There were 522 middle-aged , overweight subjects with impaired glucose tolerance who were r and omized to either a usual care control group or an intensive lifestyle intervention group . The control group received general dietary and exercise advice at baseline and had an annual physician 's examination . The subjects in the intervention group received additional individualized dietary counseling from a nutritionist . They were also offered circuit-type resistance training sessions and advised to increase overall physical activity . The intervention was the most intensive during the first year , followed by a maintenance period . The intervention goals were to reduce body weight , reduce dietary and saturated fat , and increase physical activity and dietary fiber . RESULTS The intervention group showed significantly greater improvement in each intervention goal . After 1 and 3 years , weight reductions were 4.5 and 3.5 kg in the intervention group and 1.0 and 0.9 kg in the control group , respectively . Measures of glycemia and lipemia improved more in the intervention group . CONCLUSIONS The intensive lifestyle intervention produced long-term beneficial changes in diet , physical activity , and clinical and biochemical parameters and reduced diabetes risk . This type of intervention is a feasible option to prevent type 2 diabetes and should be implemented in the primary health care system Background The aim of the School site , Play Spot , Active transport , Club fitness and Environment ( SPACE ) Study was to develop , document , and assess a comprehensive intervention in local school districts that promote everyday physical activity ( PA ) among 11 - 15-year-old adolescents . The study is based on a social ecological framework , and is design ed to implement organizational and structural changes in the physical environment . Methods / design The SPACE Study used a cluster r and omized controlled study design . Twenty-one eligible schools in the Region of Southern Denmark were matched and r and omized in seven pairs according to eight matching variables summarized in an audit tool ( crow-fly distance from residence to school for 5 - 6th grade rs ; area household income ; area education level ; area ethnicity distribution ; school district urbanity ; condition and characteristics of school outdoor areas ; school health policy ; and active transport in the local area ) . Baseline measurements with accelerometers , question naires , diaries , and physical fitness tests were obtained in Spring 2010 in 5 - 6th grade in 7 intervention and 7 control schools , with follow-up measurements to be taken in Spring 2012 in 7 - 8th grade . The primary outcome measure is objective average daily physical activity and will be supported by analyses of time spent in moderate to vigorous activity and time spent sedentary . Other secondary outcome measures will be obtained , such as , overweight , physical fitness , active commuting to/from school and physical activity in recess periods . Discussion A total of 1348 adolescents in 5 - 6th grade in the Region of Southern Denmark participated at baseline ( n = 14 schools ) . The response rate was high in all type of measurements ( 72.6 - 97.4 % ) . There were no significant differences between intervention and control groups at baseline according to selected background variables and outcome measures : gender ( p = .54 ) , age ( p = .17 ) , BMI ( p = .59 ) , waist circumference ( p = .17 ) , physical fitness ( p = .93 ) , and physical activity ( accelerometer ) ( p = .09).The r and omization and matched pair design produced equivalent groups according to central outcome measures and background variables . The SPACE for physical activity Study will provide new insights on the effectiveness of multicomponent interventions to improve adolescents ' physical activity level . Trial registration Current Controlled Trials IS RCT Background To assess the short-term impact of a comprehensive , community-based multilevel intervention on knowledge , beliefs and practice s with respect to smoking , physical activity and diet in Hangzhou , China . Methods A non-r and omised , controlled , before-after quasi-experimental trial was conducted in two intervention areas and one comparison area . The intervention built on a socioecological framework and took place across four setting s : neighbourhoods , schools , workplaces and community health centres . Two independent cross-sectional surveys of adults aged 18–64 years at baseline and a subsequent follow-up were conducted in 2008/2009 and 2011 in the intervention and comparison areas . A 2-year intervention programme was begun in mid-2009 and continued until mid-2011 . Results A total of 2016 adults at baseline and 2016 adults at follow-up completed the survey . Over the 2-year intervention period , the intervention areas showed a statistically significant decline ( 25.2 % vs 18.7 % , p<0.001 ) in the prevalence of smoking compared with the comparison area ( 18.0 % vs 16.4 % , p=0.343 ) . The proportion of individuals who had noticed anyone smoking in any of nine locations in the previous 30 days demonstrated a statistically significant decline in the intervention ( 78.9 % vs 66.5 % , p<0.001 ) and comparison ( 76.3 % vs 66.5 % , p<0.001 ) areas . The fruit and vegetable consumption score increased in a statistically significant manner in the intervention ( 24.84 vs 25.97 , p=0.036 ) and comparison ( 24.25 vs 26.67 , p<0.001 ) areas . The metabolic equivalent of physical activity increased from 1204 to 1386 ( p=0.023 ) in the intervention areas compared with 918 to 924 in the comparison area ( p=0.201 ) . Conclusions After a 2-year intervention , beneficial changes were noted in the intervention areas with respect to smoking and physical activity but not diet . A community-based multilevel intervention programme is feasible in urban China Background The beneficial effect of physical activity for the prevention of a range of chronic diseases is widely acknowledged . These conditions are most prevalent in low-income groups where physical activity levels are consistently lower . Social marketing is the government ’s recommended approach to promoting physical activity but evidence of its effectiveness is limited . The purpose of this study was to examine the effect of a social marketing campaign on the monthly recruitment , attendance and retention levels at a community-based physical activity programme in a low income area . Methods A six-month social marketing campaign was design ed and delivered in a highly-deprived suburban neighbourhood . Analysis of variance was used to assess effects on recruitment and attendance . χ2 tests of independence were used to compare dropouts and adherers and effectiveness of recruitment mechanisms . Percentages were used to compare adherence rates at intervention , pre-existing sessions in the intervention area and control area sessions . Results Attendance data were collected weekly and presented and analysed monthly to provide a view of changing participation over the six month intervention period , as compared to attendance at pre-existing sessions in the intervention area and in a control area . Recruitment into intervention sessions was significantly greater than into pre-existing and control area sessions in Month 1 ( 18.13v1.04 p = .007 , 18.13v.30 p=.005 ) , Month 5 ( 3.45v.84 p=.007 , 3.45v.30 p<.001 ) and Month 6 ( 5.60v.65 p<.001 , 5.60v.25 p<.001 ) . Attendance at intervention sessions was significantly greater in all six months than at pre-existing and control area sessions ; Month 1 ( 38.83v7.17 p<.001 , 38.83v4.67 , p<.001 ) , Month 2 ( 21.45v6.20 p<.001 , 21.45v4.00 , p<.001 ) , Month 3 ( 9.57v6.15 p<.001 , 9.57v3.77 , p<.001 ) , Month 4 ( 17.35v7.31 p<.001 , 17.35v4.75 , p<.001 ) , Month 5 ( 20.33v8.81 p=.007 , 20.33v4.54 p<.001 ) and Month 6 ( 28.72v8.28 p<.001 , 28.72v.4.00 p<.001 ) . Drop-out rates in the intervention area were similar to the control area ( 66.2%v69.9 % ) , and considerably lower than in pre-existing sessions ( 83 % ) . In months one and two , traditional marketing techniques ( posters/outdoor banners/flyers ) had the greatest influence on recruitment compared to word of mouth communication ( 84.5%v15.5 % ) . In months five and six word of mouth influenced 57.5 % of new recruits . Conclusions Direct comparisons with other programmes were difficult due to a lack of st and ard definitions of recruitment and adherence and limited reporting of findings . However when compared to pre-existing sessions and sessions delivered in a control area , monthly attendance patterns indicated that a reasonably well funded social marketing campaign increased recruitment into exercise sessions , maintained good levels of attendance and reasonable levels of adherence . Good attendance levels support on-going campaign success by offering evidence of peer and social support for the activity and increasing opportunities for social interaction . They also increase the capacity and reach of the word of mouth communication channels , the most effective form of promotion . Further study into methods of improving exercise adherence is required Background Despite the health risks , physical inactivity is common . Identifying the correlates of physical activity to inform the design of interventions to reduce the disease burden associated with physical inactivity is a public health imperative . Rural adults have a unique set of characteristics influencing their activity behaviour , and are typically understudied , especially in Engl and . The aim of this study was to identify the personal , social , and environmental correlates of physical activity in adults living in rural villages . Methods The study used baseline data from 2415 adults ( response rate : 37.7 % ) participating in the first time period of a stepped-wedge cluster r and omised trial , conducted in 128 rural villages from south-west Engl and . Data collected included demographic characteristics , social factors , perception of the local environment , village level factors ( percentage male , mean age , population density , Index of Multiple Deprivation , and sport market segmentation ) , and physical activity behaviour . R and om effects ( “ multilevel ” ) logistic regression models were fitted to the binary outcome whether individuals met physical activity guidelines , and r and om effects linear regression models were fitted to the continuous outcome MET-minutes per week leisure time physical activity , using the personal , social , environmental , and village-level factors as predictors . Results The following factors both increased the odds of meeting the recommended activity guidelines and were associated with more leisure-time physical activity : being male ( p = 0.002 ) , in good health ( p < 0.001 ) , greater commitment to being more active ( p = 0.002 ) , favourable activity social norms ( p = 0.004 ) , greater physical activity habit ( p < 0.001 ) , and recent use of recreational facilities ( p = 0.01 ) . In addition , there was evidence ( p < 0.05 ) that younger age , lower body mass index , having a physical occupation , dog ownership , inconvenience of public transport , and using recreational facilities outside the local village were associated with greater reported leisure-time physical activity . None of the village-level factors were associated with physical activity . Conclusions This study adds to the current literature on the correlates of physical activity behaviour by focusing on a population exposed to unique environmental conditions . It highlights potentially important correlates of physical activity that could be the focus of interventions targeting rural population s , and demonstrates the need to examine rural adults separately from their urban counterparts Background Only limited data are available on the development , implementation , and evaluation processes of weight gain prevention programs in adolescents . To be able to learn from successes and failures of such interventions , integral written and published reports are needed . Methods Applying the Intervention Mapping ( IM ) protocol , this paper describes the development , implementation , and evaluation of the Dutch Obesity Intervention in Teenagers ( DOiT ) , a school-based intervention program aim ed at the prevention of excessive weight gain . The intervention focussed on the following health behaviours : ( 1 ) reduction of the consumption of sugar-sweetened beverages , ( 2 ) reduction of energy intake derived from snacks , ( 3 ) decrease of levels of sedentary behaviour , and ( 4 ) increase of levels of physical activity ( i.e. active transport behaviour and sports participation).The intervention program consisted of an individual classroom-based component ( i.e. an educational program , covering 11 lessons of both biology and physical education classes ) , and an environmental component ( i.e. encouraging and supporting changes at the school canteens , as well as offering additional physical education classes).We evaluated the effectiveness of the intervention program using a r and omised controlled trial design . We assessed the effects of the intervention on body composition ( primary outcome measure ) , as well as on behaviour , behavioural determinants , and aerobic fitness ( secondary outcome measures ) . Furthermore , we conducted a process evaluation . Discussion The development of the DOiT-intervention result ed in a comprehensive school-based weight gain prevention program , tailored to the needs of Dutch adolescents from low socio-economic background Background There is growing recognition that a sedentary lifestyle is being driven , at least in part , by environmental factors that affect individuals ' physical activity choices and health behaviours . In other words , the environments in which we live , and with which we interact , have become ones that encourage lifestyle choices that decrease physical activity and encourage over-consumption of foods . However , evidence from community-led interventions to change local neighbourhood environments to support physical activity and healthy eating is lacking . This article summarises the research protocol developed to evaluate a community-led intervention " My Health Matters " aim ed at reducing health inequalities relating to increasing physical activity and healthy eating as defined by community members themselves . Methods / Design This study includes three of the most deprived electoral wards in Stoke-on-Trent . In each of these areas , environmental factors including proximity of physical activity spaces , greenspace and leisure facilities , neighbourhood connectivity and walkability , l and -use-mix and population density , traffic , safety and crime , and food outlets will be mapped using Geographical Information Systems ( GIS ) . A community postal survey of r and omly selected addresses assessing environmental characteristics relating to physical activity , perceived health status , social capital , fruit and vegetable consumption and levels of physical activity will be undertaken ( baseline and at 2 year follow-up ) . Based on baseline findings an intervention will be design ed and implemented over a 2 year period that includes the following ; use of community participatory research to build effective community partnerships ; use of partnership consensus to identify , prioritise and design intervention(s ) related to specific health disparities ; recruitment of local residents to help with the delivery and sustainability of target intervention(s ) ; and the development of local systems for ongoing monitoring and evaluation of the intervention(s ) . Discussion A community-led and multidisciplinary approach to modifying environmental factors that support and reinforce healthful behaviours may be more successful than focusing on individual behaviour change as this approach does not exclusively rely upon individual will and capacity . Study findings will be collated in 2012 and , if successful in improving levels of physical activity and healthy eating , will help to inform the design of a larger area-based , cluster r and omized controlled trial to determine effectiveness Background Physical inactivity is recognised as a public health concern within children and interventions to increase physical activity are needed . The purpose of this research was to evaluate the effect of a school-based healthy lifestyles intervention on physical activity , fruit and vegetable consumption , body composition , knowledge , and psychological variables . Method A non-r and omised controlled study involving 8 primary schools ( 4 intervention , 4 control ) . Participants were 589 children aged 7–11 years . The intervention lasted 10 months and comprised a CD-rom learning and teaching re source for teachers ; an interactive website for pupils , teachers and parents ; two highlight physical activity events ( 1 mile school runs/walks ) ; a local media campaign ; and a summer activity wall planner and record . Primary outcome measures were objective ly measured physical activity ( pedometers and accelerometers ) and fruit and vegetable consumption . Secondary outcomes included body mass index , waist circumference , estimated percent body fat , knowledge , psychological variables . Multi-level modelling was employed for the data analysis . Results Relative to children in control schools , those in intervention schools significantly increased their total time in moderate-to-vigorous physical activity ( MVPA ) ( by 9 minutes/day vs a decrease of 10 minutes/day ) , their time in MVPA bouts lasting at least one minute ( 10 minutes/day increase vs no change ) and increased daily steps ( 3059 steps per day increase vs 1527 steps per day increase ) . A similar pattern of results was seen in a subset of the least active participants at baseline . Older participants in intervention schools showed a significant slowing in the rate of increase in estimated percent body fat , BMI , and waist circumference . There were no differences between groups in fruit and vegetable intake . Extrinsic motivation decreased more in the intervention group . Conclusion The intervention produced positive changes in physical activity levels and body composition . It appeared to have little or no effect on consumption of fruit and vegetables . Schools are a suitable setting for the promotion of healthy lifestyles although more work , particularly focussed on dietary change , is needed in a variety of schools and social setting Background Community-based participatory research ( CBPR ) has been recognized as an important approach to develop and execute health interventions among marginalized population s , and a key strategy to translate research into practice to help reduce health disparities . Despite growing interest in the CBPR approach , CBPR initiatives rarely use experimental or other rigorous research design s to evaluate health outcomes . This behavioral study describes the conceptual frameworks , methods , and early findings related to the reach , adoption , implementation , and effectiveness on primary blood pressure outcomes . Methods The CBPR , social support , and motivational interviewing frameworks are applied to test treatment effects of a two-phased CBPR walking intervention , including a 6-month active intervention quasi experimental phase and 12-month maintenance r and omized controlled trial phase to test dose effects of motivational interviewing . A community advisory board helped develop and execute the culturally-appropriate intervention components which included social support walking groups led by peer coaches , pedometer diary self-monitoring , monthly diet and physical activity education sessions , and individualized motivational interviewing sessions . Although the study is on-going , three month data is available and reported . Analyses include descriptive statistics and paired t tests . Results Of 269 enrolled participants , most were African American ( 94 % ) females ( 85 % ) with a mean age of 43.8 ( SD = 12.1 ) years . Across the 3 months , 90 % of all possible pedometer diaries were su bmi tted . Attendance at the monthly education sessions was approximately 33 % . At the 3-month follow-up 227 ( 84 % ) participants were retained . From baseline to 3-months , systolic BP [ 126.0 ( SD = 19.1 ) to 120.3 ( SD = 17.9 ) mmHg ; p < 0.001 ] and diastolic BP [ 83 . 2 ( SD = 12.3 ) to 80.2 ( SD = 11.6 ) mmHg ; p < 0.001 ] were significantly reduced . Conclusions This CBPR study highlights implementation factors and signifies the community 's active participation in the development and execution of this study . Reach and representativeness of enrolled participants are discussed . Adherence to pedometer diary self-monitoring was better than education session participation . Significant decreases in the primary blood pressure outcomes demonstrate early effectiveness . Importantly , future analyses will evaluate long-term effectiveness of this CBPR behavioral intervention on health outcomes , and help inform the translational capabilities of CBPR efforts STUDY OBJECTIVE --This paper describes the objectives , design , and methods of evaluation of the impact of the coeur en santé St-Henri programme , as well as selected results from the evaluation to date . It discusses the possible effects of study design choices made to maintain the impact evaluation within budget . DESIGN --The impact of the programme is evaluated in a community trial which compares the prevalence of cardiovascular disease behavioural risk factors before and after programme implementation in the intervention and a matched comparison community , in both longitudinal cohort and independent sample surveys . In addition , repeated independent sample surveys are conducted in the intervention community to monitor awareness of and participation in the programme . PARTICIPANTS --The baseline sample for both the longitudinal cohort and independent sample surveys included 849 subjects from the intervention community ( 79.3 % of 1071 eligible subjects--8.0 % could not be contacted and 12.6 % refused ) and 825 subjects from the comparison community ( 77.8 % of 1066 eligible subjects--6.6 % could not be contacted and 15.6 % refused ) . The two surveys on awareness and participation conducted to date , included 461 ( 71.0 % of 649 eligible subjects ) and 387 ( 67.9 % of 570 eligible subjects ) subjects respectively from the intervention community . MEASUREMENTS --Baseline data for the longitudinal cohort and independent sample surveys on behavioural risk factor outcomes including use of tobacco , physical activity behaviour , high fat diet , and behaviours related to blood pressure and cholesterol control were collected in 35 minute telephone interviews in both the intervention and comparison communities . Data on awareness of and participation in the programme were collected in 10 minute interviews in the intervention community only in two independent sample surveys conducted seven and 22 months respectively after the baseline survey . RESULTS --With the exception of smoking , the intervention and comparison communities were similar at baseline with regard to the prevalence of behavioural risk factors studied . Awareness of the coeur en santé programme increased from 64.1 % in January 1993 to 72.9 % 15 months later . Participation in the programme increased from 21.3 % to 33.7 % . CONCLUSIONS --This paper presents background information on the evaluation of the impact of the coeur en santé programme , as a reference for future publications Background South Asians ( Asian Indians and Pakistanis ) are the second fastest growing ethnic group in the United States ( U.S. ) and have an increased risk of atherosclerotic cardiovascular disease ( ASCVD ) . This pilot study evaluated a culturally-salient , community-based healthy lifestyle intervention to reduce ASCVD risk among South Asians . Methods Through an academic-community partnership , medically underserved South Asian immigrants at risk for ASCVD were r and omized into the South Asian Heart Lifestyle Intervention ( SAHELI ) study . The intervention group attended 6 interactive group classes focused on increasing physical activity , healthful diet , weight , and stress management . They also received follow-up telephone support calls . The control group received translated print education material s about ASCVD and healthy behaviors . Primary outcomes were feasibility and initial efficacy , measured as change in moderate/vigorous physical activity and dietary saturated fat intake at 3- and 6-months . Secondary clinical and psychosocial outcomes were also measured . Results Participants ’ ( n = 63 ) average age was 50 ( SD = 8) years , 63 % were female , 27 % had less than or equal to a high school education , one-third were limited English proficient , and mean BMI was 30 kg/m2 ( SD ± 5 ) . There were no significant differences in change in physical activity or saturated fat intake between the intervention and control group . Compared to the control group , the intervention group showed significant weight loss ( −1.5 kg , p-value = 0.04 ) and had a greater sex-adjusted decrease in hemoglobin A1C ( −0.43 % , p-value < 0.01 ) at 6 months . Study retention was 100 % . Conclusions This pilot study suggests that a culturally-salient , community-based lifestyle intervention was feasible for engaging medically underserved South Asian immigrants and more effective at addressing ASCVD risk factors than print health education material s . Trial registration NCT01647438 , Date of Trial Registration : July 19 , Background We aim ed to evaluate the effectiveness of a community-wide campaign ( CWC ) for promoting physical activity in middle-aged and elderly people . Methods A cluster r and omized controlled trial ( RCT ) with a community as the unit of r and omization was performed using a population -based r and om- sample d evaluation by self-administered question naires in the city of Unnan , Shimane Prefecture , Japan . The evaluation sample included 6000 residents aged 40 to 79 years . We r and omly allocated nine communities to the intervention group and three to the control group . The intervention was a CWC from 2009 to 2010 to promote physical activity , and it comprised information , education , and support delivery . The primary outcome was a change in engaging in regular aerobic , flexibility , and /or muscle-strengthening activities evaluated at the individual level . Results In total , 4414 residents aged 40–79 years responded to a self-administered question naire ( 73.6 % response rate ) . Awareness of the CWC was 79 % in the intervention group . Awareness and knowledge were significantly different between the intervention and control groups , although there were no significant differences in belief and intention . The 1-year CWC did not significantly promote the recommended level of physical activity ( adjusted odds ratio : 0.97 ; 95 % confidence interval : 0.84–1.14 ) . Conclusions This cluster RCT showed that the CWC did not promote physical activity in 1 year . Significant differences were observed in awareness and knowledge between intervention and control groups as short-term impacts of the campaign . Trial registration UMIN-CTR BACKGROUND Despite well-known benefits of physical activity for older adults , about two thirds are underactive . Community-based programs are needed to facilitate increased physical activity . We examine the effectiveness of CHAMPS II , an inclusive , choice-based physical activity promotion program to increase lifetime physical activity levels of seniors . CHAMPS guided participants to choose activities that took into account their health , preferences , and abilities . It offered information on ways for them to exercise safely , motivate themselves , overcome barriers , and develop a balanced exercise regimen . METHODS A 1-year r and omized controlled trial was conducted with physically underactive seniors in a multispecialty group practice . Changes in self-reported physical activity by group were evaluated using ANCOVA , controlling for age and sex . RESULTS Of 173 r and omized subjects , 164 ( 95 % ) completed the trial . Subjects were aged 65 to 90 years ( M = 74 , SD = 6 ) ; 66 % were female . The intervention group increased estimated caloric expenditure by 487 calories/week in moderate ( or greater ) intensity activities ( MET > /= 3.0 ; p < .001 ) and by 687 calories/week in physical activities of any intensity ( p < .001 ) . Control group changes were negligible . Between-group analyses found that the changes were significantly different in both measures ( p values < .05 ) . Overweight persons especially benefited from this program . The program was as effective for women , older adults ( 75 + ) , and those who did not set aside time to exercise at baseline . CONCLUSIONS The program led to meaningful physical activity increases . Individually tailored programs to encourage lifestyle changes in seniors may be effective and applicable to health care and community setting Objective —To investigate the impact of a simple written prescription for physical activity given by a general practitioner and the effect of supplementing this with mailed information material s about physical activity . Methods —A controlled trial was conducted in 27 general practice s in New South Wales , Australia . Subjects were sequential routine care patients between 25 and 65 years old . Controls ( n = 386 ) were recruited first , and intervention subjects two weeks later . Intervention subjects were r and omised to receive a prescription only ( n = 380 ) or a prescription plus a mailed booklet ( n = 376 ) . Self reported physical activity levels were measured by interview at baseline , 6–10 weeks , and seven to eight months . Results —By intention to treat , the average changes in minutes of total physical activity did not differ significantly between the groups . Inactive people in the prescription plus supplementary booklet group were significantly more likely than controls to report an increase in their physical activity by at least 60 min/week after 6–10 weeks ( odds ratio 1.58 , 95 % confidence interval 1.06 to 2.35 ) . No significant short term improvements in self reported activity were shown in the prescription only group . In the supplemented group , the proportion reporting an increase in physical activity to 3344 kJ/week at 6–10 weeks was not significant , and neither intervention group showed significant increases in any of the outcome measures at seven to eight months by intention to treat . Treatment received analysis showed greater improvements in intervention groups , especially the prescription plus booklet group , in which the odds of inactive people in this group reporting increased activity became significant at seven to eight months . Conclusions —A prescription for physical activity from a general practitioner , supplemented by additional written material s , can lead to modest short term improvements in self reported physical activity levels among inactive patients . A prescription alone was found not to be effective AIMS To compare the impact on weight and exercise of a 2-year church-based diabetes risk reduction programme in four churches in South Auckl and , New Zeal and . METHODS A prospect i ve non-r and omized controlled study of a modular lifestyle and diabetes awareness intervention programme applying community development principles . The study involved four complete church congregations , two Samoan and two Tongan , with 516 participants at commencement . Risk of Type 2 diabetes is high among both ethnic groups . RESULTS Overall , 285 subjects were available for their second assessment . In one intervention church , weight gain was controlled ( vs. control 0 + /- 4.8 vs. + 3.1 + /- 9.8 kg , respectively ; P=0.05 ) , diabetes knowledge ( + 46 + /- 26 % vs. + 4 + /- 17 % ; P<0.001 ) and regular exercise ( at least 3 days per week : + 22 % vs. -8 % ; P=0.032 ) increased and readiness to change weight ( P=0.007 ) shifted towards maintenance ( e.g. maintenance + 41 % vs. + 8 % , respectively ) . The other intervention church increased diabetes knowledge ( + 19 + /- 24 vs. + 8 + /- 25 ; P<0.024 ) , but no other significant personal changes occurred . Attendance and perceived utility of the programme were greater in the first intervention church . CONCLUSIONS A moderate intensity , community-based , structured diabetes awareness and lifestyle programme can reduce diabetes risk , but increasing diabetes knowledge alone is not necessarily associated with healthier lifestyle choices . Continuous and detailed monitoring of penetration of interventions may be essential to help guide the timing of interventions and identify the need for additional strategies to increase participation and motivation BACKGROUND In the U.S. , Latinos report particularly high levels of inactivity and related chronic illnesses and are in need of intervention . Thus , the purpose of the current study was to culturally and linguistically adapt an empirically supported , individually tailored physical activity print intervention for Latinos and then conduct an RCT of the modified program . DESIGN An RCT was conducted . SETTING / PARTICIPANTS The sample included 93 overweight/obese ( 80 % ) Latinas with low income and acculturation . INTERVENTION Data were collected in 2007 - 2008 and analyzed by intent-to-treat in 2009 . Participants were r and omly assigned to either ( 1 ) a culturally and linguistically adapted physical activity intervention ( Seamos Activas ) or ( 2 ) a wellness contact control condition . MAIN OUTCOME MEASURES Self-report physical activity , as measured pre- and post-intervention ( 6 months , 87 % retention ) by the 7-Day Physical Activity Recall . RESULTS Moderate-intensity ( or greater ) physical activity increased from an average of 16.56 minutes/week ( SD=25.76 ) at baseline to 147.27 ( SD=241.55 ) at 6 months in the intervention arm ( n=45 ) , and from 11.88 minutes/week ( SD=21.99 ) to 96.79 ( SD=118.49 ) in the wellness contact control arm ( n=48 ) . No between-group differences were seen in overall physical activity . Intervention participants reported significantly greater increases in cognitive ( F[1 , 91]=9.53 , p=0.003 ) and behavioral processes of change ( F[1 , 91]=8.37 , p=0.005 ) and available physical activity supplies and equipment at home ( F[1 , 91]=4.17 , p=0.04 ) than control participants . CONCLUSIONS Results supported the hypothesized feasibility , acceptability , and preliminary efficacy of individually tailored physical activity print interventions among Latinas . Although more research is needed to corroborate these findings , such high-reach , low-cost approaches have great potential to positively affect public health . TRIAL REGISTRATION NCT00724165 OBJECTIVE 1 . To demonstrate that combining pedometer use with cognitive and behavioral support material s has a positive effect on physical activity ( PA ) and attitudes towards pedometer use . 2 . To investigate how familiar the study sample is with pedometers and the ' 10,000 steps/day ' recommendation . METHODS From a r and om sample , drawn from the phone book , 304 volunteered ( 18 - 75 year ) to complete a question naire about familiarity with pedometers and the ' 10,000 steps/day ' recommendation . A sample of 103 participants agreed to wear a pedometer for 3 weeks , and was r and omly assigned to a condition with cognitive and behavioral support material s ( n=51 ) or without these material s ( n=52 ) . Participants completed the International Physical Activity Question naire before and after 21 days of pedometer use and an additional question naire on the attitudes towards pedometer use . RESULTS More than 58 % had never heard of a pedometer . In both conditions , walking ( F=10 , p=0.002 ) , moderate PA ( F=11 , p=0.001 ) , and vigorous PA ( F=14 , p<0.001 ) increased over time , however no interaction effects could be found . Significantly more participants in the condition with support material s had a positive attitude towards pedometer use . CONCLUSION Wearing a pedometer , with or without support material s , may increase PA . In our study , cognitive and behavioral support material s only affected attitudes towards pedometer use . PRACTICE IMPLICATION S More research is needed to investigate the effect of combining pedometer use with support material s on a longer time base and in less motivated people The objective of this study was to evaluate the effects of the ATS-Sardegna Campaign on lifestyle and cardiovascular disease ( CVD ) risk factors in the Sardinian population . The Campaign was a community-based public health action programme funded by the Sardinian Government with a view to prevent CVD and promote healthy behaviour . It was also part of the Targeted Project FAT.MA . of the Italian National Research Council ( CNR ) , with the main purpose of evaluating the effects of this public health initiative after a five- year intervention . The evaluation was effected with three parallel procedures : individual interviews with 1486 r and omly chosen people ; assessment of eating patterns through a food-frequency question naire ; measurement of the mean levels of the major CVD risk factors in 1729 r and omly chosen subjects ( 1044 in the calendar year 1992 , and 685 in 1995 , two and five years , respectively , after the beginning of the Campaign ) . Overall , we recorded a favourable trend in eating habits in both sexes ; a significant decrease in LDL-cholesterol in males , and in systolic and diastolic blood pressure in both sexes ; a non- significant decrease in prevalence of smokers among males and increase among females . The ATS-Sardegna Campaign was the first CVD prevention programme in Italy to have attained reduction in the risk profile of an entire region at the lowest ever borne cost BACKGROUND Because preventing functional decline in older adults is a national priority and senior centers have been identified as potentially important venues for health-promotion activities , a trial of a multicomponent disability prevention program was conducted at a senior center . METHODS One hundred older adults were recruited for a 6-month r and omized clinical trial . All members of the experimental group received an exercise intervention , nutrition counseling , and a home safety assessment . Smoking and alcohol interventions were delivered to at-risk subjects . Outcome variables included the Medical Outcomes Study Short Form ( SF-36 ) health survey , the CES-Depression scale , bed days , and restricted-activity days . RESULTS A single study announcement result ed in a response sufficient to recruit 100 subjects . The exercise program was well received : 85 % of intervention subjects completed the 6-month program and adherence was excellent , with over 90 % attendance at exercise classes . After 6 months the intervention group had significantly better scores on 7 of 8 SF-36 subscales and fewer depressive symptoms than controls . CONCLUSIONS Senior centers may be excellent sites for community-based health promotion interventions : participation and adherence rates may be acceptable , interventions can be design ed that are feasible in this setting , and these interventions appear to affect health status positively . The study program improved physical and psychosocial functioning and is a promising model for preventing functional decline through activities based at senior centers Creating community-based opportunities for youth to be physically active is challenging for many municipalities . A Lexington , Kentucky community coalition design ed and piloted a physical activity program , ' VERB ™ summer scorecard ( VSS ) ' , leveraging the br and equity of the national VERB ™ --It 's What You Do ! campaign . Key elements of VSS subsequently were adopted in Sarasota County , FL . This study identified characteristics of Sarasota 's VSS participants and non- participants . Students in Grade s 5 - 8 from six r and omly selected public schools completed a survey assessing VSS participation , physical activity level , psychosocial variables , parental support for physical activity and demographics . Logistic regression showed that VSS participants were more likely to be from Grade s 5 to 6 versus Grade s 7 and 8 [ odds ratio ( OR ) = 6.055 ] and perceive high versus low parental support for physical activity ( OR = 4.627 ) . Moreover , for each unit rise in self-efficacy , the odds of VSS participation rose by 1.839 . Chi-squared automatic interaction detector ( CHAID ) analysis suggested an interaction effect between grade and school socioeconomic status ( SES ) , with a large proportion of seventh and eighth grade rs from high SES schools being non- participants ( 76.6 % ) . A VSS-style program can be expected to be more effective with tweens who are younger , in a middle SES school , having high self-efficacy and high parental support for physical activity OBJECTIVE To examine if a website-delivered physical activity intervention , that provides participants with computer-tailored feedback , can improve physical activity in the general population . METHODS Healthy adults ( n=434 ) , recruited from parents and staff of 14 primary and secondary schools in Belgium in the spring of 2005 , were allocated into one of two intervention groups ( receiving intervention with or without repeated feedback ) or a no-intervention control group . Physical activity-levels were self-reported at baseline and at 6 months ( n=285 ) , using a computerized long version of the International Physical Activity Question naire online . Repeated measures analysis of co-variances were used to examine differences between the three groups . RESULTS Intent-to-treat analysis showed significant time by group interaction effects in favor of both intervention groups compared with the control group . Significant increases were found for active transportation ( + 20 , + 24 , + 11 min/week respectively ) and leisure-time physical activity ( + 26 , + 19 , -4 min/week respectively ) ; a significant decrease for minutes sitting on weekdays ( -22 , -34 , + 4 min/day respectively ) . No significant differences were found between both intervention groups . CONCLUSION A website-delivered intervention , including computer-tailoring , was able to increase physical activity when compared to a no-intervention control group . High drop-out rate and the low number of participants who received repeated feedback indicated that engagement and retention are important challenges in e-health studies Mainstream preventive interventions often fail to reach poor population s with a high risk of cardiovascular diseases ( CVDs ) in Pakistan . A community-based CVD primary prevention project aim ed at developing approaches to reduce risk factors in such population s was established by Heartfile in collaboration with the National Rural Support Program in the district of Lodhran . The project implemented a range of activities integrated with existing social and health service mechanisms during a three year intervention period 2000/01 - 03/04 . These were targeted in 4 key setting s : community health education , mass media interventions , training of health professionals and health education through Lady Health Workers . The project received support from the Department for International Development , UK . At the community level , a pre-test-post-test quasi-experimental design was used for examining project outcomes related to the community component of the intervention . Pre and post-intervention ( training ) evaluations were conducted involving all health care providers in r and omly selected workshops in order to determine baseline levels of knowledge and the impact of training on knowledge level . In order to assess practice s of physician and non-physician health care providers patient interviews , with control comparisons were conducted at each health care facility . Significant positive changes were observed in knowledge levels at a community level in the district of intervention compared with baseline knowledge levels particularly in relation to a heart healthy diet , beneficial level of physical activity , the causes of high blood pressure and heart attack and the effects of high blood pressure and active and passive smoking on health . Significant changes in behaviors at a practice level were not shown in the district of intervention . However the project played a critical role in spurring national action for the prevention and control of non-communicable diseases and introducing sustainable public health interventions for poor communities in Pakistan AIM This paper reports a study evaluating the relationship between social and community level supports and physical activity and dietary behaviours among a low-income Latino population with multiple chronic conditions . BACKGROUND With consistently lower physical activity than whites and documented nutritional deficiencies , Latinos in the United States of America represent a disproportionate share of the population with chronic illness . This pattern of health disparities is seen across countries , where there is a struggle to raise the health status of low-income , immigrant and aboriginal communities . Social-ecological theories of health behaviour stress the importance of considering social and community support for health behaviour , and represent a useful framework for considering ways to improve physical activity and nutrition for immigrant and aboriginal groups . METHOD We report here on data from a baseline assessment of 200 patients from a health clinic in the United States of America serving a low-income , primarily Latino population . Participants were enrolled in Re sources for Health , a r and omized controlled trial to promote multi-level support for chronic illness self-management . Measures included self-reported physical activity , dietary behaviour and multi-level support for chronic illness management as well as demographic data . Baseline data reported on here were collected between February 2002 and September 2003 . FINDINGS Use of multi-level supports ( e.g. family , individual and healthcare provider ) was statistically significantly associated with meeting physical activity guidelines and better dietary behaviours . Being female and having multiple chronic conditions were also associated with better dietary behaviour . These variables explained 20 % of the variance in dietary behaviour . CONCLUSION Results support a social-ecological approach for promoting healthy behaviour in this low-income , primarily Latino sample with multiple chronic conditions . Addressing multiple levels of support for healthy behaviour is important in interventions to improve physical activity and diet , and nurses may be particularly well placed to address such issues for low-income , aboriginal and immigrant patients with chronic conditions Abstract Objective : To assess the net 5 year effects of intervention of a community based demonstration project , the Heartbeat Wales programme , on modifiable behavioural risks for prevention of cardiovascular disease . Design and setting : Quasi-experimental design comparing results from two independent cross sectional population surveys conducted in 1985 and 1990 in Wales and a matched reference area in north east Engl and . Subjects : R and om , stratified sample s of people aged 18 - 64 years ( 18 538 in 1985 and 13 045 in 1990 ) in Wales and in north east Engl and ( 1483 and 4534 , respectively ) . Intervention : A coordinated range of activities for heart health promotion in Wales entailing public education campaigns along with supportive policy and infrastructure change . In the reference area no additional community heart health promotion was planned , though considerable activity did take place , “ contaminating ” the reference area . Main outcome measures : Fifteen self reported behavioural indicators relating to dietary choice , smoking , frequency of exercise , and weight . Results : Positive changes ( for health ) in behavioural outcomes were observed among the population in Wales , including a reduction in reported smoking prevalence and improvements in dietary choice . There was no net intervention effect for the programme over and above observed change in the reference area . Conclusions : No definite conclusions can be drawn concerning the efficacy of the programme in terms of behavioural outcomes . With hindsight , the difficulties of evaluating such a complex multifaceted intervention were underestimated . Further debate on the most appropriate methods for assessing the effectiveness of community based health promotion programmes is called for . Key messages Heartbeat Wales was set up in 1985 as a community based programme to demonstrate risk reduction for cardiovascular disease Important changes were observed in modifiable risks for cardiovascular disease in Wales between 1985 and 1990 There was an unexpectedly rapid uptake of heart health promotion activity in the reference area No net intervention effects were found for the programme over and above changes in the reference area Improvements in methods of evaluation for community based health promotion programmes are The Living 4 Life study was a youth-led , school-based intervention to reduce obesity in New Zeal and . The study design was quasi-experimental , with comparisons made by two cross-sectional sample s within schools . Student data were collected at baseline ( n=1634 ) and at the end of the 3-year intervention ( n=1612 ) . A r and om-effects mixed model was used to test for changes in primary outcomes ( e.g. anthropometry and obesity-related behaviours ) between intervention and comparison schools . There were no significant differences in changes in anthropometry or behaviours between intervention and comparison schools . The prevalence of obesity in intervention schools was 32 % at baseline and 35 % at follow-up and in comparison schools was 29 % and 30 % , respectively . Within-school improvements in obesity-related behaviours were observed in three intervention schools and one comparison school . One intervention school observed several negative changes in student behaviours . In conclusion , there were no significant improvements to anthropometry ; this may reflect the intervention 's lack of intensity , insufficient duration , or that by adolescence changes in anthropometry and related behaviours are difficult to achieve . School-based obesity prevention interventions that actively involve young people in the design of interventions may result in improvements in student behaviours , but require active support from leaders within their schools OBJECTIVE To evaluate the short-term impact of comprehensive community based intervention on physical activity ( PA ) of adults living in the three urban communities of Hangzhou city . METHODS Within the framework of Community Interventions for Health ( CIH ) Program , a community trial was conducted in two urban areas ( Xiacheng district and Gongshu district ) and an urban area(Xihu district)as control , by a parallel comparison and r and om grouping based quasi-experimental design . Two independent question naire-based surveys of cross-sectional sample s in the intervention and comparison areas were used to assess the short-term impact of the intervention program . RESULTS A total of 2016 adults at baseline and 2016 adults at follow-up stages , completed the survey , including 1016 adults from the intervention areas and 1000 from the comparison area . Over the two-year intervention period , the cognitive level on benefits of physical activity in the intervention areas were trending downward . The changes observed in the comparison area did not show statistical significance . Intervention areas showed a statistically significant increase ( 1204 vs. 1386 , P = 0.023 ) in the level of physical activity(metabolic equivalent , MET-minutes/week)compared with the comparison area(918 vs. 924 , P = 0.201 ) . And results remained the same after eliminating the possible effects of age factor . CONCLUSION After a two-year intervention , beneficial changes were noted in the intervention areas with respect to the level of physical activity . A community-based intervention program on physical activity seemed feasible and effective in the urban areas of Hangzhou BACKGROUND Physical inactivity is an important health risk factor that could be addressed at the community level . PURPOSE The goal of the study was to determine whether using a community-based participatory approach with park directors and park advisory boards ( PABs ) could increase physical activity in local parks . Whether involving PABs would be more effective than working with park directors alone was also tested . DESIGN An RCT intervention from October 2007 to April 2012 was used , with partial blinding of observers to the condition . All data were analyzed in 2012 . SETTING / PARTICIPANTS Of 183 eligible parks in the City of Los Angeles , 50 neighborhood park/recreation centers serving diverse population s participated . Parks were r and omized to three study arms : ( 1 ) park-director intervention ( PD-only ) ; ( 2 ) PAB intervention ( PAB/PD ) ; and ( 3 ) a control arm . Physical activity in each park was systematic ally observed , and park users and residents living within 1 mile of the park were interviewed . INTERVENTION(S ) The intervention included assessing park use , obtaining feedback from park users and community residents , training on outreach and marketing , and giving each intervention park $ 4000 to increase park-based physical activity . The PAB/PD arm required participation and concurrence on all purchases by the PAB . MAIN OUTCOME MEASURE(S ) Change in the number of park users and change in the level of park-based physical activity , expressed as MET-hours . RESULTS Relative to control parks where physical activity declined , in both the PD-only and PAB/PD parks , physical activity increased , generating an estimated average of 600 more visits/week/park , and 1830 more MET-hours of physical activity/week/park . Both residents and park users in the intervention arms in the intervention arms reported increased frequency of exercise . No differences were noted between the PD-only and PAB/PD study arms . CONCLUSIONS Providing park directors and PABs with training on outreach and marketing , feedback on park users , and modest funds increased the amount of physical activity observed in parks Purpose . To determine whether Australia 's Walk to Work Day media campaign result ed in behavioral change among targeted groups . Methods . Pre- and postcampaign telephone surveys of a cohort of adults aged 18 to 65 years ( n = 1100 , 55 % response rate ) were r and omly sample d from Australian major metropolitan areas . Tests for dependent sample s were applied ( McNemar χ2 or paired t-test ) . Results . Among participants who did not usually actively commute to work was a significant decrease in “ car only ” use and an increase in walking combined with public transport . Among those who were employed was a significant increase in total time walking ( + 16 min/wk ; t [ 780 ] = 2.04 , p < .05 ) and in other moderate physical activity ( + l20 min/wk ; t [ 1087 ] = 4.76 , p < .005 ) , result ing in a significant decrease in the proportion who were “ inactive ” ( χ2 ( 1 ) = 6.1 , p < .05 ) . Conclusion . Although nonexperimental , the Walk to Work Day initiative elicited short-term changes in targeted behaviors among target groups . Reinforcement by integrating worksite health promotion strategies may be required for sustained effects OBJECTIVE An automated health counselor agent was design ed to promote both physical activity and fruit and vegetable consumption through a series of simulated conversations with users on their home computers . METHODS The agent was evaluated in a 4-arm r and omized trial of a two-month daily contact intervention comparing : ( a ) physical activity ; ( b ) fruit and vegetable consumption ; ( c ) both interventions ; and ( d ) a non-intervention control . Physical activity was assessed using daily pedometer steps . Daily servings of fruit and vegetables were assessed using the NIH/NCI self-report Fruit and Vegetable Scan . RESULTS Participants in the physical activity intervention increased their walking on average compared to the control group , while those in the fruit and vegetable intervention and combined intervention decreased walking . Participants in the fruit and vegetable intervention group consumed significantly more servings per day compared to those in the control group , and those in the combined intervention reported consuming more compared to those in the control group . CONCLUSION Automated health intervention software design ed for efficient re-use is effective at changing health behavior . PRACTICE IMPLICATION S Automated health behavior change interventions can be design ed to facilitate translation and adaptation across multiple behaviors There is compelling evidence supporting the benefits of increased regular physical activity in older adults . The Experience Corps program in Baltimore MD was design ed in part as a community based approach to increasing physical activity that would also appeal to older adults who have historically not utilized health promotion programs . The Baltimore Experience Corps program places older volunteers in public elementary schools for 15 h a week in roles design ed to improve the academic outcomes of children and , simultaneously , increase the physical , cognitive and social activity of volunteers . This paper reports on the change in physical activity levels among older adults associated with participation in the Baltimore Experience Corps . In a pilot r and omized controlled evaluation , older adults were r and omly assigned to Experience Corps ( EC participants ) or a waiting list control group . Ages ranged from 59–86 years , 96 % were African American , 94 % were women , and 84 % had annual incomes less than $ 15,000 . EC participants were required to serve ≥15 h a week . At follow-up after 4–8 months , an analysis of 113 r and omized volunteers revealed 53 % of the EC participants were more active than the previous year by self-report , as compared to 23 % of the controls ( p<0.01 ) . When adjusted for age , gender and education , there was a trend toward increased physical activity in the EC participants as calculated by a kilocalorie per week increase of 40 % , versus a 16 % decrease in the controls ( p=0.49 ) . EC participants who reported “ low activity ” at baseline experienced an average 110 % increase in their physical activity at follow-up . Among the controls who were in the “ low activity ” group at baseline , there was , on average , only a 12 % increase in physical activity ( p=0.03 ) . Among those who were previously active , there was no significant difference ( p=0.30 ) . The pilot results suggest that a high intensity volunteer program that is design ed as a health promotion intervention can lead , in the short-term , to significant improvements in the level of physical activity of previously inactive older adult volunteers This paper describes the preliminary steps needed to begin a community physical activity intervention in a rural context , including forming a community coalition and assessing values , beliefs , and knowledge about physical activity . A r and om mail survey ( N = 171 ) indicated relatively high activity rates , and perceived barriers consistent with the literature ( time , program convenience , safety issues ) . Perceived benefits included improving/sustaining health and looking better/improving appearance . Five focus groups added additional barriers ( e.g. , physical isolation , lack of transportation ) . Residents were unaware of many existing services and indicated a desire for more walking trails , health-related activities , and low-cost exercise facilities . The discussion focuses on the importance of establishing a community coalition and implication s for future program development and research The main goal of the preventive intervention study in one community of the German CINDI ( Countrywide Integrated Non-Communicable Diseases Intervention programme of the WHO ) area was to improve cardiovascular health by reducing the risk factors smoking , hypertension , obesity , hypercholesterolaemia , and by changing sedentary lifestyle . The intervention was performed by using the special " Three-Level- Strategy " , which is characterised by activities of primary care physicians in the usual consulting hour ( 1st level ) , with patient groups in their practice s ( 2nd level ) , and at community level ( 3rd level ) where a special work group and a co-ordinating general practice are co-operating . To evaluate the occurrence of the risk factors in practice and the local population , four cross-sectional r and om sample s ( N(total ) = 4881 ) were carried out in seven practice s from 1992 to 1995 . On the community level , 23 special exercise-based health groups ( N(total ) = 600 ) were established and were investigated by means of a question naire , related to behaviour and health beliefs . A " Local Health Information System " facilitated the evaluation , the management of the data , and the organisation of the health programme . The results of the practice sample s showed a significant reduction of smoking ( -17.8 % ) and hypertension ( -31.5 % ) ( p < 0.01 ) . The exercise-based groups were combined with nutritional counselling or relaxation and were accepted very well by the participants ( 83.8 % ) . The participants considerably improved their health behaviour : 82 % discussed health in their family , 37.3 % stated an increase of healthy nutrition , 52 % of relaxation ; 86.2 % intended to regularly increase physical activity in leisure time and 82 % could not imagine regular health training without exercise meetings . We conclude that the practice -based " Three-Level- Strategy " provides a strong support for successful long-term prevention of cardiovascular risk , particularly , when exercise-based health training sessions are performed in order to change sedentary lifestyle . When organised on community level , they might have a positive impact on the health behaviour of the whole community . Physical activity can be used as a " prodrug " for health promotion in a holistic way BACKGROUND A growing number of the population are using the Internet for health information , such as physical activity ( PA ) . The aim of this study was to examine the effectiveness of delivery modes for a behavior change program targeting PA . METHODS A r and omized trial was conducted with 192 subjects r and omly allocated to either a face-to-face , Internet-mediated , or Internet-only arm of a 12-wk intervention . Subjects included inactive adults with Internet access . The primary outcome variable was self-reported PA , assessed at four time points . RESULTS The results showed no group x time interaction for PA F(6 , 567 ) = 1.64 , p > 0.05 , and no main effect for group F(2 , 189 ) = 1.58 , p > 0.05 . However , a main effect for time F(3 , 567 ) = 75.7 , p < 0.01 was observed for each group . All groups were statistically equivalent immediately post-intervention ( p < 0.05 ) , but not at the follow-up time points ( p > 0.05 ) . The Internet-mediated and Internet-only groups showed similar increases in PA to the face-to-face group immediately post-intervention . CONCLUSIONS This study provides evidence in support of the Internet in the delivery of PA interventions and highlights avenues for future research OBJECTIVE To assess whether the " 10,000 Steps Ghent " intervention had any effect on self-reported sitting time . METHODS A multi- strategy community-based intervention was implemented in 2005 to promote physical activity ( PA ) to adults living in Ghent , Belgium . In 2005 , 648 r and omly selected participants ( aged 25 to 75 ) from the intervention community Ghent and 592 from a comparison community , completed the International Physical Activity Question naire ( IPAQ ) and a pedometer log . Of these , 440 intervention participants and 426 comparison participants completed the follow-up measurements in 2006 . RESULTS A decrease of 12 min in total daily sitting time was found in the intervention community , compared with an increase of 18 min/day in the comparison community ( F=9.5 , p=0.002 ) . The effect was seen for both weekday ( p=0.044 ) and weekend day ( p<0.001 ) sitting times . In the intervention community , total daily sitting time decreased more in the participants who increased their step counts ( -18 min/day ; t=2.5 ; p=0.012 ) , than in those who did not ( no change ; t=0.8 , ns ) . CONCLUSIONS After 1 year of intervention , total , weekday , and weekend day sitting times were reduced in the intervention community , while sitting time increased in the comparison community BACKGROUND Currently there is a great deal of interest in multi strategy community-based approaches to changing physical activity or health behaviors . The aim of this article is to describe the effectiveness of the physical activity promotion project " 10,000 Steps Ghent " after 1 year of intervention . METHODS A multi strategy community-based intervention was implemented in 2005 with follow-up measurements in 2006 to promote physical activity to adults . A local media campaign , environmental approaches , the sale and loan of pedometers , and several local physical activity projects were concurrently implemented . In 2005 , 872 r and omly selected subjects ( aged 25 to 75 ) , from the intervention community Ghent and 810 from a comparison community , participated in the baseline measurements . Of these , 660 intervention subjects and 634 comparison subjects completed the follow-up measurements in 2006 . Statistical analyses were performed in 2006 . RESULTS After one year there was an increase of 8 % in the number of people reaching the " 10,000 steps " st and ard in Ghent , compared with no increase in the comparison community . Average daily steps increased by 896 ( 95 % CI=599 - 1192 ) in the intervention community , but there was no increase in the comparison community ( mean change -135 [ 95 % CI= -432 to 162 ] ) ( F time x community=22.8 , p<0.001 ) . Results are supported by self-reported International Physical Activity Question naire ( IPAQ ) data . CONCLUSIONS The " 10,000 steps/day " message reached the Ghent population and the project succeeded in increasing pedometer-determined physical activity levels in Ghent , after 1 year of intervention Objectives : To describe a rural , hospital-based public health intervention program and to evaluate its effectiveness in cardiovascular disease ( CVD ) risk reduction using cross-sectional studies and a panel study . Methods : A rural population of 158,000 located in New York state comprised the intervention population . A similar but separate population was used for reference . A multifaceted , multimedia 5-year program provided health promotion and education initiatives to increase physical activity , decrease smoking , improve nutrition , and identify hypercholesterolemia and hypertension . To evaluate the effectiveness of the intervention , surveys were conducted at baseline in 1989 ( cross-sectional ) and at follow-up in 1994- 95 ( cross-sectional and panel ) . For cross-sectional studies , a r and om sample of adults was obtained using a three-stage cluster design . Self-reported and objective risk factor measurements were obtained . Comparison of pre- to post- changes in intervention versus reference population s was done using 2 × 2r and omized block ANOVA , 2 × 2 mixed ANOVA , and extension of the McNemar test . Results : Smoking prevalence declined ( from 27.9 % to 17.6 % ) in the intervention population . Significant adverse trends were observed for high-density lipoprotein cholesterol and triglycerides . Systolic blood pressure was reduced while diastolic blood pressure remained stable . Body mass index increased significantly in both population s. Conclusions : This rural , 5-year CVD community intervention program decreased smoking . The risk reduction may be attributable to tailoring of a multifaceted approach ( multiple risk factors , multiple messages , and multiple population subgroups ) to a target rural population . The study period was too short to identify changes in CVD morbidity and mortality OBJECTIVE The objective of this study was to test the hypothesis that community-based environmental change intervention prevents undesirable weight gain in children . METHOD The method used in this study was a two-year , non-r and omized , controlled trial ( 2003 - 2005 ) using community-based participatory methodology in three diverse cities in Massachusetts : one intervention and two socio-demographically-matched control communities ( pooled for analysis ) . Children ( n=1028 ) , with a mean age=7.61 + 1.04years participated . Interventions were made to improve energy balance by increasing physical activity options and availability of healthful foods ( Year 1 ) . To firmly secure sustainability , the study team supported policies and shifted intervention work to community members ( Year 2 ) . RESULTS Change in body mass index z-score ( BMI z ) was assessed by multiple regression , accounting for clustering within communities and adjusting for baseline covariates . Sex-specific overweight/obesity prevalence , incidence and remission were assessed . Over the two-year period , BMI z of children in the intervention community decreased by -0.06 [ p=0.005 , 95 % confidence interval : -0.08 to -0.04 ] compared to controls . Prevalence of overweight/obesity decreased in males ( OR=0.61 , p=0.01 ) and females ( OR=0.78 , p=0.01 ) and remission increased in males ( OR 3.18 , p=0.03 ) and females ( OR 1.93 , p=0.03 ) in intervention compared to controls . CONCLUSION Results demonstrate promise for preventing childhood obesity using a sustainable multi-level community-based model and reinforce the need for wide-reaching environmental and policy interventions OBJECTIVE To assess the cost-effectiveness of a primary care based intervention aim ed at increasing levels of physical activity in inactive people aged 45 - 74 . METHODS A total of 714 inactive people aged 45 - 74 , taken from two west London general practice s , were r and omised into two groups . Intervention subjects were invited to a consultation with an exercise development officer , and offered a personalised 10 week programme to increase their level of regular physical activity , combining leisure centre and home based activities . Control subjects were sent information on local leisure centres . All subjects were followed up at eight months . RESULTS There was a net 10.6 % ( 95 % confidence interval 4.5 to 16.9 % ) reduction in the proportion of people classified as sedentary in the intervention group compared with the control group , eight months after the intervention . The intervention group also reported an increase in the mean number of episodes of physical activity per week , as compared with the control group ( an additional 1.52 episodes ( 95 % confidence interval 1.14 to 1.95 ) ) . The cost of moving a person out of the sedentary group was shown to be less than 650 Pounds . The cost of moving someone to the now commonly recommended level was estimated at almost 2500 Pounds . CONCLUSIONS Moderate physical activity can be successfully encouraged in previously sedentary men and women aged 45 - 74 through a primary care based intervention . The process of recruitment was the most important variable cost . A high uptake rate would maximise cost-effectiveness , and sensitivity analysis suggests that unit costs could be halved with a more effective recruitment strategy OBJECTIVE This article describes website use and behavioral outcomes in a multi-component lifestyle intervention promoting healthy diet and exercise . METHODS A 2-year r and omized clinical trial to improve bone density in 228 adolescent girls , the intervention included a website design ed to enhance intervention adherence , retention of participants , and behavioral outcomes . Measures included diet and exercise recalls , surveys , and web-usage data . RESULTS Website use was associated with increases in calcium intake ( ss = 69.72 , p = .01 , ES = 0.15 ) and high-impact activity ( ss = 10.93 , p = .04 , ES = .13 ) . Use of web pages related to behavioral feedback and communications was not significantly associated with behavioral outcomes . The most visited website pages had content related to incentive points , caption contests , and fun facts . CONCLUSIONS Web elements of a multi-component intervention may promote retention and engagement in target behaviors . Such websites may be most acceptable to adolescent participants if they blend fun and behavioral elements , rather than exclusively focusing on behavioral changes This article describes successful recruitment and retention strategies for a community-based weight management study in two school districts in North Carolina . Recruitment and retention on both district and school levels and child and parent levels are discussed . A total of 358 children and 358 parents from eight schools in rural North Carolina participated in a r and omized controlled trial to test the effectiveness of a nutrition and exercise education , coping skills training , and exercise intervention . Recruitment and retention at the district and school level included meeting with superintendents and receiving a proper introduction to school principals and consistently clear communication throughout the study . At the school level , relationships were developed with the principal and other key personnel to keep lines of communication open during the study . Recruitment and retention strategies at the child and parent level included allowing adequate time for questions during consent and assent and providing a free nutrition and exercise program , a light meal , homework assistance , child care for other children who came to the program , and transportation vouchers if needed . Successful recruitment and retention strategies at the district and school levels and child and parent levels are important for conducting longitudinal community-based studies We have assessed the impact of a 2-year pilot church-base diabetes risk reduction programme on major lifestyle predictors of future Type 2 diabetes mellitus : exercise and weight control in a prospect i ve non-r and omized controlled study of a modular lifestyle and diabetes awareness intervention programme using a community development model . The study involved two complete church congregations from an ethnic group at high risk of diabetes ( Western Samoans ) ( intervention church n = 78 ; control church n = 144 ) . Weight remained stable ( 0+/-4.8 kg ) in the intervention church but increased by 3.1+/-9.8 kg in the control church ( p = 0.05 ) . In the intervention church , there was an associated reduction in waist circumference ( -4+/-10 cm vs + 2+/-7 cm in control , p < 0.001 ) , an increase in diabetes knowledge ( 46+/-26 % vs 4+/-17 % in control , p < 0.001 ) and an increase in the proportion exercising regularly ( + 22 % vs -8 % in control , p < 0.05 ) . Consumption of key fatty foods was also reduced in the intervention church . We conclude that diabetes risk reduction programmes based upon lifestyle change , diabetes awareness , and empowerment of high risk communities can significantly reduce risk factors for future Type 2 diabetes IMPORTANCE Identifying community-based programs that increase physical activity among diverse youth could yield sustainable tools to reduce obesity and obesity disparities . OBJECTIVE To evaluate the impact of a community-based after-school soccer and youth development program , America SCORES , on students ' physical activity , weight status , and fitness . DESIGN Cluster-r and omized trial . Study measures were collected in the fall ( baseline ) , winter ( midpoint ) , and spring ( end point ) of the 2009 - 2010 school year . SETTING After-school programs in 6 schools within a large urban school district . PARTICIPANTS All 4th and 5th grade students in after-school programs at the study schools were eligible . INTERVENTION Three schools were r and omized to receive the SCORES after-school program , delivered via the train-the-trainer model . MAIN OUTCOME MEASURES Change in minutes of after-school moderate-to-vigorous physical activity ( MVPA ) , fitness ( maximal oxygen consumption ) , and body mass index over 1 school year . RESULTS Participants ( n = 156 ) were diverse ( 42 % Latino , 32 % Asian , and 12 % African American ) and 76 ( 49 % ) had a body mass index at or above the 85th percentile . There were no significant group differences in the change in physical activity , fitness , or weight status among all students . However , among students with a body mass index at or above the 85th percentile , SCORES significantly increased MVPA after school ( 3.4 min/d ; 95 % CI , 0.3 - 6.5 ) and on Saturdays ( 18.5 minutes ; 95 % CI , 3.4 - 33.6 ) . CONCLUSIONS AND RELEVANCE Existing community-based programs such as SCORES can increase physical activity among low-income youth , particularly those most at risk for weight-related comorbidities . While evaluating existing programs presents special challenges , partnerships between communities , schools , and research ers are an important component of translational research to address obesity . TRIAL REGISTRATION clinical trials.gov Identifier : NCT01156103 BACKGROUND Intensive lifestyle interventions can reduce the incidence of type 2 diabetes in people with impaired glucose tolerance , but how long these benefits extend beyond the period of active intervention , and whether such interventions reduce the risk of cardiovascular disease ( CVD ) and mortality , is unclear . We aim ed to assess whether intensive lifestyle interventions have a long-term effect on the risk of diabetes , diabetes-related macrovascular and microvascular complications , and mortality . METHODS In 1986 , 577 adults with impaired glucose tolerance from 33 clinics in China were r and omly assigned to either the control group or to one of three lifestyle intervention groups ( diet , exercise , or diet plus exercise ) . Active intervention took place over 6 years until 1992 . In 2006 , study participants were followed-up to assess the long-term effect of the interventions . The primary outcomes were diabetes incidence , CVD incidence and mortality , and all-cause mortality . FINDINGS Compared with control participants , those in the combined lifestyle intervention groups had a 51 % lower incidence of diabetes ( hazard rate ratio [ HRR ] 0.49 ; 95 % CI 0.33 - 0.73 ) during the active intervention period and a 43 % lower incidence ( 0.57 ; 0.41 - 0.81 ) over the 20 year period , controlled for age and clustering by clinic . The average annual incidence of diabetes was 7 % for intervention participants versus 11 % in control participants , with 20-year cumulative incidence of 80 % in the intervention groups and 93 % in the control group . Participants in the intervention group spent an average of 3.6 fewer years with diabetes than those in the control group . There was no significant difference between the intervention and control groups in the rate of first CVD events ( HRR 0.98 ; 95 % CI 0.71 - 1.37 ) , CVD mortality ( 0.83 ; 0.48 - 1.40 ) , and all-cause mortality ( 0.96 ; 0.65 - 1.41 ) , but our study had limited statistical power to detect differences for these outcomes . INTERPRETATION Group-based lifestyle interventions over 6 years can prevent or delay diabetes for up to 14 years after the active intervention . However , whether lifestyle intervention also leads to reduced CVD and mortality remains unclear In this paper , we describe the measures of intervention exposure used in the cluster r and omised trial of the Well London programme , a public health intervention using community engagement and community-based projects to increase physical activity , healthy eating and mental health and well-being in 20 of the most deprived neighbourhoods in London.10 No earmarked re sources to support the development of these measures and associated data collection were provided to either the research team or to those delivering the interventions on the ground . Instead , these were derived from contractually specified performance management information reported quarterly by partners and by inclusion of questions seeking information about participation in the follow-up question naires used to measure the main trial outcomes . The exposure measures are consequently considerably less sophisticated than those used in the US studies , where earmarked funding was available ' Hartslag Limburg ' ( Dutch for Heartbeat Limburg ) , a regional cardiovascular diseases ( CVD ) prevention program , integrates a community strategy and a high-risk strategy to reduce CVD risk behaviors . The present paper focuses on the effects of the community intervention on fat intake and physical activity . The project was based on community organization principles and health education theories and methods . In order to implement the intervention , nine local Health Committees were set up , each organizing activities that facilitate and encourage people to adopt a healthier lifestyle . A pre-test-post-test control group design with two post-tests was used to evaluate the intervention . At baseline , representative r and om cohort research sample s were selected in the Maastricht region and in a control region . Data on fat intake and physical activity , and on the psychosocial determinants of these behaviors , were gathered by means of mail surveys . The present study indicates that the intervention had a significant effect on fat reduction , especially among respondents aged < or=48 years ( median age ) . Respondents in the Maastricht region were also more realistic about their fat intake at post-test as compared with the control region . Only a limited effect on intentions to increase physical activity was found BACKGROUND The Child and Adolescent Trial for Cardiovascular Health ( CATCH ) was the first multicenter school-based research study to employ the fundamentals of clinical trials including the st and ardized protocol and Manuals of Operation , a steering committee for study governance , a distributed data system , an extensive quality control system , and a Data and Safety Monitoring Board . METHOD CATCH tested the effectiveness of changes in school lunches , physical education , smoking policy , curricula , and family activities . Ninety-six elementary schools in four states were r and omized to intervention or control conditions . The baseline cohort comprised 5 , 106 ethnically diverse third grade rs followed through fifth grade . RESULTS The percentages of calories from fat and saturated fat were reduced significantly more in the intervention school lunches than among the controls . Significant increases in moderate to vigorous activity levels in existing physical education classes were made as well . Changes in self-reported dietary , physical activity , and psychosocial measures were significant . There were no significant differences in the physiological measures . Measurement error was generally low for all physiologic measures except skinfolds , indicating a high level of reliability . Across all sites , the coefficients of variation for lipids , height , and weight were less than 3 % , whereas for skinfolds , they were considerably higher , ranging from 6 to 8 % . Intraclass correlations for lipid studies were also uniformly high at 0.99 . Interobserver agreement scores for SOFIT were greater than 90 % for 9 of the 11 activities observed . Data entry error rates were low with less than five errors per 1,000 fields for all forms . CONCLUSIONS The CATCH results provided more scientific evidence on the importance of schools in the population approach to health promotion . Many of the strategies used in this complex multicenter trial in the areas of design and analysis , measurement , training , data management , and quality control protocol s might be appropriate for adoption in other studies OBJECTIVE To assess patterns of recruitment into a community-based NCI-funded physical activity and dietary lifestyle change program targeting African-American women . DESIGN Acquisition of a convenience sample to be screened for participation in a r and omized , controlled prevention intervention . SETTING African-American-owned and -operated health club located in an area of Los Angeles in which African Americans are concentrated . PARTICIPANTS 893 African-American women . RECRUITMENT STRATEGIES : Social networking/word-of-mouth , staff presentations , mass and targeted media , and physician referral . MAIN OUTCOME MEASURE Completion of screening question naire indicating a desire to enroll in the study . Screening question naire domains included self-reported height and weight , recent participation in organized weight loss programs , ability to walk one mile unassisted , current medication use , smoking status , personal medical history of cancer , sociodemographic variables , and recruitment source . RESULTS Sociodemographic and anthropometric characteristics distinguished between respondents obtained through different recruitment strategies . In particular , women with a higher body mass index ( BMI ) were more likely than those with lower BMI s ( P = .014 ) to be recruited through more personalized methods ( eg , social networking ) . CONCLUSIONS Culturally tailored recruitment strategies are critical in securing the participation of members of " hard-to-reach " population s , who are both under-represented in health promotion research and at high risk for chronic diseases UNLABELLED Contemporary health-education intervention programs are increasingly used as a tool for improving health of school children [ 1 - 4 ] . Since 1992 a Network of 13 elementary Health Promoting Schools established in Yugoslavia ( though not yet admitted to the European Network ) has been operational . The Project was approved by the Ministries of Health , Education and Ecology from the very beginning , and financially supported by the Government of Serbia since 1995 . The team of up to 40 health professionals , school principals and school project managers worked together for four years to change the working conditions in schools knowledge , attitudes and behaviour of school children and staff in order to improve their health [ 5 ] . The goal of this paper is to present results of health education intervention in changing of hygienic conditions in schools , as well as some of the attitudes , behaviour and knowledge of pupils and their parents . METHOD The study took place before and after the intervention -- at two points in time -- during 1993 and 1996 . The tri-angular approach including ( 1 ) pupils , ( 2 ) schools ( teachers , school environment ) , and ( 3 ) parents , was used . A r and om pretest and post-test study design with control group ( 12 experimental and two control schools ) has been implemented . The multiphase cluster sample was employed in order to represent all of the country typical regions . Six types of especially design ed question naires were used to provide comparable variables in the sample of pupils , their parents and teachers . Exception were 1st- grade rs and 4th- grade rs for whom information were gathered by means of a " draw- and -write " investigation technique [ 6 ] . The response rate was 88.70 % before and 98.28 % after intervention . Data were analyzed by descriptive and inferential statistics using SPSS/PC software . RESULTS Schools are somewhat less overcrowded , much cleaner and better maintained after the four-year intervention . Toilets are in a better condition , but there is still much more to be done . The 1st- and 4th- grade rs , surveyed by the draw- and -write method , mentioned numerous ways of keeping and improving health , which were summarized as fifteen health-improvement measures ( Graph 1 ) . The most frequently mentioned measures were nutrition , physical activity , general hygiene , oral and dental hygiene , sleeping and fresh air . Each of these measures was mentioned by over 20 % of the surveyed pupils . Eleven of 15 variables showed significant increase in frequencies ( at the level of at least p < 0.01 ) after the intervention . As an indicator of a nutrition behaviour , the regularity of main meals is analyzed ( Graph 2 ) . The majority of children eat regularly and the difference before and after intervention is significant only for the school meal ( c2 = 30.715 , p < 0.001 ) . Although over 70 % of children learn that general hygiene is good for health in junior grade rs , only about little more than 30 % of senior grade rs have a bath or shower every day , while others only once or twice a week . The differences are significant before and after the intervention ( c2 = 10.648 , p < 0.05 ) only for everyday practice . More than 90 % of senior- grade pupils brush their teeth at least once or several times a day . Over 60 % of children in our survey go in for sport , whereas about 20 % never do so . It seems that the intervention contributed symbolically to this practice important for health , though before-after difference is significant ( c2 = 6.673 , p < 0.05 ) . However , in the control group schools children have much less physical activity in 1996 , and this difference is significant ( c2 = 14.070 , p < 0.010 ) . The psycho-emotional status of Yugoslav young people is strongly influenced by the situation in the country the war , the economic disaster and the impact of international sanctions . Consequently , more than one-fourth of the children complained of frequent exhaustion and concentration problems , which their parents also noticed . ( ABSTRACT TRUNCATED OBJECTIVES This study assessed stages of change in fat intake , physical activity , and cigarette smoking during a r and omized controlled trial of behavioral counseling . METHODS Twenty general practice s ( primary health care centers ) were r and omized to lifestyle counseling by behavioral methods or to usual health promotion . A total of 883 patients were selected for the presence of 1 or more of the following risk factors : cigarette smoking , high cholesterol , or a combination of a high body mass index and low physical activity . Stage of change ( precontemplation , contemplation , preparation , and action/maintenance ) was assessed at baseline and after 4 and 12 months . RESULTS The odds of moving to action/maintenance for behavioral intervention vs control patients at 4 months were 2.15 ( 95 % confidence interval [ CI ] = 1.30 , 3.56 ) for fat reduction , 1.89 ( 95 % CI = 1.07 , 3.36 ) for increased physical activity , and 1.77 ( 95 % CI = 0.76 , 4.14 ) for smoking cessation . The likelihood of achieving action/maintenance was related to baseline stage for all 3 behaviors . CONCLUSIONS Brief behavioral counseling based on advice matched to stage of readiness for change may be valuable in encouraging healthy lifestyles among patients in primary care at raised risk of cardiovascular disease BACKGROUND Faith-based interventions using a community-based participatory approach hold promise for eliminating ethnic health disparities . This study evaluated the effects of a volunteer-led statewide program to increase physical activity among members of African-American churches . METHODS African Method ist Episcopal churches within six regions ( Conferences ) were r and omly assigned to receive training in the program immediately or 1 year later . A cohort of 20 r and omly selected churches and 571 members within them took part in telephone surveys at baseline ( May-September 2003 ) and 1 year ( May-August 2004 ) and 2 years later ( June-September 2005 ) . Primary outcomes were physical activity participation , meeting physical activity recommendations , and stage of readiness for physical activity change . Statistical analyses were completed in April 2006 . RESULTS Volunteers ( N=889 ) from 303 churches were trained . Among survey respondents , physical activity did not increase significantly over time , although 67 % were aware of the program . Program awareness was significantly related to all three physical activity outcomes and to fruit and vegetable consumption . Pastoral support was significantly associated with physical activity . CONCLUSIONS Although this intervention reached a large number of churches and created awareness of intervention components , no effects on physical activity behaviors were found . Potential reasons for the lack of significant effects are discussed Abstract Objective : To measure the effect of behaviourally oriented counselling in general practice on healthy behaviour and biological risk factors in patients at increased risk of coronary heart disease . Design : Cluster r and omised controlled trial . Participants : 883 men and women selected for the presence of one or more modifiable risk factors : regular cigarette smoking , high serum cholesterol concentration ( 6.5 - 9.0 mmol/l ) , and high body mass index ( 25 - 35 ) combined with low physical activity . Intervention : Brief behavioural counselling , on the basis of the stage of change model , carried out by practice nurses to reduce smoking and dietary fat intake and to increase regular physical activity . Main outcome measures : Question naire measures of diet , exercise , and smoking habits , and blood pressure , serum total cholesterol concentration , weight , body mass index , and smoking cessation ( with biochemical validation ) at 4 and 12 months . Results : Favourable differences were recorded in the intervention group for dietary fat intake , regular exercise , and cigarettes smoked per day at 4 and 12 months . Systolic blood pressure was reduced to a greater extent in the intervention group at 4 but not at 12 months No differences were found between groups in changes in total serum cholesterol concentration , weight , body mass index , diastolic pressure , or smoking cessation . Conclusions : Brief behavioural counselling by practice nurses led to improvements in healthy behaviour . More extended counselling to help patients sustain and build on behaviour changes may be required before differences in biological risk factors emerge BACKGROUND Existing evidence indicates that Inuit in A rct ic Canada are undergoing a lifestyle transition leading to decreased physical activity ( PA ) and increased body mass index ( BMI ) . Data specific to PA and BMI amongst Inuit in Nunavut , Canada , are currently limited . The present study aim ed to characterise current PA and BMI levels in a sample of Inuit adults . METHODS Inuit adults r and omly selected from a cross-sectional survey of three communities in Nunavut , Canada , completed an adapted International Physical Activity Question naire ( IPAQ ) and an anthropometric survey . Data were analysed by gender and age group using st and ardised IPAQ protocol . RESULTS Response rates ranged from 69 - 93 % . Two hundred and eighteen Inuit adults [ 180 women , 38 men ; mean ( st and ard deviation ( SD ) ) ages 42.3 ( 13.0 ) and 42.4 ( 14.8 ) years respectively ; age range 19 - 89 years ] completed the IPAQ . All men and 97 % of women allowed height and weight measurements ; the remainder were self-reported . Mean ( SD ) BMI was 27.7 ( 6.3 ) kg/m(2 ) for males and 30.3 ( 8.0 ) kg/m(2 ) for females . The largest proportion of women and participants in both age groups had a BMI in the obese category ; males were evenly split between the normal and obese categories . Self-reported PA was high , with most men , women and participants ≤50 years in the high category of PA . Participants > 50 years were evenly split across the medium and high categories . Most participants ( 72 % ) were classified as being overweight or obese , yet reported medium or high levels of PA ( 89 % ) . CONCLUSIONS The findings obtained in the present study indicate the co-existence of high BMI and high self-reported PA amongst Inuit adults OBJECTIVE . We design ed and tested a novel health promotion program for elementary schools that was based on peer teaching from older to younger schoolchildren ( “ Healthy Buddies ” ) . SUBJECTS AND METHODS . This prospect i ve pilot study compared the effect of our program ( 2–3 hours/week , 21 weeks ) in 2 Canadian elementary schools ( intervention : n = 232 children , the whole school implementing the program ; control : n = 151 ) . Older students ( 4th through 7th grade ) were given direct instruction from 1 intervention teacher and were paired with younger students ( kindergarten through 3rd grade ) for the whole school year . Students in 4th through 7th grade then acted as teachers for their younger “ buddies . ” All lessons included 3 components of healthy living : nutrition , physical activity , and healthy body image . The students first learned how to be positive buddies and learned the 3 components of a healthy life . Thereafter , they learned how to overcome challenges to living a healthy life . Outcome measures ( intervention and control schools at the beginning and end of the school year ) included vali date d question naires that assessed healthy-living knowledge , behavior and attitude , a 9-minute fitness run , self-competence , body satisfaction , disordered eating symptoms , and anthropometry ( BMI , blood pressure , and heart rate ) . RESULTS . Compared with control students , both older and younger intervention students showed an increase in healthy-living knowledge , behavior , and attitude scores and a smaller increase in systolic blood pressure . BMI and weight increased less in the intervention students in 4th through 7th grade and height more in the intervention students in kindergarten through 3rd grade . CONCLUSIONS . Our student-led curriculum improved knowledge not only in older schoolchildren but also in their younger buddies . It also decreased weight velocity in the older students . Student-led teaching may be an efficient , easy-to-implement way of promoting a healthy lifestyle from kindergarten to 7th grade Aims : Increasing population physical activity ( PA ) is a public health priority . An approach to increasing PA in an urban community , based on the social ecology model , is presented and evaluated . Methods : A quasi-experimental ( non-equivalent control group ) design was chosen to test whether this approach can increase , significantly , the population proportion that is physically active . Two deprived inner-city electoral ward areas of Sheffield , UK , with similar socio-demographic and health profiles were selected . Implementation was carried out in five phases over 21 months : preparation and piloting , initial survey estimates , community awareness campaign , PA intervention and evaluation . Impact was evaluated by recording uptake and attendance at all sessions , and using a post-intervention postal survey . At follow-up , question naires were sent to 2500 r and omly selected addresses in both areas , which assessed changes in PA , health and PA participation over the last year . Results : A pilot baseline survey confirmed similar proportions taking some form of PA on most days : intervention 36 % ( 25—47 ) , control 33 % ( 21—45 ) . At follow-up , 38 different activity groups were in place and 1275 individuals had attended at least one activity . Satisfactorily completed responses were received from 1532 ( 31 % ) , 55 % ( 846 ) intervention , 45 % ( 686 ) control . Relative to the control , the intervention sample demonstrated trends towards : being more physically active compared with one year ago , greater readiness to take up PA , better general health and improved health compared with one year ago ( p ≤ 0.001 ) . Further , 30.6 % ( intervention ) vs 18.3 % ( control ) reported an increase in PA compared with one year ago , while 13.7 % ( intervention ) vs 24.5 % ( control ) reported no intention to exercise . These differences in proportions translated to an overall effect size estimate of 0.23 for the intervention . Relative to those whose PA had remained the same , intervention area residents were more likely to report being more active ( odds ratio ( 95 % confidence interval ) = 1.79 ( 1.38—2.32 ) , p < 60 ; 0.001 ) . Conclusion : These results suggest that , even within one of the most deprived inner-city areas in the UK , a community-based social ecological approach can positively change PA behaviour and attitudes BACKGROUND Physical activity is now a public health priority , but there is only limited evidence on the effectiveness of mass-reach campaigns . INTERVENTION Paid and unpaid television and print-media advertising , physician mail-outs , and community-level support programs and strategies . SETTING / PARTICIPANTS A mass-media statewide campaign to promote regular moderate-intensity activity was conducted during February 1998 . The target group was adults aged 25 to 60 who were motivated but insufficiently active . DESIGN Cohort and independent- sample , cross-sectional representative population surveys , before and after the campaign . The intervention was conducted in the state of New South Wales , with the other states of Australia as the comparison region . MEASURES Telephone survey items on physical activity , media message awareness , physical activity knowledge , self-efficacy , and intentions . RESULTS Unprompted recall of the activity messages in the campaign state increased substantially from 2.1 % to 20.9 % ( p<0.01 ) , with small changes elsewhere in Australia ( 1.2 % to 2.6 % ) . There were large changes in prompted awareness from 12.9 % to 50.7 % ( p<0.0001 ) , much larger than changes elsewhere ( 14.1 % to 16 % , p=0.06 ) . Knowledge of appropriate moderate-intensity activity and physical activity self-efficacy increased significantly and only in the campaign state . Compared to all others , those in the target group who recalled the media message were 2.08 times more likely to increase their activity by at least an hour per week ( 95 % confidence interval = 1.51 - 2.86 ) . CONCLUSIONS This integrated campaign positively influenced short-term physical activity message recall , knowledge , and behavior of the target population , compared to the population in the region who were not exposed The Isfahan Healthy Heart Programme ( IHHP ) is a five to six year comprehensive integrated community-based programme for cardiovascular diseases ( CVD ) prevention and control via reducing CVD risk factors and improvement of cardiovascular healthy behaviour in a target population . IHHP started late in 1999 and will be finished in 2005 - 2006 . A primary survey was done to collect baseline data from interventional ( Isfahan and Najaf-Abad ) and reference ( Arak ) communities . In a two-stage sampling method , we r and omly selected 5 to 10 percent of households from r and omly selected clusters . Then individuals aged ≥19 years were selected for the survey . This way , data from 12,600 individuals ( 6300 in interventional counties and 6300 in the reference county ) was collected and stratified according to living area ( urban vs. rural ) and different age and sex groups . The sample s underwent a 30-minute interview to complete vali date d question naires containing questions on demography , socioeconomic status , smoking behaviour , physical activity , nutritional habits and other behaviour regarding CVD . Blood pressure and body mass index ( BMI ) measurements were done and fasting blood sample s were taken for two hours post load plasma glucose ( 2 hpp ) , serum ( total , HDL and LDL ) cholesterol and triglyceride levels . A twelve-lead electrocardiogram was recorded in all persons above 35 years of age . Community-wide surveillance of deaths , hospital discharges , myocardial infa rct ion and stroke registry was carried out in the intervention and control areas . Four to five years of interventions based on different categories such as mass media , community partnerships , health system involvement and policy and legislation have started in the intervention area while Arak will be followed without intervention . Considering the results of the baseline surveys . ( assessment s needed , the objectives , existing re sources and the possibility of national implementation ) the interventions were planned . They were set based on specific target groups like school children , women , work-site , health personnel , high-risk persons , and community leaders were actively engaged as decision makers . A series of teams was arranged for planning and implementation of the intervention strategies . Monitoring will be done on small sample s to assess the effect of different interventions in the intervention area . While four periodic surveys will be conducted on independent sample s to assess health behaviours related to CVD risk factors in the intervention and reference areas , the original pre-intervention subjects aged more than 35 years will be followed in both areas to assess the individual effect of interventions and outcomes like sudden death , fatal and nonfatal MI and stroke . The whole baseline survey will be repeated on the original and an independent sample in both communities at the end of the study PURPOSE The purpose of this study was to determine , in a r and omized clinical trial of 439 individuals with knee osteoarthritis , the incremental cost-effectiveness of aerobic versus weight resistance training , compared with an education control intervention . METHODS Cost estimates of the intervention were based upon the cost of purchasing from the community similar services to provide exercise or health education . Effect at 18 months was measured using several variables , including : self-reported disability score , 6-min walking distance , stair climb , lifting and carrying task , car task , and measures of pain frequency and pain intensity on ambulation and transfer . RESULTS The total cost of the educational intervention was $ 343.98 per participant . The aerobic exercise intervention cost $ 323.55 per participant , and the resistance training intervention cost $ 325.20 per participant . On all but two of the outcome variables , the incremental savings per incremental effect for the resistance exercise group was greater than for the aerobic exercise group . CONCLUSION The data obtained from this study suggest that , compared with an education control , resistance training for seniors with knee osteoarthritis is more economically efficient than aerobic exercise in improving physical function . However , the magnitude of the difference in efficiency between the two approaches is small Abstract BACKGROUND : Mind-body practice s such as yoga are widely popular , but little is known about how such exercises impact health-related quality of life . OBJECTIVE : To measure changes in health-related quality of life associated with 3 months of mind-body training as practice d in community-based setting s. DESIGN : Prospect i ve cohort study . SETTING : Eight centers for practice of mind-body training . PARTICIPANTS : One hundred ninety-four English-speaking adults who had taken no more than 10 classes at the centers prior to enrollment in the study . One hundred seventy-one ( 88 % ) returned the 3-month follow-up question naire . INTERVENTION : Administration of the SF-36 question naire at the start of training and after 3 months . MEASUREMENTS AND MAIN RESULTS : At baseline , new participants in mind-body training reported lower scores than U.S. norms for 7 of 8 domains of the SF-36 : mental health , role emotional , social , vitality , general health , body pain , and role physical ( P<.002 for all comparisons ) . After 3 months of training , within-patient change scores improved in all domains ( P<.0001 ) , including a change of + 15.5 ( st and ard deviation ±21 ) in the mental health domain . In hierarchical regression analysis , younger age ( P=.0003 ) , baseline level of depressive symptoms ( P=.01 ) , and reporting a history of hypertension ( P=.0054 ) were independent predictors of greater improvement in the SF-36 mental health score . Five participants ( 2.9 % ) reported a musculoskeletal injury . CONCLUSIONS : New participants in a community-based mind-body training program reported poor health-related quality of life at baseline and moderate improvements after 3 months of practice . R and omized trials are needed to determine whether benefits may be generalizable to physician-referred population BACKGROUND The rate of childhood obesity has more than tripled during the past 30 years . Research shows that prevention at an early age is more effective than treatment later in life . Energize is a multicomponent intervention incorporated into the school day that combines nutrition education and physical activity aim ed at maintaining healthy weight among elementary school youth . This study evaluated the effectiveness of the Energize program for changing dietary and physical activity habits compared to a control group of children not participating in the program . METHODS A total of 104 , 3rd and 4th grade rs in 3 southern Indiana elementary schools took part in the study . A quasi-experimental design was used to assess dietary and exercise habits of students in Energize and control groups through 12-week diet/activity logs and post-test question naires after controlling for the pre-test results . RESULTS Energize reduced consumption of French fries and potato chips , but did not increase physical activity . CONCLUSIONS This study provides future research ers with a foundation for preparing longer studies of Energize or to compare multiple years of a st and ardized Energize curriculum BACKGROUND Although a number of studies have tested ecologic models that postulate relationships among social networks , the built environment , and active living , few neighborhood-based studies have considered the role of crime and violence . This study investigates the degree to which individual-level demographic characteristics and neighborhood-level physical and social characteristics are associated with increased fear of crime . METHODS Data were analyzed in 2007 from a 2005 survey of 901 r and omly selected individuals living in 55 neighborhoods in Washington DC . Multilevel ordered logit regression was used to examine associations between individual-level and neighborhood-level characteristics and how often fear of crime prevents a respondent from walking outdoors . RESULTS Age and female gender were associated with an increase in fear ; the percentage of a resident 's life spent in the same neighborhood was associated with a decrease in fear . Results of cross-level interactions showed that at the neighborhood level , women were more fearful than men in neighborhoods without violence , but that the difference in fear between men and women shrinks as neighborhood violence increases . Collective efficacy was found to increase fear among black respondents and had no effect on fear among nonblack respondents . CONCLUSIONS If the study of neighborhoods and active living is to progress and contribute to both etiologic underst and ing and policy formation , it is essential that theoretical and empirical models consider the impact of violence and fear on walking . Efforts to increase active living in urban neighborhoods that do not account for the impact of crime and fear may fall short of their intended outcomes OBJECTIVES We evaluated the effects of a community-based intervention , the Academia da Cidade program ( ACP ) , on increasing leisure-time physical activity among residents of Recife , Brazil . METHODS We used the International Physical Activity Question naire to assess leisure-time physical activity and transport physical activity ( i.e. , activities involved in traveling from place to place ) levels in a r and om sample of 2047 Recife residents surveyed in 2007 . We also examined factors related to exposure to ACP ( participation in the intervention , residing near an intervention site , hearing about or seeing intervention activities ) . We estimated prevalence odds ratios ( ORs ) of moderate to high leisure-time and transport physical activity levels via intervention exposures adjusted for sociodemographic , health , and environmental variables . RESULTS Prevalence ORs for moderate to high levels of leisure-time physical activity were higher among former ( prevalence OR=2.0 ; 95 % confidence interval [CI]=1.0 , 3.9 ) and current ( prevalence OR=11.3 ; 95 % CI=3.5 , 35.9 ) intervention participants and those who had heard about or seen an intervention activity ( prevalence OR=1.8 ; 95 % CI=1.3 , 2.5 ) . Transport physical activity levels were inversely associated with residing near an ACP site . CONCLUSIONS The ACP program appears to be an effective public health strategy to increase population -level physical activity in urban developing setting BACKGROUND The Arizona Well-Integrated Screening and Evaluation for Women Across the Nation ( WISEWOMAN ) project used provider counseling , health education , and community health workers ( CHWs ) to target chronic disease risk factors in uninsured , primarily Hispanic women over age 50 . METHODS Participants were recruited from two Tucson clinics participating in the National Breast and Cervical Cancer Early Detection Program ( NBCCEDP ) . Women were r and omly assigned into one of three intervention groups : ( 1 ) provider counseling , ( 2 ) provider counseling and health education , or ( 3 ) provider counseling , health education , and CHW support . At baseline and 12 months ( 1998 - 2000 ) , participants were measured for height , weight , waist and hip circumference , and blood pressure . Blood tests were conducted to check blood glucose , cholesterol , and triglyceride levels . At each time point , participants also completed 24-hour dietary recalls and question naires focusing on their physical activity levels . RESULTS A total of 217 women participated in baseline and 12-month follow-up . Three fourths were Hispanic . All three intervention groups showed an increase in self-reported weekly minutes of moderate-to-vigorous physical activity , with no significant differences between the groups . Significantly more women who received the comprehensive intervention of provider counseling , health education , and CHW support progressed to eating five fruits and vegetables per day , compared with participants who received only provider counseling or provider counseling plus health education . CONCLUSIONS All three interventions increased moderate-to-vigorous physical activity but not fruit and vegetable consumption . The intervention group with provider counseling , health education , and CHW support significantly increased the number of women meeting national recommendations for fruit and vegetable consumption BACKGROUND Although exercise parameters such as intensity and format have been shown to influence exercise participation rates and physiological outcomes in the short term , few data are available evaluating their longer-term effects . The study objective was to determine the 2-year effects of differing intensities and formats of endurance exercise on exercise participation rates , fitness , and plasma HDL cholesterol levels among healthy older adults . METHODS AND RESULTS Higher-intensity , group-based exercise training ; higher-intensity , home-based exercise ; and lower-intensity , home-based exercise were compared in a 2-year r and omized trial . Participants were 149 men and 120 postmenopausal women 50 to 65 years of age who were sedentary and free of cardiovascular disease . Recruitment was achieved through a r and om digit-dial community telephone survey and media promotion . All exercise occurred in community setting s. For higher-intensity exercise training , three 40-minute endurance training sessions per week were prescribed at 73 % to 88 % of peak treadmill heart rate . For lower-intensity exercise , five 30-minute endurance training sessions per week were prescribed at 60 % to 73 % of peak treadmill heart rate . Treadmill exercise performance , lipoprotein levels and other heart disease risk factors , and exercise adherence were evaluated at baseline and across the 2-year period . Treadmill exercise test performance improved for all three training conditions during year 1 and was successfully maintained during year 2 , particularly for subjects in the higher-intensity , home-based condition . Subjects in that condition also showed the greatest year 2 exercise adherence rates ( P < .003 ) . Although no significant increases in HDL cholesterol were observed during year 1 , by the end of year 2 subjects in the two home-based training conditions showed small but significant HDL cholesterol increases over baseline ( P < .01 ) . The increases were particularly pronounced for subjects in the lower-intensity condition , whose exercise prescription required more frequent exercise sessions per week . For all exercise conditions , increases in HDL cholesterol were associated with decreases in waist-to-hip ratio in both men and women ( P < .04 ) . CONCLUSIONS While older adults can benefit from initiating a regular regimen of moderate-intensity exercise in terms of improved fitness levels and small improvements in HDL cholesterol levels , the time frame needed to achieve HDL cholesterol change ( 2 years ) may be longer than that reported previously for younger population s. Frequency of participation may be particularly important for achieving such changes . Supervised home-based exercise regimens represent a safe , attractive alternative for achieving sustained participation Physical inactivity and lack of nutritious diets increase children ’s risk of obesity , especially children from low-income and ethnic minority groups . To address this risk , the school-based TAKE 10 ! program was implemented to increase the physical activity and improve the nutrition of K-6th grade students in one public urban school serving a predominantly low-income , Hispanic population . In this study the research ers ( a ) evaluated the program outcomes using the physical activity and nutrition question naires provided with the TAKE 10 ! curriculum material , teacher surveys , observations , and interview data ; ( b ) evaluated the question naires provided with the TAKE 10 ! curriculum material and provided suggestions for modification ; and ( c ) described the experience of a positive partnership among school , university , and community agencies implementing the TAKE 10 ! curriculum . Based on the findings , recommendations are offered for successful physical activity and nutrition health promotion programs for these children Aim To examine the effect of a multifactorial lifestyle intervention on 5-year change in physical activity ( PA ) and to explore whether length of education had an impact on the effect of the intervention . Methods Two r and om sample s ( high intervention group A , n=11 708 ; low intervention group B , n=1308 ) were invited for a health examination , assessment of absolute risk of ischemic heart disease and individual lifestyle counselling . The participation rate was 52.5 % . High-risk individuals in group A were also offered group-based counselling on diet and PA and /or smoking cessation . High-risk individuals in group B were referred to usual care . All high-risk individuals were reinvited for examination and counselling after 1 and 3 years , and all participants were reexamined after 5 years . The control group ( group C , n=5264 , response rate 61.1 % ) answered a mailed question naire . Change in self-reported PA from baseline to 5-year follow-up was the main outcome . Level of education was classified as no vocational training , ≤4 years and > 4 years . Data were analysed using longitudinal linear regression models with r and om intercepts . Results In men , the high-intensity intervention had a beneficial effect on PA level after 5 years . The age- or time-related decrease in PA was approximately 30 min/week less compared to men in the control group ( p<0.0001 ) . Level of education had no significant impact on the effect of the intervention neither in men ( p=0.39 ) nor in women ( p=0.32 ) . Conclusion A population -based multifactorial lifestyle intervention did not influence social ine quality in PA . Keywords Lifestyle , Exercise , R and omised Intervention Study , Ischemic Heart Disease , Socioeconomic Position Purpose . To examine if a mass media campaign influenced walking differently in people in different physical environments . Design . Quasi-experimental study . Setting . Wheeling , West Virginia . Participants . R and om sample of adults age 50 to 65 years , response rate : 72.1 % ( n = 719 in intervention community , n = 753 in comparison community ) . Intervention . Mass media campaign . Measures . Self-reported measures were used in before and after telephone surveys for walking and the physical environment . Measures included 11 environmental walkability items , from which two subscales ( i.e. , usable sidewalks/aesthetics and facilities ) were extracted . Analysis . Multiple linear regression . Results . Overall , walking increased by 2.7 minutes per week ( st and ard deviation [ SD ] = 231.1 , not significant [ NS ] ) . When confined to those insufficiently active at baseline ( i.e. , < 30 minutes per day ) the minutes walked increased by 92.1 minutes ( SD = 152.9 , p < .001 ) . For the insufficiently active at baseline in the top half of the environmental factor of usable sidewalks , walking increased by 19 minutes more than in the bottom half ( NS ) . For the factor of aesthetics and facilities , people in the more walkable environment increased walking by 87 minutes more than those in the bottom half ( p < .001 ) . Conclusion . In this community-wide physical activity , intervention changes in walking after the campaign were significantly moderated by some environmental attributes . This contributes to the limited evidence on the impact of the environment in enhancing community physical activity interventions . This finding needs to be replicated in other community interventions with greater environmental variation Abstract Objective : To determine whether a community based coronary heart disease health promotion project , undertaken over four years , was associated with changes in the prevalence in adults of lifestyle risk factors known to affect the development of coronary heart disease , and to estimate whether such an approach was cost effective . Design : Prospect i ve , comparative study of the effects of a health promotion intervention on coronary heart disease lifestyle risk factors , assessed by postal question naire sent to a r and omly chosen sample , both at baseline and after four years . Subjects : Intervention and control population s of adults aged 18 - 64 in Rotherham , both from areas with a high incidence of coronary heart disease and similar socioeconomic composition . Main outcome measures : Changes in prevalence of lifestyle risk factors between the control and intervention communities from 1991 to 1995 . The effect of the intervention on certain lifestyle behaviours was evaluated using multiple logistic regression to model the proportion with a particular behaviour in the study communities as a function of age ( 18 - 40 or 41 - 64 years ) , sex , the year of observation ( 1991 or 1995 ) , and area ( intervention or control ) . Results : 6.9 % fewer people smoked and 8.7 % more drank low fat milk in the intervention area , but no other statistically significant changes between the areas were detected . The estimated cost per life year gained was £ 31 . Conclusions : It is possible to have a cost effective impact on coronary heart disease lifestyle risk factors in a population of adults over four years using only modest re sources . Key messages Little is known about the cost effectiveness of focused , heart disease health promotion projects in reducing cardiovascular risk factors over a short period in small population s of adults Research was undertaken to estimate the impact of a heart disease health promotion project — Action Heart— and relate the cost to estimates of health gain Major differences were observed in changes in prevalence of active smoking and consumption of low fat milk between the intervention and control areas over four years The estimated cost per life year gained was £ 31 Further research is required to ascertain whether the changes in risk factors will be sustained after the end of Action OBJECTIVE To examine the evolution of risk behaviors over 2 years among a community-based cohort of low-income African American preadolescents and young adolescents enrolled in a r and omized trial of an acquired immunodeficiency syndrome risk reduction intervention . DESIGN Longitudinal , community-based cohort . SETTING Nine recreation centers serving 3 public housing developments . SUBJECTS Three hundred eighty-three African American youths aged 9 through 15 years at baseline . INTERVENTIONS Frequency distributions , chi 2 analyses , and regression analyses regarding 10 risk behaviors were conducted . To assess whether a specific risk behavior or its protective ( nonrisk ) behavioral analogue , composing a risk-nonrisk behavioral complex ( eg , was sexually active and was sexually abstinent or used drugs and refrained from drugs ) , was stable over time , kappa values were determined for the 10 risk-nonrisk behavioral complexes . MAIN OUTCOME MEASURES Instrument assessing risk/ behaviors administered at baseline and every 6 months aurally and visually via talking computer . RESULTS The prevalence of sexual intercourse , cigarette smoking , alcohol consumption , and drug use increased notably over time . Drug use increased from a 6-month cumulative prevalence of 7 % at baseline to 27 % at the 24-month follow-up ( P < .001 ) . Cumulatively over the 2-year study interval , 81 % of youths had engaged in fighting , 58 % had engaged in sexual intercourse , and from 33 % to 40 % had engaged in truancy , knife or bat carrying or both , alcohol consumption , drug use , and cigarette smoking . All of the risk-nonrisk behavioral complexes except weapon carrying were stable during the semiannual assessment intervals . Fighting ( kappa = 0.22 , P < .01 ) , sexual intercourse ( kappa = 0.33 , P < .001 ) , alcohol consumption ( kappa = 0.21 , P < .001 ) , and unprotected sexual intercourse ( kappa = 0.34 , P < .05 ) were stable for 2 years . Six risk-nonrisk behavioral complexes were stable for the 2-year interval among youths aged 13 through 15 years at baseline , while only 2 risk-nonrisk behavioral complexes were stable among younger youths . The intervention seemed to affect the stability of 4 risk behaviors : truancy , drug use , unprotected sexual intercourse , and , possibly , fighting . For unprotected sexual intercourse , this intervention effect seemed to be due to stabilization of nonparticipation in risky behavior . Intervention youths were less likely to adopt a risk behavior ( ie , engage in it for > or = 2 risk assessment periods ) than control youths , but they were not less likely to experiment with a risk behavior . CONCLUSIONS There is evidence that although the prevalence of risk behaviors does change with age , most risk-nonrisk behavioral complexes seem to be relatively stable over time and stability may increase with time . Risk reduction interventions seem to decrease risk adoption , stabilize nonrisk behaviors , and possibly destabilize risk behavior OBJECTIVE The study was a non-r and omized , parallel-group comparison to evaluate the efficacy of a community-based weight reduction program with exercise and diet modification for overweight adults using existing community health services . METHODS The study population consisted of 1,115 community-dwelling people who underwent annual health checkups in 2002 and were screened by exclusion criteria ( age > 65 , body mass index ( BMI ) < 24.2 ) . They received a mail request to select one of two courses ; a usual single-session health instruction course ( control group ) or a 9-month weight management course ( intervention group ) . Forty six patients registered in the intervention group , and fifty patients in the control group . The analyzed sample consisted of 76 participants ( 9 males and 67 females ) excluding dropouts from November 2002 to July 2003 . Intervention included monthly classes ( 2 hours per class , 9 classes ) consisting of an individual support program for behavioral change and a community support program for continuation after the class . The control group participants received conventional instructions based on their health status . RESULTS No significant inter-group differences were observed at baseline , except in age and height of females . The mean BMI decreased from 27.2 ( SD = 2.8 ) kg m(-2 ) to 25.3(3.1 ) kg m(-2 ) in the intervention group , and 26.4 ( 1.7 ) kg m(-2 ) to 26.1(1.7 ) kg m(-2 ) in the control group . Repeated measures analysis of variance showed significant time and group interaction adjusted for gender and age . The proportion showing maintenance and action in stage of exercise behavior increased in the intervention group ( 31 % to 60 % ) , but remained stable in the control group ( 45 % to 48 % ) . The proportion showing maintenance and action in stage of diet behavior increased in the intervention group ( 24 % to 80 % ) , but remained stable in the control group ( 29 % to 26 % ) . CONCLUSION Community-based weight reduction programs may be effective to facilitate change in exercise and diet behavior for body weight reduction in overweight adults Although obesity affects all cultures , ethnic groups and social strata , this disorder affects African Americans , Hispanics and the poor at a disproportionate rate . The Downstart Pediatric Healthy Lifestyle Program was developed to provide a multi-disciplinary behavioral modification program for inner city families in Brooklyn , New York interested in leading a healthier , more active lifestyle . The Downstart Program uses a four-pronged approach of medical evaluation , exercise , nutritional education and lifestyle modification . A psychological evaluation is performed to determine the individual 's ability and readiness to participate in group activities . Baseline physical fitness , flexibility and muscle strength are measured , followed by a twice-weekly karate/martial arts/dance program , incorporating principles established by the President 's Council on Exercise . Nutritional and behavioral modification aspects of the program consist of weekly education about food groups , portion control , goal setting and appropriate rewards for attaining goals . Our preliminary results indicate that the Downstart Program may be a viable intervention for weight loss . Further study is needed to improve strategies for motivating patients and means and criteria for assessing long-term effects on health and lifestyle OBJECTIVE To study the effect of a community-based walking intervention on blood pressure among older people . METHOD The study design was a r and omized controlled trial conducted in a rural area of Taiwan between October 2002 and June 2003 . A total of 202 participants aged 60 years and over with mild to moderate hypertension was recruited . Participants r and omized to the intervention group ( n=102 ) received a six-month community-based walking intervention based on self-efficacy theory . A public health nurse provided both face-to-face and telephone support design ed to assist participants to increase their walking . Control group participants ( n=100 ) received usual primary health care . Primary outcome was change in systolic blood pressure and secondary outcomes were exercise self-efficacy , self-reported walking and diastolic blood pressure . RESULTS At six-month follow-up the mean change in systolic blood pressure was a decrease of 15.4 mmHg and 8.4 mmHg in the intervention and control group , respectively . The difference in mean change between the two groups was -7.0 mmHg ( 95 % CI , -11.5 to -2.5 mmHg , p=0.002 ) . Improvement in exercise self-efficacy scores was greater among intervention group participants ( mean difference 1.23 , 95 % CI , 0.5 to 2.0 , p=0.001 ) . Intervention group participants were more likely to report walking more ( p<0.0005 ) but no differences were observed in diastolic blood pressure ( p=0.19 ) . CONCLUSIONS Among hypertensive older people , a six-month community-based walking intervention was effective in increasing their exercise self-efficacy and reducing systolic blood pressure The purpose of this study was to determine whether ROCK ! Richmond , a healthy nutrition and physical activity promotion initiative of the Richmond ( Virginia ) City Department of Public Health was effectively recruiting the high-risk individuals for whom this lifestyle change intervention was intended . The effectiveness of recruitment , participant demographic and health status characteristics were compared with those of respondents to a r and om sample survey conducted 18 months earlier . Relatively high-risk residents were recruited . ROCK ! Richmond participants were disproportionately African American and female , had significantly higher body mass indices ( BMI s ) , and were more likely to report a family history of chronic disease . However , their employment , education , and income levels were higher than those of the citywide sample . Certain high-risk segments of the population were successfully reached and involved in community fitness activities . Different recruitment methods may need to be used to recruit more from among the lowest socioeconomic strata An adequate level of physical activity may maintain or promote work ability in aging workers . Project Active is a r and omized trial comparing a Lifestyle physical activity program with a Structured exercise program in sedentary but healthy adults aged 35 to 60 years . Subjects in both groups received 6 months of intensive intervention followed by 18 months of active follow-up . The total number of subjects was 235 , from which 80 subjects participated in the work ability assessment . Primary outcome measures were energy expenditure ( kcal · kg−1 · day−1 ) , cardiorespiratory fitness ( peak oxygen uptake in ml · min−1 · kg−1 ) , and the Work Ability Index . At 6 months , daily energy expenditure had increased significantly over baseline ( mean ± SD , from 33.0 ± 0.9 to 34.4 ± 1.8 kcal · kg−1 · day−1 ) and was maintained over baseline at 24 months ( 34.0 ± 2.5 kcal · kg−1 · day−1 ) . The significant increase in energy expenditure was observed particularly in moderate levels of activity . The average percentage of body fat was significantly higher at baseline compared with 6 months and 24 months . Peak oxygen uptake increased from baseline significantly during the first 6 months ( from 29.6 ± 5.7 to 30.6 ± 6.3 ml · min−1 · kg−1 ) and decreased to the baseline level ( 29.1 ± 5.5 ml · min−1 · kg−1 ) at 24 months . At baseline , the average Work Ability Index was 44.2 ± 4.0 , and it remained unchanged at 6 months ( 44.4 ± 3.9 ) and at 24 months ( 44.2 ± 3.1 ) . In conclusion , a 2-year physical activity intervention increased daily energy expenditure , reduced body fat , and maintained peak oxygen uptake in healthy , middle-aged , sedentary subjects . The average Work Ability Index score at baseline was excellent and did not change during the 2-year physical activity interventions The aim of the study was to evaluate the impact of the state-wide dissemination of a physical activity ( PA ) intervention in Fl and ers . In 2011 , a r and om sample was taken of the entire adult ( 25 - 75 years ) population of Fl and ers . Data of the Flemish sample were compared with baseline data of the intervention and control group of ' 10 000 Steps Ghent ' ( 2005 ) . In total , data of the International Physical Activity Question naire were available of 2556 respondents ( 1675 of the comparison sample and 881 of the Flemish sample ) . Pedometer data were obtained by 269 respondents of the Flemish sample and by 1236 respondents of the comparison sample . Compared with the comparison sample of 2005 , the Flemish sample reported more walking ( P < 0.001 ) , moderate ( P < 0.001 ) , vigorous ( P < 0.001 ) , work-related ( P < 0.001 ) , leisure time ( P = 0.01 ) and household PA ( P = 0.03 ) . Step count analyses revealed that the Flemish sample took more pedometer-based daily step counts ( P < 0.001 ) than the comparison sample . Furthermore , a higher proportion of respondents reaching the 10 000 steps/day goal ( P = 0.005 ) was found in the Flemish sample . A positive effect of ' 10 000 Steps Fl and ers ' was found . Results indicate that a state-wide approach based on socio-ecological models is an effective strategy to promote PA in a large population This article describes how the Grading of Recommendations Assessment , Development and Evaluation ( GRADE ) approach to grading the quality of evidence and strength of recommendations considers the Bradford Hill criteria for causation and how GRADE may relate to questions in public health . A primary concern in public health is that evidence from non-r and omised studies may provide a more adequate or best available measure of a public health strategy 's impact , but that such evidence might be grade d as lower quality in the GRADE framework . GRADE , however , presents a framework that describes both criteria for assessing the quality of research evidence and the strength of recommendations that includes considerations arising from the Bradford Hill criteria . GRADE places emphasis on recommendations and in assessing quality of evidence ; GRADE notes that r and omisation is only one of many relevant factors . This article describes how causation may relate to developing recommendations and how the Bradford Hill criteria are considered in GRADE , using examples from the public health literature with a focus on immunisation |
14,056 | 23,728,686 | Research ers found no differences between the two groups in function and quality of life or pain .
Overall , evidence is insufficient to inform the selection of different methods of pedicle screw fixation or the combined use of fusion . | BACKGROUND Spine fractures are common .
The treatment of traumatic fractures of the thoracic and lumbar spine remains controversial but surgery involving pedicle screw fixation has become a popular option .
OBJECTIVES To assess the effects ( benefits and harms ) of pedicle screw fixation for traumatic fractures of the thoracic and lumbar spine . | Abstract . Short-segment posterior instrumentation for the treatment of thoracolumbar burst fractures has been reported with a high rate of failure . Transpedicular intracorporeal grafting in combination with short-segment instrumentation has been offered as an alternative to prevent failure . However , concern still remains about the potential complication of further canal narrowing or failure of remodeling with this technique . The purpose of this prospect i ve , r and omized , controlled study is to evaluate the effect of transpedicular intracorporeal grafting on spinal canal restoration and remodeling in a group of patients treated with short-segment instrumentation for thoracolumbar burst fractures . Twenty-one patients with thoracolumbar burst fractures were r and omised into transpedicular grafting ( TPG ) ( n=11 ) and non- transpedicular grafting ( NTPG ) ( n=10 ) groups , and were prospect ively followed for an average of 50 months ( range 25–85 months ) . Groups were similar in age , type of fracture , load sharing classification and kyphotic deformity . Preoperative , postoperative and follow-up computed tomographic ( CT ) images through the level of pedicles were obtained , corrected for differences in magnification , and digitized . Areas of the spinal canals were measured and normalized by the estimated area at that level ( average of adjacent levels ) . Average kyphosis was 19.7 ° ±6.2 ° at presentation , was corrected to 1.9 ° ±4.9 ° by operation , but was found to have deteriorated to 9.1 ° ±6.4 ° at final follow-up . There were no differences between groups regarding the evolution of sagittal deformity . Spinal canal narrowing was 38.5±18.2 % at presentation , 22.1±19.8 % postoperatively , and it further improved to –2.5±16.7 % at follow-up , similar for both groups . Our results demonstrate that transpedicular intracorporeal grafting in the treatment of burst fractures does not have a detectable effect on the rate of reconstruction of the canal area or on remodeling . Spinal canal remodeling was observed to occur in all patients regardless of grafting Short segment posterior fixation is the preferred method for stabilizing thoracolumbar fractures . In case of significant disruption of the anterior column , the simple short segment construct does not ensure adequate stability . In this study , we tried to evaluate the effect of inclusion of the fractured vertebra in short segment fixation of thoracolumbar fractures . In a prospect i ve r and omized study , eighty patients with thoracolumbar fractures treated just with posterior pedicular fixation were r and omized into two groups receiving either the one level above and one level below excluding the fracture level ( bridging group ) , or including the fracture level ( including group ) . Different clinical and radiological parameters were recorded and followed . A sum of 80 patients ( 42 patients in group 1 and 38 patients in group 2 ) were enrolled in the study . The patients in both the groups showed similar clinical outcome . There was a high rate of instrumentation failure in the “ bridging ” group . The “ bridging ” group showed a mean worsening ( 29 % ) in kyphosis , whereas the “ including ” group improved significantly by a mean of 6 % . The significant effect of the “ including ” technique on the reduction of kyphotic deformity was most prominent in type C fractures . In conclusion , inclusion of the fracture level into the construct offers a better kyphosis correction , in addition to fewer instrument failures , without additional complications , and with a comparable-if not better- clinical and functional outcome . We recommend insertion of screws into pedicles of the fractured thoracolumbar vertebra when considering a short segment posterior fixation , especially in Magerl type C fractures OBJECTIVE The treatment of thoracolumbar burst fracture is a controversial issue . Although spinal fusion has been a touchstone of spinal fixation , nonfusion technique have become raising its popularity recently . Some studies suggested that nonfusion had several advantages over fusion . The aim of this prospect i ve study was to compare long segment posterior instrumentation with fusion versus long-segment posterior instrumentation without fusion . METHODS For this purpose , 42 consecutive patients were assigned to two groups . Group 1 included 21 patients treated by long segment instrumentation with fusion ( WF ) , whereas Group 2 included 21 patients treated by long segment instrumentation without fusion ( WOF ) . Long segment instrumentation was hook fixation ( claw hooks attached to second upper vertebra and infralaminar hooks attached to first upper vertebra ) above and pedicle fixation ( pedicle screws attached to first and second lower vertebrae ) below the fractured vertebra . RESULTS Measurements of local kyphosis , sagittal index and anterior vertebral height compression showed that both group had similar outcome at final follow-up . Moreover , there was no difference between the two groups according to low back outcome score . Also , implant failure rate ( 4.7 % ) was quite low in both groups . However , WF group had prolonged operative time , increased blood loss and donor site morbidity . CONCLUSIONS Radiological and clinical parameters demonstrated that spinal fusion is not necessary in long segment posterior instrumentation for the management of thoracolumbar burst fractures Study Design . A prospect i ve , r and omized study comparing two treatment methods for thoracolumbar burst fractures : short-segment instrumentation with transpedicular grafting and the same procedure without transpedicular grafting . Objective . To evaluate the efficacy of transpedicular grafting in preventing failure of short-segment fixation for the treatment of thoracolumbar burst fractures . Summary of Background Data . Short-segment pedicle instrumentation for thoracolumbar burst fractures is known to fail early because of the absence of anterior support . Additional transpedicular grafting has been offered as an alternative to prevent this failure . However , there is controversy about the results of transpedicular grafting . Methods . Twenty patients with thoracolumbar burst fractures were included in the study . The inclusion criterion was the presence of fractures through the T11–L3 vertebrae without neurologic compromise . The patients were r and omized by a simple method into two groups . Group 1 patients were treated using short-segment instrumentation with transpedicular grafting ( TPG ) ( n = 10 ) , and Group 2 patients were treated by short-segment fixation alone ( NTPG ) ( n = 10 ) . Clinical ( Likert ’s question naire ) and radiologic ( sagittal index , percentage of anterior body height compression , and local kyphosis ) outcomes were analyzed . Results . The two groups were similar in age , follow-up period , and severity of the deformity and fracture . The postoperative and follow-up sagittal index , percentage of anterior body height compression , and average correction loss in local kyphosis in both groups were not significantly different . The failure rate , defined as an increase of 10 ° or more in local kyphosis and /or screw breakage , was also not significantly different ( TPG = 50 % , NTPG = 40 % , P = 0.99 ) . Conclusions . Short-segment transpedicular instrumentation of thoracolumbar burst fractures is associated with a high rate of failure that can not be decreased by additional transpedicular intracorporeal grafting Adequate reporting of r and omized , controlled trials ( RCTs ) is necessary to allow accurate critical appraisal of the validity and applicability of the results . The CONSORT ( Consoli date d St and ards of Reporting Trials ) Statement , a 22-item checklist and flow diagram , is intended to address this problem by improving the reporting of RCTs . However , some specific issues that apply to trials of nonpharmacologic treatments ( for example , surgery , technical interventions , devices , rehabilitation , psychotherapy , and behavioral intervention ) are not specifically addressed in the CONSORT Statement . Furthermore , considerable evidence suggests that the reporting of nonpharmacologic trials still needs improvement . Therefore , the CONSORT group developed an extension of the CONSORT Statement for trials assessing nonpharmacologic treatments . A consensus meeting of 33 experts was organized in Paris , France , in February 2006 , to develop an extension of the CONSORT Statement for trials of nonpharmacologic treatments . The participants extended 11 items from the CONSORT Statement , added 1 item , and developed a modified flow diagram . To allow adequate underst and ing and implementation of the CONSORT extension , the CONSORT group developed this elaboration and explanation document from a review of the literature to provide examples of adequate reporting . This extension , in conjunction with the main CONSORT Statement and other CONSORT extensions , should help to improve the reporting of RCTs performed in this field BACKGROUND The impact of fusion as a supplement to short-segment instrumentation for the treatment of thoracolumbar burst fractures is unclear . We conducted a controlled clinical trial to define the effect of fusion on lumbar spine and patient-related functional outcomes . METHODS From 2000 to 2002 , seventy-three consecutive patients with a single-level Denis type-B burst fracture involving the thoracolumbar spine and a load-sharing score of < or=6 were managed with posterior pedicle screw instrumentation . The patients were r and omly assigned to treatment with posterolateral fusion ( fusion group , n = 37 ) or without posterolateral fusion ( nonfusion group , n = 36 ) . The patients were followed for at least five years after surgery and were assessed with regard to clinical and radiographic outcomes . Clinical outcomes were evaluated with use of the Frankel scale , the motor score of the American Spinal Injury Association , a visual analog scale , and the Short Form-36 ( SF-36 ) question naire . Radiographic outcomes were assessed on the basis of the local kyphosis angle and loss of kyphosis correction . RESULTS No significant difference in radiographic or clinical outcomes was noted between the patients managed with the two techniques . Both operative time and blood loss were significantly less in the nonfusion group compared with the fusion group ( p < 0.05 ) . Twenty-five of the thirty-seven patients in the fusion group still had some degree of donor-site pain at the time of the latest examination . CONCLUSIONS Posterolateral bone-grafting is not necessary when a Denis type-B thoracolumbar burst fracture associated with a load-sharing score of < or=6 is treated with short-segment pedicle screw fixation Objective . To evaluate the effectiveness of 2 different types of Cotrel-Dubousset instrument systems in stabilising thoracolumbar and lumbar spine fractures . Methods . Between January 1989 and December 1993 , 45 fractures in 42 patients with unstable fracture or fracture dislocation of the thoracolumbar and lumbar spines were r and omly assigned to 2 surgical treatments with Cotrel-Dubousset instrumentation — using either a long segment ( Group 1 ) or a short segment ( Group 2)— and short posterolateral fusion . Results . Consolidation of the fractured vertebral body and posterolateral fusion were achieved at a mean time of 4.5 months ; fusion rates were 75 % in Group 1 and 83 % in Group 2 . The average collapses of anterior vertebral body height in Group 1 , in the immediate postoperative period and at the final follow-up , were 15 % and 17 % , respectively ; and in Group 2 , the figures were 16 % and 24 % , respectively . The correction of vertebral height and kyphosis at the last follow-up were lost more in Group 2 ( 5.7 ° ) than in Group 1 ( 4.4 ° ) . There were neurological recoveries in 6 of the 9 cases of incomplete paraplegics , including complete recovery in 5 , and one-Frankel grade increase in one . There were 15 instrument failures in 12 patients , including screw breakage in 3 Group 1 cases and 6 Group 2 cases . The plug dislodged in 3 Group 1 cases , and the hook dislodged in 3 Group 2 cases . In other words , instrument failures were more common in Group 2 . Conclusion . Cotrel-Dubousset stabilisation of the fractured spine achieves fracture consolidation , but does not maintain the restored height and sagittal curve completely until fusion . The long rod and short fusion construct was more effective for all fracture types than was the short rod and fusion construct , although it leads to wider immobilisation of normal segments BACKGROUND To our knowledge , a prospect i ve , r and omized study comparing operative and nonoperative treatment of a thoracolumbar burst fracture in patients without a neurological deficit has never been performed . Our hypothesis was that operative treatment would lead to superior long-term clinical outcomes . METHODS From 1994 to 1998 , forty-seven consecutive patients ( thirty-two men and fifteen women ) with a stable thoracolumbar burst fracture and no neurological deficit were r and omized to one of two treatment groups : operative ( posterior or anterior arthrodesis and instrumentation ) or nonoperative treatment ( application of a body cast or orthosis ) . Radiographs and computed tomography scans were analyzed for sagittal alignment and canal compromise . All patients completed a question naire to assess any disability they may have had before the injury , and they indicated the degree of pain at the time of presentation with use of a visual analog scale . The average duration of follow-up was forty-four months ( minimum , twenty-four months ) . After treatment , patients indicated the degree of pain with use of the visual analog scale and they completed the Rol and and Morris disability question naire , the Oswestry back-pain question naire , and the Short Form-36 ( SF-36 ) health survey . RESULTS In the operative group ( twenty-four patients ) , the average fracture kyphosis was 10.1 degrees at the time of admission and 13 degrees at the final follow-up evaluation . The average canal compromise was 39 % on admission , and it improved to 22 % at the final follow-up examination . In the nonoperative group ( twenty-three patients ) , the average kyphosis was 11.3 degrees at the time of admission and 13.8 degrees at the final follow-up examination after treatment . The average canal compromise was 34 % at the time of admission and improved to 19 % at the final follow-up examination . On the basis of the numbers available , no significant difference was found between the two groups with respect to return to work . The average pain scores at the time of the latest follow-up were similar for both groups . The preinjury scores were similar for both groups ; however , at the time of the final follow-up , those who were treated nonoperatively reported less disability . Final scores on the SF-36 and Oswestry question naires were similar for the two groups , although certain trends favored those treated without surgery . Complications were more frequent in the operative group . CONCLUSION We found that operative treatment of patients with a stable thoracolumbar burst fracture and normal findings on the neurological examination provided no major long-term advantage compared with nonoperative treatment Study Design . A prospect i ve clinical trial was conducted . Objectives . To compare the results of fusion versus nonfusion for surgically treated burst fractures of the thoracolumbar and lumbar spine . Summary of Background Data . The operative results of surgically treated burst fractures with short segmental fixation have been well documented . There is no report comparing the results of fusion and nonfusion . Methods . Fifty-eight patients were included in this study , with the inclusion criteria as follows : neurologically intact spine with a kyphotic angle ≥20 ° , decreased vertebral body height ≥50 % or a canal compromise ≥50 % , incomplete neurologic deficit with a canal compromise < 50 % , complete neurologic deficit , and multilevel spinal injury or multiple traumas . All patients were r and omly assigned to fusion or nonfusion groups , and operative treatment with posterior reduction and instrumentation was carried out . Posterior fusion with autogenous bone graft was performed for the fusion group ( n = 30 ) , and no fusion procedure was done for the nonfusion group ( n = 28 ) . The average follow-up period was 41 months ( range , 24–71 months ) . Results . The average loss of kyphotic angle was not statistically significant between these 2 groups . The radiographic parameters were statistically significantly better in the nonfusion group , including angular change in the flexion-extension lateral view ( 4.8 ° vs. 1.0 ° ) , lost correction of decreased vertebral body height ( 3.6 % vs. 8.3 % ) , intraoperative estimated blood loss ( 303 mL vs. 572 mL ) , and operative time ( 162 minutes vs. 224 minutes ) . The scores on the low back outcome scale were not statistically significant for these 2 groups . Conclusions . The short-term results of short segmental fixation without fusion for surgically treated burst fractures of the thoracolumbar spine were satisfactory . The advantages of instrumentation without fusion are the elimination of donor site complications , saving more motion segments , and reducing blood loss and operative time Study Design . A prospect i ve clinical trial was conducted . Objective . To compare the clinical and radiologic late results of monosegmental transpedicular fixation versus short-segment pedicle instrumentation ( SSPI ) in management of thoracolumbar burst fractures and evaluate the efficacy of monosegmental transpedicular fixation . Summary of Background Data . SSPI ( 1 level above and 1 below the fracture level ) are accepted by many surgeons as an accepted technique for the treatment of thoracolumbar burst fractures . To preserve more motion segments , some authors have advocated monosegmental pedicle instrumentation ( MSPI ) . The recent developments showed that MSPI yielded good clinical results ; however , there were no report about comparison of clinical outcome between monosegmental and biosegmental transpedicular fixation in management of thoracolumbar burst fractures . Methods . Eighty-five patients with thoracolumbar burst fractures fulfilling the inclusion criteria were included in the study . The patients were r and omized by a simple method into 2 groups . Group 1 were treated with monosegmental transpedicular fixation ( n = 47 ) , and group 2 were treated with biosegmental transpedicular fixation ( n = 38 ) . Clinical ( Low Back Outcome Score and Oswestry Disability Index ) and radiologic ( load-sharing classification index , sagittal index , and percentage of anterior body height compression ) outcomes were analyzed . Results . The 2 groups were similar in age , follow-up period , and severity of the deformity and fracture . The postoperative and follow-up sagittal index , local kyphosis , percentage of anterior body height compression , and average correction loss in local kyphosis in both groups were not significantly different . The failure rate between the 2 surgical approaches was also not significantly different ( group 1 = 6.38 % and group 2 = 5.26 % ) . Oswestry Disability Index improved in both groups by > 25 points in a similar amount ( P = 0.23 ) . The average follow-up Low Back Outcome Score was 74.9 and 60.2 for group 1 and group 2 , respectively ( P = 0.033 ) . Conclusion . In conclusion , radiologic parameters demonstrated that both MSPI and SSPI are the effective and reliable operative techniques for selected thoracolumbar burst fractures . MSPI shortened the operative time and decreased the amount of blood loss significantly and , thus , offered better clinical results . Nevertheless , long-term studies are supposed to be performed to support the outcomes Study Design . Retrospective data analysis . Objectives . To determine spinal injury patterns and clinical outcomes in patients involved in automotive accidents . Summary of Background Data . The records of 22,858 patients collected prospect ively as part of the Trauma Audit Research Network ( UK ) Data base ( 1993–2000 ) . Methods . Analysis of the records of 1121 motorcyclists and 2718 car occupants involved in automotive trauma . Results . Spinal injury occurred in 126 ( 11.2 % ) motorcyclists and 383 ( 14.1 % ) car occupants . Victims were predominantly young ( mean ages : motorcycle 30.2 years , car 37.8 years ) and male ( motorcycle 88.9 % , car 60.6 % ) . The mean Injury Severity Scores were 18.8 and 15.1 , respectively . Isolated spinal injuries occurred in 30 ( 23.8 % ) motorcyclists and 130 ( 33.9 % ) car occupants . The thoracic spine was most commonly injured in motorcyclists ( 54.8 % ) , and the cervical spine was most commonly injured in car occupants ( 50.7 % ) . Multiple regions were injured in 14 ( 10.3 % ) motorcyclists and 33 ( 8.5 % ) car occupants . Nine motorcyclists and 43 car occupants required spinal surgery . Median hospital stays were 11.5 days ( range 0–235 days ) and 10 days ( range 0–252 days ) in the motorcyclists and car occupants , respectively . There were 13 ( 10.3 % ) motorcycle- and 26 ( 6.8 % ) car-related deaths . Conclusion . Spinal injury patterns may reflect differing mechanisms of injury between the restrained car occupant and unrestrained motorcyclist . The motorcyclists were more severely injured , had more extremity trauma , a higher mortality rate , and a spinal injury pattern consistent with forced hyperflexion of the thoracic spine . The predominance of cervical injuries and higher incidence of neck and facial injuries in car occupants may reflect abdominothoracic seat belt restraint . The high frequency of multilevel injuries reaffirms the need for vigilance in patient assessment Study Design A prospect i ve cohort study on selected consecutive patients . Objective To evaluate the efficacy of an innovative operative technique called monosegmental transpedicular fixation for the treatment of some thoracolumbar burst fractures . Summary of Background Data Short-segment pedicle screw instrumentation is accepted by many spinal surgeons as an acceptable technique for the treatment of thoracolumbar burst fractures . Preoperative evaluation using the spinal load-sharing makes this technique more reliable . To preserve more motion segments , some authors have advocated using monosegmental pedicle screw instrumentation ( MSPI ) to treat thoracolumbar fractures . However , up until now this kind of maneuver is only performed in cases of flexion distraction injuries . Methods A cohort of 20 patients with thoracolumbar burst fractures fulfilling the inclusion criteria were prospect ively su bmi tted to surgical treatment of monosegmental transpedicular fixation plus posterior fusion . All instrumentations were performed with pedicle screws inserted bilaterally into the fractured level and 1 adjacent level , either superior or inferior depending on the locating side of the intact endplate . All patients were followed up . The preoperative radiographs , the postoperative radiographs within 1 week of operation , and the radiographs of the most recent follow-up were evaluated for kyphosis correction recorded in the Sagittal Index and Load-Sharing Classification ( LSC ) index . The postoperative functional outcomes were evaluated using the Frankel Performance Scale together with the Denis Pain Scale . Results Eighteen patients were followed up successfully with an average final follow-up of 24.7±8.0 months . The focal kyphotic angulations were corrected satisfactorily with the mean Sagittal Index of preoperative 16.5±6.6 degrees , initial postoperative 4.0±2.4 degrees , and latest follow-up 4.8±4.0 degrees . No obvious loss of correction occurred except for 2 patients who both scored 8 points on the LSC Score . Postoperatively , most patients attained both functional neurologic improvement and pain relief , and only a few complications were noted . Conclusions For selected thoracolumbar burst fractures , MSPI can provide the same or better fixation and preserve more motion segments than other methods of posterior pedicle instrumentation . With preoperative evaluation using the spinal LSC system , MSPI is effective and reliable for the treatment of thoracolumbar burst fractures when properly indicated Objective : A prospect i ve r and omized study was conducted to determine whether there exist any differences in radiographic , clinical , or functional outcomes when individuals with stable burst fractures of the thoracolumbar junction without neurologic deficit are treated with either a posterior fusion with instrumentation or anterior reconstruction , fusion , and instrumentation . There exists relatively little literature evaluating the outcomes of individuals treated with anterior surgery , and no prospect i ve r and omized studies exist comparing the two treatment approaches . Methods : From May 1995 to March 2001 , a consecutive series of subjects with acute isolated burst fractures of the thoracolumbar junction ( T10-L2 ) without neurologic deficit were r and omized to receive either an anterior fusion with instrumentation or a posterior fusion with instrumentation . Radiographs including computed tomography ( CT ) were obtained . Radiographs were repeated at 2 , 4 , 6 , 12 , and 24 months . The CT scan was also repeated at 24 months . Hospital stay , cost , operating time , blood loss , complications , and patient-related functional outcomes were measured . Results : Of 43 enrolled , 38 completed a minimum of 2-year follow-up ( average : 43 months ; range : 24 - 108 months ) . Eighteen received a posterior spine fusion and 20 an anterior approach . Hospital stay and operating time were similar . Blood loss was higher in the group treated anteriorly ; however , the incidence of transfusion was the same . There were 17 “ complications ” including instrumentation removal for pain in 18 patients treated posteriorly , but only 3 minor complications in 3 patients treated anteriorly . Patient-related functional outcomes were similar for the two groups . Conclusions : Although patient outcomes are similar , anterior fusion and instrumentation for thoracolumbar burst fractures may present fewer complications or additional surgeries Study Design . Prospect i ve r and omized study . Objectives . To compare the results of the combined anterior-posterior surgery ( Group A ) with posterior “ short-segment ” transpedicular fixation ( SSTF ) ( Group B ) in mid-lumbar burst fractures . Summary of Background Data . There are no comparative r and omized clinical studies on the outcome following operative treatment of mid-lumbar fractures . Methods . Forty consecutive patients with L2–L4 fresh single A3-type/AO burst fractures and load sharing score up to 6 were r and omly selected to underwent either combined one-stage anterior stabilization with mesh cage and SSTF ( Group A ) or solely SSTF with intermediate screws in the fractured vertebra ( Group B ) . Kyphotic Gardner angle , anterior and posterior vertebral body height ( PVBHr , AVBHr ) , spinal canal encroachment ( SCE ) , SF-36 , VAS , and Frankel classification were used . Results . The follow-up observation averaged 46 and 48 months for Group A and B , respectively . Operative time , blood loss , and hospital stay were significant more in Group A. More surgical complications were observed in the Group A. After surgery , VAS was reduced to 4.3 and 3.6 for Group A and Group B , respectively . The SF-36 domains Role physical and Bodily pain improved significantly only in Group B ( P = 0.05 ) and ( P = 0.06 ) , respectively . Correction of AVBHr , PVBHr , and spinal canal clearance was similar in both groups . Spinal canal clearance did not differ between the two groups , but it was continuous until the last evaluation in Group B. The final Gardner angle loss of correction averaged 2 ° and 5 ° for Group A and Group B , respectively . The posttraumatic Gardner deformity did not significantly improve by SSTF at the final evaluation in the spines of Group B. Gardner angle correlated significantly with SCE in Group B and Group A in all three periods and in the last evaluation , respectively . Frankel grade did not correlate with loss of correction of AVBHr and PVBHr in Group A , while it significantly correlated with loss of PVBHr correction and SCE in the patients of Group B. There was no neurologic deterioration after surgery in any patient . VAS and SF-36 scores did not significantly correlate with the loss of kyphotic angle correction and AVBHr , PVBHr at the final observation in any patient of both groups . Conclusions . SSTF offered similar significant short-term correction of posttraumatic deformities associated with mid-lumbar A3-burst fractures , but better clinical results as compared to combined surgery . However , SSTF did not significantly maintain the after surgery achieved correction of local posttraumatic kyphosis at the final evaluation . Thus , SSTF is not recommended for operative stabilization of fractures with this severity The Low-Back Outcome Score has been devised as a new and accurate rating system for patients with low-back pain . Thirteen factors , such as pain , employment , sporting ability , rest required , and activities of daily living , were included ; subjective opinion was excluded . Pain and active pursuits were weighted . Presentation of the score as a question naire , excluding examination findings , eliminated both interobserver variation and observer variation with time . The score was applied retrospectively in a follow-up study of conservatively treated patients and was found to be more comprehensive and more discriminating than the Oswestry Disability Score , the Waddell Disability Rating , or the Waddell Physical impairment Rating . The Low-Back Outcome Score is recommended for further evaluation in future prospect i ve studies in low-back pain Objective : The treatment of thoracolumbar burst fracture is a controversial issue . Short-segment ( SS ) pedicle fixation has become a popular treatment option . However , there are several studies regarding the high rate of failure . The aim of this prospect i ve study was to compare SS versus long-segment ( LS ) instrumentation . Methods : For this purpose , 18 consecutive patients were assigned to two groups . Group 1 included nine patients treated by SS pedicle fixation , whereas group 2 included nine patients treated by LS instrumentation . SS instrumentation was pedicle fixation one level above and below the fractured vertebra . LS instrumentation was hook fixation ( claw hooks attached to second upper vertebra and infralaminar hooks attached to first upper vertebra ) above and pedicle fixation ( pedicle screws attached to first and second lower vertebrae ) below the fractured vertebra . Results : As a result , measurements of local kyphosis , sagittal index , and anterior vertebral height compression showed that the LS group had a better outcome at final follow-up ( P < 0.05 ) . Also , the SS group had a 55 % failure rate , whereas the LS group had prolonged operative time and increased blood loss . However , there was no difference between the two groups according to Low Back Outcome Score . Conclusions : In conclusion , radiographic parameters demonstrated that LS instrumentation is a more effective management of thoracolumbar burst fractures . Nevertheless , clinical outcome was the same between the two groups . However , our conclusions were based on posterior-only surgery . Anterior column support would negate the need for LS fixation . Also , SS would have been more successful if two above and two below pedicle screws were used Study Design . A prospect i ve clinical trial was conducted . Objective . To compare the results of nonoperative treatment versus short-segment posterior fixation using pedicle screws . Summary of Background Data . A previous study showed that nonoperative treatment with early mobilization produced good results , even when the posterior column was involved . Methods . This study involved 80 patients . Inclusion criteria required the following : neurologically intact patient , single-level closed burst fracture involving T11–L2 , no fracture dislocations or pedicle fractures , age of 18 to 65 years ( nonpathologic adult ) , and no other major organ system or musculoskeletal injuries . Patients in the nonoperative group ( n = 47 ) were allowed activity to the point of pain tolerance beginning on the day of injury using a hyperextension brace . Patients in the operative group ( n = 33 ) underwent three-level , ( one above , one at fracture level , and one below ) fixation using VSP or TSRH instrumentation . The follow-up period was 2 years . Results . The surgical group had less pain up to 3 months and a better Greenough Low Back Outcome Score up to 6 months , but the outcome was similar afterward . No neurologic deficit in any patient . In the nonoperative group , the kyphosis angle worsened by 4 ° , and the retropulsion decreased from 34 % to 15 % . In the operative group , there was one case of superficial infection and two cases of broken screws . The kyphosis angle was improved initially by 17 ° , but this was gradually lost . Hospital charges were four times higher in the operative group . Conclusions . Short-segment posterior fixation provides partial kyphosis correction and earlier pain relief , but the functional outcome at 2 years is similar . Early activity to the point of pain tolerance can be safely allowed Study Design In this prospect i ve r and omized study , the results of treating unstable thoracolumbar burst fractures by pedicle instrumentation with and without fracture level screw combination were given . Objective Our aim was to evaluate the efficacy of fracture level screw combination in achieving and maintaining correction in the treatment of unstable thoracolumbar burst fractures . Summary of Background Data Most authors reported that intraoperative correction of sagittal deformity is important for the maintenance of fracture reduction and is one of the most consistent predictor of satisfactory functional outcome . Methods Seventy-two patients with unstable thoracolumbar burst fractures were r and omized into 4 groups with equal number of patients . In group 1 , patients were treated by segmental posterior instrumentation with 2 levels above and 2 levels below the fracture level fixation , in group 2 they were treated as in group 1 with fracture level screw incorporation . In group 3 , patients were treated by short-segment posterior instrumentation with 1 level above and 1 level below , in group 4 they were treated by short-segment posterior instrumentation with fracture level screw incorporation . Clinical and radiologic parameters were evaluated before surgery , after surgery , and at follow-up . Results The average follow-up was 50 months . Fracture level screw combination provided better intraoperative correction and maintenance in the treatment of unstable thoracolumbar burst fractures , which was more prevalent in short-segment fixation group . Conclusions Reinforcement with fracture level screw combination can help to provide better kyphosis correction and offers immediate spinal stability in patients with thoracolumbar burst fracture A prospect i ve study was performed over a 1-year period in patients who had sustained blunt trauma , mostly in motor vehicle accidents . All 73 patients ( 56 male and 17 female ; age range , 2 - 94 years ; mean age , 35.2 years ) in the study had undergone intubation and ventilation at the trauma site ( mean Glasgow Coma Score , 9.9 [ range , 3 - 15 ] ; mean Injury Severity Score , 30.4 [ range , 8 - 75 ] ) and subsequently underwent three-view radiography of the cervical spine and thin-section spiral computed tomography ( CT ) of the cervicothoracic junction . Spinal fractures were detected in 20 patients and involved the cervicothoracic junction region in 12 cases . In all 12 patients , the fractures were visualized at CT , whereas in seven of 12 patients , conventional radiography failed to demonstrate injuries ( transverse process fracture of T1 [ n = 1 ] , pedicle and vertebral body fracture of C7 [ n = 1 ] , fractures of the first and second ribs [ n = 5 ] ) . Thus , routine CT of the cervicothoracic junction in a highly select group of severely injured patients helped detect occult fracture in seven of 73 patients ( 10 % ) ; however , most of these fractures were not clinical ly significant . Larger studies involving a high-risk patient population are needed to confirm these findings Objective : Significant controversy exists regarding the optimal management of thoracolumbar injuries . This is in part due to the lack of underst and ing of the natural history of various injury subtypes and the absence of a universally accepted classification scheme that facilitates communication among care providers and assists in directing treatment . The Spine Trauma Study Group has developed an injury severity score based on three major variables : the mechanism of injury determined by radiographic appearance , the integrity of the posterior ligamentous complex , and the neurologic status of the patient . By systematic ally assigning specific point values within each category based on the severity of injury , a final severity score may be generated that can be used to help direct treatment . The goal of this work is to present a proposal of a detailed treatment algorithm to assist in the nonoperative or operative management of thoracolumbar injuries . Methods : A detailed review of the world 's spinal literature was performed to ascertain predictors of instability following thoracolumbar trauma . With use of known biomechanical and clinical outcome measures , an arbitrary assignment of point values to various injury descriptors was performed . The assessment of the validity of the severity score was compared retrospectively with a variety of selected cases representing the typical injury patterns under the three major injury groups : compression , translational/rotational , and distraction injuries . Conclusions : The proposed treatment algorithm is an attempt to assist physicians using best- evidence medicine in managing thoracolumbar spinal injuries . The final point flow chart with graduated treatment recommendations is only preliminary and needs to be vali date d through prospect i ve cohort analysis . In addition , the importance of the chosen variables determining spinal stability must also be verified |
14,057 | 23,945,022 | There is strong evidence that orally administered immunotherapy can induce immunomodulatory changes and thereby promote desensitisation to a range of foods . | The aim of using oral and sublingual immunotherapy with food allergies is to enable the safe consumption of foods containing these allergens in patients with food allergies . | BACKGROUND Food allergy may be life-threatening , and patients affected need to receive accurate diagnoses and treatment . Hazelnut has often been implicated as responsible for allergic reactions , and trace quantities can induce systemic reactions . OBJECTIVE The aim of this study was to evaluate the efficacy and tolerance of sublingual immunotherapy with a st and ardized hazelnut extract in patients allergic to hazelnut . METHODS This was a r and omized , double-blind , placebo-controlled study . Inclusion criteria were a history of hazelnut allergy and positive skin prick test and double-blind placebo-controlled food challenge results . Patients were then r and omly assigned into 2 treatment groups ( hazelnut immunotherapy or placebo ) . Efficacy was assessed by double-blind , placebo-controlled food challenge after 8 to 12 weeks of treatment . Blood sample s were drawn for measurement of specific IgE , IgG(4 ) , and serum cytokines before and after treatment . RESULTS Twenty-three patients were enrolled and divided into 2 treatment groups . Twenty-two patients reached the planned maximum dose at 4 days . Systemic reactions were observed in only 0.2 % of the total doses administered . Mean hazelnut quantity provoking objective symptoms increased from 2.29 g to 11.56 g ( P = .02 ; active group ) versus 3.49 g to 4.14 g ( placebo ; NS ) . Moreover , almost 50 % of patients who underwent active treatment reached the highest dose ( 20 g ) , but only 9 % in the placebo . Laboratory data showed an increase in IgG(4 ) and IL-10 levels after immunotherapy in only the active group . CONCLUSION Our data confirm significant increases in tolerance to hazelnut after sublingual immunotherapy as assessed by double-blind , placebo-controlled food challenge , and good tolerance to this treatment BACKGROUND There are presently no available therapeutic options for patients with peanut allergy . OBJECTIVE We sought to investigate the safety , efficacy , and immunologic effects of peanut sublingual immunotherapy ( SLIT ) . METHODS After a baseline oral food challenge ( OFC ) of up to 2 g of peanut powder ( approximately 50 % protein ; median successfully consumed dose [ SCD ] , 46 mg ) , 40 subjects , aged 12 to 37 years ( median , 15 years ) , were r and omized 1:1 across 5 sites to daily peanut or placebo SLIT . A 5-g OFC was performed after 44 weeks , followed by unblinding ; placebo-treated subjects then crossed over to higher dose peanut SLIT , followed by a subsequent crossover Week 44 5-g OFC . Week 44 OFCs from both groups were compared with baseline OFCs ; subjects successfully consuming 5 g or at least 10-fold more peanut powder than the baseline OFC threshold were considered responders . RESULTS After 44 weeks of SLIT , 14 ( 70 % ) of 20 subjects receiving peanut SLIT were responders compared with 3 ( 15 % ) of 20 subjects receiving placebo ( P < .001 ) . In peanut SLIT responders , median SCD increased from 3.5 to 496 mg . After 68 weeks of SLIT , median SCD significantly increased to 996 mg ( compared with Week 44 , P = .05 ) . The median SCD at the Week 44 Crossover OFC was significantly higher than baseline ( 603 vs 71 mg , P = .02 ) . Seven ( 44 % ) of 16 crossover subjects were responders ; median SCD increased from 21 to 496 mg among responders . Of 10,855 peanut doses through the Week 44 OFCs , 63.1 % were symptom free ; excluding oral-pharyngeal symptoms , 95.2 % were symptom free . CONCLUSIONS Peanut SLIT safely induced a modest level of desensitization in a majority of subjects compared with placebo . Longer duration of therapy showed statistically significant increases in the SCD BACKGROUND Cow 's milk allergy ( CMA ) in children is a important problem in medical practice . Oral desensitization has been proposed as a therapeutic approach , but current protocol s are time-consuming and impractical . OBJECTIVES To establish a patient-friendly desensitization regimen with weekly up-dosing and to evaluate it in a r and omized controlled trial . METHODS Thirty children with IgE-mediated CMA confirmed by double-blind placebo-controlled food challenge were equally r and omized to desensitization with CM or soy milk as control . The weekly up-dosing lasted 18 weeks . The occurrence and severity of reactions after each dose was evaluated , and the desensitization was stopped if severe reactions occurred . Specific IgE and IgG4 levels to CM were measured at baseline , after 8 weeks , and at the end of the study . The double-blind food challenge was repeated once the desensitization was completed or after premature discontinuation . RESULTS Two active and 1 control patient dropped out . Full tolerance to CM ( 200 mL ) was achieved in 10 active patients and partial tolerance in 1 . Two active patients discontinued the desensitization after experiencing severe reactions , whereas no reactions occurred in controls , whose sensitivity to CM remained unchanged . A significant increase in specific IgG4 levels was found only in the active group . CONCLUSIONS This weekly up-dosing desensitization protocol for CMA performed under medical supervision was effective and reasonably safe and induced consistent immunologic changes BACKGROUND Open-label oral immunotherapy ( OIT ) protocol s have been used to treat small numbers of patients with peanut allergy . Peanut OIT has not been evaluated in double-blind , placebo-controlled trials . OBJECTIVE To investigate the safety and effectiveness of OIT for peanut allergy in a double-blind , placebo-controlled study . METHODS In this multicenter study , children ages 1 to 16 years with peanut allergy received OIT with peanut flour or placebo . Initial escalation , build-up , and maintenance phases were followed by an oral food challenge ( OFC ) at approximately 1 year . Titrated skin prick tests ( SPTs ) and laboratory studies were performed at regular intervals . RESULTS Twenty-eight subjects were enrolled in the study . Three peanut OIT subjects withdrew early in the study because of allergic side effects . During the double-blind , placebo-controlled food challenge , all remaining peanut OIT subjects ( n = 16 ) ingested the maximum cumulative dose of 5000 mg ( approximately 20 peanuts ) , whereas placebo subjects ( n = 9 ) ingested a median cumulative dose of 280 mg ( range , 0 - 1900 mg ; P < .001 ) . In contrast with the placebo group , the peanut OIT group showed reductions in SPT size ( P < .001 ) , IL-5 ( P = .01 ) , and IL-13 ( P = .02 ) and increases in peanut-specific IgG(4 ) ( P < .001 ) . Peanut OIT subjects had initial increases in peanut-specific IgE ( P < .01 ) but did not show significant change from baseline by the time of OFC . The ratio of forkhead box protein 3 (FoxP3)(hi ) : FoxP3(intermediate ) CD4 + CD25 + T cells increased at the time of OFC ( P = .04 ) in peanut OIT subjects . CONCLUSION These results conclusively demonstrate that peanut OIT induces desensitization and concurrent immune modulation . The current study continues and is evaluating the hypothesis that peanut OIT causes long-term immune tolerance BACKGROUND There are no treatments currently available for peanut allergy . Sublingual immunotherapy ( SLIT ) is a novel approach to the treatment of peanut allergy . OBJECTIVE We sought to investigate the safety , clinical effectiveness , and immunologic changes with SLIT in children with peanut allergy . METHODS In this double-blind , placebo-controlled study subjects underwent 6 months of dose escalation and 6 months of maintenance dosing followed by a double-blind , placebo-controlled food challenge . RESULTS Eighteen children aged 1 to 11 years completed 12 months of dosing and the food challenge . Dosing side effects were primarily oropharyngeal and uncommonly required treatment . During the double-blind , placebo-controlled food challenge , the treatment group safely ingested 20 times more peanut protein than the placebo group ( median , 1,710 vs 85 mg ; P = .011 ) . Mechanistic studies demonstrated a decrease in skin prick test wheal size ( P = .020 ) and decreased basophil responsiveness after stimulation with 10(-2 ) μg/mL ( P = .009 ) and 10(-3 ) μg/mL ( P = .009 ) of peanut . Peanut-specific IgE levels increased over the initial 4 months ( P = .002 ) and then steadily decreased over the remaining 8 months ( P = .003 ) , whereas peanut-specific IgG4 levels increased during the 12 months ( P = .014 ) . Lastly , IL-5 levels decreased after 12 months ( P = .015 ) . No statistically significant changes were found in IL-13 levels , the percentage of regulatory T cells , or IL-10 and IFN-γ production . CONCLUSION Peanut SLIT is able to safely induce clinical desensitization in children with peanut allergy , with evidence of immunologic changes suggesting a significant change in the allergic response . Further study is required to determine whether continued peanut SLIT is able to induce long-term immune tolerance Background : Peanut allergy is common , potentially severe and rarely resolves causing impaired quality of life . No disease‐modifying treatment exists and there is therefore a need to develop a therapeutic intervention The possibility of obtaining oral desensitization in patients with food allergy is still a matter of debate . We decided to evaluate the safety and efficacy of st and ardized protocol s for oral desensitization with the most common food allergens . Forty-two children ( ages up to 16 years ) diagnosed as affected by food allergy ( on the basis of clinical history , skin prick tests , measurement of specific IgE , and double-blind , placebo-controlled food challenge ) underwent a sublingual-oral desensitizing treatment according to new st and ardized protocol s. The control group consisted of 10 patients who followed an elimination diet . The treatment was successfully completed by 85.7 % of the patients . Specific IgE showed a significant decrease , while specific IgG4 showed a significant increase , in all treated patients . The immunological modifications observed in our patients lead us to hypothesize that oral tolerance may be mediated by the same mechanisms as those involved in traditional desensitizing treatments for respiratory and insect sting allergy Background : The possibility of inducing oral desensitization in patients with food allergy is still controversial and no st and ardized programmes are yet available IgE-mediated cow 's milk allergy ( CMA ) is a heavy burden for patients , particularly for children and their families . Allergen avoidance represents the only therapeutic option , but oral desensitization protocol s have been suggested . Because of the long duration and complexity of these protocol s we examined the feasibility of an oral tolerance induction protocol using a weekly up-dosing schedule . Children with IgE-mediated food allergy to milk , confirmed by a double-blind placebo-controlled food challenge , were recruited . Six of them were r and omized to double-blind desensitization with milk or soy formula as placebo . Seven patients underwent the protocol in open fashion . The desensitization schedule started with one drop of whole CM diluted 1:25 every week . The dose was doubled weekly until the 18th week to achieve an intake of 200 mL in approximately 4 months . Of the 13 children enrolled , 10 children received CM and 3 control children received soy formula . Full tolerance ( 200 mL of milk ) was achieved in 7 children ; in 2 children this therapeutic approach failed , because severe reactions occurred during the procedure . One patient achieved a partial tolerance ( 64 mL of milk ) . The three control children receiving placebo still showed a positive food challenge at the end of the study . A weekly up-dosing oral tolerance induction could be a viable alternative to traditional protocol s for children with IgE-mediated CMA BACKGROUND Food allergy is treated by avoidance diets in order to prevent anaphylactic reactions and to cure chronic associated symptoms . However , the natural history is left unchanged . OBJECTIVE To search for a beneficial effect of an oral desensitization protocol to allergenic foods in IgE-dependent milk or egg allergies in children . METHODS 60 children with documented cow 's milk allergy ( 13 months-6.5 years ) , and 90 children with egg allergy ( 12 months-8 years ) , were consecutively included after 6 - 12 months of avoidance diet , if a SBPCFC to 60 ml milk ( 60 ml ) or to 965 mg of raw egg white was negative . They were r and omized for uninterrupted avoidance or oral desensitization ( group A or OD ) . Six months later , a new SBPCFC was performed with , up to 200 ml of milk or 7 g of raw egg white . Prick tests and specific IgE levels were carried out simultaneously . RESULTS Data were obtained for 57 children with CMA ( 30 A and 27 OD ) , and 84 children with EA ( 35 A and 49 OD ) . The two groups ( AD or OD group ) were similar with regard to means of ages , the size of PT wheals and the level of IgEs at baseline . MILK ALLERGY : A SBPCFC to milk was positive in 11.1 % of those following OD vs. 40 % after A ( p < .025 ) . The size of PT decreased after OD and increased after A ( -3.4 mm vs. + 0.84 mm ; p < .002 ) . EGG ALLERGY : The SBPCFC to egg was positive in 30.6 % after OD vs. 48.6 % after A ( p < .1 ) . After 6 months , in the OD group , the mean size of the PT and the level of specific IgE were significantly reduced compared to the A group . In the A group , the threshold of reactivity was often lower , or more serious symptoms were observed . CONCLUSION Oral desensitization helps the egg and milk allergic children to overcome their allergies . Since the avoidance of these foods is likely to increase sensitization as well as to lower the threshold of reactivity , an active treatment is required . Further attempts to st and ardize the procedures of oral desensitization are expected BACKGROUND / AIMS Food allergy in children is still an unresolved problem that merits investigation , particularly when the food is fundamental for the child 's growth . Reports in the literature that deal with the possibility of a desensitizing treatment are sporadic and often inconsistent , and no st and ardized protocol s are yet available . In this paper we propose a st and ardized oral desensitization program for food allergy in children . METHODOLOGY The treatment was carried out in 14 cases with allergy to food ( milk in 6 cases , egg in 5 , fish in 2 and apple in 1 case ) . The control group consisted of 10 age and sex matched allergic subjects ( 5 to milk , 4 to egg and 1 to fish ) , who underwent a strict elimination diet regimen . RESULTS Compliance to treatment was satisfactory , since 12 out of the 14 treated cases ( 85.7 % ) completed the program . Treatment was successful in 100 % of the cases that completed the program : all the treated patients are now able to tolerate any food with no untoward effects or need for preventive drugs . CONCLUSIONS The proposed st and ardized oral desensitization treatment may represent a safe and convenient alternative in the management of food-allergic subjects BACKGROUND Orally administered , food-specific immunotherapy appears effective in desensitizing and potentially permanently tolerizing allergic individuals . OBJECTIVE We sought to determine whether milk oral immunotherapy ( OIT ) is safe and efficacious in desensitizing children with cow 's milk allergy . METHODS Twenty children were r and omized to milk or placebo OIT ( 2:1 ratio ) . Dosing included 3 phases : the build-up day ( initial dose , 0.4 mg of milk protein ; final dose , 50 mg ) , daily doses with 8 weekly in-office dose increases to a maximum of 500 mg , and continued daily maintenance doses for 3 to 4 months . Double-blind , placebo-controlled food challenges ; end-point titration skin prick tests ; and milk protein serologic studies were performed before and after OIT . RESULTS Nineteen patients , 6 to 17 years of age , completed treatment : 12 in the active group and 7 in the placebo group . One dropped out because of persistent eczema during dose escalation . Baseline median milk IgE levels in the active ( n = 13 ) versus placebo ( n = 7 ) groups were 34.8 kUa/L ( range , 4.86 - 314 kUa/L ) versus 14.6 kUa/L ( range , 0.93 - 133.4 kUa/L ) . The median milk threshold dose in both groups was 40 mg at the baseline challenge . After OIT , the median cumulative dose inducing a reaction in the active treatment group was 5140 mg ( range 2540 - 8140 mg ) , whereas all patients in the placebo group reacted at 40 mg ( P = .0003 ) . Among 2437 active OIT doses versus 1193 placebo doses , there were 1107 ( 45.4 % ) versus 134 ( 11.2 % ) total reactions , with local symptoms being most common . Milk-specific IgE levels did not change significantly in either group . Milk IgG levels increased significantly in the active treatment group , with a predominant milk IgG4 level increase . CONCLUSIONS Milk OIT appears to be efficacious in the treatment of cow 's milk allergy . The side-effect profile appears acceptable but requires further study BACKGROUND Hen 's egg allergy affects young children and can cause severe allergic reactions . Avoidance results in dietary limitations and can affect the quality of life , especially in cases where potentially life-threatening reactions exist . Our objective was to desensitize children with moderate-severe IgE-mediated hen 's egg allergy over a 6-month period , by introducing increasing and very gradual daily doses of raw hen 's egg in order to enable the children to assume 25ml of this food , or to induce tolerance to the highest possible dose . The protocol foresaw the egg re introduction in the home setting . METHODS In this r and omized , controlled open study , 20 hen 's egg allergic children ( 10 in the active group ) were admitted . A convincing history or a positive double-blind placebo-controlled food challenge confirmed the diagnosis . Oral desensitization was performed with increasing doses starting from 0.27 mg of hen 's egg proteins ( 1 drop of raw hen 's egg diluted 1:100 ) . We adopted an original , mathematically calculated protocol in order to ensure a constant , daily increment of doses . RESULTS 8/10 children ( 80 % ) in the active group achieved the daily intake of 25ml over a 6-month period . One child ( 10 % ) could tolerate up to 2ml/day while another child ( 10 % ) failed the desensitization . Six months after enrolment only 2 children in the control group ( 20 % ) could tolerate hen 's egg . CONCLUSIONS We successfully desensitized 8/10 children with IgE-mediated hen 's egg allergy in a 6-month period . The partial outcome in the child who could tolerate 2ml/day reduced the risk of severe reactions after unnoticed introduction of egg . A regular protocol that ensures a daily constant increase of doses helps to reduce possible adverse events , thus improving safety and effectiveness BACKGROUND Treatment of severe egg allergy is avoidance of hen 's egg ( HE ) and carrying self-injectable epinephrine . Specific oral tolerance induction ( SOTI ) seems a promising alternative treatment . However , some aspects of SOTI are still considered experimental . METHODS We evaluated the efficacy and safety of an original 6-month SOTI protocol in children with very severe HE allergy using raw HE emulsion . Twenty children ( age range : 5 - 11 yr ) were r and omized equally into a SOTI treatment group and a control group . The treatment group started SOTI and underwent a second challenge 6 months later . Control children were kept on an egg-free diet for 6 months and then underwent a second challenge . RESULTS After 6 months , 9/10 children of the SOTI group ( 90 % ) achieved partial tolerance ( at least 10 ml , but < 40 ml of raw HE emulsion , in a single dose ) and 1 ( 10 % ) was able to tolerate only 5 ml ( no tolerance ) . After 6 months , nine control children tested positive to the second challenge at a dose ≤0.9 ml of raw HE emulsion , and one reacted to 1.8 ml ( SOTI vs. control group p<0.0001 ) . All children in the SOTI group had side effects , but no child had a grade 5 reaction according to the Sampson grading . CONCLUSION Six months of SOTI with raw HE emulsion result ed in partial tolerance , with regular intake , in a significant percentage of children with severe egg allergy |
14,058 | 32,045,437 | The relative failure rate of single limited CUS remains uncertain , as the DVT prevalence was lower in these studies .
Therefore , this CUS strategy may only be safe in a selected group of low-risk patients . | BACKGROUND Compression ultrasonography ( CUS ) is the first-line imaging test in the diagnostic management of suspected deep vein thrombosis ( DVT ) of the lower extremity .
Three CUS strategies are used in clinical practice .
However , their relative diagnostic accuracy is uncertain .
OBJECTIVES This systematic review and meta- analysis aim ed to summarize and compare the diagnostic accuracy of single limited , serial limited , and whole-leg CUS for DVT . | BACKGROUND Compression ultrasonography is the mainstay of diagnosis of deep-vein thrombosis ( DVT ) of the legs . Compression ultrasonography can be extended to the entire deep venous system ( whole-leg ) or restricted to the proximal veins only ( limited ) , and the two approaches are clinical ly equivalent . We aim ed to assess the diagnostic value of an algorithm combining whole-leg and limited compression ultrasonography . METHODS We did a prospect i ve , multicentre , cohort study at eight centres in five countries . Consecutive out patients aged 18 years or older with suspected DVT underwent D-dimer measurement and pretest clinical probability assessment . DVT was ruled out without further testing if pretest probability was unlikely and D-dimer was negative ( group 1 ) . Patients in whom either pretest probability was likely or who were positive for D-dimer underwent limited compression ultrasonography only ( group 2 ) . Finally , patients in whom pretest probability was likely and who had a positive measurement for D-dimer underwent extended whole-leg compression ultrasonography ( group 3 ) . All patients in whom DVT was ruled out were followed up for 3 months . The primary outcome was the incidence of objective ly recorded venous thromboembolism . The primary analysis included all patients managed according to the study protocol . This study is registered with Clinical Trials.gov , number NCT01412242 . The final results are reported here . FINDINGS Between March 1 , 2011 , and July 31 , 2014 , 1348 consecutive out patients were referred for this study , of whom 1162 were eligible to participate . After pretest probability assessment and D-dimer testing , 351 were in group 1 , 401 in group 2 , and 410 in group 3 . Limited compression ultrasonography was positive in 12 ( 3 % ) patients in group 2 and extended whole-leg compression ultrasonography was positive in 200 ( 49 % ) patients in group 3 . 82 ( 39 % ) of all DVT diagnosed at baseline were isolated distal thromboses . 26 protocol violations were reported . Thus , 351 patients from group 1 , 371 patients in group 2 , and 202 patients in group 3 who had been excluded for DVT by the algorithm were included in the primary analysis at 3 months . One , four , and three DVTs were reported , respectively . Thus , the 3-month incidence of venous thromboembolism in untreated patients after a negative diagnostic strategy was 0·87 % ( 95 % CI 0·44 - 1·70 ) . INTERPRETATION An algorithm combining limited and whole-leg compression ultrasonography could be a reliable , safe , and convenient method for diagnostic management of out patients with clinical ly suspected DVT . FUNDING None BACKGROUND It remains unclear whether a single complete ultrasound examination , which detects calf vein thrombosis , is as safe as a baseline rapid ultrasound examination , repeated after 1 week when negative , which examines the veins in the groin and the knee . Therefore , we compared the safety and feasibility of two diagnostic ultrasound strategies , involving rapid and complete compression ultrasound ( CUS ) examination . METHODS Consecutive patients with suspected deep vein thrombosis ( DVT ) underwent clinical probability assessment . In patients with an unlikely clinical probability and a normal D-dimer finding , DVT was considered to be excluded . All others were r and omized to undergo a rapid or a single complete CUS examination . Patients in whom DVT was excluded were followed for 3 months to assess the incidence of venous thromboembolism ( VTE ) . RESULTS A total of 1002 patients were included . A clinical decision rule indicating DVT to be unlikely and a normal D-dimer finding occurred in 481 patients ( 48 % ) , with a VTE incidence of 0.4 % [ 95 % confidence interval ( CI ) 0.05 - 1.5 % ] during follow-up . DVT was confirmed in 59 of the 257 patients ( 23 % ) who underwent rapid CUS examination , and in 99 of the 264 patients ( 38 % ) who underwent complete CUS examination . VTE during follow-up occurred in four patients ( 2.0 % ; 95 % CI 0.6 - 5.1 % ) in the rapid CUS arm , and in two patients ( 1.2 % ; 95 % CI 0.2 - 4.3 % ) in the complete CUS arm . CONCLUSIONS A diagnostic strategy with a clinical decision rule , a D-dimer test and a CUS examination is safe and efficient . Both the rapid and the complete CUS test are comparable and efficient strategies , with differing advantages and disadvantages BACKGROUND Several diagnostic strategies using ultrasound imaging , measurement of D-dimer , and assessment of clinical probability of disease have proved safe in patients with suspected deep-vein thrombosis , but they have not been compared in r and omized trials . METHODS Out patients presenting with suspected lower-extremity deep-vein thrombosis were potentially eligible . Using a clinical model , physicians evaluated the patients and categorized them as likely or unlikely to have deep-vein thrombosis . The patients were then r and omly assigned to undergo ultrasound imaging alone ( control group ) or to undergo D-dimer testing ( D-dimer group ) followed by ultrasound imaging unless the D-dimer test was negative and the patient was considered clinical ly unlikely to have deep-vein thrombosis , in which case ultrasound imaging was not performed . RESULTS Five hundred thirty patients were r and omly assigned to the control group , and 566 to the D-dimer group . The overall prevalence of deep-vein thrombosis or pulmonary embolism was 15.7 percent . Among patients for whom deep-vein thrombosis had been ruled out by the initial diagnostic strategy , there were two confirmed venous thromboembolic events in the D-dimer group ( 0.4 percent ; 95 percent confidence interval , 0.05 to 1.5 percent ) and six events in the control group ( 1.4 percent ; 95 percent confidence interval , 0.5 to 2.9 percent ; P=0.16 ) during three months of follow-up . The use of D-dimer testing result ed in a significant reduction in the use of ultrasonography , from a mean of 1.34 tests per patient in the control group to 0.78 in the D-dimer group ( P=0.008 ) . Two hundred eighteen patients ( 39 percent ) in the D-dimer group did not require ultrasound imaging . CONCLUSIONS Deep-vein thrombosis can be ruled out in a patient who is judged clinical ly unlikely to have deep-vein thrombosis and who has a negative D-dimer test . Ultrasound testing can be safely omitted in such patients Objective To assess the safety of using single complete compression ultrasonography in pregnant and postpartum women to rule out deep vein thrombosis . Design Prospect i ve outcome study . Setting Two tertiary care centres and 18 private practice s specialising in vascular medicine in France and Switzerl and . Participants 226 pregnant and postpartum women referred for suspected deep vein thrombosis . Methods A single proximal and distal compression ultrasonography was performed . All women with a negative complete compression ultrasonography result did not receive anticoagulant therapy and were followed up for a three month period . Main outcome measures Symptoms of venous thromboembolism , second compression ultrasonography or chest imaging , a thromboembolic event , and anticoagulant treatment . Results 16 women were excluded , mainly because of associated suspected pulmonary embolism . Deep vein thrombosis was diagnosed in 22 out of the 210 included women ( 10.5 % ) . 10 patients received full dose anticoagulation despite a negative test result during follow-up . Of the 177 patients without deep vein thrombosis and who did not receive full dose anticoagulant therapy , two ( 1.1 % , 95 % confidence interval 0.3 % to 4.0 % ) had an objective ly confirmed deep vein thrombosis during follow-up . Conclusions The rate of venous thromboembolic events after single complete compression ultrasonography in pregnant and postpartum women seems to be within the range of that observed in studies in the non-pregnant population . These data suggest that a negative single complete compression ultrasonography result may safely exclude the diagnosis of deep vein thrombosis in this setting . Trial registration clinical trials.gov NCT00740454 Background —Serial ultrasonography is reliable for the diagnosis of deep venous thrombosis in symptomatic patients , but the low prevalence of thrombosis in this group renders the approach costly and inconvenient to patients . We studied the clinical validity of the combination of a pretest clinical probability score and a D-dimer test in the initial evaluation of patients suspected of deep venous thrombosis . Methods and Results — Patients with a normal D-dimer concentration ( < 500 fibrin equivalent units [ FEU ] & mgr;g/L ) and a non-high probability score ( <3 ) had no further testing . Patients with a normal D-dimer concentration and a high probability score ( ≥3 ) underwent one ultrasonogram . Serial ultrasonography was performed in patients with an abnormal D-dimer concentration . Patients were followed for 3 months . A total of 812 patients were evaluable for efficacy . Only 1 of 176 patients ( 0.6 % ; 95 % CI , 0.02 % to 3.1 % ) with a normal D-dimer concentration and a non-high probability score developed thrombosis during follow-up . A normal D-dimer concentration and a high probability score were found in 39 patients ; 3 of them ( 7.7 % ; 95 % CI , 1.6 % to 20.9 % ) had thrombosis at presentation , and one ( 2.8 % ; 95 % CI , 0.07 % to 14 . 5 % ) developed pulmonary embolism during follow-up . In 306 of 597 patients ( 51.3 % ) with an abnormal D-dimer concentration , thrombosis was detected by serial ultrasonography . Six patients ( 2.1 % ; 95 % CI , 0.8 % to 4 . 4 % ) developed thrombosis during follow-up . No deaths due to thromboembolism occurred during follow-up . The total need for ultrasonography was reduced by 29 % . Conclusion —The combination of a non-high pretest clinical probability score and a normal D-dimer concentration is a safe strategy to rule out deep venous thrombosis and to withhold anticoagulation In a prospect i ve study 90 patients with clinical ly suggested lower limb deep venous thrombosis ( DVT ) were examined with duplex ultrasonography ( US ) prior to venography . No attempts were made to examine the calf veins . Five ultrasound examinations were inconclusive . Thirty-four patients had DVT diagnosed at US with a sensitivity of 97 per cent and a specificity of 96 per cent . Compressibility of the vein as assessed by the real-time image was in the acute phase an easy and fast test for DVT , whereas the Doppler data failed to add to the diagnostic accuracy . Twenty-seven patients with DVT were followed during anticoagulant treatment , but only 16 regained fully compressible veins within the observation period of 3 to 6 months . Duplex sonography was useful in monitoring the changes in vein patency during anticoagulant treatment Background : Compression ultrasonography performed serially over a 7-day period is recommended for the diagnosis of deep vein thrombosis in symptomatic pregnant women , but whether this approach is safe is unknown . We evaluated the safety of withholding anticoagulation from pregnant women with suspected deep vein thrombosis following negative serial compression ultrasonography and iliac vein imaging . Methods : Consecutive pregnant women who presented with suspected deep vein thrombosis underwent compression ultrasonography and Doppler imaging of the iliac vein of the symptomatic leg(s ) . Women whose initial test results were negative underwent serial testing on 2 occasions over the next 7 days . Women not diagnosed with deep vein thrombosis were followed for a minimum of 3 months for the development of symptomatic deep vein thrombosis or pulmonary embolism . Results : In total , 221 pregnant women presented with suspected deep vein thrombosis . Deep vein thrombosis was diagnosed in 16 ( 7.2 % ) women by initial compression ultrasonography and Doppler studies ; none were identified as having deep vein thrombosis on serial testing . One patient with normal serial testing had a pulmonary embolism diagnosed 7 weeks later . The overall prevalence of deep vein thrombosis was 7.7 % ( 17/221 ) ; of these , 65 % ( 11/17 ) of cases were isolated to the iliofemoral veins and 12 % ( 2/17 ) were isolated iliac deep vein thromboses . The incidence of venous thromboembolism during follow-up was 0.49 % ( 95 % confidence interval [ CI ] 0.09%–2.71 % ) . The sensitivity of serial compression ultrasonography with Doppler imaging was 94.1 % ( 95 % CI 69.2%–99.7 % ) , the negative predictive value was 99.5 % ( 95 % CI 96.9%–100 % ) , and the negative likelihood ratio was 0.068 ( 95 % CI 0.01–0.39 ) . Interpretation : Serial compression ultrasonography with Doppler imaging of the iliac vein performed over a 7-day period excludes deep-vein thrombosis in symptomatic pregnant women Prompt , accurate diagnosis of deep vein thrombosis ( DVT ) is essential . A single , whole-leg ultrasound ( whole-leg US ) has been used to exclude DVT , but limited data exist for patients with high pretest probability ( PTP ) for DVT . This diagnostic management study tested the rate of venous thromboembolism ( VTE ) in patients with a PTP of “ DVT likely ” per the simplified Wells score when anticoagulation is withheld based on a single , negative whole-leg US . Consecutive patients presenting during coordinator shifts with a PTP of DVT likely were enrolled . Anticoagulation was withheld after a single , negative whole-leg US . The outcome was objective ly confirmed VTE in 3 months . All 167 patients completed the follow-up . A single patient death was adjudicated as possibly caused by VTE , result ing in a VTE rate of 0.60 % ( 95 % confidence interval : 0.02%-3.29 % ) . Whole-leg US should be further studied in diagnostic algorithms that utilize PTP scoring and d-dimer testing BACKGROUND The efficacy and safety of anticoagulant treatment is not established for patients with acute symptomatic deep vein thrombosis ( DVT ) of the calf . We aim ed to assess whether therapeutic anticoagulation is superior to placebo in patients with symptomatic calf DVT . METHODS In this r and omised , double-blind , placebo-controlled trial , we enrolled low-risk out patients ( without active cancer or previous venous thromboembolic disease ) with a first acute symptomatic DVT in the calf from 23 university medical centres or community medical clinics in Canada , France , and Switzerl and . We r and omly assigned ( 1:1 ) patients to receive either the low-molecular-weight heparin nadroparin ( 171 UI/kg , subcutaneously , once a day ) or placebo ( saline 0·9 % , subcutaneously , once a day ) for 6 weeks ( 42 days ) . Central r and omisation was done using a computer-generated r and omisation list , stratified by study centre . R and om allocation sequences of variable block size were central ly determined by an independent research clinical centre . Study staff , patients , and outcome assessors ( central adjudication committee ) were masked to group assignment . Numbered boxes of active drug or placebo were provided to pharmacies in identical packaging . All patients were prescribed compression stockings and followed up for 90 days . The primary efficacy outcome was a composite measure of extension of calf DVT to proximal veins , contralateral proximal DVT , and symptomatic pulmonary embolism at day 42 in the modified intention-to-treat population . The primary safety outcome was major or clinical ly relevant non-major bleeding at day 42 . The trial was registered with Clinical Trials.gov , number NCT00421538 . FINDINGS Between Feb 1 , 2008 , and Nov 30 , 2014 , we screened 746 patients , enrolling 259 patients ( 50 % of the prespecified sample size ) , before the trial steering committee terminated the trial because of expiry of study drug and slow recruitment . The intention-to-treat analysis population comprised 122 patients in the nadroparin group and 130 in the placebo group . There was no significant difference between the groups in the composite primary outcome , which occurred in four patients ( 3 % ) in the nadroparin group and in seven ( 5 % ) in the placebo group ( risk difference -2·1 % , 95 % CI -7·8 to 3·5 ; p=0·54 ) . Bleeding occurred in five patients ( 4 % ) in the nadroparin group and no patients in the placebo group ( risk difference 4·1 , 95 % CI 0·4 to 9·2 ; p=0·0255 ) . In the nadroparin group one patient died from metastatic pancreatic cancer and one patient was diagnosed with heparin-induced thrombocytopenia type 2 . INTERPRETATION Nadroparin was not superior to placebo in reducing the risk of proximal extension or venous thromboembolic events in low-risk out patients with symptomatic calf DVT , but did increase the risk of bleeding . Avoidance of systematic anticoagulation for calf DVT could have a substantial impact on individual patients and from a public health perspective . FUNDING Swiss National Science Foundation , the Programme Hospitalier de Recherche Clinique in France , and the Canadian Institutes of Health Research Suspected deep vein thrombosis ( DVT ) is a common problem facing emergency physicians . Timely diagnostic testing must be performed to accurately identify patients with DVT . The purpose of this study was to evaluate the safety and effectiveness of a management strategy that combined consideration of clinical pretest probability and a d-dimer test to evaluate patients presenting to the emergency department with suspected deep vein thrombosis ( DVT ) . A prospect i ve cohort study was performed in the emergency departments of four tertiary care institutions involving 1075 patients with suspected DVT . An emergency physician determined the pretest probability for DVT to be low , moderate , or high using an explicit clinical model . A blood sample was taken for d-dimer testing . Subsequent investigations ( compression ultrasound , venography ) were performed based upon the pretest probability and the d-dimer result . Patients considered at low pretest probability with negative d-dimer had no further diagnostic testing performed . All patients in whom the diagnosis of DVT was excluded by the algorithm did not receive anticoagulant therapy and were followed up for 90 days for the development of proximal DVT or pulmonary embolism . Overall , 195 ( 18.1 % ; 95 % CI 15.9 % to 20.6 % ) of 1075 patients were confirmed to have proximal DVT . Of the 882 patients who had proximal DVT excluded during the initial evaluation period using the algorithms , four ( 0.5 % ; 95 % CI 0.1 % to 1.2 % ) were subsequently diagnosed with proximal DVT in the follow-up period , including three patients in the low pretest probability group ( 1.0 % ; 95 % CI 0.2 % to 2.1 % ) who had normal d-dimer and no additional diagnostic testing performed . None of the 882 patients ( 0 % : 95 % CI 0 % to 0.5 % ) developed pulmonary embolism in the follow-up period . A diagnostic strategy for the evaluation of patients with suspected DVT based on pretest probability and d-dimer is safe and feasible in the emergency department setting Background The clinical picture of deep vein thrombosis ( DVT ) is nonspecific . Therefore assessment of the probability of occurrence of DVT plays a very important part in making a correct diagnosis of DVT.The aim of our prospect i ve study was to assess the accuracy of the Wells scale in primary care setting in diagnostic procedure of suspected deep vein thrombosis . Methods In the period of 20 - months ( from 2007 to 2009 ) a group of residents from one of the urban districts of Warsaw , who reported to family doctors ( 22 primary care physicians were involved in the study ) with symptoms of DVT were assessed on the probability of occurrence of deep vein thrombosis using the Wells scale . Family doctors were aware of symptoms of DVT and inclusion patients to this study was based on clinical suspicion of DVT . Patients were divided into three groups , reflecting probability of DVT of the lower limbs . To confirm DVT a compression ultrasound ( CUS ) test was established . We analyzed the relationship between a qualitative variable and a variable defined on an original scale ( incidence of DVT versus Wells scale count ) using the Mann – Whitney test . Chi-square test compared rates of DVT events in all clinical probability groups . Patient were follow up during 3 months in primary care setting . Results In the period of 20 months ( from 2007 to 2009 ) a total number of 1048 patients ( male : 250 , female : 798 mean age : 61.4 ) with symptoms suggestive of DVT of the lower extremities entered the study . Among the 100 patients classified in the group with a high probability of DVT of the lower extremities , 40 ( 40 % ) patients ( proximal DVT - 13 ; distal DVT - 27 ) were diagnosed with it ( 95 % CI [ 30.94 % -49.80 % ] ) . In the group with a moderate probability consisting of 302 patients , DVT of the lower extremities was diagnosed in 19 ( 6.29 % ) patients ( 95 % CI [ 4.06 % -9.62 % ] ) , ( proximal DVT – 1 ; distal DVT - 18 ) . Of the 646 patients with a low probability of DVT of the lower extremities distal DVT was diagnosed in 1 ( 0.15 % ) patient ( 95 % CI [ 0.03 % -0.87 % ] ) . Conclusion The Wells scale used in primary care setting demonstrated a high degree of accuracy Context Several different d-dimer assays are available to help physicians diagnose deep venous thrombosis ( DVT ) . Some are time-consuming , and some have low sensitivity . Contribution This prospect i ve study included 283 patients with low or moderate pretest probability for thrombosis who did not receive anticoagulant therapy after a negative result on a second-generation , rapid-turnaround quantitative latex test ( MDAd-Dimer ) . Only one of these patients had confirmed DVT within a 3-month follow-up period ( negative likelihood ratio , 0.05 [ 95 % CI , 0.01 to 0.23 ] ) . Implication s In patients with low or moderate pretest probability for thrombosis , a negative MDAd-Dimer result safely rules out DVT . The Editors Accurate diagnostic testing is essential when deep venous thrombosis ( DVT ) is suspected . Untreated DVT is associated with a high risk for pulmonary embolism ( 1 ) , whereas false diagnosis of DVT results in unnecessary anticoagulant therapy , with its associated risks for bleeding ( 1 , 2 - 4 ) . Although diagnostic imaging ( most commonly compression ultrasonography or contrast venography ) is widely used to evaluate suspected DVT , these tests are expensive and are often unavailable outside of regular working hours . In addition , venography , the diagnostic reference st and ard , is invasive and has associated side effects ( 5 - 7 ) . Compression ultrasonography , which is highly sensitive and specific for proximal DVT , has emerged as the diagnostic method of choice in patients with suspected DVT ( 8) . However , compression ultrasonography is expensive , requires highly trained personnel , and is not sensitive for isolated calf DVT ( 8) . Therefore , when the proximal veins are normal on initial compression ultrasonography , the test should be repeated a week later to detect proximally extending calf DVT that can cause pulmonary embolism ( 8 , 9 ) . This further increases cost and is inconvenient for the patient . Recently , the use of d-dimer testing has simplified the diagnosis of DVT . Many d-dimer assays have high sensitivity for DVT and can be used to help exclude venous thrombosis when results are negative ( 10 - 12 ) . Three d-dimer assay formats are currently available : enzyme-linked immunosorbent assays ( ELISAs ) , whole-blood erythrocyte agglutination assay ( SimpliRED , Agen Biomedical , Ltd. , Brisbane , Australia ) , and latex agglutination assays . The first and second methods have been the most extensively investigated ( 13 - 30 ) . Traditional d-dimer ELISAs , although highly sensitive , are time-consuming and are not suitable for individual patient testing ( 10 ) . Recently , rapid ELISAs that are suitable for individual testing and have high sensitivities have been developed . However , like the traditional ELISAs , some of these assays have lower specificities than other d-dimer assay formats ( 13 - 16 ) . The SimpliRED test has a sensitivity of approximately 85 % and a specificity of approximately 70 % . A negative result , in combination with normal results on a noninvasive test for DVT or low pretest probability , has been shown to exclude DVT ( 19 , 23 - 25 ) . However , not all studies have reported a high sensitivity for the SimpliRED assay ( 27 , 28 ) , raising concern that the use of this test could result in undiagnosed DVT . First-generation slide latex d-dimer assays that are interpreted subjectively are not sufficiently sensitive to exclude DVT ( 10 , 31 ) . The MDAd-Dimer assay ( Organon Teknika Corp. , now bioMrieux , Inc. , Durham , North Carolina ) is a novel , automated , second-generation quantitative latex microparticle immunoassay with a turnaround time of less than 30 minutes ( including 15 minutes for plasma preparation ) . In a retrospective study , we demonstrated that this test had a sensitivity of 96 % , a specificity of 45 % , and a negative predictive value of 98 % for a first episode of suspected venous thromboembolism ( 32 ) when a discriminant value of 0.50 g fibrinogen equivalent units (FEUs)/mL was used . These results suggested that a negative result on MDAd-Dimer can exclude venous thrombosis without further objective testing . However , in our previous study , d-dimer assays were performed in batches on platelet-poor plasma frozen at 70 C , and the results were not used to manage patients . Therefore , to test our hypothesis prospect ively , we performed a cohort study in which management decisions were based on the results of MDAd-Dimer testing . Methods This study was performed between August 1999 and November 2001 in three hospitals affiliated with McMaster University in Hamilton , Ontario , Canada ( Hamilton Health SciencesHenderson and McMaster University Divisions , and St. Joseph 's Hospital ) . These hospitals serve the city of Hamilton ( population , 460 000 ) , as well as the more than 2 million residents of central western Ontario . Each center 's research ethics board approved the study , and all patients provided written informed consent before enrollment . Patient Sample Consecutive out patients who were at least 18 years of age , had suspected first DVT , and were referred to one of the thromboembolism services of the participating hospitals were potentially eligible . More than 95 % of patients referred to these hospitals for investigation of DVT are seen in consultation with the thromboembolism service . Potentially eligible patients with one or more of the following were excluded : contraindication to contrast medium , pregnancy , treatment with therapeutic doses of anticoagulation for more than 24 hours before study entry , an ongoing requirement for anticoagulation not related to the qualifying episode ( for example , atrial fibrillation or mechanical heart valve ) , a comorbid condition likely to shorten survival to less than 3 months , geographic or social factors precluding follow-up , or inability or unwillingness to provide informed consent . Clinical Intervention After providing informed written consent , and before d-dimer testing , patients were clinical ly assessed for pretest probability of DVT ( high , moderate , or low ) . Clinical assessment was performed by using a st and ardized form containing a previously vali date d model ( Table 1 ) that includes assessment of clinical symptoms and signs , risk factors for DVT , and the presence of an alternative diagnosis ( 33 , 34 ) . In a previous study , use of this model stratified patients into high- , moderate- , or low-probability groups ( prevalences of DVT of 75 % , 17 % , and 3 % , respectively ) . In addition , the value for the comparison of pretest probability assignment by nurses and physicians was 0.75 , showing very good interobserver agreement ( 33 ) . Table 1 . St and ardized Model Used To Assess Pretest Probability In our study , a sample of venous blood was collected in 4.5-mL Vacutainer tubes ( Becton Dickinson Co. , Mountain View , California ) prefilled with 0.5 mL of 3.2 % ( 0.105 mol/L ) sodium citrate dihydrate . d-dimer testing with the MDAd-Dimer assay was performed according to manufacturer 's instructions on the MDA 180 automated coagulometer ( bioMrieux , Inc. ) . Laboratory technologists performing and interpreting the d-dimer assays were unaware of patients ' clinical presentation or the results of other objective tests . Patients with negative results on the MDAd-Dimer assay ( < 0.50 g FEU/mL ) and low or moderate pretest probability had no further testing , were not treated with anticoagulants , and were followed for 3 months to detect DVT or pulmonary embolism presumably caused by DVT missed at presentation ( Figure ) . For safety reasons , compression ultrasonography of the symptomatic leg was performed , as previously described , in patients with high pretest probability as well as in all patients with a positive result on the d-dimer test ( Figure ) ( 35 ) . The common femoral , superficial femoral , and popliteal veins , as well as the trifurcation of the calf veins , were examined ; calf veins below the trifurcation were not assessed . Patients with normal results on ultrasonography at presentation underwent repeated compression ultrasonography on days 6 to 8 and days 13 to 15 ; this strategy has a negative predictive value of 98 % ( 8) . Deep venous thrombosis was diagnosed if there was noncompressibility of the common femoral vein or popliteal vein ( with or without involvement of adjacent segments ) ( 8) . These findings have a positive predictive value of 97 % ( 8) . Isolated noncompressibility of the superficial femoral vein or trifurcation was further evaluated with venography ( 8) . Patients with normal results on serial compression ultrasonography did not receive anticoagulant therapy and were followed for 3 months . Figure . Flow chart summarizing the diagnostic process used in the study . Patients who did not receive a diagnosis of DVT were followed for 3 months to detect evidence of clinical ly significant DVT that was not diagnosed at presentation . Patients were instructed to return for reevaluation if they developed signs or symptoms suggestive of DVT or pulmonary embolism . All patients were contacted by telephone at 3 months . All patients who presented again with symptoms consistent with DVT or pulmonary embolism underwent uniform objective testing to confirm or exclude the diagnosis . These tests were performed and interpreted by physicians who were unaware of the results of the MDAd-Dimer test at presentation . Patients with leg pain or swelling during follow-up underwent compression ultrasonography of the symptomatic leg . If this did not demonstrate noncompressibility of the common femoral or popliteal vein , ipsilateral venography was performed . Deep venous thrombosis was diagnosed if an intraluminal filling defect was present in two views ( 5 ) . Because venography has been shown to have a negative predictive value of 99 % ( 6 ) , treatment was withheld and follow-up was continued in the absence of an intraluminal filling defect . In patients with suspected pulmonary embolism , a ventilationperfusion scan was obtained . A high-probability scan ( segmental or greater perfusion defect with normal ventilation ) , which has a positive predictive value of more than 85 % , was considered to The purpose of this study was to evaluate whether the determination of pretest probability using a simple clinical model and the SimpliRED D-dimer could be used to improve the management of hospitalized patients with suspected deep-vein thrombosis . Consecutive hospitalized patients with suspected deep-vein thrombosis , had their pretest probability determined using a clinical model and had a SimpliRED D-dimer assay . Patients at low pretest probability underwent a single ultrasound test . A negative ultrasound excluded the diagnosis of deep-vein thrombosis whereas a positive ultrasound was confirmed by venography . Patients at moderate pretest probability with a positive ultrasound were treated for deep-vein thrombosis whereas patients with an initial negative ultrasound underwent a single follow-up ultrasound one week later . Patients at high pretest probability with a positive ultrasound were treated whereas those with negative ultrasound underwent venography . All patients were followed for three months for the development of venous thromboembolic complications . Overall , 28 % ( 42/150 ) , and 10 % ( 5/50 ) , 21 % ( 14/71 ) and 76 % ( 22/29 ) of the low , moderate and high pretest probability patients . respectively , had deep vein thrombosis . Two of 111 ( 1.8 % ; 95 % CI = 0.02 % to 6.4 % ) patients considered to have deep vein thrombosis excluded had events during three-month follow-up . Overall 13 of 150 ( 8.7 % ) required venography and serial testing was limited to 58 of 150 ( 38.7 % ) patients . The negative predictive value of the SimpliRED D-dimer in patients with low pretest probability was 96.2 % , which is not statistically different from the negative predictive value of a negative ultrasound result in low pretest probability patients ( 97.8 % ) . Management of hospitalized patients with suspected deep-vein thrombosis based on clinical probability and ultrasound of the proximal deep veins is safe and feasible BACKGROUND When ultrasonography is used to investigate deep-vein thrombosis , serial testing is recommended for those who test negative initially . Serial testing is inconvenient for patients and costly . We aim ed to assess whether the calculation of pretest probability of deep-vein thrombosis , with a simple clinical model , could be used to improve the management of patients who present with suspected deep-vein thrombosis . METHODS Consecutive out patients with suspected deep-vein thrombosis had their pretest probability calculated with a clinical model . They then underwent compression ultrasound imaging of proximal veins of the legs . Patients at low pretest probability underwent a single ultrasound test . A negative ultrasound excluded the diagnosis of deep-vein thrombosis whereas a positive ultrasound was confirmed by venography . Patients at moderate pretest probability with a positive ultrasound were treated for deep-vein thrombosis whereas patients with an initial negative ultrasound underwent a single follow-up ultrasound 1 week later . Patients at high pretest probability with a positive ultrasound were treated whereas those with negative ultrasound underwent venography . All patients were followed up for 3 months for thromboembolic complications . FINDINGS 95 ( 16.0 % ) of all 593 patients had deep-vein thrombosis ; 3 % , 17 % , and 75 % of the patients with low , moderate , and high pretest probability , respectively , had deep-vein thrombosis . Ten of 329 patients with low pretest probability had the diagnosis confirmed , nine at initial testing and one at follow-up . 32 of 193 patients with moderate pretest probability had deep-vein thrombosis , three diagnosed by the serial ( 1 week ) test , and two during follow-up . 53 of 71 patients with high pretest probability had deep-vein thrombosis ( 49 by the initial ultrasound and four by venography ) . Only three ( 0.6 % ) of all 501 ( 95 % CI 0.1 - 1.8 ) patients diagnosed as not having deep-vein thrombosis had events during the 3-month follow-up . Overall only 33 ( 5.6 % ) of 593 patients required venography and serial testing was limited to 166 ( 28 % ) of 593 patients . INTERPRETATION Management of patients with suspected deep-vein thrombosis based on clinical probability and ultrasound of the proximal deep veins is safe and feasible . Our strategy reduced the need for serial ultrasound testing and reduced the rate of false-negative or false-positive ultrasound studies OBJECTIVE We aim ed at determining whether a negative single complete compression ultrasonography ( CUS ) of the lower limbs veins is a safe and accurate diagnostic method to rule out the diagnosis of deep venous thrombosis in pregnant and early postpartum women . DESIGN Hospital-based retrospective study . SETTING The gynaecology and vascular ultrasound units of three general hospitals in western France . PATIENTS We identified from the hospitals data bases all pregnant or up to three months postpartum women who underwent CUS for a suspicion of deep venous thrombosis between January 2002 and December 2004 . METHODS Question naires were sent to all women with a negative CUS . Their medical records were also checked . MAIN OUTCOME MEASURES We assessed the three-month thromboembolic risk and its 95 % percent confidence interval in women left untreated on the basis of a negative single complete CUS of the lower limbs . RESULTS During the study period , 162 pregnant or postpartum women underwent CUS for a suspicion of deep venous thrombosis . It was positive in 44 ( 27 % ) . The 118 women who had a negative CUS were sent the question naire . Information about the three-month follow-up was found for 107 patients ( 91 % ) . None of them experienced a thromboembolic event during follow-up : 0.0 % ( 95 % CI : 0.0 - 3.6 ) . CONCLUSIONS Single complete CUS of lower limbs veins appears to be a safe method to rule out the diagnosis of deep venous thrombosis in pregnant or early postpartum women . This has to be confirmed by a prospect i ve management study with a formal follow-up BACKGROUND D-Dimer testing is sensitive but not specific for diagnosing deep venous thrombosis ( DVT ) . Changing the use of testing and the threshold level for a positive test result on the basis of risk for DVT might improve the tradeoff between sensitivity and specificity and reduce the need for testing . OBJECTIVE To determine whether using a selective D-dimer testing strategy based on clinical pretest probability ( C-PTP ) for DVT is safe and reduces diagnostic testing compared with using a single D-dimer threshold for all patients . DESIGN R and omized , multicenter , controlled trial . Patients were allocated using a central automated system . Ultrasonographers and study adjudicators but not other study personnel were blinded to trial allocation . ( Clinical Trials.gov : NCT00157677 ) SETTING 5 Canadian hospitals . PATIENTS Consecutive symptomatic patients with a first episode of suspected DVT . INTERVENTION Selective testing ( n = 860 ) , defined as D-dimer testing for out patients with low or moderate C-PTP ( DVT excluded at D-dimer levels < 1.0 µg/mL [ low C-PTP ] or < 0.5 µg/mL [ moderate C-PTP ] ) and venous ultrasonography without D-dimer testing for out patients with high C-PTP and in patients , or uniform testing ( n = 863 ) , defined as D-dimer testing for all participants ( DVT excluded at D-dimer levels < 0.5 µg/mL ) . MEASUREMENTS The proportion of patients not diagnosed with DVT during initial testing who had symptomatic venous thromboembolism during 3-month follow-up and the proportion of patients undergoing D-dimer testing and ultrasonography . RESULTS The incidence of symptomatic venous thromboembolism at 3 months was 0.5 % in both study groups ( difference , 0.0 percentage point [ 95 % CI , -0.8 to 0.8 percentage points ] ) . Selective testing reduced the proportion of patients who required D-dimer testing by 21.8 percentage points ( CI , 19.1 to 24.8 percentage points ) . It reduced the proportion who required ultrasonography by 7.6 percentage points ( CI , 2.9 to 12.2 percentage points ) overall and by 21.0 percentage points ( CI , 14.2 to 27.6 percentage points ) in out patients with low C-PTP . LIMITATION Results may not be generalizable to all D-dimer assays or patients with previous DVT , study personnel were not blinded , and the trial was stopped prematurely . CONCLUSION A selective D-dimer testing strategy seems as safe as and more efficient than having everyone undergo D-dimer testing when diagnosing a first episode of suspected DVT . PRIMARY FUNDING SOURCE Heart and Stroke Foundation of Ontario PURPOSE To establish the safety of withholding anticoagulation therapy after negative findings at a complete lower limb ultrasonographic ( US ) examination of the symptomatic leg for suspected deep venous thrombosis ( DVT ) . MATERIAL S AND METHODS Regional ethics committee approval and patient consent were obtained . A total of 542 consecutive ambulatory patients presented to the emergency department and were prospect ively recruited from April 2001 to May 2003 . Of these patients , 16 were excluded , and radiology residents and sonographers performed a complete lower limb US examination by means of compression and Doppler US in 526 patients . Patients with negative US findings received no anticoagulation therapy , and they were observed for occurrence of any thromboembolic event for 3 months . Patients with progressive or new symptoms that were indicative of thromboembolism within the follow-up period underwent objective testing with US , computed tomographic ( CT ) pulmonary angiography , or both . RESULTS There were 413 patients ( 78.5 % ) with US findings that were negative for DVT and 113 patients ( 21.5 % ) with findings that were positive . There were 64 patients ( 56.6 % ) with DVT isolated to the calf and 49 ( 43.4 % ) with proximal DVT . Of the 413 patients with negative initial US findings , 16 ( 3.9 % ) underwent a second US examination for new or progressive symptoms of DVT , one patient ( 0.25 % ) underwent CT pulmonary angiography for suspected pulmonary embolism , and one patient ( 0.25 % ) underwent both US and CT pulmonary angiography during the 3-month follow-up period . One of these patients ( 0.24 % ; 95 % confidence interval : 0.01 % , 1.3 % ) developed pulmonary embolism , which was diagnosed with CT pulmonary angiography . DVT was not diagnosed in any patient , and no patient died during follow-up . The negative predictive value of a complete single lower limb US examination to exclude clinical ly important DVT is 99.6 % ( 95 % confidence interval : 98.4 % , 99.9 % ) . CONCLUSION A single negative complete lower limb US examination is sufficient to exclude clinical ly important DVT , and it is safe to withhold anticoagulation therapy after negative complete lower limb US findings were obtained in patients suspected of having symptomatic lower limb DVT . New or progressive symptoms require further objective imaging Impedance plethysmography ( IPG ) and compression ultrasonography ( CUS ) have been reported to be highly accurate for the diagnosis of deep vein thrombosis ( DVT ) in symptomatic patients . In many centres CUS has become the method of choice . However , direct comparisons of the accuracy of IPG to CUS have not been performed . To determine the test of choice we performed a two centre prospect i ve comparison of IPG and CUS , with venography , and determined how the size and distribution of thrombi influenced the accuracy of each test . 495 symptomatic out patients with suspected DVT had evaluable venograms . The prevalence of DVT was 27 % ( 130/495 ) , 84 % ( 109 ) of which were proximal . The sensitivity of IPG and CUS for proximal vein thrombosis was 77 % and 90 % respectively ( p = .002 ) . The specificity of IPG was 93 % whereas the specificity of CUS was 98 % ( p = 0.04 ) . There were significant differences in accuracy between the two centres as a consequence of differences in the size and location of thrombi The majority of proximal thrombi not detected by IPG and CUS involved less than 5 cm of the distal half of the popliteal vein and most of these thrombi occurred in one centre . Exclusion of these thrombi from the analysis increases the sensitivity of CUS to 99 % ( 86/87 ) and IPG to 91 % ( 72/79 ) , for proximal thrombi ( P = .019 ) . The positive predictive value of CUS was strongly influenced by the number of abnormal venous segments ( three sites were examined ) ; 100 % ( 80/80 ) if two or three sites were abnormal , but only 68 % if a single site was involved . We conclude that : 1 ) CUS is more accurate than the IPG for the diagnosis of DVT in symptomatic out patients , and this relationship holds true regardless of the size or location of the DVT , 2 ) the sensitivities of IPG and CUS are much lower for small proximal DVT , and 3 ) confirmatory venography is warranted if the abnormality with CUS is limited to one venous segment PURPOSE Accurate diagnosis of deep venous thrombosis ( DVT ) is a clinical problem in emergency practice . A prospect i ve trial was conducted comparing real-time ultrasound with contrast venography in the diagnosis of proximal DVT . METHODS Seventy patients whose clinical presentations m and ated diagnostic evaluation for DVT had real-time ultrasound of the involved leg followed by contrast venography . Initial readings of ultrasound and venography were compared with each other and with final readings to assess reliability of interpretation . RESULTS Final ultrasound readings agreed with final venogram readings in all patients . Negative initial ultrasound readings agreed with final venogram readings in 56 of 56 patients ( negative predictive value , 100 % ; 95 % confidence interval , 94 to 100 ) . Eighteen patients had positive initial ultrasound readings compared with 14 who had positive final venogram readings ( positive predictive value , 78 % ; 95 % confidence interval , 55 to 91 ) . CONCLUSION Negative real-time ultrasonography reliably excludes proximal DVT . Positive ultrasound reliably diagnoses proximal DVT only in experienced h and Colour Doppler ultrasound is a new technical development allowing simultaneous grey scale imaging and a dynamic colour flow vascular image . To date , many real time ultrasonic studies have been assessed in the diagnosis of lower limb venous thrombosis and have been shown to be accurate in the femoral and popliteal segments . A double blind prospect i ve study comparing colour Doppler with contrast venography in the diagnosis of lower limb thrombosis was performed in a group of 40 patients . Of the study group , 26 venograms were negative and 27 ultrasound examinations were negative . Of the 14 positive venograms there was one false negative colour doppler scan which missed a calf and lower popliteal thrombosis . Two cases of isolated calf vein thrombosis were successfully detected by colour Doppler . Overall , the sensitivity and specificity for detection of lower limb venous thrombosis , including calf vein assessment , were 93 % and 100 % respectively . Colour Doppler is easy to perform ; the average scanning time being 15 minutes for complete assessment of a unilateral lower limb venous system . Spontaneous flow is evident in the femoropopliteal segment , whilst proximal calf vein flow can only be appreciated with the aid of distal compression . Eccentric thrombus and partially recanalized thrombus can be shown . Although the number of isolated calf vein thromboses was small , early experience suggests colour Doppler may be useful in the assessment of proximal calf vein patency Context Simplified compression ultrasonography is useful in detecting deep venous thrombosis ( DVT ) , but repeated testing is required 5 to 7 days later to detect proximal propagation from an unvisualized calf vein . Comprehensive duplex ultrasonography examines deep veins from the inguinal ligament to the malleolus . Contribution Consecutive patients with suspected symptomatic first episodes of DVT underwent comprehensive duplex ultrasonography . Anticoagulation was withheld if results were negative , regardless of symptoms or clinical signs . On 3-month follow-up , the overall rate of symptomatic venous thrombosis was 0.8 % . Implication s An acceptably low risk for false-negative results on comprehensive duplex ultrasonography may obviate the need for repeated testing in the vast majority of patients with suspected first episodes of DVT . The Editors Ultrasonography is the most commonly used test in the United States for diagnosis of deep venous thrombosis ( DVT ) of the leg ( 1 - 4 ) . The term ultrasonography has been applied to a variety of diagnostic techniques . The most research ed technique , simplified compression ultrasonography , is highly sensitive and specific for symptomatic proximal venous thrombosis but does not detect thrombosis in the distal veins of the calf ( 1 - 8 ) . Distal DVT may propagate proximally and lead to venous thromboembolism . Therefore , a second examination with simplified compression ultrasonography performed 5 to 7 days later is necessary to detect unvisualized calf vein thrombi that have propagated proximally ( 9 - 12 ) . Repeated testing is inconvenient , and not all patients are able to return for serial tests ( 9 , 10 , 12 ) . Many follow-up tests that yield normal results must be performed to detect relatively few patients with disease ( 9 - 13 ) . In the United States , approximately 500000 patients are evaluated annually for DVT ( 14 ) . Given that results are normal on approximately 80 % of initial ultrasonography examinations ( 15 ) , and only 2 % of patients have abnormal results on serial testing 5 to 7 days later ( 9 , 10 ) , as many as 390000 repeated tests may be performed annually without detecting disease . A single noninvasive study that safely rules out DVT would be useful . Comprehensive duplex ultrasonography , which examines the deep veins from the inguinal ligament to the level of the malleolus , has not been tested prospect ively to determine whether it is adequate to detect clinical ly important calf DVT and make routine repeated scanning unnecessary . To determine whether negative results on a single examination with comprehensive duplex ultrasonography are adequately sensitive to justify withholding anticoagulation in patients with symptoms of DVT of the leg , we performed a prospect i ve cohort study of consecutive patients in whom a first episode of this disorder was suspected . The primary end point was the rate of venous thromboembolism ( including death attributed to venous thromboembolism ) when anticoagulant therapy was withheld from patients on the basis of negative results on a single examination with comprehensive duplex ultrasonography . We used 3 months of clinical follow-up to test the validity of this approach ( 16 - 18 ) . Methods Patients From April 2000 through July 2001 , we enrolled consecutive adult patients who were referred to a tertiary care hospital 's peripheral vascular laboratory for a suspected first episode of symptomatic DVT of the leg . Vascular technologists determined the absence of a history of DVT and referred patients to a study clinician , who then performed a history and physical examination and determined eligibility . Criteria for exclusion were previous DVT , pregnancy , technical inability to perform comprehensive duplex ultrasonography , anticipated inability to obtain long-term follow-up ( for example , because of homelessness ) , more than 24 hours of therapeutic anticoagulation before ultrasonography , no informed consent , or long-term anticoagulation planned for another diagnosis ( for example , atrial fibrillation ) . A priori , we determined that patients treated with therapeutic anticoagulation during the 3-month follow-up period for diagnoses unrelated to venous thromboembolism ( for example , joint replacement surgery ) would be excluded from analysis to avoid confounding results . Descriptive data , including a score of pretest probability of DVT calculated by using a vali date d scoring system ( 19 ) , were collected for each patient . Patients then underwent objective testing for DVT by comprehensive duplex ultrasonography . The LDS Hospital Institutional Review Board approved the study , and all enrolled patients provided written informed consent . Objective Testing for DVT Comprehensive , real-time B-mode ultrasonography with color Doppler analysis was performed immediately after enrollment by using the technique described by Talbot ( 20 ) . Registered vascular technologists performed all ultrasonography , and 1 of 2 certified vascular surgeons on the hospital staff interpreted the results . Vascular technologists and interpreting physicians were blinded to the enrollment clinicians ' assessment and the pretest probability score . A high-resolution , electronically focused linear array transducer with a 3.5- to 10-MHz variable frequency probe ( model 5000 scanner , ATL Corp. , Bothell , Washington ) was used for all studies . Comprehensive duplex ultrasonography was used to examine the deep veins of the symptomatic leg in all patients . Proximally , patients were examined from the level of the inguinal ligament to the adductor canal in the supine position . The popliteal vein was examined to its trifurcation in the upper calf , and the remainder of the calf veins were examined to the level of the malleolus . Compressibility was assessed at 2-cm intervals in the transverse plane . Interpreting physicians were required by protocol to characterize the study results as negative ( DVT absent ) if all imaged venous segments were fully compressible or as abnormal ( DVT present ) if a noncompressible segment was identified . Thus , the sole criterion for the diagnosis of DVT was noncompressibility of the vein . Doppler interrogation of each of these segments was performed , as was imaging distally to the level of the medial malleolus for supplemental information . Anticoagulation was withheld if the initial results of comprehensive duplex ultrasonography were negative ( the negative cohort ) , regardless of symptoms or clinical signs . Long-Term Follow-up All patients were instructed to return to the hospital immediately if they experienced symptoms or signs of venous thromboembolism . All patients in the negative cohort were interviewed at least 3 months after study enrollment and queried for specific symptoms of venous thromboembolism , institution of new medications , hospitalization , surgery , diagnostic testing , and general health . We also comprehensively review ed each patient 's electronic medical record , which included all inpatient , outpatient , diagnostic , and pharmacy services . The primary outcome measure was venous thromboembolism ( DVT , pulmonary embolism , or paradoxical embolism ) verified by objective testing or by death from venous thromboembolism . The minimum follow-up period of 3 months was chosen on the basis of previous studies ( 9 , 16 - 18 ) . Patients in whom DVT was suspected because of progressive symptoms were evaluated with repeated ultrasonography and continued long-term follow-up . Those in whom pulmonary embolism was suspected were evaluated with lung scanning , pulmonary angiography , or computed tomography angiography in conjunction with ultrasonography of the legs ( 21 - 24 ) . Method ologic Issues and Avoidance of Bias We minimized selection bias by sequentially enrolling consecutive patients . Verification bias ( 25 ) was avoided because all negative results were verified by 3 months of clinical follow-up for venous thromboembolism . Previous studies have verified that repeated ultrasonography is a highly sensitive technique for detecting DVT missed on initial ultrasonography ( 9 - 11 , 15 ) . This makes the potential incorporation bias ( 26 ) introduced by repetition of the diagnostic method less relevant . Experienced vascular surgery staff interpreted comprehensive duplex ultrasonography studies according to predefined criteria for negative and positive results . We limited interobserver variability by using a priori criteria for positive and negative results ( 20 ) and by using only 2 interpreters . A previous study found that interobserver agreement is high for this technique ( 27 ) . An independent adjudication committee blinded to the study hypothesis review ed all deaths , characterizing them as insidious or abrupt and indicating whether they were caused by venous thromboembolism . Adjudicators with substantial experience in clinical trials of venous thromboembolism review ed all records and diagnostic tests of patients in whom venous thromboembolism was suspected during the follow-up period , categorizing venous thromboembolism as present , absent , or indeterminate . A simple majority resolved disputes . Adjudicators were not involved in the care of any patients in the study and were provided with hospital and physician records , death certificates , and imaging studies . Statistical Analysis A priori , we hypothesized that the upper boundary of the exact 2-sided 95 % CI for the rate of venous thromboembolism would be less than 2.6 % when anticoagulant therapy was withheld after negative results on a single examination with comprehensive duplex ultrasonography . We chose 2.6 % because this was the event rate observed after a single simplified compression test in a previous study ( 9 ) . The sample size required to perform equivalence testing was prohibitive , so we enrolled sufficient participants to produce a negative cohort large enough to allow calculation of an exact 2-sided 95 % CI of approximately 1.5 % . We estimated that 30 % of the original sample would have positive results on ultrasonography and that the event rate would be 0.9 % in the negative BACKGROUND Serial testing with impedance plethysmography or compression ultrasonography has been demonstrated to be feasible and accurate for the detection of deep vein thrombosis ( DVT ) in symptomatic out patients , and these techniques are replacing contrast venography in this patient category . Limited data , however , are available on the clinical utility of these noninvasive tests in symptomatic hospitalized patients . The objectives of our study were to determine the feasibility of ascending contrast venography and to evaluate the accuracy of these two noninvasive methods for the detection of DVT in symptomatic hospitalized patients . METHODS A prospect i ve , " blind " comparison of impedance plethysmography and compression ultrasonography with ascending contrast venography was performed in consecutive hospitalized patients with clinical ly suspected DVT of the leg . RESULTS Of the 127 potentially eligible patients , 44 had to be excluded ; 25 of these could not undergo venography ( feasibility of venography , 80.3 % ) . The sensitivity , specificity , and positive and negative predictive values of impedance plethysmography for proximal DVT were 96 % , 83 % , 82 % , and 97 % , respectively . For compression ultrasonography , these measures for proximal DVT were 97 % , 86 % , 87 % , and 97 % , respectively . The overall prevalence of DVT was 53 % , of which 85 % was located proximally . CONCLUSIONS Contrast venography can not be performed in about 20 % of consecutive symptomatic patients . Both impedance plethysmography and compression ultrasonography are feasible and valid alternatives to contrast venography in the diagnostic treatment of these patients PURPOSE The optimal approach to diagnosing deep venous thrombosis is not entirely clear . In this prospect i ve cohort study , we aim ed to evaluate the yield of two methods of assessing the pretest probability of deep venous thrombosis-the treating physician 's implicit assessment and the Wells score , a vali date d prediction rule that incorporates signs , symptoms , and the presence or absence of an alternative diagnosis-used in isolation and in combination with D-dimer measurement . SUBJECTS AND METHODS We studied 278 patients who were referred for suspicion of deep venous thrombosis . All patients were stratified into groups of low , moderate , or high risk of deep venous thrombosis on the basis of the clinical assessment and Wells score , and underwent rapid quantitative D-dimer testing ( with a cutoff of 500 microg/mL ) , ultrasound examination , and follow-up for the occurrence of venous thromboembolism . RESULTS Eighty-two patients ( 29 % ) had a deep venous thrombosis . The accuracy of both methods was good ( area under the receiver operating characteristic curve = 0.72 ) , despite only fair agreement at the level of individual patients ( weighted kappa = 0.31 ; 95 % confidence interval [ CI ] : 0.23 to 0.40 ) . The negative predictive value of D-dimer measurement was 96 % ( 95 % CI : 91 % to 100 % ) . When restricted to patients with low pretest probability , the negative predictive value of D-dimer measurement was 100 % ( 95 % CI : 96 % to 100 % ) with the use of the Wells score and 96 % ( 95 % CI : 88 % to 100 % ) with the physician 's assessment . Our results were unchanged in analyses restricted to patients with proximal deep venous thrombosis or out patients . CONCLUSION Clinical assessment to stratify a patient 's likelihood of having deep venous thrombosis should be taught to physicians In patients clinical ly suspected of deep-vein thrombosis ( DVT ) of the lower limbs , it is safe to withhold anticoagulant therapy after a negative ultrasound ( US ) limited to the popliteal and the femoral veins , provided that this can either be repeated or combined with other diagnostic procedures . To assess the safety of withholding anticoagulants after a single negative complete US , we performed a multicenter , prospect i ve , cohort study including consecutive ambulatory out patients from institutional and private practice setting s , with a clinical ly suspected first episode of DVT . Patients fulfilling the inclusion criteria were enrolled after careful clinical assessment . A complete US examination of the proximal and the distal veins was performed according to a st and ardized and detailed protocol . Anticoagulant therapy was administered in patients with proximal or isolated distal DVT and withheld in those with negative results . The main outcome measure was the occurrence of objective ly documented clinical thromboembolic events during a three-month follow-up after a negative US . Out of 623 patients , 401 ( 64.4 % ) had a baseline negative US , were not anticoagulated and could be followed-up for three months . Two patients presented a calf DVT within three months . The incidence of venous thromboembolic events , including distal DVT , was 0.5 % [ 95 % confidence interval : 0.1 - 1.8 ] . No proximal DVT , or non-fatal or fatal pulmonary embolism occurred ( incidence : 0.0 % [ 95 % confidence interval : 0.0 - 0.9 ] ) . In conclusion , it is safe to withhold anticoagulant therapy in patients with clinical ly suspected DVT after a single , negative , complete US . Integrating this method within diagnostic strategies for DVT could improve management and be more acceptable for patients and physicians Color duplex flow imaging ( CDFI ) permits pain- and risk-free direct imaging of the deep venous system of the lower extremities . To prospect ively ascertain the accuracy and limitations of this technique , CDFI was performed in 75 lower limbs of 69 consecutive patients referred for venographic evaluation of clinical ly suspected lower extremity deep venous thrombosis ( DVT ) . The CDFI study was obtained within 24 hours of the contrast venogram . Both studies were interpreted without knowledge of the patient 's clinical findings or the results of the other test . Contrast venography was regarded as the st and ard for diagnosis of DVT . Accuracy was 99 % for detection of DVT above the knee and 81 % below the knee . Sonographic evaluation of the calf veins was technically adequate in 60 % of limbs ; accuracy was 98 % in this group . In the 40 % of limbs with technically limited CDFI studies of the calf , accuracy decreased to 57 % . Although small nonocclusive thrombi occurred infrequently in this series of symptomatic patients , CDFI missed three of four such thrombi . It is concluded that CDFI , when not technically compromised , is sufficiently accurate to definitively diagnose symptomatic lower extremity DVT OBJECTIVE To compare the findings of venous sonography with contrast venography in the detection of deep venous thrombosis ( DVT ) of the lower limbs . DESIGN Prospect i ve study . SETTING The Kenyatta National Hospital , a teaching and referral hospital in Nairobi . SUBJECTS Fifty five limbs in 44 patients with clinical suspicion of DVT were evaluated during the seven months study period ( October 2002-April 2003 ) . The ethics committee in the institution granted approval for the study and participants gave written informed consent . INTERVENTION Venous sonography in which a three step protocol involving B-mode gray scale compression sonography , colour and colour Doppler sonography was obtained after contrast venography in patients with clinical suspicion of DVT . The ultrasound examination was done within 24 hours of the contrast venogram . RESULTS The overall sensitivity of venous sonography was 88.9 % , specificity 91.8 % and accuracy 90.9 % . Considering only DVT above the calf , the sensitivity improved to 100 % . An alternative diagnosis was found by ultrasound in 48.6 % of the negative for DVT cases . CONCLUSION The accuracy of venous sonography as done locally is high and comparable to that in developed countries . We recommend that for patients with clinical suspicion of DVT , venous sonography be done as the initial imaging investigation and venography be reserved for those patients with equivocal or inadequate sonography results |
14,059 | 16,299,211 | Adverse effects were rare and significant adverse outcomes such as hypotension and oxygen desaturation could not be attributed to nitrous oxide .
Compared with patients receiving conventional analgesia , those receiving 50 % nitrous oxide did not require additional medication any more frequently and had a faster recovery from sedative effects .
The low incidence of significant adverse events from 50 % nitrous oxide suggests that this agent could be used safely by lay responders | A safe and effective form of pain relief would be an advantage in the prehospital treatment of patients experiencing extreme pain .
Although used by many emergency medical services , 50 % nitrous oxide ( an inhaled analgesic known to have good pain relief properties ) is not widely used by volunteer and semiprofessional organisations .
This review aim ed to determine whether 50 % nitrous oxide is safe for use by first responders who are not trained as emergency medical technicians . | OBJECTIVE To describe the prehospital use of a continuous positive airway pressure ( CPAP ) system for the treatment of acute respiratory failure presumed to be due to cardiogenic pulmonary edema . METHODS Prospect i ve case-series analysis . Paramedics administered CPAP via face mask at 10 cm H2O to patients believed to be in cardiogenic pulmonary edema and in imminent need of endotracheal intubation ( ETI ) . Data from run sheets and hospital records were analyzed for treatment intervals , vital signs , complications , admitting diagnoses , need for ETI , and mortality . RESULTS Nineteen patients received prehospital CPAP therapy . Mean duration of therapy was 15.5 minutes . Pre- and post-therapy pulse oximetry was available for 15 patients and demonstrated an increase from a mean of 83.3 % to a mean of 95.4 % . None of the patients were intubated in the field . Two patients who did not tolerate the CPAP mask required ETI upon arrival in the emergency department ( ED ) ; an additional five patients required ETI within 24 hours . There was one death in the series and two additional adverse events ( one aspiration pneumonia , one pneumothorax ) ; none of these were attributable to the use of CPAP . The diagnosis of cardiogenic pulmonary edema was corroborated by the ED or in-hospital physician in 13 patients ( 68 % ) . Paramedics reported no technical difficulties with the CPAP system . CONCLUSION For patients with acute respiratory failure and presumed pulmonary edema , the prehospital use of CPAP is feasible and may avert the need for ETI . Future controlled studies are needed to assess the utility and cost-effectiveness of prehospital CPAP systems The possible benefits of premedication with the antispasmodic hyoscine n-butyl bromide ( hyoscine ) and analgesia with inhaled nitrous oxide/oxygen mixture ( nitrous oxide ) were assessed in a double-blinded , placebo-controlled trial . Consecutive patients at normal risk for cancer undergoing screening flexible sigmoidoscopy were r and omly allocated to receive either ( 1 ) intravenous hyoscine 20 mg plus inhaled oxygen on dem and ( n = 40 ) , ( 2 ) sterile water injection plus inhaled nitrous oxide on dem and ( n = 48 ) , or ( 3 ) sterile water injection plus inhaled oxygen on dem and ( n = 43 ) . One recently trained primary care physician performed all procedures . Duration of the procedure , endoscopic findings , and depth of insertion were recorded . After the examination , screenees rated their degree of pain during the procedure using a visual analogue scale . Depth of insertion did not differ between the three study groups , but the duration of the procedure was significantly less in the hyoscine group ( median , 12.5 minutes ) as compared with placebo ( median , 18 minutes ; p = .0008 ) . Fifty-four percent of screenees chose to use the on-dem and gas . Pain scores were significantly lower in those individuals who inhaled nitrous oxide as compared with placebo ( p = .045 ) . Premedication with antispasmodic shortens total procedure time for flexible sigmoidoscopy by a moderately experienced endoscopist as compared with placebo . In this study , a significant number of screenees experienced discomfort during flexible sigmoidoscopy , which appeared to be reduced by offering nitrous oxide inhalation The analgesic effect of self-administered nitrous oxide 50%/oxygen 50 % ( ' Entonox " analgesic apparatus ) was compared with air given by the same method in a double-blind trial in 81 patients with myocardial infa rct ion . Self-administered nitrous oxide/oxygen , which was associated with a low frequency of side-effects , proved significantly more effective than air in the early relief of severe cardiac pain , but not in the relief of moderate or slight pain or when administration was continued after ten minutes Background Intermittent self-administered nitrous oxide has long had widespread use as an analgesic in labor , but its efficacy has not been adequately established . Questions about its effect on maternal oxygenation between labor contractions also have been raised . Methods Twenty-six women were recrulted to participate in a r and omized , double-blind , cross-over , placebo-controlled study to assess the effect of intermittent nitrous oxide inhalation on labor pain and maternal hemoglobin oxygen saturation ( SpO2 ) during the first stage of labor . Visual analog scale pain scores for each of five consecutive labor contractions were measured after administration of either nitrous oxide or compressed air . Results Mean visual analog scale pain scores for five contractions were 5.1 , 5.2 , 5.7 , 5.2 , and 5.6 ( nitrous oxide ) and 4.9 , 5.2 , 6.1 , 5.6 , and 5.7 ( compressed air ) . There were no statistically significant differences in pain when nitrous oxide as compared with compressed air was administered . Pain scores did not differ significantly over time as a function of inhaled substance ( F = 0.41 , P = 0.53 ) . The mean lowest SpO2 observed between these contractions after self-administration of nitrous oxide and air were 97 , 97 , 97 , 97 , and 97 % ( nitrous oxide ) and 97 , 96 , 96 , 96 , and 96 % ( compressed air ) . SpO2 was significantly higher after nitrous oxide administration ( F = 8.8 , P = 0.007 ) . Conclusions While intermittent self-administered 50 % nitrous oxide in oxygen does not appear to predispose parturient women to hemoglobin oxygen desaturation , its analgesic effect has yet to be clearly demonstrated OBJECTIVE : Although percutaneous liver biopsy ( PLB ) can be a painful procedure , common practice has not included intravenous sedation or analgesia Patient-administered nitrous oxide/oxygen ( N2O/O2 ) inhalation has demonstrated analgesic efficacy in various procedures associated with mild to moderate pain The aim of this study was to investigate the safety and efficacy of analgesia with N2O/O2 inhalation for PLB METHODS : One hundred consecutive patients undergoing a first PLB ( for chronic hepatitis C : 56 , for alcoholic liver disease : 23 , for miscellaneous reasons : 21 ) Patients were r and omly assigned to self-administrate from a facial mask with a dem and valve , for 5 min before and during biopsy , either a breathing mixture of 50 % N2O/O2 ( N2O group , n = 51 ) , or a breathing oxygen placebo ( P group , n = 49 ) Liver biopsy was performed at bedside after adequate local anesthesia with xylocaine At the end of the procedure , patients were asked to self-evaluate pain experienced using a visual analogue scale ( VAS ) with scoring from 0 to 100 mm . RESULTS : N2O/O2 administration result ed in the absence of pain in a significantly higher number of patients treated than in patients of the P group : 19 versus 2 , respectively ( p = 0.0001 ) . Patients receiving N2O/O2 had significantly lower pain scores than those of the P group : 12 ± 12 versus 28 ± 19 mm ( p < 0.0001 ) . No serious complication was observed . Side effects of N2O/O2 were minor and reversible . The average cost per biopsy was 4 US dollars . CONCLUSIONS : Patient-administered N2O/O2 inhalation provides safe and effective analgesia , at a reasonable cost , for PLB . Its routine use could be useful for the management of patients with chronic liver disease undergoing PLB as it may enhance patients compliance with future biopsies BACKGROUND AND STUDY AIMS Patient-administered nitrous oxide in 50 % oxygen has lately come into use as an alternative to combined opioid and benzodiazepine medication for colonoscopic procedures . A r and omized study was carried out comparing intramuscular pethidine hydrochloride 1 mg/kg with inhalation of Medimix ( a mixture of nitrous oxide in oxygen 50 % ) for relief of pain and anxiety during colonoscopy . PATIENTS AND METHODS Thirty-eight patients ( 19 in the pethidine group and 19 in the nitrous oxide group ) were studied . The following parameters were measured : blood pressure , pulse rate , and arterial oxygen saturation . At the end of the colonoscopy and before the patients left the ward , pain , nausea , and general well-being were evaluated by the patients using a visual analogue scale . The colonoscopy time , investigation conditions and the total length of hospital stay were registered . RESULTS Colonoscopy time and the colonoscopists ' opinions concerning the investigation conditions did not differ between the groups . Pain relief and patient evaluation of the total procedure were also equal between the patient groups . However , there was less nausea among the Medimix patients . Three patients in the pethidine group had oxygen saturations below 92 % . There was no desaturation during and five minutes after colonoscopy in the Medimix group . Patients in the Medimix group left the hospital on average 34 minutes earlier than patients in the pethidine group . CONCLUSIONS We conclude that the use of nitrous oxide ( Medimix ) as an analgesic is as good as pethidine for colonoscopy . Medimix has clear advantages compared to pethidine in terms of reducing nausea and shortening the hospital stay Hypoxaemia may occur after hyperventilation with nitrous oxide during labour . The purpose of this study was to assess whether diffusion hypoxia is a contributory factor . Twenty‐four parturients were r and omly allocated to receive 50 or 70 % nitrous oxide in oxygen . The median nitrous oxide inhalation time per contraction was 58 s and 33 s , respectively . The end‐tidal carbon dioxide and the minute ventilation remained unchanged . The end‐tidal oxygen concentration was lowest at 120s , reaching 15.4 % in both groups . The oxygen saturation did not differ between the groups with a lowest median value of 96 % before the start of nitrous oxide inhalation . Two parturients had episodes ofdesaturation . Both had low end‐tidal oxygen concentrations in association with the desaturation but , as the end‐tidal nitrous oxide concentrations were low , the desaturations could not be attributed to diffusion hypoxia In a r and omized trial nitrous oxide 50 % in oxygen ( Entonox ) or oxygen 100 % was given during chest physiotherapy on 23 occasions to three mechanically ventilated patients with severe head injuries . Intracranial pressure ( i.c.p . ) increased by 22.7 mm Hg ( SD 10.62 ) during chest physiotherapy with Entonox , compared with 10.5 mm Hg ( SD 10.4 ) with oxygen 100 % ( P greater than 0.02 ) . A further nine mechanically ventilated patients with severe head injuries were given Entonox without chest physiotherapy . There was a mean increase in i.c.p . of 3.8 mm Hg ( SD 2.4 ) ( P less than 0.001 ) when Entonox was given , and a mean decrease of 4.6 mm Hg ( SD 2.8 ) when the nitrous oxide was withdrawn . End-tidal carbon dioxide concentration showed almost no change during nitrous oxide administration ( decrease of 0 - -0.1 % ) . We conclude that nitrous oxide causes an increase in i.c.p . in patients with severe head injuries and exacerbates the increases in i.c.p . occurring during chest physiotherapy Summary A prospect i ve , r and omized study was undertaken to compare the effectiveness of nitrous oxide with intramuscular sedation ( meperidine and promethazine ) in providing analgesia and amnesia during the reduction and treatment of children 's fractures in an outpatient clinic setting . Fifteen patients received a 50:50 mixture of nitrous oxide and oxygen , and 15 received intramuscular injection . The two groups were similar in regard to gender distribution , age , and fracture types . Pain response was recorded using the Children 's Hospital of Eastern Ontario ( Canada ) Pain Scale ( CHEOPS ) at the time of fracture reduction and 30 min postreduction . At the first follow-up visit a question naire regarding the patient 's memory and subjective experience of the fracture reduction was answered . Data between the two groups were compared using the Mann-Whitney test . The CHEOPS scores , and the memory and subjective experience of the fracture reduction were similar between the two groups . Time in the outpatient department averaged 83 min for the intramuscular group and 30 min for the nitrous oxide group ( p < 0.01 ) . All of the nitrous oxide patients stated they would use nitrous oxide again , whereas only eight of 15 intramuscular patients stated they would try intramuscular sedation again . Nitrous oxide is as effective as intramuscular sedation in providing analgesia and amnesia in the treatment of children 's fractures while having a more rapid onset and a shorter recovery period with greater patient acceptance In this five-period r and omised double-blind crossover study , 12 healthy volunteers inhaled mixtures of nitrous oxide at concentrations of 0 % ( placebo ) ; 5 % , 10 % ; 20 % and 40 % in oxygen . Each concentration was inhaled for about 1 h , each period being on a separate day . The effects of nitrous oxide were measured using a comprehensive battery of performance tests including measures of attention , psychomotor function , memory and cognition . Mood was assessed with visual analogue scales . All tests except critical flicker fusion showed substantial effects at the highest does ( 40 % ) . No measure showed evidence of change at the lowest concentration ( 5 % ) . Several measures showed significant impairment at 10 % , viz : digit-symbol substitution , choice reaction time ( latency and total ) , tapping , and continuous attention . Subjects felt dizzy and muzzy on nitrous oxide , but no significant effect was seen on the Alert-Drowsy VAS . The dose-response profiles of the various tests showed substantial differences . Thus tapping was virtually linear , while choice reaction motor time and body sway showed steeply accelerating impairment with increasing dose . These results indicate that comparisons of profiles of drug-induced change must take into account the variable effects of dose before interpretations in terms of specific drug effects can be made BACKGROUND Intravenous sedation/analgesia for colonoscopy is accompanied with certain risks and postprocedure drowsiness . We sought to determine whether inhaled nitrous oxide ( Entonox : 50 % nitrous oxide , 50 % oxygen ) provides adequate analgesia for colonoscopy and the impact of this agent on recovery . METHODS All patients undergoing outpatient colonoscopy were considered for the study ( n = 248 ) except those with previous colonic resection . Data for patients unsuitable for r and omization ( n = 58 ) and those who declined to participate ( n = 88 ) were also analyzed . RESULTS One hundred two patients were r and omized to receive inhaled Entonox alone ( n = 56 ) or intravenous midazolam and meperidine ( n = 46 ) . Forty-nine ( 88 % ) patients r and omized to Entonox underwent complete colonoscopy without conversion to intravenous medications . Entonox patients reported more pain ( p < 0.0001 ) , tolerated colonoscopy less well ( p < 0.0001 ) , were less satisfied ( p = 0.01 ) , and less willing to undergo colonoscopy again under the same circumstances ( p = 0.04 ) . Of patients receiving intravenous medication , 91 % found colonoscopy less unpleasant and 9 % as unpleasant as anticipated ; this compares with 52 % and 21 % Entonox patients , respectively , and an additional 27 % Entonox patients who found colonoscopy more unpleasant than anticipated . Recovery was faster among Entonox patients ( median 30 versus 60 minutes , p < 0.0001 ) . CONCLUSION Entonox is less effective than midazolam with meperidine for colonoscopy but is acceptable in many patients and allows faster recovery The analgesic , subjective , and psychomotor effects of 0 , 10 , 20 , 30 , and 40 % nitrous oxide in oxygen were studied in 10 volunteers to determine if acute tolerance developed differentially to these variables . In this prospect i ve , r and omized , crossover , double-blind study , volunteers inhaled either placebo ( 100 % oxygen ) or one of the aforementioned doses of nitrous oxide for 120 min . During this period , volunteers immersed their non-dominant forearm , for 3 min , in ice-cold water at 25 , 70 and 115 min from the onset of the inhalation . At other prescribed time intervals throughout the session , mood and psychomotor performance were assessed . Subjects reported less pain intensity from the cold-water stimulus and reported the pain bothered them less as a function of increasing nitrous oxide dose ; in addition , this analgesia was significantly less as the inhalation period progressed ( i.e. , acute tolerance ) . Some subjective effects of nitrous oxide that could be considered hedonic in nature ( elation , drug liking ) also showed evidence of acute tolerance . In contrast , other subjective effects and the psychomotor-impairing effects of nitrous oxide did not change significantly during the inhalation period ( i.c . , no acute tolerance ) . The differential acute tolerance observed in this study suggests that different effects of nitrous oxide may be mediated by different neurochemical substrates In a double-blind , r and omized , placebo-controlled study of patients undergoing colonoscopy , sedation with an inhaled mixture of nitrous oxide/oxygen was compared with conventional intravenous sedation ( pethidine 50 mg , midazolam 2.5 mg ) . In the patients studied , no significant differences were noted in number of pain episodes , need for additional intravenous sedation , or patient pain scores between the group receiving the nitrous oxide/oxygen mixture ( n = 30 ) and those managed with conventional benzodiazepine/opiate injection ( n = 29 ) . Both methods were significantly more effective than placebo ( n = 30 ) . Six patients in the benzodiazepine/opiate group had oxygen desaturation , whereas none did in the nitrous oxide/oxygen group . Duration of stay after the procedure was significantly shorter in the gas inhalation group than in those receiving conventional intravenous sedation . Except for patients with severe chronic obstructive pulmonary disease , nitrous oxide/oxygen inhalation is a safe and acceptable alternative method of sedation and analgesia during colonoscopy To determine whether administration of nitrous oxide , 50 % and 70 % , could provide analgesia and anxiolysis during venous cannulation in pediatric patients , 165 ASA Physical Status 1 patients scheduled for elective surgery were studied . Children , 3 weeks to 18 yr of age , were r and omly assigned either to receive nitrous oxide , 50 % or 70 % in oxygen , or 100 % oxygen via mask or to a group breathing room air , for 3 min prior to and during venous cannulation . A blinded observer using a behavioral scale for rating pain in children performed assessment s of behavior and pain before and following venous cannulation . Children who received 50 % or 70 % nitrous oxide were more likely to be relaxed , 59 % and 84 % , respectively , and had little evidence of pain . Of those given 100 % oxygen or no mask , only 30 % and 21 % , respectively , were considered relaxed , and 16 % and 15 % had little evidence of pain during venous cannulation . Side effects were seen in 28 % of the group given 70 % nitrous oxide and included excitement , dysphoria , nausea , restlessness , and opisthotonic movements . Both 50 % and 70 % nitrous oxide in oxygen administered to pediatric patients are effective at decreasing the pain and anxiety associated with venous cannulation , but use of the latter is associated with side effects The arterial oxygen saturation of 40 mothers in the first stage of labour was monitored using pulse oximetry . Half the mothers received epidural analgesia and the rest inhaled Entonox for pain relief . Eight mothers in the Entonox group and six in the epidural group had at least one episode of significant hypoxia ( saturation < 90 % ) . There was little difference in the number of hypoxic episodes experienced by either group ( 29 in the Entonox and 21 in the epidural ) although their mean duration and severity was greater in the Entonox group . Women in labour who inhale Entonox have an appreciable incidence of arterial desaturation . Epidural analgesia reduces the severity of hypoxic episodes although it does not eliminate them Analgesic effect , labor outcome , safety and consumer satisfaction were compared in 170 primigravid women ; 50 using TENS initially for pain relief , 20 using entonox , 50 pethidine + promazine and 50 lumbar epidural . 88 % choosing epidural related it fully effective . 90 % using entonox , 96 % using TENS and 54 % given pethidine + promazine found partial relief . 82 % of patients given TENS and 80 % given pethidine + promazine required additional analgesia . This was also needed by one of the 20 patients choosing entonox . Women using entonox alone had the shortest labors and women using lumbar epidural , the longest . Operative delivery was significantly more common in women receiving lumbar epidural . No significant intergroup differences were noted in cord pH or Apgar scores . Parturients and midwives both gave high consumer satisfaction ratings to all methods — except for pethidine + promazine , whose use must therefore be question ed . The analgesic efficacy of lumbar epidural outweighs any possible side effects . Entonox appears suited to those able to cope with the earlier part of labor , drug‐free . Realization of the potential of TENS requires the design of machines specifically to cope with the quality of the pain of labor OBJECTIVE To determine the effect of an inhaled 50 % nitrous oxide/50 % oxygen mixture on measures of observed anxiety in children during laceration repair . METHODS A prospect i ve , r and omized , placebo-controlled , double-blind comparison of an inhaled 50 % nitrous oxide/50 % oxygen mixture ( treatment group ) with 100 % oxygen ( control group ) during repair of lacerations was performed . The study population was a convenience sample of children aged 2 - 7 years in an urban pediatric ED . The primary outcome variable was the change in scores before and during laceration repair with a 10-point modified Children 's Hospital of Eastern Ontario Pain Scale ( CHEOPS ) assessment . The secondary outcome variable was a 4-point anxiety scale measured before and during the procedure . RESULTS Thirty patients were entered into the study . Seventeen children inhaled the 50 % nitrous oxide/oxygen mixture and 13 inhaled 100 % oxygen during laceration repair . There was no statistically significant difference in initial CHEOPS and anxiety scores between the 2 groups ( p = 0.687 and 0.809 , respectively ) . The median CHEOPS scores in the treatment group decreased by 5 points , while those of the control patients increased by 3 ( p < 0.001 ) . The median anxiety scores in the treatment population decreased by 1 point , with an increase of 1 for the control patients ( p < 0.001 ) . CONCLUSION Administration of a 50 % nitrous oxide/50 % oxygen mixture to children during their laceration repair result ed in a significant decrease in measures of anxiety when compared with inhalation of 100 % oxygen The possibility of reducing recovery time after colonoscopy was studied using patient-administered nitrous oxide and comparing it with our st and ard treatment of ketobemidone plus midazolam . Fifty consecutive colonoscopy patients were r and omized to receive either ( i ) intravenous ketobemidone hydrochloride 2.5 mg , midazolam 2.5 mg , and breathing air from a face mask with a dem and valve ( KHM ) or ( ii ) intravenous saline and a breathing mixture of even parts of oxygen and nitrous oxide ( Entonox ) from the same valve setup . Patient discomfort during colonoscopy was assessed using visual analogue scales . All patients were allowed to stay for recovery as long as they wanted , and the time was measured . Modified re collection tests were performed prior to colonoscopy and when the patients left the Endoscopy Unit , in order to study the degree of mental impairment induced by the procedure and the medication . All patients had complete colonoscopies of the same duration in both groups . Discomfort during colonoscopy was rated the same in both groups ( 2p = 0.6413 ) . Both groups of patients scored identically in the precolonoscopy re collection test . Most patients had a lower score after colonoscopy , but Entonox-treated patients scored significantly better than those with KHM ( 2p = 0.0250 ) . Patients treated with Entonox opted to leave the Unit directly after the procedure ( median 0 minutes ; interquartile range 0 - 5 minutes ) compared to 38 minutes for those with KHM ( interquartile range 10 - 75 min ) , 2p < 0.001 . It seems from our data that nitrous oxide gives pain relief equal to that in our st and ard treatment . ( ABSTRACT TRUNCATED AT 250 WORDS The objective of this study was to determine the efficacy of nitrous oxide in the therapy of acute migraine symptoms in emergency department ( ED ) patients . This was a prospect i ve , r and omized , double blind study of patients presenting to an ED . All eligible patients had a prior diagnosis and symptoms consistent with migraine headache and a normal neurological examination . Patients were r and omized to receive either 50 % nitrous oxide and 50 % oxygen or 100 % oxygen over 20 minutes . All patients completed a visual analog pain scale before and immediately after intervention . Initial pain scores and change in pain scores between the two groups were compared . There were 22 patients enrolled , 10 in the nitrous oxide group and 12 in the oxygen group . The groups were similar in age , gender , duration of headache , and initial pain scores . Pain scores decreased significantly in the nitrous oxide group ( median change , 69 to 21 mm , P = .02 ) . The oxygen group did not show significant change in pain scores ( median change , 78.5 to 72 , P = .09 ) . Eighty percent of patients receiving nitrous oxide required no rescue medication at the completion of the intervention , compared with 17 % of those receiving 100 % oxygen ( P = .008 ) . Twenty minutes after termination of intervention , 60 % of patients who had received nitrous oxide still required no rescue medication , compared with 8 % of those who had received 100 % oxygen ( P = .02 ) . Nitrous oxide shows efficacy in ED short-term treatment of acute migraine headache |
14,060 | 28,068,364 | Our analysis showed that stenting failed to improve the stone-free rate , and instead , it result ed in additional complications .
However , ureteral stents are valuable in preventing unplanned re-hospitalization . | BACKGROUND AND AIM Ureteroscopic lithotripsy ( URL ) and extracorporeal shock wave lithotripsy ( ESWL ) are two widely used methods for the treatment of ureteral stones .
The need for ureteral stenting during these procedures is controversial .
In this meta- analysis , we evaluated the benefits and disadvantages of ureteral stents for the treatment of ureteral stones . | PURPOSE A prospect i ve r and omized controlled trial was performed to determine whether stents may be eliminated after uncomplicated ureteroscopic lithotripsy for ureteral stones . MATERIAL S AND METHODS A total of 58 patients underwent uncomplicated ureteroscopic intracorporeal lithotripsy . After stone fragmentation patients were r and omized to a nonstented ( 29 ) or a stented ( 29 ) treatment group . Intracorporeal lithotripsy was performed with the holmium laser in 57 cases and by electrohydraulic lithotripsy in 1 without balloon dilation or the extraction of stone fragments . Patients were followed 1 , 6 and 12 weeks postoperatively . In stented cases the stent was removed at 1 week . Outcome measures included postoperative symptoms assessed with a visual analog scale , postoperative analgesic requirements , complications and the stone-free rate . RESULTS At 1 week the symptoms of flank pain , abdominal pain , dysuria and frequency were significantly greater in the stented group ( p < 0.005 ) . There were no differences in symptoms in the groups at subsequent followup visits . There was no difference in treatment groups in terms of the amount of analgesic required in the recovery room or during 1 week after ureteroscopy . Similarly there was no difference in the number of patients requiring antiemetics . One patient in the stented group required hospitalization for genitourinary sepsis and 1 patient in the nonstented group visited the emergency room for postoperative vomiting . The stone-free rate was 100 % in each group . CONCLUSIONS These results demonstrate that after ureteroscopic intracorporeal lithotripsy with the holmium laser patients with a stent have significantly greater irritative and painful symptoms than those without a stent in the early postoperative period . There was no difference in nonstented and stented ureteroscopy with respect to complications or stone-free status . Therefore , we believe that routine stenting after ureteroscopic intracorporeal lithotripsy with the holmium laser is not required as long as the procedure is uncomplicated and performed without balloon dilation of the ureteral orifice Purpose To determine the need for pre-treatment stenting in patients undergoing extracorporeal shockwave lithotripsy ( ESWL ) for ureteral stones sized 4–10 mm . Methods A prospect i ve r and omized study was conducted between September 2009 and March 2011 . Included 156 patients r and omized in stented and non-stented groups and underwent a maximum of 3 ESWL sessions . Radiographic follow-up was used to assess the stone fragmentation and clearance . Results were compared in terms of stone-free rates , post-treatment morbidity and complications . Results Overall efficacy was 76.9 % . Stone-free rates were statistically significantly lower ( P = 0.026 ) in the stented group ( 68.6 % ) compared to the non-stented ones ( 83.7 % ) . Furthermore , stenting was significantly correlated with post-treatment lower urinary tract symptoms ( P ≤ 0.001 ) , need for more ESWL sessions ( P = 0.019 ) and possibility for operation due to ESWL failure ( P = 0.026 ) . A multivariate analysis was conducted to identify the parameters which may predict complete stone removal after ESWL . Stone size ( P = 0.026 ) , stone location ( P = 0.011 ) and stenting ( P = 0.007 ) were the most significant factors . Conclusions ESWL is an efficient and safe treatment for 4- to 10-mm ureteral stones . Pre-treatment stenting is limiting stone-free rates and is significantly influencing post-ESWL morbidity and quality of life in a negative manner , while it contributes minimally to the prophylaxis of complications BACKGROUND AND PURPOSE Insertion of a ureteral stent is routinely done after ureteroscopy . Recently , several authors have question ed routine stenting after ureteroscopy for distal ureteral stones . We report our results of a r and omized study comparing ureteroscopy with and without placement of stents for distal ureteral stones . PATIENTS AND METHODS A total of 48 patients undergoing ureteroscopy for distal ureteral stones were r and omized to a stented group ( N = 26 ) or a nonstented group ( N = 22 ) . Ureteroscopy was carried out with Wolf 8.5F semirigid endoscope , and the Swiss Lithoclast was used as the source of energy . Any stent was removed at 3 weeks . Patients were assessed for success , operative time , postoperative pain score , analgesic requirement , stent-related symptoms , and risk of ureteral stricture formation . Baseline variables were not significantly different in the two groups . RESULTS There was no significant difference in the two treatment groups with regard to need for ureteral dilation , use of intracorporeal lithotripsy , or occurrence of intraoperative and postoperative complications . A successful outcome was achieved in 100 % of both groups . The mean pain score on day 0 was 5.23 + /- 0.95 of 10 in the stented group and 4.82 + /- 0.96 in the nonstented group ; this difference was not statistically significant . Similarly , the analgesic requirement in the two treatment groups was not significantly different . However , patients with stents had significantly more pain ( including flank pain with voiding : P = 0.01 ) , urgency ( P = 0.04 ) and dysuria ( P < 0.01 ) . Radiologic follow-up was available for 83.33 % of the patients at the 3-month visit . None of the patients had evidence of ureteral stricture or residual stone fragments . CONCLUSION In select patients undergoing ureteroscopy for distal ureteral stones , stents can be safely omitted . Patients without stents have significantly fewer lower-urinary symptoms of pain , urgency , and dysuria and are not at risk of increased complications . Avoiding stents may be particularly cost effective in developing countries PURPOSE We performed a prospect i ve , r and omized clinical trial to evaluate the outcome of ureteral stents for solitary ureteral stones 2 cm or less in moderately or severely obstructed systems using shock wave lithotripsy . MATERIAL S AND METHODS Between 2001 and 2004 , 186 patients who met study criteria were r and omized into 2 groups . Group 1 received a pre-shock wave lithotripsy 6Fr Double-J stent and group 2 had no stent . Patients were treated with a Dornier MFL 5000 lithotripter . Results were compared in terms of clearance rates , number of shock waves and sessions , irritative voiding symptoms , incidence of complications and secondary interventions . Failure was defined as the need for additional procedure(s ) for stone extraction . RESULTS Overall 164 patients ( 88.2 % ) became stone-free after shock wave lithotripsy . Complete stone fragmentation was achieved after 1 to 3 and more than 3 session in 108 ( 58.1 % ) , 30 ( 16.1 % ) , 13 ( 7 % ) and 14 patients ( 7.5 % ) , respectively . Ureteral stent insertion did not affect the stone-free rate , which was 84.9 % and 91.4 % in groups 1 and 2 , respectively ( p = 0.25 ) . There was no statistical difference in the re-treatment rate , flank pain or temperature in the 2 groups . However , all patients in the stented group significantly complained of side effects attributable to the stent , including dysuria , suprapubic pain , hematuria , pyuria and positive urinary culture . CONCLUSIONS Pretreatment stenting provides no advantage over in situ shock wave lithotripsy for significantly obstructing ureteral calculi . Shock wave lithotripsy is reasonable initial therapy for ureteral stones 2 cm or less that cause moderate or severe hydronephrosis PURPOSE We determined the differences in outcome between ureteral stenting and nonstenting following uncomplicated ureteroscopy for distal ureteral stones . MATERIAL S AND METHODS A total of 220 patients treated with successful ureteroscopy for distal ureteral stones were r and omized to 2 equal groups according to postoperative placement of a ureteral stent ( Cook Irel and , National Technological Park , Irel and ) , including group 1 - -without a stent and group 2 - -with a stent . Outcome measures were flank pain and dysuria at 48 hours and 1 week , early postoperative complications , analgesia need , rehospitalization , return to normal physical activity , stone-free rate , stone recurrence and late postoperative complications . Patients were followed a mean + /- SD of 25 + /- 9 months ( range 12 to 49 ) . RESULTS Early postoperative complications , including low grade fever , hematuria and urinary tract infection , were observed in 22 patients ( 20 % ) in group 1 and 19 ( 19 % ) in group 2 , a difference of no significant value . Mean initial hospitalization and time to return to normal physical activity were not different between the 2 groups . At 48 hours and 1 week there was no significant difference in flank pain between the 2 groups , while dysuria was significantly less in the nonstented group . The amount of analgesics required in the recovery room was not different but after discharge from the hospital stented patients used a larger amount of analgesia while the stent was still in the ureter . The stone-free rate at 4 weeks was 100 % in each group . Late postoperative sequelae , including stone recurrence and ureteral narrowing , were reported in 6 patients ( 5.5 % ) in group 1 and 4 ( 3.6 % ) in group 2 , a difference of no significant value . CONCLUSIONS Uncomplicated ureteroscopy for treatment of distal ureteral stones is safe without stent placement . Patients without stents have significantly fewer irritative bladder symptoms and are not at risk of increased complications BACKGROUND AND PURPOSE Ureteral stent placement after ureteroscopic lithotripsy has some advantages and disadvantages . In this r and omized study , the necessity of ureteral stent placement after uncomplicated ureteroscopy for impacted ureteral stones was assessed . MATERIAL S AND METHODS Between 2005 and 2007 , 60 evaluable patients were equally r and omized to groups with and without stents . Patients underwent ureteroscopic pneumatic lithotripsy for ureteral stones . The operation was completed with or without stent placement according to the r and omization order . Excretory urography was performed 3 months after the procedure . All stents were cystoscopically removed at the third postoperative week . Sociodemographic and clinical variables ( age , sex , stone location , stone size , operative time , hospital stay , narcotic and nonnarcotic analgesic use ) , and postoperative complications ( fever , pain delaying discharge , emergency department visit , urinary retention , stent-related irritative symptoms ) were evaluated . RESULTS Mean stone size was not significantly different in both groups . Mean operative time was significantly longer in the stent group : 30.5 + /- 9.6 vs 43.7 + /- 11.6 minutes . On the operation day and until postoperative day ( POD ) 5 , narcotic ( P = 0.004 ) and nonnarcotic analgesic ( P = not significant ) use was more frequent in the no-stent group . At POD 5 and later , although narcotic and nonnarcotic analgesic use were frequently necessary in the stent group , both were almost unnecessary in the no-stent patients . Stent-related irritative symptoms were overwhelmingly higher ( 10 % vs 93 % ) in the stent group . Discharge was delayed ( 23 % vs 10 % ) and unplanned emergency department visits ( 20 % vs 10 % ) were exercised almost two times more commonly in the no-stent group . Stone-free rates were identical ( n = 29/30 ; 97 % ) in both groups . CONCLUSION Routine placement of a ureteral stent is not m and atory in patients without complications after ureteroscopic lithotripsy for impacted ureteral stones . Stent placement can be argued and agreed with the patients preoperatively in the light of the data presented above OBJECTIVE To verify if post-ureteroscopy ( URS ) stenting is still necessary as a routine strategy , or if some cases can be treated without . METHODS Between August 2004 and April 2005 , 85 patients were admitted to the Urology Department at the Nephrology and Urology Center , Al-Thawra Hospital , Yemen with ureteric stones of different size and site . All were scheduled and treated by the ureteroscopy method . According to prospect i ve pure r and omization , 45 patients were left non-stented at the end of the operation ( non-stented group ) , while 40 patients were left with stent ( stented group ) . RESULTS The ages of the non-stented group ranged between 6 - 70 years ( mean 34.36 + /- 15.53 ) , while the size of the stones ranged between 5 - 20 mm ( mean 8.4 + /- 3.1 ) . They were 33 males and 12 females . Regarding the site , 26 stones were in the right , and 19 in the left ureter . In the stented group , the ages ranged between 14 - 70 years ( mean 39.35 + /- 13.36 ) , while the size of the stones ranged between 6 - 16 mm ( mean 9.9 + /- 3.2 ) . They were 34 males and 6 females . Twenty-five stones were in the right ureter , and 15 in the left . Success was 100 % in the non-stented group , while it was 39 out of 40 in the stented group . The 2 groups were compared statistically for postoperative analgesia , color clearance of urine and hospital stay , and found significantly different . However , for operative time , the difference was insignificant . CONCLUSION When treating ureteric stones by ureteroscopy , postoperative stenting should not be used as routine , but should be limited to those with ureteric injury , bigger sizes and prolonged operative time . The non-stenting method decreases the need for postoperative analgesia , time of color clearance and hospital stay PURPOSE To evaluate the hypothesis that prophylactic insertion of Double-J stents after uncomplicated transurethral lithotripsy ( TUL ) can decrease the number of episodes of renal colic and their intensity in patients with recurrent ureteral stones ( those with three or more episodes of stone formation ) . PATIENTS AND METHODS During a prospect i ve r and omized clinical trial from May 1999 to January 2004 , 195 patients with recurrent ureteral stones were included in our study ; 94 had stents in place for 4 weeks , and 101 patients remained stentless ( control group ) . A few patients in each group had residual stone disease . All patients were followed-up for a mean period of 24 months and question ed about the number and intensity of their episodes of renal colic , and were also evaluated for their rates of spontaneous stone passage . RESULTS Spontaneous passage of stones was seen in 43 patients ( 45.7 % ; CI 95 % , 35.7 , 55.8 ) who underwent stenting , and 35 patients ( 34.7 % ; CI 95 % , 25.4 , 43.9 ) in the stentless group ( P > 0.05 ) . The number of episodes of renal colic was significantly lower in the stented group ( P < 0.001 ) . CONCLUSION Insertion of Double-J stents for 4 weeks after uncomplicated TUL in patients with recurrent ureteral stones significantly decreases the number of episodes of ureteral colic , although it does not decrease the rate of stone formation Abstract Objectives To evaluate the efficacy of tamsulosin therapy in reducing ureteral double-J stent morbidity by evaluating USSQ , IPSS , QOL and VAS ( primary objective ) and to evaluate the morbidity and or complication(s ) associated with indwelling double-J ureteral stent(s ) and to evaluate the safety of tamsulosin therapy for “ morbidity associated with double-J stents ” by evaluating its tolerability , side effects and adverse events if any ( secondary objective ) as per protocol . Methods After institutional review board approval , 60 consecutive patients with a double-J ureteral stent inserted after percutaneous nephrolithotomy or ureteroscopic stone treatment were r and omly assigned to receive tamsulosin 0.4 mg , or a placebo for 4 weeks . The vali date d USSQ , VAS and IPSS were completed before stent insertion , at 3 days and 4 weeks after stent insertion and at 2 weeks after stent removal . Data were statistically analyzed for efficacy and tolerability of one drug over the other using Wilcoxon signed-rank test , Mann – Whitney test and Student ’s t test . Results Patients receiving tamsulosin compared with the placebo showed significant decrease in urinary index score , pain index score , work performance score , VAS score at loin area , VAS score at flank , VAS score at suprapubic area , average VAS score , need for antibiotics , number of hospital visits ( P < 0.05 ) at the end of fourth weeks . Decrease in values were also observed in IPSS score , general health score , quality of sex score and IPSS- quality of life ( QOL ) score in patients taking tamsulosin but , however , the decrease was not significant . No patients discontinued medication because of side effects . Conclusion We conclude that ureteral stenting using double-J stents with concomitant tamsulosin therapy was generally well tolerated , safe , effective and significantly beneficial in reducing stent morbidity in the majority of our patients . We advocate the routine use of concomitant tamsulosin therapy in eligible patients undergoing ureteral stenting in order to minimize stent morbidity BACKGROUND Stents were used routinely after ureteroscopy to prevent postoperative ureteral obstruction . However , because of the recognized complications of stents , non-stenting is the new trend after uncomplicated ureteroscopy . The wall of the bilharzial ureter is characteristically thick and may be calcified . The aim of this study is to see if the non-stenting trend could be applied to ureteroscopic manipulation of stones in bilharzial ureters . PATIENTS AND METHODS In this prospect i ve study , 56 patients , with evidence of bilharzial lesions in the urinary tract , undergoing ureteroscopy for distal ureteral stones were included . After successful uncomplicated stone fragmentation and extraction , patients were r and omized into two groups . Group A includes 28 patients in whom double J 6-Fr polyurethane stents were placed for 3 weeks . Group B includes 28 non-stented patients . Postoperative fever , loin pain , lower urinary tract symptoms and change in the degree of hydronephrosis were reported . RESULTS There was no significant difference in the mean age of patients and stone size in both groups . The mean operative time was 43 + /- 14 min in group A and 38 + /- 11 in group B. There was no significant difference in the mean loin pain score , in the first postoperative 48 h , in both groups ( 4.4 + /- 0.8 in group A and 4.9 + /- 0.5 in group B ) . Patients in group A had , significantly , more flank pain with voiding ( P < 0.01 ) , voiding pain ( P = 0.04 ) , frequency ( P = 0.01 ) and urgency ( P = 0.04 ) . Radiologic follow-up was available for 24 patients in group A and 23 patients in group B at the 3-month visit . Hydronephrosis had improved in all patients , in both groups , with no evidence of ureteral stricture . CONCLUSION Routine placement of stents after uncomplicated ureteroscopy for distal ureteral stones is unnecessary in bilharzial ureters . Moreover , it might be unadvisable because lower urinary tract symptoms and voiding loin pain are more in patients with ureteral stents and hydronephrosis is equally improved in stented and non-stented patients PURPOSE We conducted a prospect i ve , r and omized controlled study to investigate the advantages and disadvantages of ureteral stenting after ureteroscopic lithotripsy . MATERIAL S AND METHODS A total of 60 patients who underwent ureteroscopic lithotripsy were equally r and omized into a stented or a nonstented group . The inclusion criteria were stone 6 to 10 mm . , absence of polyp or stricture in the ureter and no mucosal injury during ureteroscopy . The operation was performed with a 6Fr rigid ureteroscope without ureteral dilation and stones were fragmented with a 1.9Fr electrohydraulic lithotriptor without extraction . A 7Fr double pigtail stent was placed in the stented group for 3 days after ureteroscopy . Urinalysis , plain x-ray and renosonography were performed before and after lithotripsy in each patient . Subjective symptoms and pain score were recorded on admission to the hospital and 3 days postoperatively . RESULTS The stone-free rate was 100 % in each group and preoperative hydronephrosis equally resolved in both groups . Mean pain score plus or minus st and ard deviation improved significantly in the nonstented ( 6.33 + /- 1.81 preoperatively to 2.30 + /- 1.93 postoperatively , paired Student 's t test p < 0.0001 ) and stented ( 7.10 + /- 1.03 to 2.30 + /- 2.22 , p < 0.0001 ) group . There was no statistical difference in pain reduction between the 2 groups ( p = 0.18 ) . The amount of extra parenteral analgesic used was similar in both groups . One patient in the nonstented group visited the emergency room for postoperative renal colic , 25 ( 83.3 % ) patients in the stented group complained of at least 1 irritative bladder symptom and only 4 ( 13.3 % ) in the nonstented group experienced bladder discomfort . CONCLUSIONS After uncomplicated ureteroscopic electrohydraulic lithotripsy patients without ureteral stenting tend to have similar renal function recovery and satisfactory pain reduction with less irritative symptoms compared to those treated with a ureteral stent . We suggest that it is not necessary to place a ureteral stent routinely after uncomplicated ureteroscopic electrohydraulic lithotripsy for stones smaller than 1 cm We conducted a prospect i ve , r and omized study to evaluate whether postoperative ureteral stenting is necessary after ureteroscopic holmium laser lithotripsy . A total of 115 consecutive patients with distal or middle ureteral calculi amenable to ureteroscopic holmium laser lithotripsy were prospect ively r and omized into stented group ( n = 58 ) and nonstented group ( n = 57 ) . The stent was routinely placed in the treated ureter for 2 weeks . The outcomes were measured with postoperative patient symptoms , stone-free rates , early and late postoperative complications , and cost-effectiveness . The postoperative symptoms were measured with Ureteral Stent Symptom Question naire ( USSQ ) . All patients completed a 12-week follow-up . There was no significant difference between two groups with respect to the patient age , stone size , stone location and mean operative time . According to the USSQ , the symptoms of the stented group were significantly worse compared to the nonstented group ( P = 0.0001 ) . In the stented group , two patients had high fever for 1 week after the operation , stent migration was found in two patients , and the stents had to be removed earlier in five patients because of severe pain or hematuria . The cost of the stented group was significantly higher than the nonstented group . The stone-free rate was 100 % in both groups . No hydronephrosis or ureteral stricture was detected by intravenous pyelogram in the 12th week postoperative follow-up . In conclsion , we believe that routine stenting after ureteroscopic intracorporeal lithotripsy with the holmium laser is not necessary as long as the procedure is uncomplicated for distal or middle ureteral calculis less than 2 cm PURPOSE We assessed the cost-effectiveness of routine ureteral stenting after ureteroscopic stone removal . MATERIAL S AND METHODS Of 295 consecutive patients who underwent rigid ureteroscopic stone removal 133 in group 1 and 162 in group 2 were r and omized to receive and not receive a stent , respectively , after the procedure . Operative time , stone size , stone location , success rate , postoperative pain and complications were analyzed in each group . RESULTS There were no statistically significant differences in the 2 groups regarding stone size , stone location , success rate , postoperative pain or complications . However , in group 1 operative time was significantly longer than in group 2 ( chi-square test p = 0.019 ) . The hospital charge per patient when placing and not placing a stent after ureteroscopy for stone removal was $ 9,900.95 and $ 3,661.78 , respectively . The female patients with a stent without a suture required an extra charge for stent removal in the operating room , while no men had a stent with a suture . CONCLUSIONS Routine catheter placement after ureteroscopic stone removal increased operative time and did not seem to improve patient outcome . The cost was 30 % that without a stent Purpose Our aim was to evaluate the role of balloon dilatation of the ureteral orifice on the decision to stent after ureteroscopy . Material s and methods We prospect ively enrolled 505 patients from two clinics , undergoing ureteroscopy ( URS ) for urolithiasis . Patients having balloon dilatation of the ureteral orifice and uncomplicated ureteroscopy were r and omized to be either stented ( n = 144 ) or nonstented ( n = 142 ) . Ureteroscopy was done with a 9.8 rigid ureteroscope . For dilatation of ureteral orifice , 18Fr-4 cm balloons were used ( Uromax ™ , Boston Scientific , USA ) . Holmium laser or pneumatic devices were used for lithotripsy . In the second postoperative week , patients were asked to assess : pain , dysuria , and urgency using a 10-cm visual analog score ( VAS ) and unplanned visits . In each visit , urinalysis , urine culture , plain X-ray , and ultrasound examinations were performed . Six months after URS , follow-up IVU was performed to evaluate ureteral narrowing . Results for the separate clinics were not revealed until the end of study . Results There were no significant differences between the two groups regarding gender , age , preoperative serum creatinine levels , stone size , stone side and location , lithotripsy type , pain , infectious complications , unplanned visits , and ureteral narrowing . However , irritative symptoms were more common in the stented group . Success rates of 97.8 and 97.2 % were similar in the unstented and stented groups . Conclusion In uncomplicated URS , balloon dilatation of the ureteral orifice should not significantly affect the decision for or against stent placement . Avoiding stents lowers costs and gives fewer irritative symptoms PURPOSE We compare postoperative pain , stone-free rates and complications after ureteroscopic treatment of distal ureteral calculi with or without the use of ureteral stents . MATERIAL S AND METHODS A total of 113 patients with distal ureteral calculi amenable to ureteroscopic treatment were prospect ively r and omized into stented ( 53 ) and unstented ( 60 ) groups . Stones were managed with semirigid ureteroscopes with or without distal ureteral dilation and /or intracorporeal lithotripsy . Preoperative and postoperative pain question naires were obtained from each patient . Patients with stents had them removed 3 to 10 days postoperatively . Radiographic followup was performed postoperatively to assess stone-free rates and evidence of obstruction . RESULTS Six patients r and omized to the unstented group were withdrawn from the study after significant intraoperative ureteral trauma was recognized , including 3 ureteral perforations , that required ureteral stent placement , leaving 53 with stents and 54 without for analysis . Patients with stents had statistically significantly more postoperative flank pain ( p = 0.005 ) , bladder pain ( p < 0.001 ) , urinary symptoms ( p = 0.002 ) , overall pain ( p < 0.001 ) and total narcotic use ( p < 0.001 ) compared to the unstented group . Intraoperative ureteral dilation or intracorporeal lithotripsy did not statistically significantly affect postoperative pain or narcotic use in either group ( p > 0.05 in all cases ) . Overall mean stone size in our study was 6.6 mm . There were 4 ( 7.4 % ) patients without stents who required postoperative readmission to the hospital secondary to flank pain . All patients ( 85 % ) who underwent imaging postoperatively were without evidence of obstruction or ureteral stricture on followup imaging ( mean followup plus or minus st and ard deviation 1.8 + /- 1.5 months ) , and the stone-free rate was 99.1 % . CONCLUSIONS Uncomplicated ureteroscopy for distal ureteral calculi with or without intraoperative ureteral dilation can safely be performed without placement of a ureteral stent . Patients without stents had significantly less pain , fewer urinary symptoms and decreased narcotic use postoperatively OBJECTIVE To evaluate short-term ureteral catheterization in patients undergoing ureteroscopic lithotripsy for ureteral calculi . METHODS Patients ( n = 140 ) with ureteral calculi who were c and i date s for ureterolithotripsy were enrolled . Stone size was 5 - 10 mm . The operation was performed with an 8 - 9.8F semirigid ureteroscope without active dilatation and stones were fragmented with a 1F pneumatic lithotrite . Uncomplicated cases ( 109 patients ) were r and omized to catheterized ( C ) and noncatheterized ( NC ) groups . In the 54 C group patients , a polyurethane catheter ( 5F ) was passed through the ureter after lithotripsy with the end attached to a Foley placed in urethra , which was removed after 24h . Postoperatively , all patients were evaluated for flank and suprapubic pain , renal colic , irritative urinary symptoms , peritonism , frequency of analgesic usage , urinary tract infection , duration of hospitalization , postdischarge visits ( due to renal colic/pain ) , readmission , and residual stone rates . RESULTS On the first postoperative day , the percentage of patients experiencing flank pain and renal colic was significantly higher in the NC group ( 76 % and 45 % ) compared with the C group ( 20 % and 2 % ) ; 67 % of NC patients required analgesic administration during hospital stay versus 20 % of C patients ( p<0.001 ) . Suprapubic pain and urethral irritation were reported by 13 % and 37 % of C patients , respectively , and 5 % and 4 % of NC patients . However , peritonism was developed more often in NC patients ( 27 % vs. 13 % ) . Hospital stay was 1 d for all patients . Three days postoperatively , 40 % of NC patients complained of at least one episode of flank pain compared with 7 % of C patients ( p<0.001 ) . Incidence of urinary tract infections was 4 % in NC and 7 % in C group patients . Postdischarge visits were necessary in 20 % of NC patients and 5 % of C patients . No patient in either group required readmission . No complaints were reported nor residual stones discovered on 2-wk follow-up radiographs in either group . CONCLUSIONS Short-term ureteral catheterization in uncomplicated ureteroscopy and lithotripsy has a role in reducing early postoperative morbidities . It may also decrease pain and colic after discharge The purpose of our trial was to evaluate whether stents could be eliminated after uncomplicated ureteroscopic lithotripsy for ureteral stones and the indications of ureteral stent placement . A total of 228 patients underwent uncomplicated ureteroscopic intracorporeal lithotripsy . After the procedures , patients without marked ureteral edema , polypoid change or stent placement were treated as a control group . The other patients were r and omized to two groups . Patients were followed on the first postoperative day , 6 and 12 weeks , postoperatively . In stented cases the stent was removed after 1 week . Outcome measures included visual analog scale assessment , postoperative analgesic requirements , complications and the stone-free rate . On the first postoperative day the symptoms of flank pain , dysuria and frequency were significantly greater in the stented group ( P < 0.0001 ) . The overall perioperative complication rate , including fever , pyuria , flank and loin pain , was 3.3 % ( 3/90 ) in group 1 , 16.9 % ( 12/71 ) in group 2 , and 41.8 % ( 28/67 ) in group 3 . We believe that in selected patients undergoing ureteroscopy for ureteral stone , stents can be safely omitted . Patients without stents have significantly less stent-related symptoms and are not at higher risk of complications with smooth ureteral mucosa . When there is ureteral edema or polypoid change with pyuria , ureteral stents should be indwelled to avoid severe postoperative complications OBJECTIVES We conducted a study to assess the need for routine ureteral stenting after ureteroscopic stone removal using Lithoclast pneumatic intracorporeal lithotripsy . MATERIAL S AND METHODS A total of 104 patients , prospect ively divided in two groups to receive ( group A , 52 patients ) or not ( group B , 52 patients ) a stent after stone removal , underwent ureteroscopy for the treatment of ureteral lithiasis . The procedure was performed with the patient under either general or epidural anesthesia . A semirigid ureteroscope ( Wolf 8.9 Fr ) was used in all cases and intracorporeal lithotripsy with ballistic energy was performed . In group A a double pigtail ureteral 4.8 or 6 Fr polyurethane stent was placed following ureteroscopy . All patients were closely evaluated on follow-up examinations . The outcomes measured were postoperative patient pain , lower urinary tract symptoms , the need for hospital care as a result of the postoperative pain and late postoperative complications . RESULTS The two patient groups were comparable with respect to the baseline variables of patient gender and age , stone location and mean stone size . Mean operative time plus or minus st and ard deviation ( S.D. ) in group A was 42 + /- 15 minutes ( range 20 - 65 ) compared to 37 + /- 20 ( range 15 - 60 ) in group B. Operative time was not significantly longer when a stent was placed ( p = 0.17 ) . At day 3 the mean visual analog pain score in group B was much higher than in group A ( p = 0.01 ) . Dysuria , hematuria and frequency/urgency were more prevalent in the stented group , although without statistically significant difference . Readmission to the hospital for unremitting pain was necessary in 12 of 104 patients ( 11.5 % ) all being in unstented group ( p < 0.05 ) . The incidence of anatomical ureteral narrowing on IVP at 6 months follow-up was not statistically different between the two groups . CONCLUSIONS In our experience , using Swiss Lithoclast ballistic energy to fragment stones , routine stent placement is advisable also after uncomplicated ureteroscopic lithotripsy without ureteral dilation . Further prospect i ve r and omized studies are needed to assess the role of stenting after ureteroscopic lithotripsy , considering different energies sources , scopes , diameter and site of the stones in the ureter PURPOSE Routine use of ureteral stents before extracorporeal shock wave lithotripsy of kidney stones between 10 and 20 mm . is controversial . We conducted a prospect i ve r and omized clinical trial to evaluate the outcome of ureteral stents for treating solitary kidney stones between 10 and 20 mm . or solitary proximal ureteral stones less than 20 mm . with shock wave lithotripsy . MATERIAL S AND METHODS A total of 97 patients who met the aforementioned criteria were r and omized between March 1994 to July 1997 into group 1-no stent , group 2-a 4.7Fr multi-length stent and group 3-a 7Fr multi-length stent . The patients were treated with the Dornier HM3 lithotriptor ( Dornier Medical Systems , Inc. , Marietta , Georgia ) and monitored for stone-free rate , number of days lost from work , number of patients requiring rehospitalization , emergency room visits , irritative voiding symptom score and pain symptom score . RESULTS Objective outcome was obtained from 91 patients based on a followup of at least 3 months . The overall stone-free rate was 80 % , with a re-treatment rate of 7 % . The number of days lost from work was approximately 2 , with no significant differences among individual groups or subgroups . The hospitalization rate and number of emergency room visits in group 1 ( 22 % ) were statistically higher compared to groups 2 ( 7 % ) and 3 ( 7 % ) . The irritative voiding symptom score was statistically higher in the stented groups 2 and 3 compared to the nonstented group 1 . CONCLUSIONS Although ureteral stents are associated with more irritative symptoms , their use result ed in fewer hospital readmissions and emergency room visits compared to when no stent was used to treat solitary kidney stones of 10 to 20 mm . or solitary proximal ureteral stones less than 20 mm . Size 4.7Fr stents may be preferable over 7Fr stents when used in conjunction with shock wave lithotripsy OBJECTIVE To determine whether post-operative ureteral stenting is necessary after ureteroscopic lithotripsy for the treatment of middle and distal ureteral calculi . METHODS The trial was carried out in the Department of Urology of West China Hospital , Sichuan University , Chengdu , China , between May 2005 and May 2006 . A total of 110 patients underwent uncomplicated ureteroscopic lithotripsy . After the procedure , patients were r and omized to a non-stented ( n=55 ) , or stented ( n=55 ) group . The stent was routinely placed for 3 weeks . Outcome measures included operative time , visual analog scale , post-operative analgesic requirements , complications , and the stone-free rate . RESULTS The incidence of hematuria was higher and the operative time was longer in the stented group compared to the non-stented group . At 48 hours post-operatively , the symptoms of flank pain and abdominal pain were significantly greater in the stented group . There was no statistical difference in the 2 groups , in terms of irritative symptom , analgesic use , and complications . The stone-free rate was almost 100 % in both groups . CONCLUSION Uncomplicated ureteroscopic lithotripsy can be safely performed without the placement of a ureteral stent . Patients without stents had less operative time , pain and hematuria PURPOSE We compared a current cohort of patients who underwent ureteroscopy to a cohort from the early 1980s to determine changes in success , indications and long-term complications of the procedure . MATERIAL S AND METHODS A chart review was performed of 194 patients who underwent 209 ureteroscopic procedures at our institution during 1992 . This group was then statistically compared to 317 patients who underwent 346 ureteroscopies between 1982 and 1985 . RESULTS The current indications for ureteroscopy were calculus extraction ( 67 % of the cases ) , diagnosis ( 28 % ) and stent manipulation ( 5 % ) . These indications differed from those of the early series , in which 84 % of all ureteroscopies were performed for calculus extraction and 16 % for diagnosis . Overall ureteroscopic success rate increased from 86 to 96 % ( p < 0.001 ) . Success of stone extraction improved from 89 to 95 % ( p = 0.08 , distal success rate 95 to 97 % and proximal success rate 72 to 77 % ) . Success of diagnostic inspections increased from 73 to 98 % ( p < 0.001 ) . In the early series failure was usually due to inability to traverse the ureter ( 54 % of the cases ) , while currently failure is due almost exclusively to impassable ureteral strictures ( 63 % ) . The overall complication rate decreased from 20 to 12 % ( p = 0.01 ) and the rate of significant complications decreased from 6.6 to 1.5 % ( p < 0.05 ) . Clinical followup ( mean 36 months ) for all patients and radiological followup ( mean 9.8 months ) for 67 % of eligible patients detected only 1 ureteral stricture . The remaining patients were asymptomatic after the ureteroscopic procedure . CONCLUSIONS Improvements in ureteroscope design , accessories and technique have led to a significant increase in the success of diagnostic and therapeutic ureteroscopy while decreasing morbidity . Outpatient ureteroscopic stone extraction , particularly for distal ureteral calculi , is almost uniformly successful with low morbidity . The long-term complication rate of ureteroscopy is 0.5 % PURPOSE A prospect i ve r and omized controlled trial was conducted to evaluate whether postoperative ureteral stenting is necessary after ureteroscopic laser lithotripsy . MATERIAL S AND METHODS A total of 58 patients with unilateral ureteral stones were r and omized into either stented or unstented groups . Ureteroscopic laser lithotripsy was performed using a semirigid ureteroscope ( 6.5/7Fr ) and holmium laser without ureteral orifice dilation . There were no selection criteria regarding stone size , location , preoperative ureteral obstruction and hydronephrosis . Endoscopic evidence of stone impaction or mucosal edema/damage did not exclude a patient from the study . Ureteral perforation on completion retro grade pyelogram was the only intraoperative criterion for study exclusion . Postoperative pain scores and symptoms were recorded . Excretory urography was performed to document stone-free status and stricture formation . Radionuclide scan was performed selectively to exclude functional obstruction when ureteral narrowing was found on excretory urogram . RESULTS Mean stone size + /- SD was 9.7 + /- 4.0 mm . ( range 4 to 27 ) . Proximal ureteral stones accounted for 43 % of all stones . Stented and unstented groups were comparable with respect to demographic data , stone parameters , preoperative obstruction and hydronephrosis . There was no significant difference in operating time , laser energy used , stone impaction and mucosal edema/damage between the 2 groups . Postoperative pain and symptoms were more severe and frequent ( p < 0.05 ) in the stented group . However , there was no difference in the incidence of postoperative sepsis and unplanned medical visits . The stone-free and stricture formation rates showed no statistical difference between the 2 groups . CONCLUSIONS Ureteral stenting is not necessary after uncomplicated ureteroscopic laser lithotripsy for ureteral stones . Ureteral stent increases the incidence of pain and urinary symptoms but does not prevent postoperative urinary sepsis and unplanned medical visits . Severity of preoperative obstruction and intraoperative ureteral trauma were not shown to be determining factors for stenting |
14,061 | 27,665,425 | Results and conclusions : All three obesity treatments result in statistically significant reductions in hip bone mineral density ( BMD ) and increases in bone turnover relative to pre-treatment values , with the reductions in hip BMD being strongest for bariatric surgery , notably Roux-en Y gastric bypass ( RYGB , 8%–11 % of pre-surgical values ) and weakest for dietary restriction ( 1%–1.5 % of pre-treatment values ) .
Weight loss pharmaceuticals ( orlistat or the glucagon-like peptide-1 receptor agonist , liraglutide ) induced no greater changes from pre-treatment values than control , despite greater weight loss .
There is suggestive evidence that liraglutide may increase bone mineral content ( BMC ) – but not BMD – and reduce fracture risk , but more research is required to clarify this .
However , a pressing outst and ing question is whether this BMD reduction contributes to increased fracture risk , as has been observed after RYGB , and whether any such increase in fracture risk outweighs the risks of staying obese ( unlikely ) | Abstract Background : New evidence suggests that obesity is deleterious for bone health , and obesity treatments could potentially exacerbate this .
Material s and methods : This narrative review , largely based on recent systematic review s and meta-analyses , synthesizes the effects on bone of bariatric surgery , weight loss pharmaceuticals and dietary restriction . | BACKGROUND Caloric restriction ( CR ) , energy intake reduced below ad libitum ( AL ) intake , increases life span in many species . The implication s for humans can be clarified by r and omized controlled trials of CR . METHODS To determine CR 's feasibility , safety , and effects on predictors of longevity , disease risk factors , and quality of life in nonobese humans aged 21 - 51 years , 218 persons were r and omized to a 2-year intervention design ed to achieve 25 % CR or to AL diet . Outcomes were change from baseline resting metabolic rate adjusted for weight change ( " RMR residual " ) and core temperature ( primary ) ; plasma triiodothyronine ( T3 ) and tumor necrosis factor-α ( secondary ) ; and exploratory physiological and psychological measures . RESULTS Body mass index averaged 25.1 ( range : 21.9 - 28.0 kg/m(2 ) ) . Eighty-two percent of CR and 95 % of AL participants completed the protocol . The CR group achieved 11.7±0.7 % CR ( mean ± st and ard error ) and maintained 10.4±0.4 % weight loss . Weight change in AL was negligible . RMR residual decreased significantly more in CR than AL at 12 months ( p = .04 ) but not 24 months ( M24 ) . Core temperature change differed little between groups . T3 decreased more in CR at M12 and M24 ( p < .001 ) , while tumor necrosis factor-α decreased significantly more only at M24 ( p = .02 ) . CR had larger decreases in cardiometabolic risk factors and in daily energy expenditure adjusted for weight change , without adverse effects on quality of life . CONCLUSIONS Sustained CR is feasible in nonobese humans . The effects of the achieved CR on correlates of human survival and disease risk factors suggest potential benefits for aging-related outcomes that could be eluci date d by further human studies Bone turnover is increased during weight loss in postmenopausal women and can be suppressed with calcium supplementation . In this study , we assessed the influence of energy restriction with and without calcium supplementation ( 1 g/day ) in premenopausal women . Thirty-eight obese premenopausal women ( body mass index [ BMI ] of 35.0 + /- 3.9 kg/m2 ) completed a 6-month study of either moderate weight loss or weight maintenance . During weight loss , women were r and omly assigned to either a calcium supplementation ( n = 14 ) or placebo group ( n = 14 ) and lost 7.5 + /- 2.5 % of their body weight . The control group of women ( n = 10 ) maintained their body weight . Total body and lumbar bone mineral density ( LBMD ) and content were measured by dual-energy X-ray absorptiometry ( DXA ) at baseline and after weight loss . Throughout the study , blood and urine sample s were collected to measure bone turnover markers and hormones . During moderate energy restriction , dietary calcium intake decreased ( p < 0.05 ) and the bone resorption marker deoxypyridinoline ( DPD ) increased slightly ( p < or = 0.05 ) without evidence of bone loss . Calcium supplementation during weight loss tended to increase lumbar BMD by 1.7 % ( p = 0.05 ) compared with the placebo or weight maintenance groups . In contrast to our previous findings in postmenopausal women , premenopausal obese women who consume a low calcium diet do not lose bone over a 6-month period , whether their weight is stable or decreasing moderately BACKGROUND / OBJECTIVES : Moderate , long-term weight loss results in the loss of bone mass in overweight or obese premenopausal women . However , whether these changes persist during weight maintenance or regain remains to be determined . SUBJECTS/ METHODS : Overweight or obese ( body mass index : 25.8–42.5 kg/m2 ) women ( n=40 ) with at least two risk factors for the metabolic syndrome participated in this 12-month study that examined the effects of prescribed weight loss and regain , with or without exercise , on bone turnover and on bone mineral density ( BMD ) in a subset of participants ( n=24 ) . During the first 6 month , participants lost ∼10 % of their initial body weight via energy restriction and supervised aerobic exercise . Following weight loss , participants were r and omly assigned to either an exercise or a no exercise treatment for the regain ( + 50 % of weight lost ) phase . A one-way ( time ) repeated measures one-factor analysis of variance ( RMANOVA ) tested the effects of weight loss on BMD and bone turnover , and a two-way RMANOVA ( time , exercise ) was used to examine the effects of exercise during weight regain . RESULTS : Hip ( P=0.007 ) and lumbar spine ( P=0.05 ) BMD decreased with weight loss , and remained reduced after weight regain with or without exercise . Likewise , the weight-loss-associated increases in osteocalcin ( P<0.001 ) and C-terminal peptide of type I collagen ( P<0.001 ) persisted following weight regain , independent of exercise . CONCLUSIONS : The results of the present study , which is the first to examine changes in bone mass and turnover during carefully controlled weight regain , suggest that weight-loss-induced perturbations in bone mass and turnover persist after partial weight regain , regardless of whether regular weight-bearing aerobic exercise was continued Orlistat is a gastrointestinal lipase inhibitor that is used to reduce dietary fat absorption and to enhance weight loss in subjects consuming a hypocaloric diet . To assess whether orlistat has an effect on the metabolism of six minerals , a 21-d , double-blind , r and omized , parallel-group , placebo-controlled mineral balance study was conducted in obese ( body mass index > 30 kg/m(2 ) ) men . Subjects consumed a hypocaloric diet with a constant daily mineral content and received daily oral treatment with orlistat ( 120 mg three times daily ) ( n = 14 ) or placebo ( three times daily ) ( n = 14 ) for 21 d. After a 14-d equilibration period , calcium , phosphorus , magnesium , iron , copper and zinc balances were assessed for d 15 - 21 . In addition , the effect of diet and orlistat treatment on bone metabolism was estimated from measurement of biomarkers of bone formation and bone resorption . Serum and urine electrolytes were also measured at baseline and at the end of treatment . Orlistat inhibited fat absorption by approximately 33 % ( P < 0.05 ) . There were no significant differences in mineral apparent absorption , urinary mineral loss or mineral balance between the orlistat and placebo groups . Markers of bone turnover and serum and urine electrolytes did not differ between the orlistat and placebo groups . Orlistat was well tolerated ; adverse events were of mild or moderate intensity , and the majority of these events were unrelated or remotely related to study treatment . In obese men consuming a hypocaloric diet , the administration of orlistat had no significant effect on the balance of six selected minerals . In addition , biomarkers of bone turnover , as well as serum and urine electrolytes , were not affected by orlistat treatment BACKGROUND Weight loss is associated with bone loss , but this has not been examined in overweight premenopausal women . OBJECTIVE The aim of this study was to assess whether overweight premenopausal women lose bone with moderate weight loss at recommended or higher than recommended calcium intakes . DESIGN Overweight premenopausal women [ n = 44 ; x ( + /-SD ) age : 38 + /- 6.4 y ; body mass index ( BMI ): 27.7 + /- 2.1 kg/m(2 ) ] were r and omly assigned to either a normal ( 1 g/d ) or high ( 1.8 g/d ) calcium intake during 6 mo of energy restriction [ weight loss ( WL ) groups ] or were recruited for weight maintenance at 1 g Ca/d intake . Regional bone mineral density and content were measured by dual-energy X-ray absorptiometry , and markers of bone turnover were measured before and after weight loss . True fractional calcium absorption ( TFCA ) was measured at baseline and during caloric restriction by using a dual-stable calcium isotope method . RESULTS The WL groups lost 7.2 + /- 3.3 % of initial body weight . No significant decrease in BMD or rise in bone turnover was observed with weight loss at normal or high calcium intake . The group that consumed high calcium showed a strong relation ( r = 0.71 ) between increased femoral neck bone mineral density and increased serum 25-hydroxyvitamin D. No significant effect of weight loss on TFCA was observed , and the total calcium absorbed was adequate at 238 + /- 81 and 310 + /- 91 mg/d for the normal- and high-calcium WL groups , respectively . CONCLUSION Overweight premenopausal women do not lose bone during weight loss at the recommended calcium intake , which may be explained by sufficient amounts of absorbed calcium BACKGROUND Recent findings suggest that higher levels of intermuscular adipose tissue ( IMAT ) are associated with glucose dysregulation , lower levels of muscle strength , and a heightened risk of disability . Although several studies have described adaptations in muscle after reduced physical activity , the change in IMAT in healthy young adults is unknown . OBJECTIVE The objective was to determine whether reduced lower limb activity alters IMAT in healthy young adults and to assess whether this change affects muscle strength loss . DESIGN The subjects ( 6 men and 12 women aged 19 - 28 y ) underwent a 4-wk control period , which was followed by 4 wk of unilateral lower limb suspension . Volumes of whole muscle , subcutaneous adipose tissue , and IMAT were assessed by using magnetic resonance imaging in the thigh and calf . Muscle strength was assessed during maximal voluntary isometric contractions . RESULTS No changes were observed in the control period . Reduced physical activity decreased thigh and calf muscle volumes by 7.4 % and 7.9 % ( P < 0.001 ) , respectively ; no significant change in subcutaneous adipose tissue was observed . Additionally , IMAT increased in both regions ; the increase was larger in the calf ( 20 % ) than in the thigh ( 14.5 % ) ( P < or= 0.005 ) and was partially explained by the loss in muscle ( R(2 ) = 26 % ) . The loss in strength was greater in the thigh ( 20.4 % ) than in the calf ( 15 % ) . Strength loss was associated with increases in IMAT ( P = 0.039 ) after adjustment for the loss in muscle , initial strength , initial IMAT , and initial muscle volume . CONCLUSIONS IMAT accumulates markedly after reduced activity in healthy young adults . Increases in IMAT may contribute to losses in muscle strength associated with reduced physical activity , but the mechanism responsible is yet to be determined BACKGROUND Calorie restriction ( CR ) is promoted to increase longevity , yet this regimen could lead to bone loss and fracture and therefore affect quality of life . METHODS Forty-six individuals were r and omized to 4 groups for 6 months : ( 1 ) healthy diet ( control group ) ; ( 2 ) 25 % CR from baseline energy requirements ( CR group ) ; ( 3 ) 25 % energy deficit by a combination of CR and increased aerobic exercise ( CR + EX group ) ; and ( 4 ) low-calorie diet ( 890 kcal/d ; goal , 15 % weight loss ) followed by weight maintenance ( LCD group ) . Bone mineral density ( total body and hip by dual-energy x-ray absorptiometry ) and serum bone markers ( bone-specific alkaline phosphatase , osteocalcin , cross-linked C-telopeptide of type I collagen , and cross-linked N-telopeptide of type I collagen ) were measured at baseline and after 6 months . RESULTS Mean + /- SE body weight was reduced by -1.0 % + /- 1.1 % ( control ) , -10.4 % + /- 0.9 % ( CR ) , -10.0 % + /- 0.8 % ( CR + EX ) , and -13.9 % + /- 0.7 % ( LCD ) . Compared with the control group , none of the groups showed any change in bone mineral density for total body or hip . Bone resorption by serum cross-linked C-telopeptide of type I collagen was increased in all 3 intervention groups , with the largest change observed in the LCD group ( CR , 23 % + /- 10 % ; CR + EX , 22 % + /- 9 % ; and LCD , 74 % + /- 16 % vs control , 4 % + /- 10 % ) . Serum levels of cross-linked N-telopeptide of type I collagen were also increased in the LCD group . With regard to bone formation , bone alkaline phosphatase levels were decreased in the CR group ( -23 % + /- 10 % ) but were unchanged in the CR + EX , LCD , and control groups . CONCLUSIONS Moderate CR , with or without exercise , that preserves calcium intake for 6 months leads to large changes in body composition without significant bone loss in young adults . Longer studies with assessment s of bone architecture are needed to confirm that CR nutrient-dense diets have no deleterious effect on bone health . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00099151 CONTEXT Bariatric surgery is common and may be associated with deleterious effects on the skeleton . OBJECTIVE Our objective was to assess bone metabolism and bone mineral density ( BMD ) after Roux-en-Y gastric bypass . DESIGN AND SETTING We conducted a 1-yr prospect i ve longitudinal study at a university hospital bariatric surgery practice and metabolic bone disease unit . PARTICIPANTS Participants included 23 obese ( mean body mass index 47 kg/m(2 ) ) men and women , aged 20 - 64 yr . MAIN OUTCOME MEASURES Serum PTH , 25-hydroxyvitamin D , osteocalcin , and urinary N-telopeptide , and BMD were assessed . RESULTS Patients lost 45 + /- 2 kg 1 yr postoperatively ( P < 0.01 ) . PTH increased early ( 3 months , 43 - 50 pg/ml ; P < 0.001 ) and urinary calcium dropped ( 161 - 92 mg/24 h ; P < 0.01 ) , despite doubling of calcium intake ( 1318 - 2488 mg/d ; P < 0.001 ) . Serum 25-hydroxyvitamin D concentrations were unchanged ( 23 - 26 ng/ml ) , although vitamin D intake increased by 260 % ( 658 IU/d at baseline to 1698 IU/d at 12 months ; P < 0.05 ) . Markers of bone remodeling rose ( P < 0.01 for both urinary N-telopeptide and osteocalcin ) , whereas BMD decreased at the femoral neck ( 9.2 % , P < 0.005 ) and at the total hip ( 8.0 % , P < 0.005 ) . These declines were strongly associated with the extent of weight loss ( femoral neck : r = 0.90 , P < 0.0001 ; and total hip : r = 0.65 , P = 0.02 ) . Lumbar spine and distal radius sites did not change . CONCLUSIONS After Roux-en-Y gastric bypass , there was evidence of calcium and vitamin D malabsorption . Bone turnover increased , and hip bone density rapidly declined . The decline in hip BMD was strongly associated with weight loss itself . Vigilance for nutritional deficiencies and bone loss in patients both before and after bariatric surgery is crucial CONTEXT Recent studies indicate that glucagon-like peptide (GLP)-1 regulates bone turnover , but the effects of GLP-1 receptor agonists ( GLP-1 RAs ) on bone in obese weight-reduced individuals are unknown . OBJECTIVE To investigate the role of GLP-1 RAs on bone formation and weight loss-induced bone mass reduction . DESIGN R and omized control study . SETTING Outpatient research hospital clinic . PARTICIPANTS Thirty-seven healthy obese women with body mass index of 34 ± 0.5 kg/m(2 ) and age 46 ± 2 years . INTERVENTION After a low-calorie-diet-induced 12 % weight loss , participants were r and omized to treatment with or without administration of the GLP-1 RA liraglutide ( 1.2 mg/d ) for 52 weeks . In case of weight gain , up to two meals per day could be replaced with a low-calorie-diet product to maintain the weight loss . MAIN OUTCOME MEASURES Total , pelvic , and arm-leg bone mineral content ( BMC ) and bone markers [ C-terminal telopeptide of type 1 collagen ( CTX-1 ) and N-terminal propeptide of type 1 procollagen ( P1NP ) ] were investigated before and after weight loss and after 52-week weight maintenance . Primary endpoints were changes in BMC and bone markers after 52-week weight maintenance with or without GLP-1 RA treatment . RESULTS Total , pelvic , and arm-leg BMC decreased during weight maintenance in the control group ( P < .0001 ) , but not significantly in the liraglutide group . Thus , total and arm-leg BMC loss was four times greater in the control group compared to the liraglutide group ( estimated difference , 27 g ; 95 % confidence interval , 5 - 48 ; P = .01 ) , although the 12 % weight loss was maintained in both groups . In the liraglutide group , the bone formation marker P1NP increased by 16 % ( 7 ± 3 μg/L ) vs a 2 % ( -1 ± 4 μg/L ) decrease in the control group ( P < .05 ) . The bone resorption marker CTX-1 collagen did not change during the weight loss maintenance phase . CONCLUSIONS Treatment with a long-acting GLP-1 RA increased bone formation by 16 % and prevented bone loss after weight loss obtained through a low-calorie diet , supporting its role as a safe weight-lowering agent Roux-en-Y gastric bypass surgery ( RYGB ) is an effective treatment of morbid obesity , with positive effects on obesity-related complications . The treatment is associated with bone loss , which in turn might increase fracture risk . The aim of this study was to evaluate changes in bone mineral density ( BMD ) and bone architecture assessed using dual-energy X-ray absorptiometry ( DXA ) and high-resolution peripheral quantitative computed tomography ( HR-pQCT ) , 6 and 12 months after RYGB , and correlate them to changes in selected biochemical markers . A prospect i ve cohort study included 25 morbidly obese patients ( 10 males , 15 females ) . Patients were examined with DXA of the hip and spine , HR-pQCT of radius and tibia , and blood sampling before and 6 and 12 months after RYGB . Patients lost in average 33.5 ± 12.1 kg ( 25.8 ± 8.5 % ) in 12 months . In tibia , we found significant loss of total , cortical and trabecular volumetric BMD after 12 months ( all p < 0.001 ) . Microarchitectural changes involved lower trabecular number , increased trabecular separation , and network inhomogeneity along with thinning of the cortex . Estimated bone failure load was decreased after 12 months ( p = 0.005 ) . We found only minor changes in radius . Results demonstrate significant alterations of bone microarchitecture suggesting an accelerated endosteal resorption along with disintegration of the trabecular structure which result ed in a loss of estimated bone strength in tibia . Such changes may underlie the recently reported increased risk of fracture in bariatric patients after surgery . We only observed bone structural changes in the weight-bearing bone , which indicates that mechanical un-loading is the primary mediator To evaluate the influence of extravertebral calcification on spinal bone density determinations , we measured lumbar vertebral density in 71 hospitalized and 58 normal men using dual photon absorptiometry . The extent of vascular and osteophytic calcification was grade d from lateral lumbar radiographs . Fifty-five ( 43 % ) of the subjects had identifiable osteophytes , and 86 ( 67 % ) had vascular calcifications . Despite similar ages and weights in subjects with and without ostephytes , those with osteophytes had greater spinal density ( 1.34 vs. 1.17 g/cm2 ; P less than 0.001 ) , and there was a strong correlation between osteophyte severity and spinal density ( r = 0.41 ; P less than 0.00001 ) . Proximal femoral density was not different in those with and without osteophytes . The distribution of osteophytes in this population was not r and om , and as a result , the presence of osteophytes obscured the the relationship of bone density to age as well as the comparison of hospitalized to normal men . Vascular calcification had a minimal effect on vertebral density . In summary , osteophytic calcification exerted an important influence on the measurement of spinal bone density in men . This effect should be considered in both clinical and research applications of integral vertebral density measures OBJECTIVE To investigate the effect of treatment with the glucagon-like peptide 1 receptor agonist exenatide on weight loss and metabolic parameters in obese nondiabetic women . RESEARCH DESIGN AND METHODS Forty-one obese women ( aged 48 ± 11 years and BMI 33.1 ± 4.1 kg/m2 ) participated in a 35-week r and omized , double-blind , placebo-controlled , crossover study , including two 16-week treatment periods separated by a 3-week washout period . There was no lifestyle intervention . The primary outcome was change in body weight . RESULTS Subjects treated with exenatide lost an average of 2.49 ± 0.66 kg compared with a 0.43 ± 0.63 kg weight gain during placebo treatment . Weight loss with exenatide treatment was noted at 2 weeks . The degree of weight loss could be stratified . A total of 30 % of subjects were high responders who lost ≥5 % body weight ( −7.96 ± 0.52 % ) , 39 % were moderate responders who lost < 5 % body weight ( −2.43 ± 0.45 % ) , and 31 % were nonresponders who gained weight ( 1.93 ± 0.53 % ) . Waist circumference also decreased significantly with exenatide treatment . Subjects experienced more nausea during exenatide treatment compared with placebo , but the severity decreased over time and did not correlate with weight loss . CONCLUSIONS Short-term exenatide treatment was associated with modest weight loss and decreased waist circumference in a cohort of obese nondiabetic women . A subset of individuals demonstrated robust weight loss that was detected very early in the course of treatment BACKGROUND Bone loss often accompanies weight loss induced by caloric restriction ( CR ) , but whether bone loss accompanies similar weight loss induced by exercise ( EX ) is unknown . We tested the hypothesis that EX-induced weight loss is associated with less bone loss compared with CR-induced weight loss . METHODS Forty-eight adults ( 30 women ; 18 men ; mean + /- SD age , 57 + /- 3 years ; and mean + /- SD body mass index , 27 + /- 2 kg/m2 ) were r and omized to 1 of 3 groups for 1 year : CR group ( n = 19 ) , regular EX group ( n = 19 ) , or a healthy lifestyle ( HL ) control group ( n = 10 ) . Primary outcome measure was change in hip and spine bone mineral density ( BMD ) . Secondary outcomes were bone markers and hormones . RESULTS Body weight decreased similarly in the CR and EX groups ( 10.7 % + /- 6.3 % [ -8.2 + /- 4.8 kg ] vs 8.4 % + /- 6.3 % [ -6.7 + /- 5.6 kg ] ; P = .21 ) , whereas weight did not change in the HL group ( -1.2 % + /- 2.5 % [ -0.9 + /- 2.0 kg ] ) . Compared with the HL group , the CR group had decreases in BMD at the total hip ( -2.2 % + /- 3.1 % vs 1.2 % + /- 2.1 % ; P = .02 ) and intertrochanter ( -2.1 % + /- 3.4 % vs 1.7 + /- 2.8 % ; P = .03 ) . The CR group had a decrease in spine BMD ( -2.2 % + /- 3.3 % ; P = .009 ) . Despite weight loss , the EX group did not demonstrate a decrease in BMD at any site . Body weight changes correlated with BMD changes in the CR ( R = 0.61 ; P = .007 ) but not in the EX group . Bone turnover increased in both CR and EX groups . CONCLUSIONS CR-induced weight loss , but not EX-induced weight loss , is associated with reductions in BMD at clinical ly important sites of fracture . These data suggest that EX should be an important component of a weight loss program to offset adverse effects of CR on bone Abstract : The diagnosis of osteoporosis is based on bone mass measurement . To avoid the errors associated with the measurement of spinal bone density the total hip has been accepted as the st and ard measurement site . This information is not available for many early measurements . We have assessed whether it is possible to derive clinical ly useful information about total hip bone mineral density ( BMD ) from measurements at other hip sites . The bone mass measurements of 46 patients participating in a current trial of therapy for osteoporosis were review ed . The total hip BMD as directly measured was compared with that obtained from the formula : Total hip BMD = 0.48 × Neck BMD + 0.62 × Trochanteric BMD + 0.03 . In 30 patients with follow-up data the rate of change in hip BMD over a year was also determined by both methods . In the pretreatment state there was good agreement between the two measures ( r2 = 0.96 , SEE 0.012 g/cm2 ) . If the formula was used to compute a change in total hip BMD , the agreement between both methods remained good . However , the st and ard error of the estimate of the change represented 59 % of the observed change . This indicates that the error associated with this estimate is too great to allow clinical ly meaningful conclusions to be drawn from calculated total hip BMD . We conclude that , whilst it may be possible to obtain reasonable point estimates of total hip BMD from other measures in the hip , these estimates are too imprecise to allow conclusions about change in BMD to be made Weight loss reduces bone mass and increases the risk of osteoporosis . This study was undertaken to assess changes of bone metabolism following Roux-en-Y gastric bypass ( RYGB ) and adjustable silicone gastric b and ing ( ASGB ) as compared to nonoperated controls of morbidly obese subjects . Fourteen female and 5 male patients with a mean ( + /-SEM ) age of 44.3 + /- 1.8 years participated in the 24-month prospect i ve study . Nine patients underwent ASGB , 4 patients RYGB operation , and 6 patients were included in the control group . Bone metabolism was assessed by determination of serum parathyroid hormone ( PTH ) , osteocalcin , urinary deoxypyridinoline , and dual energy x-ray absorptiometry ( DXA ) before , and 6 , 12 , and 24 months after intervention . The body mass index ( BMI ) decreased from 41.0 + /- 1.1 to 34.0 + /- 1.4 kg/m2 in the ASGB group ( P = .001 ) , from 42.7 + /- 2.2 to 30.5 + /- 2.2 kg/m2 in the RYGB group ( P = .006 ) , and remained unchanged in the control group ( from 41.2 + /- 1.2 to 41.4 + /- 1.4 kg/m2 ) after 24 months . Bone mineral content ( BMC ) showed no significant change in the ASGB group ( from 3,079 + /- 140 to 3,064 + /- 129 g ) and in the control group ( from 2,945 + /- 130 to 2,940 + /- 111 g ) , whereas it decreased from 2,968 + /- 111 to 2,621 + /- 139 g in the RYGB group ( P = .005 ) . The loss in BMC was accompanied by significant increases in urinary deoxypyridinoline ( P < .05 ) and in serum osteocalcin ( P < .01 ) after RYGB , suggesting both , increased bone resorption and increased bone formation . The authors were aware of the fact that the study groups were small and conclusions need to be regarded as preliminary . However , the RYGB operation result ed in enhanced weight loss and significant net loss of bone mass in comparison to ASGB and obese control subjects . Patients losing large amounts of body weight should be monitored regularly regarding prevention of osteoporosis OBJECTIVE : To investigate the influence of the pancreas lipase inhibitor orlistat ( OLS ) on calcium metabolism , bone turnover , bone mass , bone density and body composition when given for obesity as adjuvant to an energy- and fat-restricted diet . DESIGN : R and omized controlled double-blinded trial of treatment with OLS 120 mg three times daily or placebo for 1 y . SUBJECTS : Thirty obese subjects with a mean body mass index ( BMI ) of 36.9±3.7 kg/m2 and a mean age of 41±11 y. Sixteen patients were assigned to OLS and 14 to placebo . MEASUREMENTS : Dual energy X-ray absorptiometry ( DXA ) measurements of bone mineral and body composition included total bone mineral content ( T BMC ) , total bone mineral density ( TBMD ) , lumbar spine BMC and BMD , forearm BMC and BMD , fat mass ( FM ) , fat free-mass ( FFM ) , percentage fat mass ( FM% ) as well as a DXA estimate of the body weight . Body composition ( FM , FFM and FM% ) was estimated by total body potassium ( TBK ) . Indices of calcium metabolism and bone turnover included serum values of ionized calcium ( Ca++ ) , iPTH ( parathyroid hormone ) , alkaline phosphatase , 25(OH)-vitamin D , 1,25(OH)2 vitamin D and osteocalcin as well as fasting urinary ratios of hydroxyproline/creatinine and Ca/creatinine ( fU-OHpr/creat , fUCa/creat ) . RESULTS : There were no significant differences between OLS and placebo groups as to any of the body composition variables ( FFM , FM , FM% ) at baseline or after 1 y treatment . Weight loss was of 11.2±7.5 kg in the OLS group and 8.1±7.5 kg in the placebo group ( NS ) . The changes in FM and FM% were significant in both groups determined by DXA as well as by TBK , but the group differences between these changes were not significant . The composition of the weight loss was approximately 80 % fat in both groups . FFM only changed significantly by DXA in the OLS group ( −1.3 kg ) , but the difference from the placebo group was not significant . Forearm BMD in both groups , forearm BMC in the OLS group and TBMD in the placebo group fell discretely but significantly , but there were no significant group differences between the OLS and the placebo-treated group . All biochemical variables except s-osteocalcin changed significantly after 1 y in the OLS group , disclosing a pattern of an incipient negative vitamin D balance , a secondary increase in PTH-secretion , and an increase in bone turnover with the emphasis on an increase in resorption parameters ( fU-OHpr/creat , fUCa/creat ) . In the placebo group , only s-25(OH)vitamin D and fU-OHpr/creat changed significantly , but the pattern was also that of a deteriorated vitamin D status and an increase in PTH levels and bone turnover . The only biochemical variable which was significantly different between OLS and placebo groups after one year was the fU-OHpr/creat ratio , which increased from 12.0 to 20.1 in the OLS group but only from 10.9 to 13.2 in the placebo group . CONCLUSION : One year 's treatment with OLS induces a lipid malabsorption which enhances a dietary weight loss without any significant deleterious effects on body composition . OLS induces a relative increase in bone turnover in favour of resorption , possibly due to malabsorption of vitamin D and /or calcium . However , no changes in bone mass or density are seen after 1 y of OLS treatment apart from those explained by the weight loss itself . Thus 1 y of OLS treatment seems safe from a ‘ bone preserving ’ point of view . A vitamin D and calcium supplement should be taken during the treatment Previously , we reported significant bone mineral density ( BMD ) loss in postmenopausal women after modest weight loss . It remains unclear whether the magnitude of BMD change in response to weight loss is appropriate ( i.e. , proportional to weight loss ) and whether BMD is recovered with weight regain . We now report changes in BMD after a 1-year follow-up . Subjects ( n = 23 ) in this secondary analysis were postmenopausal women r and omized to placebo as part of a larger trial . They completed a 6-month exercise-based weight loss program and returned for follow-up at 18 months . Dual-energy X-ray absorptiometry ( DXA ) was performed at baseline , 6 , and 18 months . At baseline , subjects were aged 56.8 ± 5.4 years ( mean ± s.d . ) , 10.0 ± 9.2 years postmenopausal , and BMI was 29.6 ± 4.0 kg/m(2 ) . They lost 3.9 ± 3.5 kg during the weight loss intervention . During follow-up , they regained 2.9 ± 3.9 kg . Six months of weight loss result ed in a significant decrease in lumbar spine ( LS ) ( -1.7 ± 3.5 % ; P = 0.002 ) and hip ( -0.04 ± 3.5 % ; P = 0.03 ) BMD that was accompanied by an increase in a biomarker of bone resorption ( serum C-terminal telopeptide of type I collagen , CTX : 34 ± 54 % ; P = 0.08 ) . However , weight regain was not associated with LS ( 0.05 ± 3.8 % ; P = 0.15 ) or hip ( -0.6 ± 3.0 % ; P = 0.81 ) bone regain or decreased bone resorption ( CTX : -3 ± 37 % ; P = 0.73 ) . The findings suggest that BMD lost during weight reduction may not be fully recovered with weight regain in hormone-deficient , postmenopausal women . Future studies are needed to identify effective strategies to prevent bone loss during periods of weight loss BACKGROUND Vitamin D deficiency is associated with obesity ; whether repletion supports weight loss and changes obesity-related biomarkers is unknown . OBJECTIVE We compared 12 mo of vitamin D3 supplementation with placebo on weight , body composition , insulin , and C-reactive protein ( CRP ) in postmenopausal women in a weight-loss intervention . DESIGN A total of 218 overweight/obese women ( 50 - 75 y of age ) with serum 25-hydroxyvitamin D [ 25(OH)D ] ≥10 ng/mL but < 32 ng/mL were r and omly assigned to weight loss + 2000 IU oral vitamin D3/d or weight loss + daily placebo . The weight-loss intervention included a reduced-calorie diet ( 10 % weight loss goal ) and 225 min/wk of moderate-to-vigorous aerobic activity . Mean 12-mo changes in weight , body composition , serum insulin , CRP , and 25(OH)D were compared between groups ( intent-to-treat ) by using generalized estimating equations . RESULTS A total of 86 % of participants completed the 12-mo measurements . The mean ( 95 % CI ) change in 25(OH)D was 13.6 ( 11.6 , 15.4 ) ng/mL in the vitamin D3 arm compared with -1.3 ( -2.6 , -0.3 ) ng/mL in the placebo arm ( P < 0.0001 ) . Changes in weight [ -7.1 ( -8.7 , -5.7 ) compared with -7.4 ( -8.1 , -5.4 ) kg ] , body mass index ( in kg/m(2 ) : both -2.8 ) , waist circumference [ -4.9 ( -6.7 , -2.9 ) compared with -4.5 ( -5.6 , -2.6 ) cm ] , percentage body fat [ -4.1 ( -4.9 , -2.9 ) compared with -3.5 ( -4.5 , -2.5 ) ] , trunk fat [ -4.1 ( -4.7 , -3.0 ) compared with -3.7 ( -4.3 , -2.9 ) kg ] , insulin [ -2.5 ( -3.4 , -1.7 ) compared with -2.4 ( -3.3 , -1.4 ) μU/mL ] , and CRP [ -0.9 ( -1.2 , -0.6 ) compared with -0.79 ( -0.9 , -0.4 ) mg/L ] [ corrected ] were similar between groups ( all P > 0.05 ) . Compared with women who achieved 25(OH)D < 32 ng/mL , women r and omly assigned to vitamin D who became replete ( ie , 25(OH)D ≥32 ng/mL ) lost more weight [ -8.8 ( -11.1 , -6.9 ) compared with -5.6 ( -7.2 , -5.0 ) kg ; P = 0.05 ] , waist circumference [ -6.6 ( -9.3 , -4.3 ) compared with -2.5 ( -4.6 , -2.0 ) cm ; P = 0.02 ] , and percentage body fat [ -4.7 ( -6.1 , -3.5 ) compared with -2.6 ( -3.9 , -2.2 ) ; P = 0.04 ] . Among women with complete pill counts ( 97 % adherence ) , the mean decrease in CRP was 1.18 mg/mL ( 46 % ) in the vitamin D arm compared with 0.46 mg/mL ( 25 % ) in the placebo arm ( P = 0.03 ) . CONCLUSIONS Vitamin D3 supplementation during weight loss did not increase weight loss or associated factors compared with placebo ; however , women who became replete experienced greater improvements . This trial was registered at clinical trials.gov as NCT01240213 Several studies , using dual-energy X-ray absorptiometry ( DXA ) , have reported substantial bone loss after bariatric surgery . However , profound weight loss may cause artifactual changes in DXA areal bone mineral density ( aBMD ) results . Assessment of volumetric bone mineral density ( vBMD ) by quantitative computed tomography ( QCT ) may be less susceptible to such artifacts . We assessed changes in BMD of the lumbar spine and proximal femur prospect ively for 1 year using DXA and QCT in 30 morbidly obese adults undergoing Roux-en-Y gastric bypass surgery and 20 obese nonsurgical controls . At 1 year , subjects who underwent gastric bypass surgery lost 37 ± 2 kg compared with 3 ± 2 kg lost in the nonsurgical controls ( p < 0.0001 ) . Spine BMD declined more in the surgical group than in the nonsurgical group whether assessed by DXA ( -3.3 versus -1.1 % , p = 0.034 ) or by QCT ( -3.4 versus 0.2 % , p = 0.010 ) . Total hip and femoral neck aBMD declined significantly in the surgical group when assessed by DXA ( -8.9 versus -1.1 % , p < 0.0001 for the total hip and -6.1 versus -2.0 % , p = 0.002 for the femoral neck ) , but no changes in hip vBMD were noted using QCT . Within the surgical group , serum P1NP and CTX levels increased by 82 % ± 10 % and by 220 % ± 22 % , respectively , by 6 months and remained elevated over 12 months ( p < 0.0001 for all ) . Serum calcium , vitamin D , and PTH levels remained stable in both groups . We conclude that moderate vertebral bone loss occurs in the first year after gastric bypass surgery . However , striking declines in DXA aBMD at the proximal femur were not confirmed with QCT vBMD measurements . These discordant results suggest that artifacts induced by large changes in body weight after bariatric surgery affect DXA and /or QCT measurements of bone , particularly at the hip OBJECTIVE To investigate the prevalence and incidence of clinical fractures in obese , postmenopausal women enrolled in the Global Longitudinal study of Osteoporosis in Women ( GLOW ) . METHODS This was a multinational , prospect i ve , observational , population -based study carried out by 723 physician practice s at 17 sites in 10 countries . A total of 60,393 women aged ≥ 55 years were included . Data were collected using self-administered question naires that covered domains that included patient characteristics , fracture history , risk factors for fracture , and anti-osteoporosis medications . RESULTS Body mass index ( BMI ) and fracture history were available at baseline and at 1 and 2 years in 44,534 women , 23.4 % of whom were obese ( BMI ≥ 30 kg/m(2 ) ) . Fracture prevalence in obese women at baseline was 222 per 1000 and incidence at 2 years was 61.7 per 1000 , similar to rates in nonobese women ( 227 and 66.0 per 1000 , respectively ) . Fractures in obese women accounted for 23 % and 22 % of all previous and incident fractures , respectively . The risk of incident ankle and upper leg fractures was significantly higher in obese than in nonobese women , while the risk of wrist fracture was significantly lower . Obese women with fracture were more likely to have experienced early menopause and to report 2 or more falls in the past year . Self-reported asthma , emphysema , and type 1 diabetes were all significantly more common in obese than nonobese women with incident fracture . At 2 years , 27 % of obese women with incident fracture were receiving bone protective therapy , compared with 41 % of nonobese and 57 % of underweight women . CONCLUSIONS Our results demonstrate that obesity is not protective against fracture in postmenopausal women and is associated with increased risk of ankle and upper leg fractures We reported that weight loss induces bone loss which is prevented by exercise training ; however , the mechanism for this observation remains unclear . Sclerostin , an inhibitor of bone formation , has been found to increase in states of unloading and may mediate the changes in bone metabolism associated with weight loss and exercise . The objective of the study was to determine the effect of lifestyle intervention in obese older adults on sclerostin levels , and on hip geometry parameters . A total of 107 obese ( body mass index [ BMI ] ≥ 30 kg/m(2 ) ) older ( ≥65 years ) adults were r and omly assigned to control , diet , exercise , and combined diet-exercise for 1 year . Sclerostin levels were measured by ELISA at baseline , 6 months , and 12 months , while hip geometry parameters were obtained from bone mineral density ( BMD ) images done by dual-energy X-ray absorptiometry using hip structure analysis at baseline and 12 months . Both the diet and diet-exercise groups had significant decreases in body weight ( -9.6 % and -9.4 % , respectively ) , whereas weight was stable in the exercise and control groups . Sclerostin levels increased significantly and progressively in the diet group ( 6.6 % ± 1.7 % and 10.5 % ± 1.9 % at 6 and 12 months , respectively , all p < 0.05 ) , whereas they were unchanged in the other groups ; in particular , they were stable in the diet-exercise group ( 0.7 % ± 1.6 % and 0.4 % ± 1.7 % at 6 and 12 months , respectively , all p = 0.05 ) . Hip geometry parameters showed significant decreases in cross-sectional area , cortical thickness , and BMD ; and increases in buckling ratio at the narrow neck , intertrochanter , and femoral shaft . These negative changes on bone geometry were not observed in the diet-exercise group . Significant correlations between changes in sclerostin and changes in certain hip geometry parameters were also observed ( p < 0.05 ) . In conclusion , the increase in sclerostin levels with weight loss that was prevented by exercise may partly mediate the negative effects of weight loss on bone metabolism and the osteoprotective effect of exercise training Studies that evaluate the influence of gastric bypass ( RYGP ) on bone mass are limited to short-term follow-up . We analysed changes in bone mineral density ( BMD ) three years after surgery and evaluated the main determinants of the development of bone disease . Prospect i ve study of 59 morbidly obese white women aged 46 ± 8 years . BMD scanning using DEXA and plasma determinations of calcium , parathyroid hormone , 25-hydroxyvitamin D and insulin-like growth factor-I were made prior , at 12 months and 3 years after surgery . In the first postoperative year BMD decreased at femoral neck ( FN ) 10.2 % and in the lumbar spine ( LS ) 3.2 % , in the third year it additionally decreased 2.7 % and 3.1 % , respectively . BMD at both sites remained above the values of women of the same age . In the follow-up , 1.7 % developed osteoporosis at FN and 6.8 % at LS . Patients with bone disease were older , the percentage of women with menopause was greater in this group and had lower initial and final values of lean mass . The percentage of BMD loss at FN remained positively associated with the percentage of lean mass loss [ β 0.304 , p = 0.045 ] , and menopause [ β 0.337 , p = 0.025 ] . Major osteoporotic fracture and hip fracture risk was low even in menopausal patients ( 3.1 % and 0.40 % , respectively ) . After RYGP menopausal women and those with greater lean mass loss are at higher risk of BMD loss but progression to osteoporosis is uncommon and the risk of fracture is low The objective of this study was to characterize changes in metabolic bone parameters following bariatric surgery . Seventy-three obese adult patients who underwent either gastric b and ing ( GB ) , Roux-en-Y gastric bypass ( RYGB ) , or biliopancreatic diversion with duodenal switch ( BPD/DS ) were followed prospect ively for 18 months postoperatively . Changes in the calcium-vitamin D axis ( 25-hydroxyvitamin D ( 25OHD ) , 1,25-dihydroxyvitamin D ( 1,25(OH)(2)D ) , calcium , parathyroid hormone ( PTH ) ) , markers of bone formation ( osteocalcin , bone-specific alkaline phosphatase ) and resorption ( urinary N-telopeptide ( NTx ) ) , as well as bone mineral density ( BMD ) were assessed at 3-month intervals during this time period . Bariatric surgery result ed in significant and progressive weight loss over 18 months . With supplementation , 25OHD levels increased 65.3 % ( P < 0.0001 ) by 3 months , but leveled off and decreased < 30 ng/ml by 18 months . PTH initially decreased 21.4 % ( P = 0.01 ) at 3 months , but later approached presurgery levels . 1,25(OH)(2)D increased significantly starting at month 12 ( 50.3 % increase from baseline , P = 0.008 ) , and was positively associated with PTH ( r = 0.82 , P = 0.0001 ) . When stratified by surgery type , median PTH and 1,25(OH)(2)D levels were higher following combined restrictive and malabsorptive operations ( RYGB and BPD/DS ) compared to GB . Bone formation/resorption markers were increased by 3 months ( P < 0.05 ) and remained elevated through 18 months . Radial BMD decreased 3.5 % by month 18 , but this change was not significant ( P = 0.23 ) . Our findings show that after transient improvement , preoperative vitamin D insufficiency and secondary hyperparathyroidism persisted following surgery despite supplementation . Postoperative secondary hyperparathyroidism was associated with increased 1,25(OH)(2)D levels and increased bone turnover markers Weight reduction induces bone loss by several factors , and the effect of higher protein ( HP ) intake during caloric restriction on bone mineral density ( BMD ) is not known . Previous study design s examining the longer-term effects of HP diets have not controlled for total calcium intake between groups and have not examined the relationship between bone and endocrine changes . In this r and omized , controlled study , we examined how BMD ( areal and volumetric ) , turnover markers , and hormones [ insulin-like growth factor 1 ( IGF-1 ) , IGF-binding protein 3 ( IGFBP-3 ) , 25-hydroxyvitamin D , parathyroid hormone ( PTH ) , and estradiol ] respond to caloric restriction during a 1-year trial using two levels of protein intake . Forty-seven postmenopausal women ( 58.0 ± 4.4 years ; body mass index of 32.1 ± 4.6 kg/m(2 ) ) completed the 1-year weight-loss trial and were on a higher ( HP , 24 % , n = 26 ) or normal protein ( NP , 18 % , n = 21 ) and fat intake ( 28 % ) with controlled calcium intake of 1.2 g/d . After 1 year , subjects lost 7.0 % ± 4.5 % of body weight , and protein intake was 86 and 60 g/d in the HP and NP groups , respectively . HP compared with NP diet attenuated loss of BMD at the ultradistal radius , lumbar spine , and total hip and trabecular volumetric BMD and bone mineral content of the tibia . This is consistent with the higher final values of IGF-1 and IGFBP-3 and lower bone-resorption marker ( deoxypyridinoline ) in the HP group than in the NP group ( p < .05 ) . These data show that a higher dietary protein during weight reduction increases serum IGF-1 and attenuates total and trabecular bone loss at certain sites in postmenopausal women Weight loss therapy to improve health in obese older adults is controversial because it causes further bone loss . Therefore , it is recommended that weight loss therapy should include an intervention such as exercise training ( ET ) to minimize bone loss . The purpose of this study was to determine the independent and combined effects of weight loss and ET on bone metabolism in relation to bone mineral density ( BMD ) in obese older adults . One-hundred-seven older ( age > 65 years ) obese ( body mass index [ BMI ] ≥ 30 kg/m(2 ) ) adults were r and omly assigned to a control group , diet group , exercise group , and diet-exercise group for 1 year . Body weight decreased in the diet ( -9.6 % ) and diet-exercise ( -9.4 % ) groups , not in the exercise ( -1 % ) and control ( -0.2 % ) groups ( between-group p < 0.001 ) . However , despite comparable weight loss , bone loss at the total hip was relatively less in the diet-exercise group ( -1.1 % ) than in the diet group ( -2.6 % ) , whereas BMD increased in the exercise group ( 1.5 % ) ( between-group p < 0.001 ) . Serum C-terminal telopeptide ( CTX ) and osteocalcin concentrations increased in the diet group ( 31 % and 24 % , respectively ) , whereas they decreased in the exercise group ( -13 % and -15 % , respectively ) ( between-group p < 0.001 ) . In contrast , similar to the control group , serum CTX and osteocalcin concentrations did not change in the diet-exercise group . Serum procollagen propeptide concentrations decreased in the exercise group ( -15 % ) compared with the diet group ( 9 % ) ( p = 0.04 ) . Serum leptin and estradiol concentrations decreased in the diet ( -25 % and -15 % , respectively ) and diet-exercise ( -38 % and -13 % , respectively ) groups , not in the exercise and control groups ( between-group p = 0.001 ) . Multivariate analyses revealed that changes in lean body mass ( β = 0.33 ) , serum osteocalcin ( β = -0.24 ) , and one-repetition maximum ( 1-RM ) strength ( β = 0.23 ) were independent predictors of changes in hip BMD ( all p < 0.05 ) . In conclusion , the addition of ET to weight loss therapy among obese older adults prevents weight loss-induced increase in bone turnover and attenuates weight loss-induced reduction in hip BMD despite weight loss-induced decrease in bone-active hormones OBJECTIVE To determine the 2-year outcomes of Roux-en-Y gastric bypass ( RYGB ) and sleeve gastrectomy ( SG ) vs. intensive medical therapy ( IMT ) on lean body mass , total bone mass , and bone mineral density ( BMD ) measures from the STAMPEDE trial . METHODS 54 subjects ( BMI : 36 ± 1 kg/m(2 ) , age : 48 ± 4 years ) with type 2 diabetes ( T2DM ) ( HbA1c : 9.7 ± 2 % ) were r and omized to IMT , RYGB , or SG and underwent DXA at baseline and at 1 and 2 years . RESULTS At 2 years , the reduction in BMI was similar after RYGB and SG and was greater than IMT ( P < 0.001 ) . Lean mass was reduced by ∼10 % , total bone mineral content reduced by ∼8 % , and hip BMD reduced by ∼9 % in both surgical groups and was significantly greater than IMT despite increases in vitamin D intake in all groups . The change in hip BMD correlated with weight loss ( r = 0.84 , P < 0.0001 ) and changes in lean mass ( r = 0.74 , P < 0.0001 ) and leptin ( r = 0.53 , P < 0.0001 ) . Peripheral fractures were self-reported in RYGB ( 4/18 patients ) , SG ( 2/19 patients ) , and IMT ( 4/16 patients ) . CONCLUSIONS Surgically induced weight loss is associated with modest reductions in lean mass , bone mineral content , and BMD , despite calcium and vitamin D supplementation in patients with T2DM . Awareness for bone loss is indicated for patients undergoing bariatric procedures |
14,062 | 23,369,532 | Findings from these studies support the presence of HPA axis hyperactivity and a blunted HPA axis response to stress at the onset of psychosis . | Up to now studies on hypothalamic-pituitary-adrenal ( HPA ) axis activity in psychosis have shown inconsistent findings .
These inconsistencies have been often ascribed to confounding effects of long duration of illness and chronic treatment with psychotropic medications of the subjects studied ( chronic psychosis ) .
In the last years , several studies have focused on the study of subjects at their first episode of psychosis to overcome these possible confounders .
The aim of this paper was to review the literature investigating HPA axis activity in first episode psychosis . | An altered function of the hypothalamic-pituitary-adrenal axis is assumed to be characteristic for Posttraumatic Stress Disorder ( PTSD ) , although there is inconsistent empirical evidence . Only few studies examined the awakening cortisol response and a daytime profile in PTSD . Salivary cortisol levels were measured at seven intervals from awakening until 8 PM in trauma-exposed subjects with ( N=29 ) and without PTSD ( N=19 ) and in 15 non-exposed controls . While the three groups did not differ with respect to their first cortisol level immediately after awakening , the expected cortisol increase to awakening 15 - 60 min later was significantly lower in PTSD patients compared to non-PTSD subjects and healthy controls . This effect remained stable when trauma-exposed subjects with comorbid major depression were excluded from the analysis . A significant negative correlation between the overall cortisol secretion ( AUC(G ) ) and overall PTSD symptomatology and hyper-arousal symptoms was found . The findings are discussed in light of the hypothesis of a counterregulation of hyper-arousal symptoms and chronic stress in PTSD Subjects at their first psychotic episode show an enlarged volume of the pituitary gl and , but whether this is due to hypothalamic – pituitary – adrenal ( HPA ) axis hyperactivity , or to stimulation of the prolactin-secreting cells by antipsychotic treatment , is unclear . We measured pituitary volume , using 1.5-mm , coronal , 1.5 T , high-resolution MRI images , in 78 patients at the first psychotic episode and 78 age- and gender-matched healthy controls . In all , 18 patients were antipsychotic-free ( 12 of these were antipsychotic-naïve ) , 26 were receiving atypical antipsychotics , and 33 were receiving typical antipsychotics . As hypothesized , patients had a larger pituitary volume than controls ( + 22 % , p<0.001 ) . When divided by antipsychotic treatment , and compared to controls , the pituitary volume was 15 % larger in antipsychotic-free patients ( p=0.028 ) , 17 % larger in patients receiving atypicals ( p=0.01 ) , and 30 % larger in patients receiving typicals ( p<0.001 ) . Patients receiving typicals not only had the largest pituitary volume compared to controls but also showed a trend for a larger pituitary volume compared to the other patients grouped together ( + 11 % , p=0.08 ) . When divided by diagnosis , and compared to controls , the pituitary volume was 24 % larger in patients with schizophrenia/schizophreniform disorder ( n=40 , p<0.001 ) , 19 % larger in depressed patients ( n=13 , p=0.022 ) , 16 % larger in bipolar patients ( n=16 , p=0.037 ) , and 12 % larger in those with other psychoses ( n=9 , p=0.2 ) . In conclusion , the first-episode of a psychotic disorder is associated with a larger pituitary independently of the presence of antipsychotic treatment , and this could be due to activation of the HPA axis . Typical antipsychotics exert an additional enlarging effect on pituitary volume , likely to be related to activation of prolactin-secreting cells . This activation of the hormonal stress response could participate to the important metabolic abnormalities observed in patients with psychosis OBJECTIVES Higher rates of dexamethasone test ( DST ) nonsuppression in schizophrenia have been attributed to depressive symptoms , suicidality and negative symptoms . No study concerning first-episode schizophrenia has yet been published . DESIGN In patients hospitalised for the first time with first-episode schizophrenia the DST has been performed before , at the end of the acute treatment and after one year . At the same time the clinical evaluation with PANSS was performed . A cortisol value > 5 microgram/dl in either of the postdexamethasone sample s indicated nonsuppression of cortisol . RESULTS A total of 56 males were included . 18 % of pts were DST nonsuppressors at medication-free baseline , 5 % and 16 % after acute treatment and after one year respectively . After 1 year 42/56 of patients fulfilled the criteria of remission . The rate of nonsuppression was 21.4 % , 5 % and 16.4 % in remitters and 7 % , 7 % and 14.3 % in nonremitters . Significant differences in the whole group were found between postdexamethasone cortisolemia at discharge on the one h and and on admission and at the one-year follow-up on the other . Significant correlations were observed between postdexamethasone cortisolemia and negative symptoms at the end of acute treatment . MAIN FINDINGS In first-episode schizophrenia the short-term treatment led to a decrease in cortisolemia and rates of nonsuppression and an increase at a one-year follow-up . CONCLUSIONS Rates of DST nonsuppression in schizophrenia including first-episode schizophrenia are influenced by the stage of illness and medication status . The impairment of feedback regulation of cortisol secretion may be related to different biopathogenetic mechanisms depending on the phase of the illness Rationale Increased activity of the hypothalamic – pituitary – adrenal ( HPA ) axis is an important aspect of the pathophysiology of major depression and schizophrenia . Despite the usefulness of atypical antipsychotics in the treatment of depression and their positive influence on cognitive functioning possibly related to their impact on cortisol , little is known about their effect on HPA axis function . Objective Therefore , this double-blind , placebo-controlled , r and omized cross-over study investigated the influence of the atypical antipsychotics quetiapine and olanzapine in comparison with haloperidol and placebo on plasma adrenocorticotropic hormone ( ACTH ) , cortisol , and prolactin levels . Eleven healthy male volunteers were studied during four sessions one week apart , orally receiving placebo , quetiapine ( 50 mg ) , olanzapine ( 5 mg ) , or haloperidol ( 3 mg ) . Blood sample s were taken at hourly intervals from 0900 until 1700 hours . For ACTH , cortisol , and prolactin a significant effect of treatment condition ( p≤0.005 ; p≤0.035 ; p≤0.0001 , respectively ) for area under the curve ( AUC ) was found . In comparison to placebo , quetiapine and olanzapine significantly reduced ACTH ( p≤0.002 ; p≤0.05 , respectively ) and cortisol ( p≤0.005 ; p≤0.03 , respectively ) . No effect of haloperidol on AUC of ACTH or cortisol levels was observed . In comparison with placebo , haloperidol ( p≤0.0001 ) and olanzapine ( p≤0.0001 ) elevated AUC of prolactin plasma levels , whereas no significant effect was observed for quetiapine as a main effect of treatment condition . The atypical antipsychotics ’ strong influence on HPA-function with pronounced ACTH and cortisol lowering is possibly related to the atypicals ’ blockade of serotonergic receptors , but blockade of adrenergic or histaminergic receptors may play a role as well . The observed HPA-axis down-regulation may be clinical ly important for the atypicals ’ effects on depressive symptomatology and cognitive functioning BACKGROUND An early response to antipsychotic treatment in patients with psychosis has been associated with a better course and outcome . However , factors that predict treatment response are not well understood . The onset of schizophrenia and related disorders has been associated with increased levels of stress and hyper-activation of the hypothalamic-pituitary-adrenal ( HPA ) axis . This study examined whether pituitary volume at the onset of psychosis may be a potential predictor of early treatment response in first-episode psychosis ( FEP ) patients . METHODS We investigated the relationship between baseline pituitary volume and symptomatic treatment response over 12 weeks using mixed model analysis in a sample of 42 drug-naïve or early treated FEP patients who participated in a controlled dose-finding study of quetiapine fumarate . Logistic regression was used to examine predictors of treatment response . Pituitary volume was measured from magnetic resonance imaging scans that were obtained upon entry into the trial . RESULTS Larger pituitary volume was associated with less improvement in overall psychotic symptoms ( Brief Psychiatric Rating Scale ( BPRS ) P=0.031 ) and positive symptoms ( BPRS positive symptom subscale P=0.010 ) . Regardless of gender , patients with a pituitary volume at the 25th percentile ( 413 mm(3 ) ) were approximately three times more likely to respond to treatment by week 12 than those at the 75th percentile ( 635 mm(3 ) ) ( odds ratio=3.07 , CI : 0.90 - 10.48 ) . CONCLUSION The association of baseline pituitary volumes with early treatment response highlights the importance of the HPA axis in emerging psychosis . Potential implication s for treatment strategies in early psychosis are discussed The bilateral communication between the immune and neuroendocrine systems plays an essential role in modulating the adequate response of the hypothalamic – pituitary – adrenal ( HPA ) axis to the stimulatory influence of cytokines and stress-related mediators . Growing evidence suggests that neuro-immune-endocrine crosstalk may be impaired in schizophrenia . We determined the relationship between cortisol , cytokines interleukin-2 ( IL-2 ) and interleukin-6 ( IL-6 ) , and symptoms in schizophrenia during treatment with typical and atypical antipsychotic drugs . Subjects included 30 healthy controls ( HC ) and 78 schizophrenic ( SCH ) in- patients . SCH were r and omly assigned to 12-week treatment with 6 mg/day of risperidone or 20 mg/day of haloperidol using a double-blind design . Clinical efficacy was determined using the Positive and Negative Syndrome Scale ( PANSS ) . Serum cortisol and IL-2 levels were assayed by radioimmunometric assay , and serum IL-6 levels by quantitative enzyme-linked immunosorbent assay . Following a 2-week washout period , serum levels of cortisol , IL-2 , and IL-6 were increased in patients with schizophrenia compared to HC . Elevations in cortisol were associated with increase in both IL-2 and IL-6 in SCH . Moreover , elevations in cortisol were associated with negative symptoms and IL-2 with positive symptoms . In all , 12 weeks of risperidone treatment significantly decreased elevated cortisol and improved negative symptoms , but produced similar effects on IL-2 and IL-6 as well as on positive symptoms compared to haloperidol . The improvement of negative symptoms was related to the change in cortisol . Our results suggest that the imbalance in the HPA axis and cytokine system in patients with SCH is implicated in clinical symptoms , and is improved with atypical antipsychotic treatment Dynamic testing of the hypothalamic-pituitary-adrenal axis in schizophrenia has yielded conflicting results , which may be related to patient selection and previous exposure to psychotropic medication . The objective of this study was to determine the pattern of corticotropin ( ACTH ) and cortisol release in response to metoclopramide ( a dopamine antagonist ) , which appears to be unique in its ability to release vasopressin ( AVP ) , in drug naive patients with schizophrenia experiencing their first episode of psychosis . In this study , we examined AVP , ACTH and cortisol release in response to metoclopramide in 10 drug-naive , first-episode male patients with a DSM IV diagnosis of paranoid schizophrenia and compared them to healthy control subjects matched for age , sex and smoking status . Patients , as compared to controls had higher levels of baseline plasma cortisol ( 375.5+/-47.4/l vs. 273.8+/-42.2 nmol/l , respectively ; t=2.48 , df=9 , p < 0.02 ) and plasma ACTH ( 14.9+/-0.85 vs. 11.3+/-0.57 pg/ml , respectively ; t=4.29 , df=9 , p<0.001 ) . AVP levels were lower in patients though this did not reach statistical significance ( 0.89+/-0.09 vs. 1.3+/-0.08 pmol/l , respectively ; t=1.97 , df=9 , p<0.07 ) . A repeated measures 2-way ANOVA to compare responses to metoclopramide over time between the two groups yielded a significant group by time interaction for cortisol ( F=11.3 , df=6 , 108 , p<0.001 ) and ACTH ( F=15.65 , df=6 , 108 , p<0.002 ) . Post hoc Tukey 's test revealed significant differences between the two groups at + 30 , + 45 , + 60 , + 90 and + 120 min for cortisol ( p<0.01 ) and at + 30 , + 45 , + 60 and + 90 min for ACTH ( p<0.01 ) . The group by time interactions continued to remain significant when cortisol ( F=10.9 , df=6 , 107 , p<0.001 ) and ACTH ( F=13.04 , df=6 , 108 , p<0.002 ) were entered as co-variates . There was a significant positive correlation between AVP and cortisol responses in patients ( r=0.65 , df=8 , p<0.01 ) . Male patients with paranoid schizophrenia release greater amounts of ACTH and cortisol in responses to metoclopramide-induced AVP secretion than control subjects BACKGROUND Evidence for basal hypothalamic-pituitary-adrenal ( HPA ) axis dysfunction in schizophrenia is less consistent than that seen in major depression . Potential reasons include sampling procedures and the use of patients on antipsychotic medications which may suppress the HPA axis . Therefore , the objective of this study was to determine whether first episode , drug naïve patients with schizophrenia have evidence of basal HPA axis dysfunction by measuring plasma levels of AVP , ACTH and cortisol from 13:00 to 16:00 h , a time frame which is believed to reflect 24 h concentrations of HPA axis activity . METHOD In this cross-sectional study , plasma levels of AVP , ACTH and cortisol were measured in 12 ( 7 males and 5 females ) ( mean age + /-SD=33.6+/-12.6 years ) patients with DSM-IV schizophrenia and compared with those found in age- and sex-matched healthy controls . RESULTS Patients and controls did not differ in terms of their 13:00 h cortisol and AVP . However , patients with schizophrenia had higher levels of ACTH as compared to control subjects at 13:00 h ( 41.3+/-14.6 vs. 12.4+/-1.1 pg/ml respectively ; t=1.99 , df=11 , p < 0.05 ) . In comparison to controls subjects , patients with schizophrenia , had higher mean ( + /-SE ) AUC of ACTH ( 26.3+/-6.2 vs. 13.9 nmol/l , respectively ; t=2.86 , df=11 , p < 0.02 ) and cortisol ( 279.4+/-26.0 vs. 213.1+/-18.4 nmol/l , respectively ; t=3.72 , df=11 , p < 0.01 ) . Though , patients with schizophrenia , in comparison to control subjects , had lower mean ( + /-SE ) AUC of AVP ( 0.87+/-0.24 vs. 1.42+/-0.34 pmol/l , respectively ; t=2.29 , df=11 , p < 0.02 ) . CONCLUSIONS First episode , drug naïve patients with schizophrenia show evidence of basal overactivity of the pituitary-adrenal axis Background / Aims : Schizotypy is viewed as a dimensional trait ranging from healthy people to schizophrenic spectrum patients . Stress activates the hypothalamic-pituitary-adrenal ( HPA ) axis , and accumulated evidence suggests that schizophrenia is associated with altered HPA axis function ; however , HPA axis function in relation to schizotypal personality has not been well documented . Methods : We examined the relationship between schizotypal traits as assessed with the Schizotypal Personality Question naire ( SPQ ) and cortisol responses to the combined dexamethasone/corticotropin- releasing hormone test in 141 healthy volunteers . Subjects were divided into three groups based on their cortisol responses to the dexamethasone/corticotropin-releasing hormone test : incomplete suppressors , moderate suppressors , and enhanced suppressors . SPQ scores were compared between these three groups using the analysis of covariance , controlling for age and sex . Results : The analysis of covariance showed significant main effects of the suppressor status on the ideas of reference and suspiciousness/paranoid ideation subscales and cognitive-perceptual factor . Post-hoc analyses with Bonferroni correction revealed that the enhanced suppressors scored significantly higher than the moderate suppressors on these SPQ indices . Conclusion : These results indicate that non clinical schizotypal traits in healthy adults are associated with blunted cortisol reactivity , potentially suggesting a shared neuroendocrinological mechanism across schizophrenia spectrum pathology Pharmacotherapy of schizophrenia is associated with the stressful side effects . Muscle rigidity causes distress , discomfort and poor compliance . The aim of the study was to determine the relationship between plasma hormones ( cortisol and prolactin/PRL ) and muscle rigidity in female schizophrenic patients treated with olanzapine or fluphenazine . In a r and omized , double-blind 22-weeks study , 12 patients were treated with olanzapine ( 5 - 20 mg/day ) and 10 patients received fluphenazine ( 6 - 21 mg/day ) . Treatment with olanzapine moderately decreased , while treatment with fluphenazine significantly increased plasma cortisol levels and muscle rigidity . The marked and moderate increase in plasma PRL levels were found in patients treated with fluphenazine and olanzapine , respectively . The results suggested that olanzapine induced moderate neuroendocrine effects and a reduction in rigidity as compared to fluphenazine treatment BACKGROUND Dehydroepi and rosterone ( DHEA ) and its sulphate form ( DHEA ) are neuroactive steroids with antiglucocorticoid properties . An imbalance in the ratio of cortisol to DHEA(S ) has been implicated in the pathophysiology of stress-related psychiatric disorders . This study prospect ively investigated circulating cortisol , DHEAS and their ratio in first-episode psychosis ( FEP ) patients compared to healthy controls , and their relationship to perceived stress , psychotic , negative and mood symptoms . METHODS Blood cortisol and DHEAS levels were obtained in 39 neuroleptic-naïve or minimally-treated FEP patients and 25 controls . Twenty-three patients and 15 controls received repeat assessment s after 12 weeks . Perceived stress was assessed using the Perceived Stress Scale and symptoms were assessed in patients using st and ard rating scales . RESULTS At baseline , no differences were observed in cortisol , DHEAS or the cortisol/DHEAS ratio between patients and controls . There were also no group differences in the change in these biological variables during the study period . Within FEP patients , decreases in cortisol and the cortisol/DHEAS ratio over time were directly related to the improvement in depression ( r = 0.45 ; p = 0.031 , r = 0.52 ; p = 0.01 ) , negative ( r = 0.51 ; p = 0.006 , r = 0.55 ; p = 0.008 ) and psychotic symptoms ( cortisol only , r = 0.53 ; p = 0.01 ) . Perceived stress significantly correlated with DHEAS ( r = 0.51 ; p = 0.019 ) and the cortisol/DHEAS ratio ( r = -0.49 ; p = 0.024 ) in controls , but not patients , possibly reflecting an impaired hormonal response to stress in FEP patients . CONCLUSIONS These findings further support the involvement of the stress system in the pathophysiology of psychotic disorders , with implication s for treatment strategies that modulate these neurosteroids |
14,063 | 21,072,453 | We consider that the available evidence suggests that to give antiviral treatment for chronic hepatitis B is a cost-effective intervention for many health systems , including ours .
It has varying indexes of cost-effectiveness according to the evaluated regimens . | null | null |
14,064 | 24,331,296 | A majority of the studies revealed that lower extremity amputees have increased postural sway in the st and ing posture .
Asymmetry in body weight , which is mainly distributed in the non-amputated leg , was described . | Postural control has been widely evaluated for the normal population and different groups over the past 20 years .
Numerous studies have investigated postural control in quiet st and ing posture among amputees .
However , a comprehensive analysis is lacking on the possible contributing factors to balance .
The present systematic review highlights the current findings on variables that contribute to balance instability for lower extremity amputees . | This study was aim ed at identifying changes in equilibrium and movement control strategies in transtibial amputees ( TTA ) related to both the biomechanical changes and the loss of afferent inflow . The coordinations between equilibrium and movement were studied in traumatical TTA and in controls during transition from bipedal to monopodal stance . TTA failed to perform the task in a high percentage of trials both when the sound and the prosthetic limb were supporting . Significant differences were also found between TTA and controls in the duration of the weight transfer phase , in the length of the initial centre of pressure ( CP ) displacement and in the electromyographic ( EMG ) patterns . Despite adaptive posturomotor control strategies , transition from bipedal to monopodal stance remains a difficult task to perform for TTA , both when the supporting limb is the affected one and when the sound one is . The results of this study are discussed with respect to the rehabilitation programme and the prosthesis design for transtibial amputees BACKGROUND Regaining effective postural control after lower limb amputation requires complex adaptation strategies in both the prosthesis side and the non-amputated side . The objective in this study is to determine the individual contribution of the ankle torques generated by both legs in balance control during dynamic conditions . METHODS Subjects ( 6 transfemoral and 8 transtibial amputees ) stood on a force platform mounted on a motion platform and were instructed to st and quietly . The experiment consisted of 1 static and 3 perturbation trials of 90 s duration each . The perturbation trials consisted of continuous r and omized sinusoidal platform movements of different amplitude in the sagittal plane . Weight distribution during the static and dynamic perturbation trials was calculated by dividing the average vertical force below the prosthesis foot by the sum of forces below both feet . The Dynamic Balance Control represents the ratio between the stabilizing mechanism of the prosthetic leg and the stabilizing mechanism of the non-amputated leg . The stabilizing mechanism is calculated from the corrective ankle torque in response to sway . The relationship between the prosthetic ankle stiffness and the performance during the platform perturbations was calculated . FINDINGS All patients showed a ( non-significant ) weight bearing asymmetry in favor of the non-amputated leg . The Dynamic Balance Control ratio showed that the contribution of both legs to balance control was even more asymmetrical . Moreover , the actual balance contribution of each leg was not tightly coupled to weight bearing in each leg , as was the case in healthy controls . There was a significant positive correlation between the prosthetic ankle stiffness and the Dynamic Balance Control . INTERPRETATION The Dynamic Balance Control provides , in addition to weight distribution , information to what extent the stabilizing mechanism of the corrective ankle torque of both legs contributes to balance control . Knowledge of the stiffness properties may optimize the prescription process of prosthetic foot in lower leg amputee subjects in relation to st and ing stability |
14,065 | 25,385,179 | There was no significant increase in a risk of high- grade neutropenia or leukopenia in patients receiving trastuzumab .
Treatment with trastuzumab is associated with a significantly higher risk of high- grade infection and febrile neutropenia . | Infections related to anti-HER2 monoclonal antibodies ( mAbs ) , trastuzumab and pertuzumab , have been reported in clinical trials .
It is not yet clear whether these drugs increase an infection risk or not .
We performed a systematic review and meta- analysis to assess the risk of infections associated with anti-HER2 mAbs . | BACKGROUND Studies with pertuzumab , a novel anti-HER2 antibody , show improved efficacy when combined with the established HER2-directed antibody trastuzumab in breast cancer therapy . We investigated the combination of pertuzumab or trastuzumab , or both , with docetaxel and the combination of pertuzumab and trastuzumab without chemotherapy in the neoadjuvant setting . METHODS In this multicentre , open-label , phase 2 study , treatment-naive women with HER2-positive breast cancer were r and omly assigned ( 1:1:1:1 ) central ly and stratified by operable , locally advanced , and inflammatory breast cancer , and by hormone receptor expression to receive four neoadjuvant cycles of : trastuzumab ( 8 mg/kg loading dose , followed by 6 mg/kg every 3 weeks ) plus docetaxel ( 75 mg/m(2 ) , escalating , if tolerated , to 100 mg/m(2 ) every 3 weeks ; group A ) or pertuzumab ( loading dose 840 mg , followed by 420 mg every 3 weeks ) and trastuzumab plus docetaxel ( group B ) or pertuzumab and trastuzumab ( group C ) or pertuzumab plus docetaxel ( group D ) . The primary endpoint , examined in the intention-to-treat population , was pathological complete response in the breast . Neither patients nor investigators were masked to treatment . This study is registered with Clinical Trials.gov , number NCT00545688 . FINDINGS Of 417 eligible patients , 107 were r and omly assigned to group A , 107 to group B , 107 to group C , and 96 to group D. Patients given pertuzumab and trastuzumab plus docetaxel ( group B ) had a significantly improved pathological complete response rate ( 49 of 107 patients ; 45·8 % [ 95 % CI 36·1 - 55·7 ] ) compared with those given trastuzumab plus docetaxel ( group A ; 31 of 107 ; 29·0 % [ 20·6 - 38·5 ] ; p=0·0141 ) . 23 of 96 ( 24·0 % [ 15·8 - 33·7 ] ) women given pertuzumab plus docetaxel ( group D ) had a pathological complete response , as did 18 of 107 ( 16·8 % [ 10·3 - 25·3 ] ) given pertuzumab and trastuzumab ( group C ) . The most common adverse events of grade 3 or higher were neutropenia ( 61 of 107 women in group A , 48 of 107 in group B , one of 108 in group C , and 52 of 94 in group D ) , febrile neutropenia ( eight , nine , none , and seven , respectively ) , and leucopenia ( 13 , five , none , and seven , respectively ) . The number of serious adverse events was similar in groups A , B , and D ( 15 - 20 serious adverse events per group in 10 - 17 % of patients ) but lower in group C ( four serious adverse events in 4 % of patients ) . INTERPRETATION Patients given pertuzumab and trastuzumab plus docetaxel ( group B ) had a significantly improved pathological complete response rate compared with those given trastuzumab plus docetaxel , without substantial differences in tolerability . Pertuzumab and trastuzumab without chemotherapy eradicated tumours in a proportion of women and showed a favourable safety profile . These findings justify further exploration in adjuvant trials and support the neoadjuvant approach for accelerating drug assessment in early breast cancer . FUNDING F Hoffmann-La Roche BACKGROUND We present the combined results of two trials that compared adjuvant chemotherapy with or without concurrent trastuzumab in women with surgically removed HER2-positive breast cancer . METHODS The National Surgical Adjuvant Breast and Bowel Project trial B-31 compared doxorubicin and cyclophosphamide followed by paclitaxel every 3 weeks ( group 1 ) with the same regimen plus 52 weeks of trastuzumab beginning with the first dose of paclitaxel ( group 2 ) . The North Central Cancer Treatment Group trial N9831 compared three regimens : doxorubicin and cyclophosphamide followed by weekly paclitaxel ( group A ) , the same regimen followed by 52 weeks of trastuzumab after paclitaxel ( group B ) , and the same regimen plus 52 weeks of trastuzumab initiated concomitantly with paclitaxel ( group C ) . The studies were amended to include a joint analysis comparing groups 1 and A ( the control group ) with groups 2 and C ( the trastuzumab group ) . Group B was excluded because trastuzumab was not given concurrently with paclitaxel . RESULTS By March 15 , 2005 , 394 events ( recurrent , second primary cancer , or death before recurrence ) had been reported , triggering the first scheduled interim analysis . Of these , 133 were in the trastuzumab group and 261 in the control group ( hazard ratio , 0.48 ; P<0.0001 ) . This result crossed the early stopping boundary . The absolute difference in disease-free survival between the trastuzumab group and the control group was 12 percent at three years . Trastuzumab therapy was associated with a 33 percent reduction in the risk of death ( P=0.015 ) . The three-year cumulative incidence of class III or IV congestive heart failure or death from cardiac causes in the trastuzumab group was 4.1 percent in trial B-31 and 2.9 percent in trial N9831 . CONCLUSIONS Trastuzumab combined with paclitaxel after doxorubicin and cyclophosphamide improves outcomes among women with surgically removed HER2-positive breast cancer . ( Clinical Trials.gov numbers , NCT00004067 and NCT00005970 . To assess anti-tumor activity of sequential epirubicin/cyclophosphamide followed by docetaxel with the r and omized addition of celecoxib in HER2 negative patients or trastuzumab in HER2 positive patients . From May 2004 till October 2007 , 340 patients with stage II and III breast adenocarcinoma , ineligible for breast conserving surgery , received eight sequential three weekly cycles of EC-D [ epirubicin ( 75 mg/m2)–cyclophosphamide ( 750 mg/m2 ) for four cycles followed by docetaxel ( 100 mg/m2 ) for four cycles ] . HER2-negative patients ( N = 220 ) were r and omized to receive concomitantly with docetaxel celecoxib 800 mg/day during cycles 5–8 or no additional treatment , while HER2-positive patients confirmed by FISH ( N = 120 ) were r and omized to trastuzumab concomitant to docetaxel ( 8 mg/kg then 6 mg/kg IV every 3 weeks ) or no additional preoperative treatment . In the HER2 negative group , pCR ( grade 1 and 2 of Chevallier ’s classification ) was observed in 11.5 and 13 % of patients treated without and with neoadjuvant Celecoxib , respectively . In the HER2 positive group , pCR rate reached 26 % in those who received neoadjuvant trastuzumab versus 19 % in the others . There was no unexpected toxicity , no cardiac toxicity , and no toxic death . Triple negative breast cancers experience the highest pCR rate of 30 % . Celecoxib is not likely to improve pCR rates in addition to EC-D in patients with HER2-negative tumor . In HER2-positive tumor patients , trastuzumab added to ECD leads to increased pCR rates . It was the only combination to deserve further study according to the two-stage Fleming ’s design used in this trial Background A r and omized Phase II study evaluated the activity of weekly paclitaxel versus its combination with trastuzumab for treatment of patients with advanced breast cancer overexpressing HER-2 . Patients and methods Among 124 patients r and omized , 123 are assessable for toxicity and 118 for response . Patients received weekly paclitaxel single agent ( 80 mg/m2 ) or combined with trastuzumab ( 4 mg/kg loading dose , then weekly 2 mg/kg ) . HER-2 overexpression was determined by immunohistochemistry ( IHC ) . Patients with 2+/3 + IHC scores were eligible . IHC was compared with HER-2 serum extracellular domain ( ECD ) . Results Patient characteristics were similar in the two arms . Both treatments were feasible and well tolerated with no grade 4 hematologic toxicity . No patient developed cardiac toxicity . The combined treatment was statistically significant superior for overall response rate ( ORR ) ( 75 % vs. 56.9 % ; P = 0.037 ) , particularly in the subset of IHC 3 + patients ( 84.5 % vs. 47.5 % ; P = 0.00050 ) . A statistically significant better median time to progression was seen in the subgroup with IHC 3 + ( 369 vs. 272 days ; P = 0.030 ) and visceral disease ( 301 vs. 183 days ; P = 0.0080 ) treated with combination . Multivariable analysis of predictive factors showed that only IHC score retained statistically significant value for ORR ( P = 0.0035 ) . Conclusion Weekly paclitaxel plus trastuzumab is highly active and safe and it is superior to paclitaxel alone in patients with IHC score of 3 + BACKGROUND The monoclonal antibody trastuzumab has survival benefit when given with chemotherapy to patients with early , operable , and metastatic breast cancer that has HER2 ( also known as ERBB2 ) overexpression or amplification . We aim ed to assess event-free survival in patients with HER2-positive locally advanced or inflammatory breast cancer receiving neoadjuvant chemotherapy with or without 1 year of trastuzumab . METHODS We compared 1 year of treatment with trastuzumab ( given as neoadjuvant and adjuvant treatment ; n=117 ) with no trastuzumab ( 118 ) , in women with HER2-positive locally advanced or inflammatory breast cancer treated with a neoadjuvant chemotherapy regimen consisting of doxorubicin , paclitaxel , cyclophosphamide , methotrexate , and fluorouracil . R and omisation was done with a computer program and minimisation technique , taking account of geographical area , disease stage , and hormone receptor status . Investigators were informed of treatment allocation . A parallel cohort of 99 patients with HER2-negative disease was included and treated with the same chemotherapy regimen . Primary endpoint was event-free survival . Analysis was by intention to treat . This study is registered , number IS RCT N86043495 . FINDINGS Trastuzumab significantly improved event-free survival in patients with HER2-positive breast cancer ( 3-year event-free survival , 71 % [ 95 % CI 61 - 78 ; n=36 events ] with trastuzumab , vs 56 % [ 46 - 65 ; n=51 events ] without ; hazard ratio 0.59 [ 95 % CI 0.38 - 0.90 ] ; p=0.013 ) . Trastuzumab was well tolerated and , despite concurrent administration with doxorubicin , only two patients ( 2 % ) developed symptomatic cardiac failure . Both responded to cardiac drugs . INTERPRETATION The addition of neoadjuvant and adjuvant trastuzumab to neoadjuvant chemotherapy should be considered for women with HER2-positive locally advanced or inflammatory breast cancer to improve event-free survival , survival , and clinical and pathological tumour responses . FUNDING F Hoffmann-La Roche BACKGROUND Trastuzumab , a recombinant monoclonal antibody against HER2 , has clinical activity in advanced breast cancer that overexpresses HER2 . We investigated its efficacy and safety after excision of early-stage breast cancer and completion of chemotherapy . METHODS This international , multicenter , r and omized trial compared one or two years of trastuzumab given every three weeks with observation in patients with HER2-positive and either node-negative or node-positive breast cancer who had completed locoregional therapy and at least four cycles of neoadjuvant or adjuvant chemotherapy . RESULTS Data were available for 1694 women r and omly assigned to two years of treatment with trastuzumab , 1694 women assigned to one year of trastuzumab , and 1693 women assigned to observation . We report here the results only of treatment with trastuzumab for one year or observation . At the first planned interim analysis ( median follow-up of one year ) , 347 events ( recurrence of breast cancer , contralateral breast cancer , second nonbreast malignant disease , or death ) were observed : 127 events in the trastuzumab group and 220 in the observation group . The unadjusted hazard ratio for an event in the trastuzumab group , as compared with the observation group , was 0.54 ( 95 percent confidence interval , 0.43 to 0.67 ; P<0.0001 by the log-rank test , crossing the interim analysis boundary ) , representing an absolute benefit in terms of disease-free survival at two years of 8.4 percentage points . Overall survival in the two groups was not significantly different ( 29 deaths with trastuzumab vs. 37 with observation ) . Severe cardiotoxicity developed in 0.5 percent of the women who were treated with trastuzumab . CONCLUSIONS One year of treatment with trastuzumab after adjuvant chemotherapy significantly improves disease-free survival among women with HER2-positive breast cancer . ( Clinical Trials.gov number , NCT00045032 . PURPOSE The objective of this study was to determine whether the addition of trastuzumab to chemotherapy in the neoadjuvant setting could increase pathologic complete response ( pCR ) rate in patients with human epidermal growth factor receptor 2 ( HER2 ) -positive disease . PATIENTS AND METHODS Forty-two patients with HER2-positive disease with operable breast cancer were r and omly assigned to either four cycles of paclitaxel followed by four cycles of fluorouracil , epirubicin , and cyclophosphamide or to the same chemotherapy with simultaneous weekly trastuzumab for 24 weeks . The primary objective was to demonstrate a 20 % improvement in pCR ( assumed 21 % to 41 % ) with the addition of trastuzumab to chemotherapy . The planned sample size was 164 patients . RESULTS Prognostic factors were similar in the two groups . After 34 patients had completed therapy , the trial 's Data Monitoring Committee stopped the trial because of superiority of trastuzumab plus chemotherapy . pCR rates were 25 % and 66.7 % for chemotherapy ( n = 16 ) and trastuzumab plus chemotherapy ( n = 18 ) , respectively ( P = .02 ) . The decision was based on the calculation that , if study continued to 164 patients , there was a 95 % probability that trastuzumab plus chemotherapy would be superior . Of the 42 r and omized patients , 26 % in the chemotherapy arm achieved pCR compared with 65.2 % in the trastuzumab plus chemotherapy arm ( P = .016 ) . The safety of this approach is not established , although no clinical congestive heart failure was observed . A more than 10 % decrease in the cardiac ejection fraction was observed in five and seven patients in the chemotherapy and trastuzumab plus chemotherapy arms , respectively . CONCLUSION Despite the small sample size , these data indicate that adding trastuzumab to chemotherapy , as used in this trial , significantly increased pCR without clinical congestive heart failure PURPOSE Trastuzumab , a humanized antibody against the human epidermal growth factor receptor type 2 ( HER2 ) , has shown high efficacy in breast cancer . We prospect ively investigated its efficacy given simultaneously with anthracycline-taxane-based neoadjuvant chemotherapy . PATIENTS AND METHODS Patients with operable or locally advanced , HER2-positive tumors were treated preoperatively with four cycles of epirubicin/cyclophosphamide followed by four cycles of docetaxel with or without capecitabine ( EC-T[X ] ) and trastuzumab 6 mg/kg ( with a loading dose of 8 mg/kg ) every 3 weeks during all chemotherapy cycles . Patients with HER2-negative tumors treated in the same study with the same chemotherapy but without trastuzumab were used as a reference group . Results Of 1,509 participants , 445 had HER2-positive tumors treated with trastuzumab and chemotherapy . Pathologic complete response ( pCR ; defined as no invasive or in situ residual tumors in the breast ) rate was 31.7 % , which was 16 % higher than that in the reference group ( 15.7 % ) . HER2-positive patients without response to the first four cycles of EC showed an unexpectedly high pCR rate of 16.6 % ( 3.3 % in the reference group ) . Breast conservation rate was 63.1 % and comparable to that of the reference group ( 64.7 % ) . EC-T(X ) plus trastuzumab was associated with more febrile neutropenia and conjunctivitis , but with a comparable short-term cardiac toxicity profile as the reference group . CONCLUSION This trial confirms that combining trastuzumab with anthracycline-taxane-based neoadjuvant chemotherapy results in a high pCR rate without clinical ly relevant early toxicity . Combination of chemotherapy with trastuzumab should be considered when neoadjuvant treatment is given to patients with HER2-positive breast cancer PURPOSE Oncologists prescribe anticancer drugs based on results of phase III r and omized clinical trials ( RCTs ) , but some safety concerns appear only later in up date d drug labels . Here , we analyze adverse drug reactions ( ADRs ) of targeted anticancer agents from up date d drug labels and their reporting in corresponding pivotal RCTs . METHODS We search ed the US Food and Drug Administration ( FDA ) Web site for approved targeted anticancer drugs with up date s of their labels related to safety in 2008 and 2009 and at least one RCT referenced in the up date d drug label . For each drug , serious ADRs , including potentially fatal ADRs , were identified from the up date d label . Published reports of RCTs referenced in the label were search ed to determine whether they described these ADRs . RESULTS We identified 12 eligible targeted anticancer agents with 36 corresponding RCTs referenced in up date d drug labels . There were 76 serious ADRs reported in up date d drug labels , and 50 % ( n = 38 ) were potentially fatal . Of these , 39 % ( n = 30 ) of all serious ADRs and 39 % ( n = 15 ) of potentially fatal ADRs were not described in any published report of RCTs , whereas 49 % and 58 % , respectively , were not described in initial drug labels . After a median 4.3 years between initial approval and up date of drug labels , 42 % ( n = 5 ) of targeted cancer agents acquired one or more boxed warnings ( the highest level of FDA alert ) . CONCLUSION Published reports of pivotal RCTs and initial drug labels contain limited information about serious ADRs of targeted anticancer agents . Rare but serious ADRs may be important causes of morbidity and mortality in general oncologic practice PURPOSE NCCTG ( North Central Cancer Treatment Group ) N9831 is the only r and omized phase III trial evaluating trastuzumab added sequentially or used concurrently with chemotherapy in resected stages I to III invasive human epidermal growth factor receptor 2-positive breast cancer . PATIENTS AND METHODS Patients received doxorubicin and cyclophosphamide every 3 weeks for four cycles , followed by paclitaxel weekly for 12 weeks ( arm A ) , paclitaxel plus sequential trastuzumab weekly for 52 weeks ( arm B ) , or paclitaxel plus concurrent trastuzumab for 12 weeks followed by trastuzumab for 40 weeks ( arm C ) . The primary end point was disease-free survival ( DFS ) . RESULTS Comparison of arm A ( n = 1,087 ) and arm B ( n = 1,097 ) , with 6-year median follow-up and 390 events , revealed 5-year DFS rates of 71.8 % and 80.1 % , respectively . DFS was significantly increased with trastuzumab added sequentially to paclitaxel ( log-rank P < .001 ; arm B/arm A hazard ratio [ HR ] , 0.69 ; 95 % CI , 0.57 to 0.85 ) . Comparison of arm B ( n = 954 ) and arm C ( n = 949 ) , with 6-year median follow-up and 313 events , revealed 5-year DFS rates of 80.1 % and 84.4 % , respectively . There was an increase in DFS with concurrent trastuzumab and paclitaxel relative to sequential administration ( arm C/arm B HR , 0.77 ; 99.9 % CI , 0.53 to 1.11 ) , but the P value ( .02 ) did not cross the prespecified O'Brien-Fleming boundary ( .00116 ) for the interim analysis . CONCLUSION DFS was significantly improved with 52 weeks of trastuzumab added to adjuvant chemotherapy . On the basis of a positive risk-benefit ratio , we recommend that trastuzumab be incorporated into a concurrent regimen with taxane chemotherapy as an important st and ard-of-care treatment alternative to a sequential regimen |
14,066 | 27,922,911 | Conclusions : Based on this meta- analysis , newer P2Y12 inhibitors were significantly more effective than clopidogrel in the events of myocardial infa rct ion and cardiovascular death in patients with ACS , although the incidence of thrombosis in MI-defined bleeding was higher compared with clopidogrel | Aims : New P2Y12 adenosine diphosphate receptor antagonists have been used in the treatment of acute coronary syndrome ( ACS ) with different results .
This systematic review analyzed and compared the evidence from large , clinical trials regarding the efficacy of clopidogrel relative to that of cangrelor , prasugrel , and ticagrelor in reducing the incidence of cardiovascular events in patients with ACS . | Background Clopidogrel is administered to prevent stent thrombosis ; however , the uniformity of platelet inhibition after treatment and the influence of pretreatment reactivity on drug response have not been described . Methods and Results Platelet aggregation ( 5 and 20 μmol/L ADP ) , the activation of glycoprotein IIb/IIIa ( PAC‐1 antibody ) , and the expression of P‐selectin were measured in patients undergoing elective coronary stenting ( n=96 ) at baseline and at 2 hours , 24 hours , 5 days , and 30 days after stenting . All patients received aspirin ( 325 mg ) . Clopidogrel ( 300 mg ) was administered in the catheterization laboratory and followed by 75 mg daily . There was marked interindividual variability in drug response as measured by all markers that showed a normal distribution . Resistance , defined as baseline aggregation ( % ) minus posttreatment aggregation ( % ) ≤10 % by 5 μmol/L ADP , was present in 31 % and 15 % of patients at 5 and 30 days , respectively . Patients with the highest pretreatment platelet reactivity remained the most reactive at 24 hours after treatment ( P<0.0001 ) . Conclusions Interindividual variability in the platelet inhibitory response from clopidogrel occurs in patients undergoing elective coronary stenting . Patients with high pretreatment reactivity are least protected . Alternative pharmacological strategies and the association of adverse ischemic events should be investigated in these patients . ( Circulation . 2003 ; 107:2908‐2913 . Aim MULTIPRAC was design ed to provide insights into the use and outcomes associated with prehospital initiation of antiplatelet therapy with either prasugrel or clopidogrel in the context of primary percutaneous coronary intervention . After a previous report on efficacy and safety outcomes during hospitalization , we report here the 1-year follow-up data , including cardiovascular ( CV ) mortality . Methods and results MULTIPRAC is a multinational , prospect i ve registry of patients with ST-elevation myocardial infa rct ion ( STEMI ) from 25 hospitals in nine countries , all of which had an established practice of prehospital start of dual antiplatelet therapy in place . The key outcome was CV death at 1 year . Among 2,036 patients followed-up through 1 year , 49 died ( 2.4 % ) , 10 during the initial hospitalization and 39 within 1 year after hospital discharge . The primary analysis was based on the P2Y12-inhibitor , used from prehospital loading dose through hospital discharge . Prasugrel ( n=824 ) was more commonly used than clopidogrel ( n=425 ) . The observed 1-year rates for CV death were 0.5 % with prasugrel and 2.6 % with clopidogrel . After adjustment for differences in baseline characteristics , treatment with prasugrel was associated with a significantly lower risk of CV death than treatment with clopidogrel ( odds ratio 0.248 ; 95 % confidence interval 0.06–0.89 ) . Conclusion In STEMI patients from routine practice undergoing primary angioplasty , who were able to start oral antiplatelet therapy prehospital , treatment with prasugrel as compared to clopidogrel was associated with a lower risk of CV death at 1-year follow-up BACKGROUND Despite improvements in the emergency treatment of myocardial infa rct ion ( MI ) , early mortality and morbidity remain high . The antiplatelet agent clopidogrel adds to the benefit of aspirin in acute coronary syndromes without ST-segment elevation , but its effects in patients with ST-elevation MI were unclear . METHODS 45,852 patients admitted to 1250 hospitals within 24 h of suspected acute MI onset were r and omly allocated clopidogrel 75 mg daily ( n=22,961 ) or matching placebo ( n=22,891 ) in addition to aspirin 162 mg daily . 93 % had ST-segment elevation or bundle branch block , and 7 % had ST-segment depression . Treatment was to continue until discharge or up to 4 weeks in hospital ( mean 15 days in survivors ) and 93 % of patients completed it . The two prespecified co- primary outcomes were : ( 1 ) the composite of death , reinfa rct ion , or stroke ; and ( 2 ) death from any cause during the scheduled treatment period . Comparisons were by intention to treat , and used the log-rank method . This trial is registered with Clinical Trials.gov , number NCT00222573 . FINDINGS Allocation to clopidogrel produced a highly significant 9 % ( 95 % CI 3 - 14 ) proportional reduction in death , reinfa rct ion , or stroke ( 2121 [ 9.2 % ] clopidogrel vs 2310 [ 10.1 % ] placebo ; p=0.002 ) , corresponding to nine ( SE 3 ) fewer events per 1000 patients treated for about 2 weeks . There was also a significant 7 % ( 1 - 13 ) proportional reduction in any death ( 1726 [ 7.5 % ] vs 1845 [ 8.1 % ] ; p=0.03 ) . These effects on death , reinfa rct ion , and stroke seemed consistent across a wide range of patients and independent of other treatments being used . Considering all fatal , transfused , or cerebral bleeds together , no significant excess risk was noted with clopidogrel , either overall ( 134 [ 0.58 % ] vs 125 [ 0.55 % ] ; p=0.59 ) , or in patients aged older than 70 years or in those given fibrinolytic therapy . INTERPRETATION In a wide range of patients with acute MI , adding clopidogrel 75 mg daily to aspirin and other st and ard treatments ( such as fibrinolytic therapy ) safely reduces mortality and major vascular events in hospital , and should be considered routinely This r and omized , active-controlled , double-blind study assessed the pharmacodynamics , pharmacokinetics and safety of ticagrelor in Japanese patients and a smaller cohort of non-Japanese Asian patients . The study recruited patients aged 20–80 years who had received aspirin 75–100 mg/day for ≥2 weeks and had percutaneous coronary intervention or acute coronary syndrome > 3 months previously . Patients received 4 weeks ’ treatment with ticagrelor 45 mg bid , ticagrelor 90 mg bid or clopidogrel 75 mg qd ( all with aspirin ) . The inhibition of platelet aggregation ( IPA , final-extent ) and pharmacokinetics of ticagrelor were assessed on days 1 and 28 . Overall , 139 Asian patients were r and omized ( ticagrelor 45 mg bid , n = 50 ; ticagrelor 90 mg bid , n = 43 ; clopidogrel , n = 46 ) of whom 118 were Japanese . Mean final-extent IPA was greater with ticagrelor 90 mg bid versus ticagrelor 45 mg bid and with both ticagrelor doses versus clopidogrel . At the end of the dosing interval on day 28 , mean final-extent IPA was 10.0 % higher ( 95 % confidence interval 0.5–19.5 % ) for ticagrelor 90 mg bid versus ticagrelor 45 mg bid , 15.1 % higher ( 5.8–24.4 % ) for ticagrelor 45 mg bid versus clopidogrel , and 25.1 % higher ( 15.5–34.7 % ) for ticagrelor 90 mg bid versus clopidogrel . In Japanese patients , exposure to ticagrelor and its active metabolite AR-C124910XX increased dose-proportionally . The safety profile of ticagrelor was consistent with previous studies . Ticagrelor was associated with enhanced IPA versus clopidogrel in Japanese patients OBJECTIVES Our goal was to compare the safety and initial efficacy of AZD6140 , the first reversible oral adenosine diphosphate receptor antagonist , with clopidogrel in patients with non-ST-segment elevation acute coronary syndromes ( NSTE-ACS ) . BACKGROUND AZD6140 achieves higher mean levels of platelet inhibition than clopidogrel in patients with stable coronary artery disease . METHODS A total of 990 patients with NSTE-ACS , treated with aspirin and st and ard therapy for ACS , were r and omized in a 1:1:1 double-blind fashion to receive either twice-daily AZD6140 90 mg , AZD6140 180 mg , or clopidogrel 300-mg loading dose plus 75 mg once daily for up to 12 weeks . RESULTS The primary end point , the Kaplan-Meier rate of major or minor bleeding through 4 weeks , was 8.1 % in the clopidogrel group , 9.8 % in the AZD6140 90-mg group , and 8.0 % in the AZD6140 180-mg group ( p = 0.43 and p = 0.96 , respectively , vs. clopidogrel ) ; the major bleeding rates were 6.9 % , 7.1 % , and 5.1 % , respectively ( p = 0.91 and p = 0.35 , respectively , vs. clopidogrel ) . Although not statistically significant , favorable trends were seen in the Kaplan-Meier rates of myocardial infa rct ion ( MI ) over the entire study period ( MI : 5.6 % , 3.8 % , and 2.5 % , respectively ; p = 0.41 and p = 0.06 , respectively , vs. clopidogrel ) . In a post-hoc analysis of continuous electrocardiograms , mostly asymptomatic ventricular pauses > 2.5 s were more common , especially in the AZD6140 180-mg group ( 4.3 % , 5.5 % , and 9.9 % , respectively ; p = 0.58 and p = 0.01 , respectively , vs. clopidogrel ) . CONCLUSIONS This initial experience with AZD6140 in patients with ACS showed no difference in major bleeding but an increase in minor bleeding at the higher dose with encouraging results on the secondary end point of MI . This agent is currently being studied in a large outcomes trial in 18,000 patients with ACS BACKGROUND Despite current treatments , patients who have acute coronary syndromes without ST-segment elevation have high rates of major vascular events . We evaluated the efficacy and safety of the antiplatelet agent clopidogrel when given with aspirin in such patients . METHODS We r and omly assigned 12,562 patients who had presented within 24 hours after the onset of symptoms to receive clopidogrel ( 300 mg immediately , followed by 75 mg once daily ) ( 6259 patients ) or placebo ( 6303 patients ) in addition to aspirin for 3 to 12 months . RESULTS The first primary outcome --a composite of death from cardiovascular causes , nonfatal myocardial infa rct ion , or stroke -- occurred in 9.3 percent of the patients in the clopidogrel group and 11.4 percent of the patients in the placebo group ( relative risk with clopidogrel as compared with placebo , 0.80 ; 95 percent confidence interval , 0.72 to 0.90 ; P<0.001 ) . The second primary outcome --the first primary outcome or refractory ischemia -- occurred in 16.5 percent of the patients in the clopidogrel group and 18.8 percent of the patients in the placebo group ( relative risk , 0.86 ; 95 percent confidence interval , 0.79 to 0.94 ; P<0.001 ) . The percentages of patients with in-hospital refractory or severe ischemia , heart failure , and revascularization procedures were also significantly lower with clopidogrel . There were significantly more patients with major bleeding in the clopidogrel group than in the placebo group ( 3.7 percent vs. 2.7 percent ; relative risk , 1.38 ; P=0.001 ) , but there were not significantly more patients with episodes of life-threatening bleeding ( 2.2 percent [ corrected ] vs. 1.8 percent ; P=0.13 ) or hemorrhagic strokes ( 0.1 percent vs. 0.1 percent ) . CONCLUSIONS The antiplatelet agent clopidogrel has beneficial effects in patients with acute coronary syndromes without ST-segment elevation . However , the risk of major bleeding is increased among patients treated with clopidogrel BACKGROUND Dual-antiplatelet therapy with aspirin and a thienopyridine is a cornerstone of treatment to prevent thrombotic complications of acute coronary syndromes and percutaneous coronary intervention . METHODS To compare prasugrel , a new thienopyridine , with clopidogrel , we r and omly assigned 13,608 patients with moderate-to-high-risk acute coronary syndromes with scheduled percutaneous coronary intervention to receive prasugrel ( a 60-mg loading dose and a 10-mg daily maintenance dose ) or clopidogrel ( a 300-mg loading dose and a 75-mg daily maintenance dose ) , for 6 to 15 months . The primary efficacy end point was death from cardiovascular causes , nonfatal myocardial infa rct ion , or nonfatal stroke . The key safety end point was major bleeding . RESULTS The primary efficacy end point occurred in 12.1 % of patients receiving clopidogrel and 9.9 % of patients receiving prasugrel ( hazard ratio for prasugrel vs. clopidogrel , 0.81 ; 95 % confidence interval [ CI ] , 0.73 to 0.90 ; P<0.001 ) . We also found significant reductions in the prasugrel group in the rates of myocardial infa rct ion ( 9.7 % for clopidogrel vs. 7.4 % for prasugrel ; P<0.001 ) , urgent target-vessel revascularization ( 3.7 % vs. 2.5 % ; P<0.001 ) , and stent thrombosis ( 2.4 % vs. 1.1 % ; P<0.001 ) . Major bleeding was observed in 2.4 % of patients receiving prasugrel and in 1.8 % of patients receiving clopidogrel ( hazard ratio , 1.32 ; 95 % CI , 1.03 to 1.68 ; P=0.03 ) . Also greater in the prasugrel group was the rate of life-threatening bleeding ( 1.4 % vs. 0.9 % ; P=0.01 ) , including nonfatal bleeding ( 1.1 % vs. 0.9 % ; hazard ratio , 1.25 ; P=0.23 ) and fatal bleeding ( 0.4 % vs. 0.1 % ; P=0.002 ) . CONCLUSIONS In patients with acute coronary syndromes with scheduled percutaneous coronary intervention , prasugrel therapy was associated with significantly reduced rates of ischemic events , including stent thrombosis , but with an increased risk of major bleeding , including fatal bleeding . Overall mortality did not differ significantly between treatment groups . ( Clinical Trials.gov number , NCT00097591 [ Clinical Trials.gov ] . BACKGROUND Variation in and irreversibility of platelet inhibition with clopidogrel has led to controversy about its optimum dose and timing of administration in patients with acute coronary syndromes . We compared ticagrelor , a more potent reversible P2Y12 inhibitor with clopidogrel in such patients . METHODS At r and omisation , an invasive strategy was planned for 13 408 ( 72.0 % ) of 18 624 patients hospitalised for acute coronary syndromes ( with or without ST elevation ) . In a double-blind , double-dummy study , patients were r and omly assigned in a one-to-one ratio to ticagrelor and placebo ( 180 mg loading dose followed by 90 mg twice a day ) , or to clopidogrel and placebo ( 300 - 600 mg loading dose or continuation with maintenance dose followed by 75 mg per day ) for 6 - 12 months . All patients were given aspirin . The primary composite endpoint was cardiovascular death , myocardial infa rct ion , or stroke . Analyses were by intention to treat . This trial is registered with Clinical Trials.gov , number NCT00391872 . FINDINGS 6732 patients were assigned to ticagrelor and 6676 to clopidogrel . The primary composite endpoint occurred in fewer patients in the ticagrelor group than in the clopidogrel group ( 569 [ event rate at 360 days 9.0 % ] vs 668 [ 10.7 % ] , hazard ratio 0.84 , 95 % CI 0.75 - 0.94 ; p=0.0025 ) . There was no difference between clopidogrel and ticagrelor groups in the rates of total major bleeding ( 691 [ 11.6 % ] vs 689 [ 11.5 % ] , 0.99 [ 0.89 - 1.10 ] ; p=0.8803 ) or severe bleeding , as defined according to the Global Use of Strategies To Open occluded coronary arteries , ( 198 [ 3.2 % ] vs 185 [ 2.9 % ] , 0.91 [ 0.74 - 1.12 ] ; p=0.3785 ) . INTERPRETATION Ticagrelor seems to be a better option than clopidogrel for patients with acute coronary syndromes for whom an early invasive strategy is planned Background The efficacy and safety of ticagrelor compared with clopidogrel in acute coronary syndrome has not previously been evaluated in an Eastern Asian population , which is recognized to have a different response to P2Y12 antagonists compared with the Caucasian population in real‐life situations . Methods A multicenter retrospective pilot study was performed to evaluate 928 consecutive patients with acute coronary syndrome , receiving aspirin and one P2Y12 antagonist ( 324 ticagrelor or 604 clopidogrel ) . Using propensity score matching , 448 patients were selected and divided into two equal groups . Kaplan – Meier analysis was used to study patient survival and event‐free status using the log‐rank test . Independent covariates were identified using univariate in a multivariate Cox proportional hazard model . Results In the overall cohort , significant differences were observed for certain variables between the two groups . During the mean 164.3 (±116.4)‐day follow‐up in the overall cohort , ticagrelor treatment had no significant effect on the primary efficacy endpoint ( myocardial infa rct ion , stroke , or vascular death ) ; however , in the matched cohort , ticagrelor showed a lower incidence of primary endpoint ( hazard ratio : 0.56 ; 95 % confidence interval : 0.30–1.04 ; p = 0.07 ) and stroke ( hazard ratio : 0.15 ; 95 % confidence interval : 0.02–1.24 ; p = 0.08 ) with marginal statistical significance , and a similar bleeding rate . The protective effect of ticagrelor treatment was consistent for all subgroups . More patients treated with ticagrelor experienced dyspnea ( 21.0 % vs. 11.6 % , p = 0.007 ) , and P2Y12 antagonist treatment was consequently discontinued . Conclusion Ticagrelor treatment could provide a marginally favorable effect at the expense of an increased risk of dyspnea in real‐life situations . This pilot study provides a scientific basis to call for a larger , suitably powered Phase 4 prospect i ve or observational study in this ethnic population BACKGROUND Intravenous cangrelor , a rapid-acting , reversible adenosine diphosphate ( ADP ) receptor antagonist , might reduce ischemic events during percutaneous coronary intervention ( PCI ) . METHODS In this double-blind , placebo-controlled study , we r and omly assigned 5362 patients who had not been treated with clopidogrel to receive either cangrelor or placebo at the time of PCI , followed by 600 mg of clopidogrel . The primary end point was a composite of death , myocardial infa rct ion , or ischemia-driven revascularization at 48 hours . Enrollment was stopped when an interim analysis concluded that the trial would be unlikely to show superiority for the primary end point . RESULTS The primary end point occurred in 185 of 2654 patients receiving cangrelor ( 7.0 % ) and in 210 of 2641 patients receiving placebo ( 8.0 % ) ( odds ratio in the cangrelor group , 0.87 ; 95 % confidence interval [ CI ] , 0.71 to 1.07 ; P=0.17 ) ( modified intention-to-treat population adjusted for missing data ) . In the cangrelor group , as compared with the placebo group , two prespecified secondary end points were significantly reduced at 48 hours : the rate of stent thrombosis , from 0.6 % to 0.2 % ( odds ratio , 0.31 ; 95 % CI , 0.11 to 0.85 ; P=0.02 ) , and the rate of death from any cause , from 0.7 % to 0.2 % ( odds ratio , 0.33 ; 95 % CI , 0.13 to 0.83 ; P=0.02 ) . There was no significant difference in the rate of blood transfusion ( 1.0 % in the cangrelor group and 0.6 % in the placebo group , P=0.13 ) , though major bleeding on one scale was increased in the cangrelor group , from 3.5 % to 5.5 % ( P<0.001 ) , because of more groin hematomas . CONCLUSIONS The use of periprocedural cangrelor during PCI was not superior to placebo in reducing the primary end point . The prespecified secondary end points of stent thrombosis and death were lower in the cangrelor group , with no significant increase in the rate of transfusion . Further study of intravenous ADP blockade with cangrelor may be warranted . ( Clinical Trials.gov number , NCT00385138 . Background —Despite the current st and ard antiplatelet regimen of aspirin and clopidogrel ( with or without glycoprotein IIb/IIIa inhibitors ) in percutaneous coronary intervention patients , periprocedural and postprocedural ischemic events continue to occur . Prasugrel ( CS-747 , LY640315 ) , a novel potent thienopyridine P2Y12 receptor antagonist , has the potential to achieve higher levels of inhibition of ADP-induced platelet aggregation than currently approved doses of clopidogrel . Methods and Results —Joint Utilization of Medications to Block Platelets Optimally – Thrombolysis In Myocardial Infa rct ion 26 ( JUMBO-TIMI 26 ) was a phase 2 , r and omized , dose-ranging , double-blind safety trial of prasugrel versus clopidogrel in 904 patients undergoing elective or urgent percutaneous coronary intervention . Patients were r and omized to either st and ard dosing with clopidogrel or 1 of 3 prasugrel regimens . Subjects were monitored for 30 days for bleeding and clinical events . The primary end point of the trial was clinical ly significant ( TIMI major plus minor ) non – CABG-related bleeding events in prasugrel- versus clopidogrel-treated patients . Hemorrhagic complications were infrequent , with no significant difference between patients treated with prasugrel or clopidogrel in the rate of significant bleeding ( 1.7 % versus 1.2 % ; hazard ratio , 1.42 ; 95 % CI , 0.40 , 5.08 ) . In prasugrel-treated patients , there were numerically lower incidences of the primary efficacy composite end point ( 30-day major adverse cardiac events ) and of the secondary end points myocardial infa rct ion , recurrent ischemia , and clinical target vessel thrombosis . Conclusions —In this phase 2 study , which was design ed to assess safety when administered at the time of percutaneous coronary intervention , prasugrel and clopidogrel both result ed in low rates of bleeding . The results of this trial serve as a foundation for the large phase 3 clinical trial design ed to assess both efficacy and safety Objective To assess safety up to 1 year of follow-up associated with prasugrel and clopidogrel use in a prospect i ve cohort of patients with acute coronary syndromes ( ACS ) . Methods Between 2009 and 2012 , 2286 patients invasively managed for ACS were enrolled in the multicentre Swiss ACS Bleeding Cohort , among whom 2148 patients received either prasugrel or clopidogrel according to current guidelines . Patients with ST-elevation myocardial infa rct ion ( STEMI ) preferentially received prasugrel , while those with non-STEMI , a history of stroke or transient ischaemic attack , age ≥75 years , or weight < 60 kg received clopidogrel or reduced dose of prasugrel to comply with the prasugrel label . Results After adjustment using propensity scores , the primary end point of clinical ly relevant bleeding events ( defined as the composite of Bleeding Academic Research Consortium , BARC , type 3 , 4 or 5 bleeding ) at 1 year , occurred at a similar rate in both patient groups ( prasugrel/clopidogrel : 3.8%/5.5 % ) . Stratified analyses in subgroups including patients with STEMI yielded a similar safety profile . After adjusting for baseline variables , no relevant differences in major adverse cardiovascular and cerebrovascular events were observed at 1 year ( prasugrel/clopidogrel : cardiac death 2.6%/4.2 % , myocardial infa rct ion 2.7%/3.8 % , revascularisation 5.9%/6.7 % , stroke 1.0%/1.6 % ) . Of note , this study was not design ed to compare efficacy between prasugrel and clopidogrel . Conclusions In this large prospect i ve ACS cohort , patients treated with prasugrel according to current guidelines ( ie , in patients without cerebrovascular disease , old age or underweight ) had a similar safety profile compared with patients treated with clopidogrel . Clinical trial registration number SPUM-ACS : NCT01000701 ; COMFORTABLE AMI : NCT00962416 Background — Ticagrelor is the first reversibly binding oral P2Y12 receptor antagonist . This is the first study to compare the onset and offset of platelet inhibition ( IPA ) with ticagrelor using the PLATO ( PLATelet inhibition and patient Outcomes ) trial loading dose ( 180 mg ) with a high loading dose ( 600 mg ) of clopidogrel . Methods and Results — In a multicenter , r and omized , double-blind study , 123 patients with stable coronary artery disease who were taking aspirin therapy ( 75 to 100 mg/d ) received ticagrelor ( 180-mg load , 90-mg BID maintenance dose [ n=57 ] ) , clopidogrel ( 600-mg load , 75-mg/d maintenance dose [ n=54 ] ) , or placebo ( n=12 ) for 6 weeks . Greater IPA ( 20 & mgr;mol/L ADP , final extent ) occurred with ticagrelor than with clopidogrel at 0.5 , 1 , 2 , 4 , 8 , and 24 hours after loading and at 6 weeks ( P<0.0001 for all ) ; by 2 hours after loading , a greater proportion of patients achieved > 50 % IPA ( 98 % versus 31 % , P<0.0001 ) and > 70 % IPA ( 90 % versus 16 % , P<0.0001 ) in the ticagrelor group than in the clopidogrel group , respectively . A faster offset occurred with ticagrelor than with clopidogrel ( 4-to-72–hour slope [ % IPA/h ] −1.04 versus −0.48 , P<0.0001 ) . At 24 hours after the last dose , mean IPA was 58 % for ticagrelor versus 52 % for clopidogrel ( P = NS ) . IPA for ticagrelor on day 3 after the last dose was comparable to clopidogrel at day 5 ; IPA on day 5 for ticagrelor was similar to clopidogrel on day 7 and did not differ from placebo ( P = NS ) . Conclusions — Ticagrelor achieved more rapid and greater platelet inhibition than high-loading-dose clopidogrel ; this was sustained during the maintenance phase and was faster in offset after drug discontinuation . Clinical Trial Registration Information— URL : http://www . clinical trials.gov . Unique identifier : NCT00528411 BACKGROUND The intensity of antiplatelet therapy during percutaneous coronary intervention ( PCI ) is an important determinant of PCI-related ischemic complications . Cangrelor is a potent intravenous adenosine diphosphate (ADP)-receptor antagonist that acts rapidly and has quickly reversible effects . METHODS In a double-blind , placebo-controlled trial , we r and omly assigned 11,145 patients who were undergoing either urgent or elective PCI and were receiving guideline -recommended therapy to receive a bolus and infusion of cangrelor or to receive a loading dose of 600 mg or 300 mg of clopidogrel . The primary efficacy end point was a composite of death , myocardial infa rct ion , ischemia-driven revascularization , or stent thrombosis at 48 hours after r and omization ; the key secondary end point was stent thrombosis at 48 hours . The primary safety end point was severe bleeding at 48 hours . RESULTS The rate of the primary efficacy end point was 4.7 % in the cangrelor group and 5.9 % in the clopidogrel group ( adjusted odds ratio with cangrelor , 0.78 ; 95 % confidence interval [ CI ] , 0.66 to 0.93 ; P=0.005 ) . The rate of the primary safety end point was 0.16 % in the cangrelor group and 0.11 % in the clopidogrel group ( odds ratio , 1.50 ; 95 % CI , 0.53 to 4.22 ; P=0.44 ) . Stent thrombosis developed in 0.8 % of the patients in the cangrelor group and in 1.4 % in the clopidogrel group ( odds ratio , 0.62 ; 95 % CI , 0.43 to 0.90 ; P=0.01 ) . The rates of adverse events related to the study treatment were low in both groups , though transient dyspnea occurred significantly more frequently with cangrelor than with clopidogrel ( 1.2 % vs. 0.3 % ) . The benefit from cangrelor with respect to the primary end point was consistent across multiple prespecified subgroups . CONCLUSIONS Cangrelor significantly reduced the rate of ischemic events , including stent thrombosis , during PCI , with no significant increase in severe bleeding . ( Funded by the Medicines Company ; CHAMPION PHOENIX Clinical Trials.gov number , NCT01156571 . ) BACKGROUND Although P2Y12 antagonists are effective in patients with non-ST-segment elevation ( NSTE ) acute coronary syndromes , the effect of the timing of administration -- before or after coronary angiography -- is not known . We evaluated the effect of administering the P2Y12 antagonist prasugrel at the time of diagnosis versus administering it after the coronary angiography if percutaneous coronary intervention ( PCI ) was indicated . METHODS We enrolled 4033 patients with NSTE acute coronary syndromes and a positive troponin level who were scheduled to undergo coronary angiography within 2 to 48 hours after r and omization . Patients were r and omly assigned to receive prasugrel ( a 30-mg loading dose ) before the angiography ( pretreatment group ) or placebo ( control group ) . When PCI was indicated , an additional 30 mg of prasugrel was given in the pretreatment group at the time of PCI and 60 mg of prasugrel was given in the control group . RESULTS The rate of the primary efficacy end point , a composite of death from cardiovascular causes , myocardial infa rct ion , stroke , urgent revascularization , or glycoprotein IIb/IIIa inhibitor rescue therapy ( glycoprotein IIb/IIIa bailout ) through day 7 , did not differ significantly between the two groups ( hazard ratio with pretreatment , 1.02 ; 95 % confidence interval [ CI ] , 0.84 to 1.25 ; P=0.81 ) . The rate of the key safety end point of all Thrombolysis in Myocardial Infa rct ion ( TIMI ) major bleeding episodes , whether related or not related to coronary-artery bypass grafting ( CABG ) , through day 7 was increased with pretreatment ( hazard ratio , 1.90 ; 95 % CI , 1.19 to 3.02 ; P=0.006 ) . The rates of TIMI major bleeding and life-threatening bleeding not related to CABG were increased by a factor of 3 and 6 , respectively . Pretreatment did not reduce the rate of the primary outcome among patients undergoing PCI ( 69 % of the patients ) but increased the rate of TIMI major bleeding at 7 days . All the results were confirmed at 30 days and in prespecified subgroups . CONCLUSIONS Among patients with NSTE acute coronary syndromes who were scheduled to undergo catheterization , pretreatment with prasugrel did not reduce the rate of major ischemic events up to 30 days but increased the rate of major bleeding complications . ( Funded by Daiichi Sankyo and Eli Lilly ; ACCOAST Clinical Trials.gov number , NCT01015287 . ) |
14,067 | 30,397,940 | The results are equivocal as to whether nursing interventions performed at home and nursing interventions performed in hospital with follow-up improve breathlessness in people with chronic obstructive pulmonary disease | AIM To critically review and synthesize the findings of studies that evaluated the effectiveness of nursing interventions for improving breathlessness in adults with chronic obstructive pulmonary disease .
BACKGROUND Systematic review s of nursing interventions for breathlessness in people with chronic obstructive pulmonary disease have not been specifically addressed . | Pulmonary rehabilitation is beneficial for patients with chronic lung disease . However , long-term maintenance has been difficult to achieve after short-term treatment . We evaluated a telephone-based maintenance program after pulmonary rehabilitation in 172 patients with chronic lung disease recruited from pulmonary rehabilitation graduates . Subjects were r and omly assigned to a 12-month maintenance intervention with weekly telephone contacts and monthly supervised reinforcement sessions ( n = 87 ) or st and ard care ( n = 85 ) and followed for 24 months . Except for a slight imbalance between sexes , experimental and control groups were equivalent at baseline and showed similar improvements after rehabilitation . During the 12-month intervention , exercise tolerance ( maximum treadmill workload and 6-minute walk distance ) and overall health status ratings were better maintained in the experimental group together with a reduction in hospital days . There were no group differences for other measures of pulmonary function , dyspnea , self-efficacy , generic and disease-specific quality of life , and health care use . By 24 months , there were no significant group differences . Patients returned to levels close to but above prerehabilitation measures . We conclude that a maintenance program of weekly telephone calls and monthly supervised sessions produced only modest improvements in the maintenance of benefits after pulmonary rehabilitation Background Dyspnea ( SOB ) , dyspnea-related anxiety ( DA ) , and exercise performance have been shown to improve after exercise training in patients with Chronic Obstructive Pulmonary Disease ( COPD ) . However , there are no published descriptions of the changes in dyspnea intensity or dyspnea-related anxiety during or across the exercise training sessions . Objectives To describe and compare the differences in the patterns of change in SOB , DA , and exercise performance during 12 exercise training sessions with and without nurse coaching . Methods Forty-five dyspnea-limited patients with COPD were r and omly assigned to nurse-monitored ( ME ) or nurse-coached exercise ( CE ) . SOB and DA were rated on a 200 mm VAS every 2 minutes during each of 12 treadmill training sessions . Results Warm-up , peak , cool-down , mean SOB , and peak SOB/stage remained constant over the exercise sessions , with increasing exercise performance for both groups over the 12 sessions ( p < .001 ) . There was a significant difference in the pattern of mean SOB over time between the ME and CE group ( p < . 05 ) . Mean , peak DA , and peak DA/stage showed a rapid decrease within the first 4 sessions ( p < . 05 ) with no significant differences between the groups . Warm-up and cool-down DA remained constant . There were large intra- and inter-subject variations in the rating of dyspnea and dyspnea-related anxiety within and across sessions . Conclusions As theoretically proposed , both groups significantly decreased their DA over the training sessions . This decrease was early in the sessions and was not accompanied by a decrease in the SOB . In contrast , subjects maintained a nearly constant mean and peak SOB with increasing exercise performance , suggesting that people may have a dyspnea threshold above which they are unable to tolerate greater dyspnea . Description of the changes in dyspnea and the affective response during training need to be exp and ed , while study ing the type and timing of strategies to enhance the improvement in dyspnea and dyspnea-related anxiety Chronic obstructive pulmonary disease ( COPD ) is disabling , with symptoms such as chronic cough , phlegm , wheezing , shortness of breath and increased infections of the respiratory passage . The aim was to examine the effects of a structured educational intervention programme at a nurse-led primary health care clinic ( PHCC ) on quality of life ( QoL ) , knowledge about COPD and smoking cessation in patients with COPD . This study had an experimental design in which 52 patients with COPD from a Swedish primary care setting were r and omized into two groups ( intervention or control ) . Both groups received st and ard care but patients in the intervention group were also offered two visits to a nurse specialized in COPD care . The purpose of the visits was to increase the patients ' self-care ability and their knowledge about COPD . The study was approved by the local Research Ethics Committee . Data were collected using two question naires , one pertaining to knowledge about COPD and smoking habits and St. George 's Respiratory Question naire , addressing how QoL was affected by the patients ' respiratory symptoms . The intervention and control groups answered both question naires on their first and last visits to the PHCC . A statistically significant increase was noted in the intervention group on QoL , the number of patients who stopped smoking and patients ' knowledge about COPD at the follow-up , 3 - 5 months after intervention . However , a confounding factor may have been that one of the research ers ( Eva Osterlund Efr aims son ) , as a nurse in the PHCC , performed the intervention . This implies that patients were in a dependent relationship which may have affected the responses in a favourable direction . Our findings show that conventional care alone did not have an effect on patients ' QoL and smoking habits . Instead , the evidence suggests that a structured programme with self-care education is needed to motivate patients for life-style changes Objectives : To determine the effects of a nurse led intermediate care programme in patients who have been hospitalised with an acute exacerbation of chronic obstructive pulmonary disease ( AE COPD ) . Design : R and omised controlled trial . Setting : Community and hospital care in west London . Participants : 122 patients with COPD . Intervention : A care package incorporating initial pulmonary rehabilitation and self-management education , provision of a written , personalised COPD action plan , monthly telephone calls and 3 monthly home visits by a specialist nurse for a period of 2 years . Main outcome measure : Hospital readmission rate . Secondary outcomes : Unscheduled primary care consultations and quality of life . Results : There were no differences in hospital admission rates or in exacerbation rates between the two groups . Self-management of exacerbations was significantly different and the intervention group were more likely to be treated with oral steroids alone or oral steroids and antibiotics , and the initiators of treatment for exacerbations were statistically more likely to be the patients themselves . 12 patients in the control group died during the 2 year period , eight as a result of COPD , compared with six patients in the intervention group , of whom one died from COPD . This is a significant difference . When the numbers were adjusted to reflect the numbers still alive at 2 years , in the intervention group patients reported a total of 171 unscheduled contacts with their general practitioner ( GP ) and in the control group , 280 contacts . The number needed to treat was 0.558—ie , for every one COPD patient receiving the intervention and self-management advice , there were 1.79 fewer unscheduled contacts with the GP . Conclusions : An intermediate care package incorporating pulmonary rehabilitation , self-management education and the receipt of a written COPD action plan , together with regular nurse contact , is associated with a reduced need for unscheduled primary care consultations and a reduction in deaths due to COPD but did not affect the hospital readmission rate Objectives To determine the effectiveness of early assisted discharge for chronic obstructive pulmonary disease ( COPD ) exacerbations , with home care provided by generic community nurses , compared with usual hospital care . Design Prospect i ve , r and omised controlled and multicentre trial with 3-month follow-up . Setting Five hospitals and three home care organisations in the Netherl and s. Participants Patients admitted to the hospital with an exacerbation of COPD . Patients with no or limited improvement of respiratory symptoms and patients with severe unstable comorbidities , social problems or those unable to visit the toilet independently were excluded . Intervention Early discharge from hospital after 3 days inpatient treatment . Home visits by generic community nurses . Primary outcome measure was change in health status measured by the Clinical COPD Question naire ( CCQ ) . Treatment failures , readmissions , mortality and change in generic health-related quality of life ( HRQL ) were secondary outcome measures . Results 139 patients were r and omised . No difference between groups was found in change in CCQ score at day 7 ( difference in mean change 0.29 ( 95 % CI −0.03 to 0.61 ) ) or at 3 months ( difference in mean change 0.04 ( 95 % CI –0.40 to 0.49 ) ) . No difference was found in secondary outcomes . At day 7 there was a significant difference in change in generic HRQL , favouring usual hospital care . Conclusions While patients ’ disease-specific health status after 7-day treatment tended to be somewhat better in the usual hospital care group , the difference was small and not clinical ly relevant or statistically significant . After 3 months , the difference had disappeared . A significant difference in generic HRQL at the end of the treatment had disappeared after 3 months and there was no difference in treatment failures , readmissions or mortality . Early assisted discharge with community nursing is feasible and an alternative to usual hospital care for selected patients with an acute COPD exacerbation . Trial registration : Netherl and sTrialRegister NTR 1129 Objective To assess the long term effects of two different modes of disease management ( comprehensive self management and routine monitoring ) on quality of life ( primary objective ) , frequency and patients ’ management of exacerbations , and self efficacy ( secondary objectives ) in patients with chronic obstructive pulmonary disease ( COPD ) in general practice . Design 24 month , multicentre , investigator blinded , three arm , pragmatic , r and omised controlled trial . Setting 15 general practice s in the eastern part of the Netherl and s. Participants Patients with COPD confirmed by spirometry and treated in general practice . Patients with very severe COPD or treated by a respiratory physician were excluded . Interventions A comprehensive self management programme as an adjunct to usual care , consisting of four tailored sessions with ongoing telephone support by a practice nurse ; routine monitoring as an adjunct to usual care , consisting of 2 - 4 structured consultations a year with a practice nurse ; or usual care alone ( contacts with the general practitioner at the patients ’ own initiative ) . Outcome measures The primary outcome was the change in COPD specific quality of life at 24 months as measured with the chronic respiratory question naire total score . Secondary outcomes were chronic respiratory question naire domain scores , frequency and patients ’ management of exacerbations measured with the Nijmegen telephonic exacerbation assessment system , and self efficacy measured with the COPD self-efficacy scale . Results 165 patients were allocated to self management ( n=55 ) , routine monitoring ( n=55 ) , or usual care alone ( n=55 ) . At 24 months , adjusted treatment differences between the three groups in mean chronic respiratory question naire total score were not significant . Secondary outcomes did not differ , except for exacerbation management . Compared with usual care , more exacerbations in the self management group were managed with bronchodilators ( odds ratio 2.81 , 95 % confidence interval 1.16 to 6.82 ) and with prednisolone , antibiotics , or both ( 3.98 , 1.10 to 15.58 ) . Conclusions Comprehensive self management or routine monitoring did not show long term benefits in terms of quality of life or self efficacy over usual care alone in COPD patients in general practice . Patients in the self management group seemed to be more capable of appropriately managing exacerbations than did those in the usual care group . Trial registration Clinical trials NCT00128765 AIMS AND OBJECTIVES To test the effect of a Health Belief Model-based nursing intervention on healthcare outcomes in Chinese patients with moderate to severe COPD . BACKGROUND The Health Belief Model ( HBM ) has been internationally vali date d in a variety of chronic conditions . However , nursing intervention based on the HBM is less explored in Chinese patients with COPD . DESIGN A r and omised controlled trial . METHODS Enrolled patients were r and omly assigned to the intervention and control groups . Patients in the intervention group received a 20- to 30-minute HBM-based nursing intervention every 2 days during the hospitalisation period after disease conditions were stable , with additional follow-ups after discharge . Patients in the control group received routine nursing care . RESULTS Patients had significantly increased scores of health belief and self-efficacy after receiving the HBM-based nursing intervention . After receiving the 3-month follow-up , patients in the intervention group had significantly higher mean total scores in the Health Belief Scale and the COPD Self-Efficacy Scale , as well as in all the subscales , than those in the control group except the perceived disease seriousness . Results showed that the value of FEV1 /FVC ratio had a significant difference between study groups before and after the intervention . Results also indicated that mean scores of the Dyspnea Scale , 6-minute walking distance and ADL were significantly different between the groups and between the study time-points . CONCLUSIONS Among patients with moderate to severe COPD , nursing intervention based on the HBM can enhance their health belief and self-efficacy towards the disease management , decrease dyspnoea and improve exercise tolerance and ADL . RELEVANCE TO CLINICAL PRACTICE Nurses can use the HBM-based intervention to enhance patients ' health belief and self-efficacy towards the management of COPD , and subsequently benefit healthcare outcomes Background Breathing programs have been reported to have positive effects in alleviating symptoms and optimizing pulmonary function in patients with chronic obstructive pulmonary disease ( COPD ) . However , patients with stable disease may drop out of such programs if they are not modified to the individual ’s exercise tolerance level , or if they are not easy to perform in the home . Little is known about the effectiveness of web-based home breathing programs for dyspnea . The purpose of this study was to evaluate the effectiveness of an online breathing program which included an animated diagram and video-guided instruction on pulmonary function , exercise capacity , and health-related quality of life in patients with COPD . Methods Sixty patients with stable COPD were r and omized 1:1 to an experimental group ( n = 30 ) or a control group ( n = 30 ) . Subjects in the experimental group trained for four months using an online program which included an animated diagram and video-guided instruction while the control group received conventional patient education on discharge from hospital . Forced expiratory volume , forced expiratory volume in one second (FEV1)/forced vital capacity ( % ) , peak expiratory volume , six-minute walking distance test , and responses to the St George ’s Respiratory Question naire were assessed before and after the intervention . Results Patients in the two groups were well matched for demographic and clinical characteristics at baseline . All outcome measures showed significant improvement in the experimental group but not in the control group . Conclusion The online training program result ed in improved pulmonary function , exercise capacity , and health status . Therefore , it is strongly recommended that patients with stable COPD be trained with such programs The aim of this study was to evaluate the long-term outcome of an outpatient pulmonary rehabilitation programme ( PRP ) in patients with chronic airway obstruction ( CAO ) . In 61 CAO patients ( 35 asthmatics and 26 chronic obstructive pulmonary disease ( COPD ) ) lung and respiratory muscle function , exercise tolerance ( by symptom limited cycloergometer and walking tests ) , dyspnoea ( Borg scale , visual analogue scale ( VAS ) , baseline and transitional dyspnoea index ( BDI and TDI , respectively ) ) and quality of life ( St George 's Respiratory Question naire ( SGRQ ) ) were assessed at baseline ( to ) , at discharge ( t1 ) and 12 months postdischarge ( t2 ) . Preprogramme and post-programme hospital admissions and exacerbations of disease were also recorded . In comparison with baseline , no significant change was observed in lung function tests in either diagnostic group , either at t1 or at t2 . In both groups improvements in respiratory muscle strength , exercise tolerance , Borg scale and VAS reported at t1 were partially reduced at t2 . Analysis of variance showed that these changes over time were similar in the two groups . Mean values of SGRQ and BDI/TDI improved at t1 , and , unlike exercise tolerance , did not worsen at t2 . However , a clinical ly relevant difference in SGRQ between t2 and to was reported only in 56 % of asthmatics and 52 % of COPD patients . Compared with the preceding 2 yrs , in the year following PRP , hospital admissions and disease exacerbations decreased significantly in both diagnostic groups . Regardless of diagnosis , patients with chronic airway obstruction who underwent an outpatient pulmonary rehabilitation programme maintained an improved quality of life 12 months postdischarge despite a partial loss of the improvement in exercise tolerance The purpose of this study was to examine the effects of two postrehabilitation programmes on functional exercise tolerance and health-related quality of life in patients with chronic obstructive pulmonary disease ( COPD ) . Subjects with COPD ( n=109 ) were r and omised to receive either enhanced follow-up ( EF ) or conventional follow-up ( CF ) . Subjects in the EF group attended a monthly support group and received a telephone call from a staff member at the midpoint ( 2 weeks ) between their visits . Both groups had scheduled appointments with a physical therapist and physician at 3‐monthly intervals after discharge . Longitudinal data were recorded in 85 subjects ( 37 EF and 48 CF ) . Over the course of the study , there was no difference in distance walked in 6 min between the two groups but a significant difference for time and a group-time interaction . There was no difference in total chronic respiratory disease question naire score between groups at baseline or at any time interval despite a significant difference with time . There was a clear deterioration in functional exercise capacity and health-related quality of life after completion of respiratory rehabilitation but no difference between the groups Purpose : This study assessed effects of a brief self‐care support intervention ( SCSI ) to promote health‐related quality of life ( HRQoL ) and self‐care adherence among elderly patients with COPD in Korea . Design : A single‐blinded , r and omized pre‐/posttest design Methods : A total of 40 participants were consecutively recruited from eligible patients admitted with an exacerbation of COPD to a department of pulmonology at a university hospital . Twenty participants were r and omly divided into two groups : an experimental group and a control group . The experimental group received an SCSI utilizing a motivational interview . All participants were assessed with peak expiratory flow rate and 6‐minute walking distance test , and answered Saint George 's Respiratory Question naire ( SGRQ ) and a question naire on self‐care adherence at pre‐intervention and 2 months postintervention . Findings : After the intervention , SGRQ scores for symptom , activity , impact , and total were significantly lower and self‐care adherence scores of medication and exercise were significantly higher in the experimental group . Conclusions : This study confirmed the short‐tem effectiveness of a nurse‐led self‐management intervention for pulmonary rehabilitation on quality of life and self‐care adherence among elderly patients with COPD . Further studies are warranted to verify effective strategies to improve exercise capacity for this population . Clinical relevance : Our findings suggest a brief intervention for rehabilitation nursing with more retainable , feasible , and cost‐effective strategies to enhance self‐management among the elderly patients with COPD The purpose of this study was to examine the effects of a home-based pulmonary rehabilitation program on lung function , dyspnea , exercise tolerance , and quality of life in 23 Koreans with moderate to severe chronic lung disease . The outcome measures were forced expiratory volume in 1s ( FEV1 , % predicted ) , Borg score , 6 min walking distance ( 6MWD ) , and chronic respiratory disease question naire ( CRDQ ) . Experimental group ( n=15 ) performed the 8-week home-based pulmonary rehabilitation program , composed of inspiratory muscle training , upper and lower extremity exercise , relaxation , and telephone visit . Patients in control group ( n=8 ) were only given educational advice . The experimental group showed a lower level of exertional dyspnea , more exercise tolerance , and greater improvement in health-related quality of life than the control group ( p<0.05 ) . Lung function was not statistically different . This study yielded evidence for the beneficial effects of home-based pulmonary rehabilitation program BACKGROUND Smoking cessation is the primary disease modifying intervention for chronic obstructive pulmonary disease ( COPD ) . SETTING A Regional Respiratory Centre ( RRC ) out-patient department in Northern Irel and . METHODS A r and omised controlled trial ( RCT ) evaluated the effectiveness of brief advice alone or accompanied by individual nurse support or group support facilitated by nurses . Smoking status was biochemically vali date d and stage of change , nicotine addiction and dyspnoea were recorded at 2 , 3 , 6 , 9 and 12 months . PARTICIPANTS Ninety-one cigarette smokers with COPD were enrolled in the study ( mean age 61 years , 47 female ) . RESULTS After 12 months cessation rates were not significantly different between groups ( p=0.7 ) , but all groups had a significant reduction in their nicotine addiction ( p=0.03 - 0.006 ) . No changes in subjects ' motivation or dyspnoea were detected over the 12 months . CONCLUSION Patients with COPD were unable to stop smoking regardless of the type of support they received . Harm reduction may be a more appropriate goal than complete cessation for intractable smokers and nurses must evaluate their role in this arena & NA ; The goal of this study was to determine the effectiveness of nurse‐led , home‐based pulmonary rehabilitation in patients with stage 3 or 4 chronic obstructive pulmonary disease ( COPD ) , according to the Global Initiative for COPD ( GOLD ) staging system . The study consisted of 32 patients —a nurse‐led , home‐based pulmonary rehabilitation group ( 16 ) and a control group ( 16 ) . In the rehabilitation program , patients received education about their diseases and performed breathing exercises and lower‐ and upper‐extremity aerobic exercises at their homes during the 3‐month period of the study . There was meaningful improvement in the rehabilitation group in terms of pulmonary function tests ( FEV1 % predicted value ) , artery blood gases ( PaCO2 ) , quality of life , dyspnea , and functional capacity . On the other h and , no meaningful change was observed in the control group . The study showed that the nurse‐led , home‐based pulmonary rehabilitation program had positive effects on the patients with COPD Purpose : This study was to examine the effectiveness of a nurse‐led 6‐month comprehensive pulmonary rehabilitation program for stage IV chronic obstructive pulmonary disease patients receiving home oxygen therapy . Design : A controlled clinical study was performed . Methods : Face‐to‐face and telephone interviews were conducted with the intervention group , whereas conventional education was given to the control group . Findings : Fifteen participants were analyzed in each group . There were no improvements in physiological outcomes ; however , the severity of dyspnea , social activity , and walking distance significantly improved in the intervention group , and consequently quality of life was improved . Three patients in the intervention group received treatment for cold‐like‐symptoms but did not require hospitalization . However , five patients in the control group received treatment for cold‐like‐symptoms and two required hospitalization . Conclusions : The findings demonstrate that our program contributes to patients ' learning of self‐management skills and significantly improves dyspnea , social activity level , walking distance , and overall quality of life BACKGROUND The Chronic Respiratory Question naire ( CRQ ) and the St George 's Respiratory Question naire ( SGRQ ) are the two most widely used quality of life question naires in chronic obstructive pulmonary disease ( COPD ) . A study was undertaken to compare directly the self-administered version of the CRQ and the SGRQ with respect to feasibility , internal consistency , validity , and sensitivity to changes result ing from bronchodilator therapy . METHODS One hundred and forty four patients with moderate or severe COPD were r and omly assigned to receive three months of treatment with either salmeterol , salmeterol + ipratropium bromide , or placebo . Quality of life was measured at baseline and after 12 weeks of treatment . RESULTS The proportions of missing values per patient were low for both question naires ( 0.54 % for the CRQ and 2 % for the SGRQ ) . The internal consistency was good for both question naires ( Cronbach 's alpha coefficients > /= 0.84 for the CRQ and > /= 0.76 for the SGRQ ) . Factor analysis confirmed the original domain structure of the CRQ but not of the SGRQ . Correlations with forced expiratory volume in one second ( FEV(1 ) ) % predicted and peak expiratory flow rate ( PEFR ) were low for both question naires but better for the SGRQ than for the CRQ . The ability to discriminate between subjects with different levels of FEV(1 ) was somewhat better for the SGRQ . The correlations with symptom scores were comparable for both question naires . Cross sectionally , the scores of the two question naires were moderately to highly correlated ( coefficients ranged from 0.35 to 0.72 ) . Longitudinally , these correlations were lower ( coefficients ranged from 0.17 to 0.54 ) but were still significant . The CRQ total and emotions score and the SGRQ symptoms score were the most responsive to change . The SGRQ symptoms domain was the only domain where the improvement in patients receiving combination treatment crossed the threshold for clinical relevance . CONCLUSIONS Since this analysis of reliability , validity , and responsiveness to change did not clearly favour one instrument above the other , the choice between the CRQ and the SGRQ can be based on other considerations such as the required sample size or the availability of reference values Purpose : This r and omized controlled trial examined the effect harmonica playing has on various clinical , psychosocial , and functional outcomes among chronic obstructive pulmonary disease ( COPD ) patients in pulmonary rehabilitation ( PR ) . Method : Twenty‐eight participants ( Age 69.9 ± 1.8 ; FEV1 Predicted 41.9 ± 2.0 % ) were recruited from an outpatient PR program . Participants were r and omly assigned to one of two groups , traditional PR ( C ; n = 16 ) or traditional PR plus harmonica playing ( HT ; n = 9 ) . The HT group was provided a harmonica and one‐on‐one instruction by PR staff . Patients were given practice exercises to perform for at least 5 minutes , but not exceeding 20 minutes twice/day , 5 days/week . Results : No significant differences were found between groups . The combined sample improved significantly in their perception of shortness of breath , quality of life , and distance walked in 6 minutes . Conclusion : Harmonica playing does not significantly affect the clinical , psychosocial , or functional status of COPD patients enrolled in PR BACKGROUND Pulmonary rehabilitation seems to be an effective intervention in patients with chronic obstructive pulmonary disease . We undertook a r and omised controlled trial to assess the effect of outpatient pulmonary rehabilitation on use of health care and patients ' wellbeing over 1 year . METHODS 200 patients with disabling chronic lung disease ( the majority with chronic obstructive pulmonary disease ) were r and omly assigned a 6-week multidisciplinary rehabilitation programme ( 18 visits ) or st and ard medical management . Use of health services was assessed from hospital and general- practice records . Analysis was by intention to treat . FINDINGS There was no difference between the rehabilitation ( n=99 ) and control ( n=101 ) groups in the number of patients admitted to hospital ( 40 vs 41 ) but the number of days these patients spent in hospital differed significantly ( mean 10.4 [ SD 9.7 ] vs 21.0 [ 20.7 ] , p=0.022 ) . The rehabilitation group had more primary -care consultations at the general-practitioner 's premises than did the control group ( 8.6 [ 6.8 ] vs 7.3 [ 8.3 ] , p=0.033 ) but fewer primary -care home visits ( 1.5 [ 2.8 ] vs 2.8 [ 4.6 ] , p=0.037 ) . Compared with control , the rehabilitation group also showed greater improvements in walking ability and in general and disease-specific health status . INTERPRETATION For patients chronically disabled by obstructive pulmonary disease , an intensive , multidisciplinary , outpatient programme of rehabilitation is an effective intervention , in the short term and the long term , that decreases use of health services Since the relationships between pulmonary function , exercise capacity , and functional state or quality of life are generally weak , a self report question naire has been developed to determine the effect of treatment on quality of life in clinical trials . One hundred patients with chronic airflow limitation were asked how their quality of life was affected by their illness , and how important their symptoms and limitations were . The most frequent and important items were used to construct a question naire evaluating four dimensions : dyspnoea , fatigue , emotional function , and the patient 's feeling of control over the disease ( mastery ) . Reproducibility , tested by repeated administration to patients in a stable condition , was excellent : the coefficient of variation was less than 12 % for all four dimensions . Responsiveness ( sensitivity to change ) was tested by administering the question naire to 13 patients before and after optimisation of their drug treatment and to another 28 before and after participation in a respiratory rehabilitation programme . In both cases large , statistically significant improvements in all four dimensions were noted . Changes in question naire score were correlated with changes in spirometric values , exercise capacity , and patients ' and physicians ' global ratings . Thus it has been shown that the question naire is precise , valid , and responsive . It can therefore serve as a useful disease specific measure of quality of life for clinical trials AIMS AND OBJECTIVES This study presents a discussion of the physiological and psychological efficacy of a self-regulation protocol in lowering acute exacerbation symptoms in patients with chronic obstructive pulmonary disease . BACKGROUND Patients with chronic obstructive pulmonary disease are often troubled by acute exacerbation and must learn how to prevent this . DESIGN A two-group , pretest-post-test experimental design was used in this study . METHODS Data were collected between January-July 2008 . Sixty-four participants were r and omly assigned either to an intervention ( n = 33 ) or to a comparison ( n = 31 ) group . Both groups were assessed on four separate occasions , namely pretest , post-test 1 ( 5th week ) , post-test 2 ( 9th week ) and post-test 3 ( 13th week ) . The intervention group received a four-week self-regulation protocol . The comparison group received the self-regulation guidebook only . The Borg Dyspnea Scale , the Symptom Distress Scale , the Pulmonary Functional Status Scale , the chronic obstructive pulmonary disease Self-Efficacy Scale and the peak expiratory flow were used to measure differences between pretest and post-test values . RESULTS On the 5th , 9th and 13th weeks after the self-regulation protocol intervention , we found significantly better scores in the four scales in the intervention group compared to those in the comparison group . On the 9th and 13th weeks , there was a significantly greater peak expiratory flow in the intervention group . The intervention group also showed a lower rate of unscheduled physician visits because of acute exacerbation than the comparison group . CONCLUSION The findings indicate that the self-regulation protocol developed in this study could significantly assist participants to control their individual symptoms and avoid acute exacerbation . RELEVANCE TO CLINICAL PRACTICE Healthcare professionals could apply the protocol developed in this study to assist patients to learn the strategies of self-regulation to prevent their acute exacerbation symptoms AIMS AND OBJECTIVES To evaluate the outcome of a coherent nursing practice in the form of partnership that addresses the complexity of living with chronic obstructive pulmonary disease . BACKGROUND Chronic obstructive pulmonary disease is a wide-ranging and progressive chronic disease that not only requires relentless attentiveness of the persons having the disease but also the families involved . Particular consideration is called for in health care for those with an advanced and complicated stage of the disease . The nursing practice , grounded in the theoretical framework of ' partnership as practice ' , is participatory comprehensive , long-term and dynamic to individual patient-family needs . DESIGN Retrospective and prospect i ve pretest-post-test intervention study . Methods . Eleven men and 39 women participated ( n = 50 ) . Mean age was 66 years . The majority ( n = 36 ) had severe chronic obstructive pulmonary disease ( GOLD stage III and IV ) . Actual study period was six months ( T2 ) . Hospital admission data were collected six months prior to ( T1 ) and six months after that period ( T3 ) , a total of 18 months . RESULTS Hospital admission rate and days spent in hospital because of chronic obstructive pulmonary disease were significantly reduced . Disease-specific health-related quality of life measured by St. George 's Respiratory Question naire improved significantly . For those with clinical anxiety and depression , both decreased significantly . Of those who were underweight , body mass index improved significantly . Abstinence from smoking changed non-significantly . Capability in the use of inhaler medications improved . CONCLUSIONS These results are in contrast to previous studies on outpatient nursing care for people with chronic obstructive pulmonary disease . The participatory nature of partnership with dialogue as central and which was uniquely implemented in this study might be of particular relevance for individuals and families living with chronic obstructive pulmonary disease . RELEVANCE TO CLINICAL PRACTICE Complex and comprehensive health needs of people with chronic obstructive pulmonary disease and their families may be effectively addressed in partnership centred on dialogue together with efficient intra- and interdisciplinary collaboration |
14,068 | 30,328,947 | Conclusions Our systematic review and meta- analysis support the hypothesis that baseline prolonged PR interval is a predictor of all-cause mortality , heart failure hospitalization , and composite outcome in CRT patients | Background Recent studies suggest that baseline prolonged PR interval is associated with worse outcome in cardiac resynchronization therapy ( CRT ) .
However , a systematic review and meta- analysis of the literature have not been made .
Objective To assess the association between baseline prolonged PR interval and adverse outcomes of CRT by a systematic review of the literature and a meta- analysis . | Background —The electrocardiographic PR interval increases with aging , differs by race , and is associated with atrial fibrillation ( AF ) , pacemaker implantation , and all-cause mortality . We sought to determine the associations between PR interval and heart failure , AF , and mortality in a biracial cohort of older adults . Methods and Results —The Health , Aging , and Body Composition ( Health ABC ) Study is a prospect i ve , biracial cohort . We used multivariable Cox proportional hazards models to examine PR interval ( hazard ratios expressed per SD increase ) and 10-year risks of heart failure , AF , and all-cause mortality . Multivariable models included demographic , anthropometric , and clinical variables in addition to established cardiovascular risk factors . We examined 2722 Health ABC participants ( aged 74±3 years , 51.9 % women , and 41 % black ) . We did not identify significant effect modification by race for the outcomes studied . After multivariable adjustment , every SD increase ( 29 ms ) in PR interval was associated with a 13 % greater 10-year risk of heart failure ( 95 % confidence interval , 1.02–1.25 ) and a 13 % increased risk of incident AF ( 95 % confidence interval , 1.04–1.23 ) . PR interval > 200 ms was associated with a 46 % increased risk of incident heart failure ( 95 % confidence interval , 1.11–1.93 ) . PR interval was not associated with increased all-cause mortality . Conclusions —We identified significant relationships of PR interval to heart failure and AF in older adults . Our findings extend prior investigations by examining PR interval and associations with adverse outcomes in a biracial cohort of older men and women BACKGROUND Prolonged interatrial conduction time ( IACT ) can be associated with abnormal left atrial ( LA ) function but has not been characterized in patients with left ventricular ( LV ) systolic dysfunction ( LVSD ) and QRS intervals > 130 ms . METHODS Two-dimensional Doppler echocardiography and Doppler tissue imaging ( DTI ) were performed in 41 patients with LVSD ( mean LV ejection fraction , 26 + /- 5 % ) and 41 similarly aged normal controls . Two-dimensional measurements included LV volume and ejection fraction and LA volume for the determination of LA emptying fraction and LA ejection fraction . IACT was defined as the time from the onset of the P wave to the onset of the DTI-derived late diastolic ( A ' ) velocity at the lateral mitral annulus . Two-dimensional Doppler measurements were reassessed in patients with LVSD 4 + /- 2 months after cardiac resynchronization therapy ( CRT ) . RESULTS IACT was longer in patients with compared to controls ( 105 + /- 25 vs 74 + /- 12 ms , P < .001 ) ; none of the controls had an IACT > 100 ms . In patients with LVSD , IACT was correlated modestly with measurements of LA volume ( r = .41-.48 , all P values < .009 ) but not with measurements of LA function . Patients with LVSD with IACTs > 100 ms ( n = 20 ) prior to CRT had larger LA volumes and lower indices of LA function after CRT compared to those with IACTs < or = 100 ms . Significant reductions in LV end-systolic volumes and increases in LV ejection fractions occurred in both groups after CRT . CONCLUSION DTI-derived IACT can be prolonged in patients with severe LVSD and wide QRS intervals . An IACT > 100 ms can affect LA remodeling and function at early follow-up after CRT but does not influence the response in LV end-systolic volume or ejection fraction BACKGROUND AND PURPOSE First-degree atrioventricular ( AV ) block in relation to the outcome of cardiac resynchronization therapy ( CRT ) has not been well examined . METHODS Patients who received a CRT defibrillator or pacemaker between January 2002 and September 2010 at Mayo Clinic were classified into 2 groups : normal PR interval and prolonged PR interval . St and ard sensed ( 100 milliseconds ) and paced ( 130 milliseconds ) AV delay was programmed after CRT . Clinical presentations and echocardiography were assessed before CRT and at a median of 6 months after CRT . RESULTS The normal PR interval group ( n=199 ) had greater improvements in heart failure functional class ( mean [ SD ] , 0.7 [ 0.8 ] vs 0.5 [ 0.9 ] ; P=.03 ) and left ventricular ejection fraction ( 9.4 % [ 12.4 % ] vs 5.9 % [ 9.5 % ] ; P=.007 ) than the prolonged PR group ( n=204 ) . CONCLUSION Compared with prolonged PR interval , the presence of normal PR interval was associated with a greater improvement in heart failure BACKGROUND Based on current patient selection criteria , a significant proportion of recipients of cardiac resynchronization therapy ( CRT ) do not respond to treatment . The purpose of this analysis is to identify predictors and characterize the timing of response to CRT in patients with advanced heart failure . METHODS Patients r and omized to receive CRT in the MIRACLE and MIRACLE-ICD trials , design ed to assess the benefit of CRT compared with st and ard medical therapy in patients with advanced heart failure , left ventricular ejection fraction < 0.35 , and QRS > or = 130 milliseconds , were included for this analysis . Patients with an improvement of > or = 1 New York Heart Association ( NYHA ) class from baseline to the 6-month follow-up were considered responders and those who had no change or worse NYHA class or died were classified as nonresponders . Responders were subdivided into early ( within 1 - 3 months ) and late ( 6 months ) . RESULTS One hundred forty-three ( 64 % ) of 224 and 190 ( 61 % ) of 313 patients in the MIRACLE and MIRACLE-ICD trials , respectively , responded to therapy , with 81 ( 57 % ) of 143 and 100 ( 53 % ) of 190 responding early . Several but differing factors predicted CRT response and timing in the two trials with a high sensitivity ( 89%-90 % ) but , owing to a low specificity ( 31%-49 % ) , a modest predictive accuracy ( 66%-75 % ) . CONCLUSIONS Based on improvement of > or = 1 NYHA class , less than two thirds of patients enrolled in the MIRACLE or MIRACLE-ICD trials responded to CRT , with just more than half responding within the first month . Several factors predicted CRT response and timing , but given their modest predictive accuracy , comparable for both studies , additional methods for selecting c and i date s most likely to benefit from CRT are needed AIMS In CARE-HF , cardiac resynchronization therapy ( CRT ) lowered morbidity and mortality in patients with moderate to severe heart failure . We examined whether baseline and follow-up electrocardiographic characteristics might predict long-term outcome . METHODS AND RESULTS CARE-HF r and omly assigned 409 patients to medical therapy ( MT ) plus CRT , and 404 patients to MT alone . Electrocardiographic measurements were made at baseline during sinus rhythm , and at 3 months during paced or spontaneous rhythm depending on treatment assignment . Favourable outcome was defined as freedom from death , urgent transplantation , or cardiovascular hospitalization . Among patients assigned to CRT , 39 % had unfavourable outcomes including 55 deaths . By single variable analysis , ( i ) prolonged PR interval , left QRS axis ( but not QRS duration ) , and left bundle branch block ( BBB ) at baseline , and ( ii ) heart rate , PR , and QRS duration at 3 months predicted unfavourable outcome . By multiple variable analysis , treatment assignment ( P = 0.0001 ) , PR ( P = 0.0004 ) , and right BBB ( P < 0.00013 ) at baseline predicted outcome , whereas baseline JTc and QRS duration at 3 months predicted all-cause mortality and heart failure hospitalization ( P = 0.0071 ) . CONCLUSION In CARE-HF , QRS duration at baseline did not predict outcome , but QRS at 3 months was a predictor by single variable analysis . Patients with prolonged PR interval and the 5 % of patients with right BBB had a particularly high event rate Purpose Heart failure ( HF ) is a major cause of morbidity and mortality , and ventricular dyssynchrony is an important contributor . The ReThinQ trial reported no improvement with cardiac resynchronization therapy ( CRT ) in HF patients with left ventricular ejection fraction ( LVEF ) < 35 % , narrow QRS ( < 130 ms ) , New York Heart Association ( NYHA ) class III , and echocardiographically detected dyssynchrony , in spite of echocardiographic optimization . We investigated whether a subset of narrow QRS patients might derive benefit from CRT , based on baseline PR interval . Methods We retrospectivelyanalyzed the 87 patients from ReThinQ who were r and omized to CRT . Patients were divided into two groups : baseline PR interval < 180 ms and baseline PR interval ≥180 ms . The primary outcome was change in VO2 max at 6 months ; secondary outcomes were change in LVEF , 6-min walk distance , and change in NYHA class . Results Forty-six patients had PR < 180 ms and 41 had PR ≥ 180 ms . The baseline characteristics were similar in the two groups . As compared to patients with a short PR interval , at 6 months , only patients with PR ≥ 180 ms showed a statistically significant increase in VO2 max from 12.2 to 13.6 mL/kg min ( P = 0.045 ) . Similarly , LVEF was significantly improved only in the long PR group ( 0.26 to 0.28 , P = 0.038 ) . A greater percentage of patients in the long PR group showed improvement by at least one NYHA class ( 59 vs. 35 % , P = 0.033 ) . Conclusions A longer baseline PR interval may allow more efficacious delivery of CRT by allowing programming of physiologic AV delays . A short baseline PR interval may contribute to LV under-filling and CRT non-response BACKGROUND The influence of PR prolongation on outcomes after cardiac resynchronization therapy ( CRT ) is uncertain . OBJECTIVE To determine whether PR prolongation predicts outcomes in potential CRT c and i date s and whether CRT benefits these c and i date s regardless of baseline PR interval . METHODS A data base of 1520 patients fulfilling criteria for CRT implant ( the COMPANION Trial ) was examined . Patients assigned to normal ( PR < 200 ms ) or prolonged ( PR ≥ 200 ms ) cohorts were compared within the optimal pharmacologic therapy ( OPT ) and CRT groups regarding an endpoint of all-cause mortality or heart failure hospitalization . CRT was compared with OPT in normal and prolonged PR interval groups . An interaction test was performed to determine whether CRT influenced outcome as a function of PR interval . RESULTS PR prolongation was present in 52 % of COMPANION subjects . R and omization to CRT was associated with a reduction in the endpoint , but the strength of the association was greater for those with prolonged PR ( hazard ratio = 0.54 ; P < .01 ) versus normal PR ( hazard ratio = 0.71 ; P = .02 ) intervals . CRT ( vs OPT ) was associated with reduction in the endpoint for subjects with normal or prolonged PR intervals . Reduction in relative risk ( CRT vs OPT ) was 29 % ( P = .02 ) for those with normal PR intervals but was 46 % ( P < .01 ) for those with PR prolongation . No interaction was detected between PR interval cohort and treatment ( P = .17 ) . CONCLUSIONS PR prolongation may affect mortality and heart failure hospitalizations in patients with systolic dysfunction , heart failure , and wide QRS complexes . The effect of PR prolongation may be attenuated by CRT The purpose of this study was to prospect ively determine the incidence of diastolic mitral and tricuspid regurgitation in atrioventricular ( AV ) block using Doppler echocardiography . The temporal relation between mitral and tricuspid diastolic insufficiency and the diastolic murmur recorded in patients with complete heart block was also investigated . Twenty-two consecutive patients with AV block ( referred to the Echo-Doppler laboratory for routine clinical studies ) , aged 18 to 87 years , were enrolled in the study . Eleven patients had third degree AV block and a ventricular-inhibited ( VVI ) pacemaker , two patients had second degree AV block , seven patients had first degree AV block , one patient had blocked premature atrial complexes and one patient had atrial flutter with 4:1 AV block . Diastolic mitral regurgitation was detected in 20 patients , and diastolic tricuspid regurgitation in 21 . A mid-diastolic murmur was detected in all patients except in the three youngest . The murmur occurred before diastolic regurgitation and coincided with peak forward flow through the AV valve after atrial contraction . M-mode mitral valve echocardiograms obtained in nine patients demonstrated near closure of some portions of the mitral valve after atrial contraction . Effective closure of the valve , however , did not occur unless ventricular systole supervened . In conclusion , diastolic mitral and tricuspid regurgitation are almost universally present in patients with AV block and are associated with a diastolic murmur . The murmur coincides with forward AV valve flow . Diastolic regurgitation is silent . Effective AV valve closure is not established until ventricular systole occurs , as demonstrated by M-mode echocardiographic recording of the mitral valve |
14,069 | 30,328,197 | The present systematic review showed an association of PPIs and SSRIs with an increased implant failure rate . | OBJECTIVES The aim of this systematic review was to investigate the association between the intake of systemic medications that may affect bone metabolism and their subsequent impact on implant failures . | In aesthetic sites , the integrity of the facial bone wall dimension in the anterior maxilla is jeopardized by physiologic and structural changes post extraction . An effective regenerative protocol is key to reestablish and maintain the hard and soft tissue dimensions over time . The present prospect i ve case series study examined the effectiveness of early implant placement with simultaneous contour augmentation through guided bone regeneration with a 2-layer composite graft in post extraction single-tooth sites over an observation period of 10 y among 20 patients . The median peri-implant bone loss was 0.35 mm between the 1- and 10-y examination . A success rate of 95 % was obtained , with pleasing aesthetic outcomes and a high median Pink Esthetic Score ( 8) . Implant crowns ( ICs ) revealed significant median facial recession between IC10y and IC1y ( 0.17 mm ) . The facial bone wall dimensions were assessed by preoperative cone beam computed tomography and 2 subsequent scans taken at 6 and 10 y. The median facial bone wall thickness increased significantly from 0 mm at surgery to 1.67 mm at the 10-y examination . The facial vertical bone wall peak ( DIC ) was located at a median distance of 0.16 mm coronal to the implant shoulder . The facial vertical bone loss of DIC amounted to 0.02 mm between 6 and 10 y. Equivalence testing was performed for the null hypothesis of a difference of > 0.2 mm per year between 2 respective time points , showing stable bone conditions . Modulating factors influencing the regenerative outcomes at 10 y were the preoperative proximal crest width and soft tissue thickness . In conclusion , the present study confirmed the long-term effectiveness of early implant placement with simultaneous contour augmentation through guided bone regeneration with a 2-layer composite graft in post extraction single-tooth sites offering stable bone conditions with low risks of mucosal recessions over an observation period of 10 y ( Clinical Trials.gov NCT03252106 ) OBJECTIVE Our purpose was to measure the agreement , reliability , construct validity , and feasibility of a measurement tool to assess systematic review s ( AMSTAR ) . STUDY DESIGN AND SETTING We r and omly selected 30 systematic review s from a data base . Each was assessed by two review ers using : ( 1 ) the enhanced quality assessment question naire ( Overview of Quality Assessment Question naire [ OQAQ ] ) ; ( 2 ) Sacks ' instrument ; and ( 3 ) our newly developed measurement tool ( AMSTAR ) . We report on reliability ( interobserver kappas of the 11 AMSTAR items ) , intraclass correlation coefficients ( ICCs ) of the sum scores , construct validity ( ICCs of the sum scores of AMSTAR compared with those of other instruments ) , and completion times . RESULTS The interrater agreement of the individual items of AMSTAR was substantial with a mean kappa of 0.70 ( 95 % confidence interval [ CI ] : 0.57 , 0.83 ) ( range : 0.38 - 1.0 ) . Kappas recorded for the other instruments were 0.63 ( 95 % CI : 0.38 , 0.78 ) for enhanced OQAQ and 0.40 ( 95 % CI : 0.29 , 0.50 ) for the Sacks ' instrument . The ICC of the total score for AMSTAR was 0.84 ( 95 % CI : 0.65 , 0.92 ) compared with 0.91 ( 95 % CI : 0.82 , 0.96 ) for OQAQ and 0.86 ( 95 % CI : 0.71 , 0.94 ) for the Sacks ' instrument . AMSTAR proved easy to apply , each review taking about 15 minutes to complete . CONCLUSIONS AMSTAR has good agreement , reliability , construct validity , and feasibility . These findings need confirmation by a broader range of assessors and a more diverse range of review The purpose s of this preliminary study are to assess the risk of developing bisphosphonate-related osteonecrosis of the jaw ( BRONJ ) in a patient with osteoporosis using zoledronic acid and to report the results of a 1-year prospect i ve clinical study regarding 5 immediately inserted implants in the anterior m and ible . For this comparative prospect i ve study , 24 female patients , aged ≥54 years , were chosen , all with partially edentulous m and ibles . Group A consisted of 12 patients with osteoporosis taking zoledronic acid receiving a once-yearly intravenous infusion of zoledronic acid ( 5 mg ) . Control group B consisted of 12 other patients without osteoporosis and not taking drugs . In both groups , the remaining teeth were extracted before 120 implants , 3.7-mm wide and 16-mm long , were immediately installed in the interforaminal region of the m and ibles . The 1-year implant survival rate was 100 % . No apparent necrotic bone was observed among patients receiving zoledronic acid ( group A ) after implant surgery . Immediate implant osseointegration can be successful in a patient with osteoporosis using bisphosphonates , suggesting the safety of implantology as a treatment modality BACKGROUND Phosphate-induced hyperparathyroidism still represents an intriguing problem in dialysis patients . Postpr and ial hyperphosphataemia is considered to be the main stimulus to parathyroid hyperfunction , and therefore many efforts have focused on the use of phosphate binders to prevent phosphate absorption . METHODS We investigated whether the pH-mediated gastric ionization of calcium phosphate dietary salts is necessary for its intestinal absorption . In eight normal subjects we measured 24-h urinary calcium phosphate excretion and the postpr and ial blood calcium phosphate profile after a meal containing 1 g of calcium and 2 g of phosphate salts in a crossover placebo-omeprazole study . On two occasions the subjects received either placebo or omeprazole 60 mg/day 2 days before and during the day test . RESULTS Serum gastrin levels were measured as an indicator of achlorhydria and were 13.7 + /- 1 pg/ml after placebo and 30.4 + /- 4.7 after omeprazole ( P < 0.003 ) . Postpr and ial plasma phosphate profiles were not significantly different between the two studies ( + 36 + /- 8 % after placebo and + 24 + /- 8 % after omeprazole , NS ) , while plasma calcium increased by + 6.1 + /- 1 % after placebo and decreased by -4.2 + /- 0.7 % after omeprazole ( P < 0.01 ) . The 24-h urinary phosphate excretion was 1068 + /- 85 mg after placebo and 773 + /- 55 after omeprazole ( P < 0.002 ) , while the 24-h urinary calcium excretion was 360 + /- 21 after placebo and 238 + /- 15 after omeprazole ( P < 0.0001 ) . A negative relationship was observed between absolute changes in plasma gastrin and those in urinary calcium ( P < 0.009 ) and phosphate ( P < 0.05 ) . CONCLUSIONS The inhibition of gastric acid secretion by omeprazole significantly reduces both urinary phosphate and calcium excretion after an oral load . The behaviour of the postpr and ial calcium-phosphate plasma profile suggests that gastric acid inhibition is more effective in reducing calcium rather than phosphate dietary salts absorption in normal subjects PURPOSE This r and omised double-blind placebo-controlled trial was carried out to investigate the effect of a one-week post-operative course of 600 mg of ibuprofen taken four times a day on marginal bone level around dental implants . MATERIAL S AND METHODS A total of 61 patients were allocated to the ibuprofen ( 31 patients ) or placebo group ( 30 patients ) . Overall , 132 implants were inserted , 67 implants in the ibuprofen group and 65 implants in the placebo group . Preparation of the implant sites was carried out with an intermittent drilling sequence adapted to the fixture diameter and the local bone quality according to the Astra Tech implant installation guide . The primary outcome measure was the change in marginal bone level around dental implants from the baseline ( 2 weeks post-placement ) to the 3- and 6-month radiographic examinations . The paralleling technique and a film holder coupled to a beam aim ing device were used to take the periapical radiographs . Measurement of changes in bone level was made using a viewing box and x8 magnifier . RESULTS Two patients from the ibuprofen group were unable to complete the prescribed course of ibuprofen owing to a minor self-reported stomach upset . A patient from the control group did not attend any of the scheduled appointments following implant placement . A total of three patients dropped out . All implants survived in either group during the 6-month observation period . The mean marginal bone level changes from the baseline were ( -0.33 mm ) at the 3-month and ( -0.29 mm ) at the 6-month follow-up for the ibuprofen group while the corresponding values for the placebo group were ( -0.12 mm ) and ( -0.30 mm ) . There were no statistically significant differences between groups for mean marginal bone level changes at 3 months ( P = 0.27 ) or 6 months ( P = 0.97 ) . CONCLUSIONS Administration of a short course of systemic ibuprofen for post-operative pain management subsequent to implant placement may not have a significant effect on the marginal bone around dental implants in the early healing period |
14,070 | 30,761,962 | Intake of whole grain , cereal fibre and bran were similarly associated with lower risk of CVD-related outcomes .
Within the initial analysis , where studies used the recognised whole grain definition , results were less likely to show attenuation after adjustment for cereal fibre content .
The fibre component of grain foods appears to play an important role in protective effects of whole grains .
Adjusting for fibre content , associations remained , suggesting that additional components within the whole grain , and the bran component , may contribute to cardio-protective association . | Whole grain intake is associated with lower CVD risk in epidemiological studies .
It is unclear to what extent cereal fibre , located primarily within the bran , is responsible .
This review aim ed to evaluate association between intake of whole grain , cereal fibre and bran and CVD risk . | OBJECTIVE To identify the dietary , lifestyle and socio-economic factors associated with the intake of whole grains ( WG ) in Norway , Sweden and Denmark . DESIGN A cross-sectional study . SETTING Sub sample of the Sc and inavian cohort ' HELGA ' consisting of three prospect i ve cohorts : The Norwegian Women and Cancer Study ; The Northern Sweden Health and Disease Study ; and the Danish Diet , Cancer and Health Study . SUBJECTS A total of 8702 men and women aged 30 - 65 years . Dietary data are from one 24 h dietary recall and data on socio-economic status and lifestyle factors including anthropometric values are from the baseline collection of data . RESULTS Vegetables , fruits , dairy products , fish and shellfish , coffee , tea and margarine were directly associated with the intake of WG , whereas red meat , white bread , alcohol and cakes and biscuits were inversely associated . Smoking and BMI were consistently inversely associated with the intake of WG . Furthermore , length of education was directly associated with the intake of WG among women . CONCLUSIONS The intake of WG was found to be directly associated with healthy diet , lifestyle and socio-economic factors and inversely associated with less healthy factors , suggesting that these factors are important for consideration as potential confounders when study ing WG intake and disease associations Subjects with obesity and elevated fasting blood glucose are at high risk of developing type 2 diabetes which may be reduced by a dietary intervention leading to an improvement of insulin resistance . We investigated the potential of a whole-grain based dietary product ( WG ) with reduced starch content derived from double-fermented wheat during a hypo-energetic diet to positively influence body weight , fasting blood glucose , insulin resistance and lipids in comparison to a nutrient-dense meal replacement product ( MR ) in a r and omized two-way cross-over study with two 4-week treatment periods separated by a 2-week wash-out . Subjects replaced at least two daily meals with WG and MR , respectively , targeting for a consumption of 200 g of either product per day . Total daily energy intake was limited to 7120 kJ. Thirty-one subjects ( BMI 33.9 ( SD 2.7 ) kg/m2 , fasting blood glucose 6.3 ( SD 0.8 ) mmol/l ) completed the study . In both treatment groups body weight ( -2.5 ( SD 2.0 ) v. - 3.2 ( SD 1.6 ) kg for WG v. MR ) , fasting blood glucose ( -0.4 ( SD 0.3 ) v. -0.5 ( SD 0.5 ) mmol/l ) , total cholesterol ( -0.5 ( SD 0.5 ) v. -0.6 ( SD 0.5 ) mmol/l ) , TAG ( -0.3 ( SD 0.9 ) v. -0.3 ( SD 1.2 ) mmol/l ) and homeostasis model assessment ( HOMA ) insulin resistance score ( -0.7 ( SD 0.8 ) v. -1.1 ( SD 1.7 ) microU/ml x mmol/l ) improved ( P < 0.05 ) with no significant differences between the treatments . After statistical adjustment for the amount of body weight lost , however , the comparison between both groups revealed that fasting serum insulin ( P = 0.031 ) and HOMA insulin resistance score ( P = 0.049 ) improved better with WG than with MR . We conclude that WG favourably influences metabolic risk factors for type 2 diabetes independent from the amount of body weight lost during a hypo-energetic diet In 1998 , the American Heart Association convened Prevention Conference V to examine strategies for the identification of high-risk patients who need primary prevention . Among the strategies discussed was the measurement of markers of inflammation.1 The Conference concluded that “ many of these markers ( including inflammatory markers ) are not yet considered applicable for routine risk assessment because of : ( 1 ) lack of measurement st and ardization , ( 2 ) lack of consistency in epidemiological findings from prospect i ve studies with endpoints , and ( 3 ) lack of evidence that the novel marker adds to risk prediction over and above that already achievable through the use of established risk factors . ” The National Cholesterol Education Program Adult Treatment Panel III Guidelines identified these markers as emerging risk factors,1a which could be used as an optional risk factor measurement to adjust estimates of absolute risk obtained using st and ard risk factors . Since these publications , a large number of peer- review ed scientific reports have been published relating inflammatory markers to cardiovascular disease ( CVD ) . Several commercial assays for inflammatory markers have become available . As a consequence of the exp and ing research base and availability of assays , the number of inflammatory marker tests ordered by clinicians for CVD risk prediction has grown rapidly . Despite this , there has been no consensus from professional societies or governmental agencies as to how these assays of markers of inflammation should be used in clinical practice . On March 14 and 15 , 2002 , a workshop titled “ CDC/AHA Workshop on Inflammatory Markers and Cardiovascular Disease : Applications to Clinical and Public Health Practice ” was convened in Atlanta , Ga , to address these issues . The goals of this workshop were to determine which of the currently available tests should be used ; what results should be used to define high risk ; which patients should be tested ; and the indications for which the tests would be most useful . These Background Control of body weight by balancing energy intake and energy expenditure is of major importance for the prevention of type 2 diabetes , but the role of specific dietary factors in the etiology of type 2 diabetes is less well established . We evaluated intakes of whole grain , bran , and germ in relation to risk of type 2 diabetes in prospect i ve cohort studies . Methods and Findings We followed 161,737 US women of the Nurses ' Health Studies ( NHSs ) I and II , without history of diabetes , cardiovascular disease , or cancer at baseline . The age at baseline was 37–65 y for NHSI and 26–46 y for NHSII . Dietary intakes and potential confounders were assessed with regularly administered question naires . We documented 6,486 cases of type 2 diabetes during 12–18 y of follow-up . Other prospect i ve cohort studies on whole grain intake and risk of type 2 diabetes were identified in search es of MEDLINE and EMBASE up to January 2007 , and data were independently extracted by two review ers . The median whole grain intake in the lowest and highest quintile of intake was , respectively , 3.7 and 31.2 g/d for NHSI and 6.2 and 39.9 g/d for NHSII . After adjustment for potential confounders , the relative risks ( RRs ) for the highest as compared with the lowest quintile of whole grain intake was 0.63 ( 95 % confidence interval [ CI ] 0.57–0.69 ) for NHSI and 0.68 ( 95 % CI 0.57–0.81 ) for NHSII ( both : p-value , test for trend < 0.001 ) . After further adjustment for body mass index ( BMI ) , these RRs were 0.75 ( 95 % CI 0.68–0.83 ; p-value , test for trend < 0.001 ) and 0.86 ( 95 % CI 0.72–1.02 ; p-value , test for trend 0.03 ) respectively . Associations for bran intake were similar to those for total whole grain intake , whereas no significant association was observed for germ intake after adjustment for bran . Based on pooled data for six cohort studies including 286,125 participants and 10,944 cases of type 2 diabetes , a two-serving-per-day increment in whole grain consumption was associated with a 21 % ( 95 % CI 13%–28 % ) decrease in risk of type 2 diabetes after adjustment for potential confounders and BMI . Conclusions Whole grain intake is inversely associated with risk of type 2 diabetes , and this association is stronger for bran than for germ . Findings from prospect i ve cohort studies consistently support increasing whole grain consumption for the prevention of type 2 diabetes BACKGROUND Certain dietary components may play a role in the prevention of type 2 diabetes . OBJECTIVE We examined prospect ively the associations between whole- and refined-grain intake and the risk of type 2 diabetes in a large cohort of men . DESIGN Men from the Health Professionals Follow-up Study without a history of diabetes or cardiovascular disease in 1986 ( n = 42898 ) were followed for < /=12 y. Intakes of whole and refined grains , measured every 4 y by use of food-frequency question naires , were used to predict subsequent type 2 diabetes risk through multivariate analysis . RESULTS We ascertained 1197 cases of incident type 2 diabetes . After adjustment for age ; physical activity ; cigarette smoking ; alcohol consumption ; family history of diabetes ; and fruit , vegetable , and energy intakes , the relative risk of type 2 diabetes was 0.58 ( 95 % CI : 0.47 , 0.70 ; P for trend < 0.0001 ) comparing the highest with the lowest quintile of whole-grain intake . The association was moderately attenuated when additionally adjusted for body mass index ( relative risk : 0.70 ; 95 % CI : 0.57 , 0.85 ; P for trend = 0.0006 ) . Intake of refined grains was not significantly associated with risk of type 2 diabetes . After further adjustment for magnesium intake , cereal fiber intake , and glycemic load , the association between whole grains and type 2 diabetes was attenuated and the trend no longer significant . CONCLUSIONS In men , a diet high in whole grains is associated with a reduced risk of type 2 diabetes in men that may be mediated by cereal fiber . Efforts should be made to replace refined-grain with whole-grain foods BACKGROUND No studies have examined whether increased consumption of oat cereal , rich in soluble fiber , favorably alters lipoprotein particle size and number . OBJECTIVE We examined the effects of large servings of either oat or wheat cereal on plasma lipids , lipoprotein subclasses , lipoprotein particle diameters , and LDL particle number . DESIGN Thirty-six overweight men aged 50 - 75 y were r and omly assigned to consume daily for 12 wk either oat or wheat cereal providing 14 g dietary fiber/d . Before and after the intervention , plasma lipid and lipoprotein subclasses were measured with proton nuclear magnetic resonance spectroscopy , and whole-body insulin sensitivity was estimated with the frequently sample d intravenous-glucose-tolerance test . RESULTS Time-by-treatment interactions ( P < 0.05 ) for LDL cholesterol ( oat : -2.5 % ; wheat : 8.0 % ) , small LDL cholesterol ( oat : -17.3 % ; wheat : 60.4 % ) , LDL particle number ( oat : -5.0 % ; wheat : 14.2 % ) , and LDL : HDL cholesterol ( oat : -6.3 % ; wheat : 14.2 % ) were observed . Time-by-treatment interactions were nearly significant for total cholesterol ( oat : -2.5 % ; wheat : 6.3 % ; P = 0.08 ) , triacylglycerol ( oat : -6.6 % ; wheat : 22.0 % ; P = 0.07 ) , and VLDL triacylglycerol ( oat : -7.6 % ; wheat : 2.7 % ; P = 0.08 ) . No significant time-by-treatment interactions were observed for HDL cholesterol , HDL-cholesterol subclasses , or LDL , HDL , and VLDL particle diameters . Insulin sensitivity did not change significantly with either intervention . CONCLUSIONS The oat compared with the wheat cereal produced lower concentrations of small , dense LDL cholesterol and LDL particle number without producing adverse changes in blood triacylglycerol or HDL-cholesterol concentrations . These beneficial alterations may contribute to the cardioprotective effect of oat fiber We demonstrated similar plasma concentrations and urinary losses but lower erythrocyte magnesium concentrations ( 2.18 + /- 0.04 vs 1.86 + /- 0.03 mmol/L , P less than 0.01 ) in twelve aged ( 77.8 + /- 2.1 y ) vs 25 young ( 36.1 + /- 0.4 y ) , nonobese subjects . Subsequently , aged subjects were enrolled in a double-blind , r and omized , crossover study in which placebo ( for 4 wk ) and chronic magnesium administration ( CMA ) ( 4.5 g/d for 4 wk ) were provided . At the end of each treatment period an intravenous glucose tolerance test ( 0.33 g/kg body wt ) and a euglycemic glucose clamp with simultaneous [D-3H]glucose infusion and indirect calorimetry were performed . CMA vs placebo significantly increased erythrocyte magnesium concentration and improved insulin response and action . Net increase in erythrocyte magnesium significantly and positively correlated with the decrease in erythrocyte membrane microviscosity and with the net increase in both insulin secretion and action . In aged patients , correction of a low erythrocyte magnesium concentration may allow an improvement of glucose h and ling BACKGROUND Dietary carbohydrates may influence the development of type 2 ( non-insulin-dependent ) diabetes , for example , through effects on blood glucose and insulin concentrations . OBJECTIVE We examined the relations of baseline intake of carbohydrates , dietary fiber , dietary magnesium , and carbohydrate-rich foods and the glycemic index with incidence of diabetes . DESIGN This was a prospect i ve cohort study of 35988 older Iowa women initially free of diabetes . During 6 y of follow-up , 1141 incident cases of diabetes were reported . RESULTS Total grain , whole-grain , total dietary fiber , cereal fiber , and dietary magnesium intakes showed strong inverse associations with incidence of diabetes after adjustment for potential nondietary confounding variables . Multivariate-adjusted relative risks of diabetes were 1.0 , 0.99 , 0.98 , 0.92 , and 0.79 ( P for trend : 0.0089 ) across quintiles of whole-grain intake ; 1.0 , 1.09 , 1.00 , 0.94 , and 0.78 ( P for trend : 0.005 ) across quintiles of total dietary fiber intake ; and 1.0 , 0.81 , 0.82 , 0.81 , and 0.67 ( P for trend : 0.0003 ) across quintiles of dietary magnesium intake . Intakes of total carbohydrates , refined grains , fruit and vegetables , and soluble fiber and the glycemic index were unrelated to diabetes risk . CONCLUSION These data support a protective role for grains ( particularly whole grains ) , cereal fiber , and dietary magnesium in the development of diabetes in older women The hypocholesterolemic effects of oat bran ( OB ) have been recently challenged . To carefully document the hypocholesterolemic effects of OB , 20 hypercholesterolemic men admitted to a metabolic ward were r and omly allocated to either OB or wheat bran ( WB ) for 21 d after a 7-d control-diet period . Control and treatment diets were design ed to be identical in energy content and nutrients , differing only in the amount of soluble fiber . After 21 d , OB significantly decreased total cholesterol by 12.8 % ( P less than 0.001 ) , low-density-lipoprotein cholesterol by 12.1 % ( P less than 0.004 ) , and apolipoprotein B-100 by 13.7 % ( P less than 0.001 ) whereas WB had no significant effect . High-density-lipoprotein cholesterol and apolipoprotein A-I did not change significantly in either group . Serum triglycerides decreased by 10 % in both groups but the decrease was only significant ( P less than 0.04 ) in WB subjects . OB but not WB significantly reduced total cholesterol and other atherogenic lipoprotein fractions independent of other dietary changes BACKGROUND Epidemiologic studies that directly examine changes in whole-grain consumption in relation to weight gain are sparse , and characterization of this association has been obscured by method ologic inconsistencies in the assessment of whole grains . OBJECTIVE We aim ed to ascertain the associations between changes in new quantitative estimates of whole-grain intake and 8-y weight gain among US men . DESIGN The study was conducted in a prospect i ve cohort of 27 082 men aged 40 - 75 y at baseline in 1986 . Data on lifestyle factors were obtained periodically by using self-reported question naires , and participants measured and reported their body weight in 1986 and 1994 . RESULTS In multivariate analyses , an increase in whole-grain intake was inversely associated with long-term weight gain ( P for trend < 0.0001 ) . A dose-response relation was observed , and for every 40-g/d increment in whole-grain intake from all foods , weight gain was reduced by 0.49 kg . Bran that was added to the diet or obtained from fortified-grain foods further reduced the risk of weight gain ( P for trend = 0.01 ) , and , for every 20 g/d increase in intake , weight gain was reduced by 0.36 kg . Changes in cereal and fruit fiber were inversely related to weight gain . No associations were observed between changes in refined-grain or added germ consumption and body weight . CONCLUSIONS The increased consumption of whole grains was inversely related to weight gain , and the associations persisted after changes in added bran or fiber intakes were accounted for . This suggests that additional components in whole grains may contribute to favorable metabolic alterations that may reduce long-term weight gain BACKGROUND Previous studies have suggested that a daily intake of 3 servings of whole-grain foods is associated with a reduced risk of coronary heart disease ( CHD ) . However , methods for the assessment of whole-grain intake differ . Furthermore , any additional effects of added bran and germ , which are components of whole grains , have not been reported . OBJECTIVE The objective was to evaluate the association of whole-grain , bran , and germ intakes ( with the use of new quantitative measures ) with the incidence of CHD . DESIGN This was a prospect i ve cohort study of 42,850 male health professionals aged 40 - 75 y at baseline in 1986 who were free from cardiovascular disease , cancer , and diabetes . Daily whole-grain , bran , and germ intakes were derived in grams per day from a detailed semiquantitative dietary question naire . RESULTS During 14 y of follow-up , we documented 1818 incident cases of CHD . After cardiovascular disease risk factors and the intakes of bran and germ added to foods were controlled for , the hazard ratio of CHD between extreme quintiles of whole-grain intake was 0.82 ( 95 % CI : 0.70 , 0.96 ; P for trend=0.01 ) . The hazard ratio of CHD in men with the highest intake of added bran was 0.70 ( 95 % CI : 0.60 , 0.82 ) compared with men with no intake of added bran ( P for trend < or = 0.001 ) . Added germ was not associated with CHD risk . CONCLUSION This study supports the reported beneficial association of whole-grain intake with CHD and suggests that the bran component of whole grains could be a key factor in this relation To define the type of dietary fibre of fibre analogue with the greatest potential use in diabetic treatment , groups of four to six volunteers underwent 50-g glucose tolerance tests ( GTT ) with and without the addition of either guar , pectin , gum tragacanth , methylcellulose , wheat bran , or cholestyramine equivalent to 12 g fibre . The addition of each substance significantly reduced blood glucose concentration at one or more points during the GTT and generally reduced serum insulin concentrations . The greatest flattening of the glucose response was seen with guar , but this effect was abolished when hydrolysed non-viscous guar was used . The reduction in the mean peak rise in blood glucose concentration for each substance correlated positively with its viscosity ( r = 0.926 ; P less than 0.01 ) , as did delay in mouth-to-caecum transit time ( r = 0.885 ; P less than 0.02 ) . Viscous types of dietary fibre are therefore most likely to be therapeutically useful in modifying postpr and ial hyperglycaemia OBJECTIVE Cereal fiber intake is linked to reduced risk of type 2 diabetes in epidemiological observations . The pathogenic background of this phenomenon is unknown . Based on recent findings , we hypothesized that intake of purified insoluble oat fiber may improve whole-body insulin sensitivity . RESEARCH DESIGN AND METHODS A r and omized , controlled , single-blind , cross-over study was performed , and 17 overweight or obese subjects with normal glucose metabolism were analyzed . After consumption of nine macronutrient-matched portions of fiber-enriched bread ( white bread enriched with 31.2 g insoluble fiber/day ) or control ( white bread ) over a time period of 72 h , whole-body insulin sensitivity was assessed by euglycemic-hyperinsulinemic clamp . Energy intake was individually adjusted by providing st and ardized liquid meals . Hydrogen breath tests were performed to control for dietary adherence . RESULTS When analyzing the entire cohort , whole-body glucose disposal was improved after fiber consumption ( M value 6.56 + /- 0.32 vs. 6.07 + /- 0.27 mg . min(-1 ) . kg(-1 ) ; P = 0.043 ) . Thirteen subjects had increased hydrogen breath test concentrations after fiber consumption , indicating probable dietary adherence . Restricting analysis to these subjects , improvements in M value ( 6.85 + /- 0.34 vs. 6.06 + /- 0.32 mg . min(-1 ) . kg(-1 ) ; P = 0.003 ) and insulin sensitivity , expressed as M/I ratio ( M value divided by mean serum insulin at steady state : 3.73 + /- 0.23 vs. 3.21 + /- 0.27 ; P = 0.02 ) , after fiber consumption were more pronounced . Plasma lipids , serum magnesium , ghrelin , and adiponectin concentrations , as well as substrate utilization and body weight , were not significantly changed by fiber intake ( P > 0.15 ) . CONCLUSIONS Increased insoluble dietary fiber intake for 3 days significantly improved whole-body insulin sensitivity . These data suggest a potential mechanism linking cereal fiber intake and reduced risk of type 2 diabetes BACKGROUND Prospect i ve data on the relation between whole grain intake and incident hypertension in men are limited , and no previous studies have quantitatively estimated total grams of whole grains in relation to risk of hypertension . OBJECTIVE The purpose of this study was to estimate the association of whole-grain intake ( g/d ) and risk of incident hypertension in a large prospect i ve cohort of men . DESIGN The Health Professionals Follow-Up Study is a prospect i ve cohort consisting of 51,529 male health professionals ranging in age from 40 to 75 y at enrollment in 1986 . Baseline and up date d measurement of whole-grain intake as well as important covariates were measured , and 31,684 participants without known hypertension , cancer , stroke , or coronary heart disease were followed prospect ively for 18 y through 2004 for onset of hypertension . RESULTS A total of 9227 cases of incident hypertension were reported over the 18 y of follow-up . In multivariate-adjusted analyses , whole-grain intake was inversely associated with risk of hypertension , with a relative risk ( RR ) of 0.81 ( 95 % CI : 0.75 - 0.87 ) in the highest compared with the lowest quintile ( P for trend < 0.0001 ) . In the multivariate model , total bran was inversely associated with hypertension , with a relative risk ( RR ) of 0.85 ( 95 % CI : 0.78 , 0.92 ) in the highest compared with the lowest quintile ( P for trend : 0.002 ) . CONCLUSIONS In summary , we found an independent inverse association between intake of whole grains and incident hypertension in men . Bran may play an important role in this association . These findings have implication s for future dietary guidelines and prevention of hypertension BACKGROUND It is known that obesity , sodium intake , and alcohol consumption factors influence blood pressure . In this clinical trial , Dietary Approaches to Stop Hypertension , we assessed the effects of dietary patterns on blood pressure . METHODS We enrolled 459 adults with systolic blood pressures of less than 160 mm Hg and diastolic blood pressures of 80 to 95 mm Hg . For three weeks , the subjects were fed a control diet that was low in fruits , vegetables , and dairy products , with a fat content typical of the average diet in the United States . They were then r and omly assigned to receive for eight weeks the control diet , a diet rich in fruits and vegetables , or a " combination " diet rich in fruits , vegetables , and low-fat dairy products and with reduced saturated and total fat . Sodium intake and body weight were maintained at constant levels . RESULTS At base line , the mean ( + /-SD ) systolic and diastolic blood pressures were 131.3+/-10.8 mm Hg and 84.7+/-4.7 mm Hg , respectively . The combination diet reduced systolic and diastolic blood pressure by 5.5 and 3.0 mm Hg more , respectively , than the control diet ( P<0.001 for each ) ; the fruits- and -vegetables diet reduced systolic blood pressure by 2.8 mm Hg more ( P<0.001 ) and diastolic blood pressure by 1.1 mm Hg more than the control diet ( P=0.07 ) . Among the 133 subjects with hypertension ( systolic pressure , > or = 140 mm Hg ; diastolic pressure , > or = 90 mm Hg ; or both ) , the combination diet reduced systolic and diastolic blood pressure by 11.4 and 5.5 mm Hg more , respectively , than the control diet ( P<0.001 for each ) ; among the 326 subjects without hypertension , the corresponding reductions were 3.5 mm Hg ( P<0.001 ) and 2.1 mm Hg ( P=0.003 ) . CONCLUSIONS A diet rich in fruits , vegetables , and low-fat dairy foods and with reduced saturated and total fat can substantially lower blood pressure . This diet offers an additional nutritional approach to preventing and treating hypertension Recommendations for whole-grain ( WG ) intake are based on observational studies showing that higher WG consumption is associated with reduced CVD risk . No large-scale , r and omised , controlled dietary intervention studies have investigated the effects on CVD risk markers of substituting WG in place of refined grains in the diets of non-WG consumers . A total of 316 participants ( aged 18 - 65 years ; BMI > 25 kg/m2 ) consuming < 30 g WG/d were r and omly assigned to three groups : control ( no dietary change ) , intervention 1 ( 60 g WG/d for 16 weeks ) and intervention 2 ( 60 g WG/d for 8 weeks followed by 120 g WG/d for 8 weeks ) . Markers of CVD risk , measured at 0 ( baseline ) , 8 and 16 weeks , were : BMI , percentage body fat , waist circumference ; fasting plasma lipid profile , glucose and insulin ; and indicators of inflammatory , coagulation , and endothelial function . Differences between study groups were compared using a r and om intercepts model with time and WG intake as factors . Although reported WG intake was significantly increased among intervention groups , and demonstrated good participant compliance , there were no significant differences in any markers of CVD risk between groups . A period of 4 months may be insufficient to change the lifelong disease trajectory associated with CVD . The lack of impact of increasing WG consumption on CVD risk markers implies that public health messages may need to be clarified to consider the source of WG and /or other diet and lifestyle factors linked to the benefits of whole-grain consumption seen in observational studies BACKGROUND Higher intake of fiber , especially cereal fiber , has been associated with reduced risk of cardiovascular events and mortality . However , there are limited data on the effect of fiber intake on measures of progression of coronary artery disease ( CAD ) . The aim was to examine the association between intakes of total fiber and fiber from different dietary sources and progression of coronary-artery atherosclerosis among women with established CAD . METHODS A prospect i ve cohort study involved postmenopausal women ( n = 229 ) participating in the Estrogen Replacement and Atherosclerosis trial . Usual fiber intake was estimated at baseline using a food frequency question naire . Quantitative coronary angiography was performed at baseline and after 3.2 + /- 0.6 ( mean + /- SD ) years to assess changes in mean minimum coronary artery diameter and mean percent stenosis . RESULTS Compared to lower intakes , > 3 g/4184 kJ ( 1000 kcal ) of cereal fiber or > 6 servings of whole grains per week were associated with smaller decline in minimum coronary artery diameter ( cereal fiber : -0.09 + /- 0.02 vs -0.04 + /- 0.02 mm , P = .03 ; whole grains : -0.10 + /- 0.02 vs -0.06 + /- 0.02 mm , P = .04 ) after adjustments for age , cardiovascular risk factors , and dietary intakes of saturated and polyunsaturated fat , cholesterol , and alcohol . Progression in percent stenosis tended to be less in women with higher intake of cereal fiber ( P = .10 ) or whole-grain foods ( P = .09 ) , after similar adjustments . Intakes of total , fruit , and vegetable fiber , and number of servings of refined grain , fruits , or vegetable were not associated with progression . CONCLUSIONS Higher intakes of cereal fiber and whole-grain products are associated with less progression of coronary atherosclerosis in postmenopausal women with established CAD OBJECTIVE Several large prospect i ve studies have shown that baseline levels of C-reactive protein ( CRP ) are an independent predictor of cardiovascular events among apparently healthy individuals . However , prospect i ve data on whether CRP predicts cardiovascular events in diabetic patients are limited so far . RESEARCH DESIGN AND METHODS To investigate the association between plasma CRP levels and incidence of cardiovascular events among men with type 2 diabetes , we followed prospect ively a cohort of 746 American men aged 46 - 81 years who were free of cardiovascular diseases at the time of blood collection in 1993 - 1994 . RESULTS During an average of 5 years of follow-up ( 3,986 person-years ) , we identified 103 incident cardiovascular events ( 18 myocardial infa rct ion , 70 coronary artery bypass grafting or angioplasty , and 15 stroke ) , confirmed by medical records . After adjustment for age , BMI , smoking , alcohol consumption , physical activity , family history of coronary heart disease , history of high blood pressure , history of high serum cholesterol , aspirin use , and fasting status as well as for fibrinogen , creatinine , HbA(1c ) , and non-HDL cholesterol levels , CRP remained significantly associated with an increased risk of cardiovascular events . The relative risks for quartiles were 1.00 , 1.51 , 2.52 , and 2.62 ( 95 % CI : 1.29 - 5.32 ; P for trend : 0.011 ) . We observed no effect modifications by plasma levels of LDL cholesterol , HDL cholesterol , non-HDL cholesterol , apolipoprotein B , HbA(1c ) , and fibrinogen or by BMI . CONCLUSIONS High plasma levels of CRP were associated with an increased risk of incident cardiovascular events among diabetic men , independent of currently established lifestyle risk factors , blood lipids , and glycemic control OBJECTIVE While various weight-management approaches produce weight loss , they may differ in dietary quality . We monitored changes in nutrient intakes in overweight and obese subjects on three different weight-management programs . DESIGN R and omized clinical trial ( pilot study ) with two 12-week phases : phase 1 , weekly counseling ; phase 2 , monitoring only . SUBJECTS/ SETTING One hundred eighty nonsmoking , sedentary overweight and obese adults began this outpatient study ; 134 ( body mass index [ calculated as kg/m(2)]=30.9+/-2.4 ; age=42.3+/-1.2 years ) were used in analyses . INTERVENTION Twenty-four weeks of exercise only ( control group ) , hypocaloric diet plus exercise , or hypocaloric diet with fiber-rich whole-grain cereals plus exercise . MAIN OUTCOME MEASURES At weeks 0 , 12 , and 24 , diet quality was assessed by 3-day food records and body weight was measured . STATISTICAL ANALYSES PERFORMED Three-way analysis of variance with repeated measures . RESULTS The hypocaloric diet with fiber-rich whole-grain cereals plus exercise decreased energy intake more than exercise only ( P=0.032 ) . By week 12 , the hypocaloric diet with fiber-rich whole-grain cereals plus exercise and the hypocaloric diet plus exercise decreased total fat more than exercise only , which was sustained in the hypocaloric diet with fiber-rich whole-grain cereals plus exercise at 24 weeks ( P<0.001 ) . At weeks 12 and 24 , the hypocaloric diet with fiber-rich whole-grain cereals plus exercise reduced saturated fat intake more than exercise only . The hypocaloric diet with fiber-rich whole-grain cereals plus exercise increased total fiber , insoluble fiber ( both P<0.001 ) , magnesium ( P=0.004 ) , and vitamin B-6 ( P=0.002 ) intakes more than the hypocaloric diet plus exercise and exercise only . Calcium and vitamin E intakes were inadequate in all groups . Weight loss was similar in the hypocaloric diet with fiber-rich whole-grain cereals plus exercise and the hypocaloric diet plus exercise . CONCLUSIONS Weight-reduction strategies may be associated with reduced intake of micronutrients , such as calcium and vitamin E. However , a hypocaloric diet with fiber-rich whole-grain cereal is effective for improving or maintaining other aspects of dietary quality during weight loss Foods high in dietary fiber may play an important role in regulating body weight . Few observational studies have examined the relationship between dietary fiber from different sources and body fat in older adults . Our objectives were to examine the associations among grain intake ( whole and refined ) , dietary fiber and fiber sources , and body fat among older adults . We used data from 434 free-living adults ( 177 men and 257 women ) aged between 60 and 80 y. Dietary intake was estimated from a 126-item semiquantitative FFQ . Percent body fat and percent trunk fat mass were measured by whole-body dual-energy X-ray absorptiometry . After adjustment for covariates , whole-grain intake was inversely associated with BMI [ 26.8 kg/m(2 ) ( 25.7 - 28.1 ) vs. 25.8 kg/m(2 ) ( 24.6 - 27.1 ) , ( 95 % CI ) ; P-trend = 0.08 ] , percent body fat [ 34.5 % ( 32.7 - 36.3 ) vs. 32.1 % ( 30.1 - 34.1 ) ; P-trend = 0.02 ] , and percent trunk fat mass [ 43.0 % ( 40.4 - 45.5 ) vs. 39.4 % ( 36.7 - 42.1 ) ; P-trend = 0.02 ] in the lowest compared with the highest quartile category of whole-grain intake . Refined grain intake was not associated with any measure of body fat distribution . Cereal fiber was inversely associated with BMI [ 27.3 kg/m(2 ) ( 26.1 - 28.6 ) vs. 25.4 kg/m(2 ) ( 24.3 - 26.7 ) ; P-trend = 0.012 ] , percent body fat [ 34.7 % ( 32.8 - 36.6 ) vs. 31.5 % ( 29.4 - 33.5 ) ; P-trend = 0.004 ] , and percent trunk fat mass [ 42.8 % ( 40.2 - 45.4 ) vs. 37.8 % ( 35.0 - 40.6 ) ; P-trend = 0.001 ] . No significant association was observed between intakes of total fiber , vegetable or fruit fiber , and body composition measurements . Higher intakes of cereal fiber , particularly from whole-grain sources , are associated with lower total percent body fat and percent trunk fat mass in older adults Background Intakes of whole grains and cereal fiber have been inversely associated with the risk of chronic diseases ; however , their relation with total and disease-specific mortality remain unclear . We aim ed to prospect ively assess the association of whole grains and cereal fiber intake with all causes and cause-specific mortality . Methods The study included 367,442 participants from the prospect i ve NIH-AARP Diet and Health Study ( enrolled in 1995 and followed through 2009 ) . Participants with cancer , heart disease , stroke , diabetes , and self-reported end-stage renal disease at baseline were excluded . Results Over an average of 14 years of follow-up , a total of 46,067 deaths were documented . Consumption of whole grains were inversely associated with risk of all-cause mortality and death from cancer , cardiovascular disease ( CVD ) , diabetes , respiratory disease , infections , and other causes . In multivariable models , as compared with individuals with the lowest intakes , those in the highest intake of whole grains had a 17 % ( 95 % CI , 14–19 % ) lower risk of all-cause mortality and 11–48 % lower risk of disease-specific mortality ( all P for trend < 0.023 ) ; those in the highest intake of cereal fiber had a 19 % ( 95 % CI , 16–21 % ) lower risk of all-cause mortality and 15–34 % lower risk of disease-specific mortality ( all P for trend < 0.005 ) . When cereal fiber was further adjusted , the associations of whole grains with death from CVD , respiratory disease and infections became not significant ; the associations with all-cause mortality and death from cancer and diabetes were attenuated but remained significant ( P for trend < 0.029 ) . Conclusions Consumption of whole grains and cereal fiber was inversely associated with reduced total and cause-specific mortality . Our data suggest cereal fiber is one potentially protective component |
14,071 | 31,879,212 | INTERPRETATION This review can accelerate efforts to improve global health by leading to more strategic investment in programmes that promote gender e quality and target restrictive gender norms among young people .
Such programmes can lead to a lifetime of improved health and wellbeing by challenging not only attitudes and behaviours related to gender at an early age , but also the gendered systems that surround them . | BACKGROUND In the context of the Sustainable Development Goals and the shifting global burden of disease , this systematic review analyses the evidence from rigorously evaluated programmes that seek to transform the gendered social norms undermining the health and wellbeing of children , adolescents , and young adults .
The aim of this study was threefold : to describe the l and scape of gender-transformative programmes that attempt to influence health-related outcomes ; to identify mechanisms through which successful programmes work ; and to highlight where gaps might exist in implementation and evaluation . | Adolescent females in Zimbabwe are at high risk for HIV acquisition . Shaping the Health of Adolescents in Zimbabwe ( SHAZ ! ) was a r and omized controlled trial of a combined intervention package including life-skills and health education , vocational training , micro-grants and social supports compared to life-skills and health education alone . SHAZ ! was originally envisioned as a larger effectiveness trial , however , the intervention was scaled back due to context ual and economic conditions in the country at the time . SHAZ ! enrolled 315 participants r and omly assigned to study arm within blocks of 50 participants ( 158 intervention and 157 control ) . The intervention arm participants showed statistically significant differences from the control arm participants for several outcomes during the two years of follow up including ; reduced food insecurity [ IOR = 0.83 vs. COR = 0.68 , p-0.02 ] , and having their own income [ IOR = 2.05 vs. COR = 1.67 , p = 0.02 ] . Additionally , within the Intervention arm there was a lower risk of transactional sex [ IOR = 0.64 , 95 % CI ( 0.50 , 0.83 ) ] , and a higher likelihood of using a condom with their current partner [ IOR = 1.79 , 95 % CI ( 1.23 , 2.62 ) ] over time compared to baseline . There was also evidence of fewer unintended pregnancies among intervention participants [ HR = 0.61 , 95 % CI ( 0.37 , 1.01 ) ] , although this relationship achieved only marginal statistical significance . Several important challenges in this study included the coordination with vocational training programs , the political and economic instability of the area at the time of the study , and the difficulty in creating a true st and ard of care control arm . Overall the results of the SHAZ ! study suggest important potential for HIV prevention intervention packages that include vocational training and micro-grants , and lessons for further economic livelihoods interventions with adolescent females . Further work is needed to refine the intervention model , and test the impact of the intervention at scale on biological outcomes . Trial Registration Clinical Trials.gov There is promising evidence that poverty-targeted cash transfer programs can have positive impacts on adolescent transitions to adulthood in re source poor setting s , however existing research is typically from small scale programs in diverse geographic and cultural setting s. We provide estimates of the impact of a national unconditional cash transfer program , the Kenya Cash Transfer for Orphans and Vulnerable Children , on pregnancy and early marriage among females aged 12 to 24 , four years after program initiation . The evaluation was design ed as a clustered r and omized controlled trial and ran from 2007 to 2011 , capitalizing on the existence of a control group , which was delayed entry to the program due to budget constraints . Findings indicate that , among 1549 females included in the study , while the program reduced the likelihood of pregnancy by five percentage points , there was no significant impact on likelihood of early marriage . Program impacts on pregnancy appear to work through increasing the enrollment of young women in school , financial stability of the household and delayed age at first sex . The Kenyan program is similar in design to most other major national cash transfer programs in Eastern and Southern Africa , suggesting a degree of generalizability of the results reported here . Although the objective of the program is primarily poverty alleviation , it appears to have an important impact on facilitating the successful transition of adolescent girls into adulthood We r and omly assigned the Shifting Boundaries interventions to 30 public middle schools in New York City , enrolling 117 sixth and seventh grade classes ( over 2,500 students ) to receive a classroom , a building , a combined , or neither intervention . The classroom intervention included a six-session curriculum emphasizing the laws and consequences for perpetrators of dating violence and sexual harassment ( DV/H ) , the social construction of gender roles , and healthy relationships . The building-based intervention included the use of building-based restraining orders , higher levels of faculty/security presence in safe/unsafe “ hot spots ” mapped by students , and posters to increase DV/H awareness and reporting . Student surveys were implemented at baseline , immediately after the intervention , and 6-months post-intervention . As hypothesized , behaviors improved as a result of the interventions . The building-only and the combined interventions were effective in reducing sexual violence victimization involving either peers or dating partners at 6-months post-intervention . This was mirrored by reductions in sexual violence perpetration by peers in the building-only intervention . While the preponderance of results indicates that the interventions were effective , an anomalous result ( increase in sexual harassment victimization reports that was contradicted by lower frequency estimates ) did emerge . However , after analysis these anomalous results were deemed to be most likely spurious . The success of the building-only intervention alone is important because it can be implemented with very few extra costs to schools In this experiment , 123 sixth and seventh grade classrooms from Clevel and area schools were r and omly assigned to one of two five-session curricula addressing gender violence/sexual harassment ( GV/SH ) or to a no-treatment control . Three-student surveys were administered . Students in the law and justice curricula , compared to the control group , had significantly improved outcomes in awareness of their abusive behaviors , attitudes toward GV/SH and personal space , and knowledge . Students in the interaction curricula experienced lower rates of victimization , increased awareness of abusive behaviors , and improved attitudes toward personal space . Neither curricula affected perpetration or victimization of sexual harassment . While the intervention appeared to reduce peer violence victimization and perpetration , a conflicting finding emerged — the intervention may have increased dating violence perpetration ( or at least the reporting of it ) but not dating violence victimization OBJECTIVE To determine whether an interactive curriculum that integrates dating violence prevention with lessons on healthy relationships , sexual health , and substance use reduces physical dating violence ( PDV ) . DESIGN Cluster r and omized trial with 2.5-year follow-up ; prespecified subgroup analyses by sex . SETTING Grade 9 health classes . PARTICIPANTS A total of 1722 students aged 14 - 15 from 20 public schools ( 52.8 % girls ) . Intervention A 21-lesson curriculum delivered during 28 hours by teachers with additional training in the dynamics of dating violence and healthy relationships . Dating violence prevention was integrated with core lessons about healthy relationships , sexual health , and substance use prevention using interactive exercises . Relationship skills to promote safer decision making with peers and dating partners were emphasized . Control schools targeted similar objectives without training or material s. MAIN OUTCOME MEASURES The primary outcome at 2.5 years was self-reported PDV during the previous year . Secondary outcomes were physical peer violence , substance use , and condom use . Analysis was by intention-to-treat . RESULTS The PDV was greater in control vs intervention students ( 9.8 % vs 7.4 % ; adjusted odds ratio , 2.42 ; 95 % confidence interval , 1.00 - 6.02 ; P = .05 ) . A significant group x sex interaction effect indicated that the intervention effect was greater in boys ( PDV : 7.1 % in controls vs 2.7 % in intervention students ) than in girls ( 12.1 % vs 11.9 % ) . Main effects for secondary outcomes were not statistically significant ; however , sex x group analyses showed a significant difference in condom use in sexually active boys who received the intervention ( 114 of 168 ; 67.9 % ) vs controls ( 65 of 111 [ 58.6 % ] ) ( P < .01 ) . The cost of training and material s averaged CA$16 per student . CONCLUSION The teaching of youths about healthy relationships as part of their required health curriculum reduced PDV and increased condom use 2.5 years later at a low per-student cost Background An emerging model for sexuality education is the rights-based approach , which unifies discussion s of sexuality , gender norms , and sexual rights to promote the healthy sexual development of adolescents . A rigorous evaluation of a rights-based intervention for a broad population of adolescents in the U.S. has not previously been published . This paper evaluates the immediate effects of the Sexuality Education Initiative ( SEI ) on hypothesized psychosocial determinants of sexual behavior . Methods A cluster-r and omized trial was conducted with ninth- grade students at 10 high schools in Los Angeles . Classrooms at each school were r and omized to receive either a rights-based curriculum or basic sex education ( control ) curriculum . Surveys were completed by 1,750 students ( N = 934 intervention , N = 816 control ) at pretest and immediate posttest . Multilevel regression models examined the short-term effects of the intervention on nine psychosocial outcomes , which were hypothesized to be mediators of students ’ sexual behaviors . Results Compared with students who received the control curriculum , students receiving the rights-based curriculum demonstrated significantly greater knowledge about sexual health and sexual health services , more positive attitudes about sexual relationship rights , greater communication about sex and relationships with parents , and greater self-efficacy to manage risky situations at immediate posttest . There were no significant differences between the two groups for two outcomes , communication with sexual partners and intentions to use condoms . Conclusions Participation in the rights-based classroom curriculum result ed in positive , statistically significant effects on seven of nine psychosocial outcomes , relative to a basic sex education curriculum . Longer-term effects on students ’ sexual behaviors will be tested in subsequent analyses . Trial registration Clinical Trials.gov NCT02009046 Objective To assess the impact of Stepping Stones , a HIV prevention programme , on incidence of HIV and herpes simplex type 2 ( HSV-2 ) and sexual behaviour . Design Cluster r and omised controlled trial . Setting 70 villages ( clusters ) in the Eastern Cape province of South Africa . Participants 1360 men and 1416 women aged 15 - 26 years , who were mostly attending schools . Intervention Stepping Stones , a 50 hour programme , aims to improve sexual health by using participatory learning approaches to build knowledge , risk awareness , and communication skills and to stimulate critical reflection . Villages were r and omised to receive either this or a three hour intervention on HIV and safer sex . Interviewers administered question naires at baseline and 12 and 24 months and blood was tested for HIV and HSV-2 . Main outcome measures Primary outcome measure : incidence of HIV . Other outcomes : incidence of HSV-2 , unwanted pregnancy , reported sexual practice s , depression , and substance misuse . Results There was no evidence that Stepping Stones lowered the incidence of HIV ( adjusted incidence rate ratio 0.95 , 95 % confidence interval 0.67 to 1.35 ) . The programme was associated with a reduction of about 33 % in the incidence of HSV-2 ( 0.67 , 0.46 to 0.97 ; P=0.036)—that is , Stepping Stones reduced the number of new HSV-2 infections over a two year period by 34.9 ( 1.6 to 68.2 ) per 1000 people exposed . Stepping Stones significantly improved a number of reported risk behaviours in men , with a lower proportion of men reporting perpetration of intimate partner violence across two years of follow-up and less transactional sex and problem drinking at 12 months . In women desired behaviour changes were not reported and those in the Stepping Stones programme reported more transactional sex at 12 months . Conclusion Stepping Stones did not reduce incidence of HIV but had an impact on several risk factors for HIV — notably , HSV-2 and perpetration of intimate partner violence . Trial Registration Clinical Trials NCT00332878 With an increase in sexual activity among young adults in Vietnam and associated risks , there is a need for evidence -based sexual health interventions . This evaluation of three sexual health programs based on the Protection Motivation Theory ( PMT ) was conducted in 12 communes in Ha Noi , Nha Trang City , and Ninh Hoa District . Inclusion criteria included unmarried youth 15–20 years residing in selected communes . Communes were r and omly allocated to an intervention , and participants were r and omly selected within each commune . The intervention programs included Vietnamese Focus on Kids ( VFOK ) , the gender-based program Exploring the World of Adolescents ( EWA ) , and EWA plus parental and health provider education ( EWA+ ) . Programs were delivered over a ten-week period in the communities by locally trained facilitators . The gender-based EWA program with parental involvement ( EWA+ ) compared to VFOK showed significantly greater increase in knowledge . EWA+ in comparison to VFOK also showed significant decrease at immediate postintervention for intention to have sex . Sustained changes are observed in all three interventions for self-efficacy condom use , self-efficacy abstinence , response efficacy for condoms , extrinsic rewards , and perceived vulnerability for HIV . These findings suggest that theory-based community programs contribute to sustained changes in knowledge and attitudes regarding sexual risk among Vietnamese adolescents Men and women living in r and omly selected 1st-year dormitories participated in tailored single-sex sexual assault prevention or risk-reduction programs , respectively . An evaluation of the men ’s project is presented ( N = 635 ) . The program incorporated social norms and byst and er intervention education and had an impact on self-reported sexual aggression and an effect on men ’s perceptions that their peers would intervene when they encountered inappropriate behavior in others . Relative to the control group , participants also reported less reinforcement for engaging in sexually aggressive behavior , reported fewer associations with sexually aggressive peers , and indicated less exposure to sexually explicit media Adolescent relationship abuse ( ARA ) is a significant public health problem . Coaching Boys Into Men ( CBIM ) is an evidence -based ARA prevention program that trains coaches to deliver violence prevention messages to male athletes . Assessing acceptability and impact of CBIM on coaches may inform prevention efforts that involve these important adults in health promotion among youth . As part of a two-armed cluster-r and omized controlled trial of CBIM in 16 high schools in Northern California , coaches completed baseline and postseason surveys ( n = 176 ) to assess their attitudes and confidence delivering the program . Coaches in the intervention arm also participated in interviews ( n = 36 ) that explored program acceptability , feasibility , and impact . Relative to controls , intervention coaches showed increases in confidence intervening when witnessing abusive behaviors among their athletes , greater byst and er intervention , and greater frequency of violence-related discussion s with athletes and other coaches . Coaches reported the program was easy to implement and valuable for their athletes . Findings illustrate the value of exploring attitudinal and behavioral changes among ARA prevention implementers , and suggest that coaches can gain confidence and enact behaviors to discourage ARA among male athletes . Coaches found the program to be feasible and valuable , which suggests potential for long-term uptake and sustainability Using methods of community-based participatory research , a prospect i ve r and omized controlled trial of a violence prevention program based on Latino cultural values was implemented with elementary school children in a Mexican American community . Community members participated in intervention program selection , implementation , and data collection . High-risk students who participated in the program had greater nonviolent self-efficacy and demonstrated greater endorsement of program values than did high-risk students in the control group . This collaborative partnership was able to combine community-based participatory research with a rigorous study design and provide sustained benefit to community partners Of the world 's 1.2 billion adolescents ( 10 - 19 years ) , India is home to the largest number globally , about 243 million . However not much is known about the health of young adolescent girls ( 11 - 14 years ) in India who enter puberty with substantial nutritional and health deficits . Identifying early adolescence as a " gateway " moment , the Saloni pilot study is ar and omized control trial ( RCT ) to improve nutrition , hygiene and reproductive health behaviors in 30 schools in rural Uttar Pradesh ( UP ) , India . A prevention model that includes Sadharanikaran , an ancient Indian theory of communication , guided the development of the intervention . The Saloni strategy includes a 10 session in-school intervention based on compassion , self efficacy , emotional well being , peer and parental support , packaged in the form of short , easy-to-use instructional modules . A diary design ed to engage adolescent girls is provided to each girl . The cluster RCT was conducted from January 2010 to October 2011 with adolescent girls ( 11 - 14 years of age ) in Hardoi district . The trial is a two-level , nested RCT with the unit of r and omization being the block with 15 schools in the intervention arm and 15 schools in the control arm . A sample of 1200 girls was r and omly selected . The intervention had a significant impact on more than 13 preventive health behaviors . About 65 percent girls in the intervention group had adopted 13 or more health behaviors at end line compared 4.5 percent in the control group at end line and 5 percent at baseline . Behavioral impact was demonstrated in all three areas of nutrition , hygiene and reproductive health . The study provides evidence that early adolescence is indeed a " gateway moment " to build nutritional and health reserves Introduction Parenting programmes are increasingly popular for reducing children ’s exposure to interpersonal violence in low/middle-income countries , but there is limited evidence on their effectiveness . We investigated the incremental impact of adding a caregiver component to a life skills programme for adolescent girls , assessing girls ’ exposure to violence ( sexual and others ) and caregivers ’ gender attitudes and parenting behaviours . Methods In this two-arm , single-blinded , cluster r and omised controlled trial , we recruited 869 adolescent girls aged 10–14 and 764 caregivers in South Kivu , Democratic Republic of Congo . Following a baseline survey , participants were divided into 35 clusters based on age , language and location . Eighteen clusters were r and omised to the treatment arm and 17 clusters to the wait-list control arm . Adolescent girls in both arms received 32 life skills sessions ; caregivers in the treatment arm received 13 complementary caregiver sessions . The primary outcome was girls ’ self-reported exposure to sexual violence in the last 12 months ; secondary outcomes included self-reports of specific forms of sexual violence , physical and emotional violence , transactional sex , child marriage for girls and parenting behaviours for caregivers . Intent-to-treat and per- protocol analyses were conducted . Results At 12 months of follow-up , the intervention showed no impact on sexual violence ( adjusted OR=0.95 ; 95 % CI 0.65 to 1.37 ) or any secondary outcomes for girls . The intervention was associated with improved supportive parenting behaviours . Protocol adherence was also associated with improvements in these outcomes . Conclusion While the caregiver curriculum improved some parenting outcomes , additional programmatic adaptations may be needed to reduce adolescent girls ’ violence exposure in humanitarian setting s. Trial registration number NCT02384642 Introduction Interpersonal violence is a critical public health concern in humanitarian context s , but evidence of effective violence prevention programmes targeting adolescent girls is lacking . We investigated the efficacy of a life skills and safe spaces programme to reduce adolescent girls ’ experiences of interpersonal violence in a refugee setting . Methods In this two-arm , single-blinded , cluster r and omised controlled trial , we recruited 919 Sudanese and South Sudanese girls ages 13–19 years residing in refugee camps in Ethiopia . Girls were divided into 31 clusters , with 457 and 462 participants assigned to the intervention and control arms , respectively . Intervention clusters received 30 life skills sessions delivered in safe spaces and 8 complementary sessions for caregivers . The primary outcome was exposure to sexual violence in the previous 12 months . Secondary outcomes included disaggregated forms of sexual violence , physical violence , emotional violence , transactional sex , child marriage , feelings of safety , attitudes around rites of passage and perceptions of social support . Intent-to-treat analysis was used . Results At 12-month follow-up , the intervention was not significantly associated with reduction in exposure to sexual violence ( adjusted OR = 0.96 , 95 % CI 0.59 to 1.57 ) , other forms of violence , transactional sex or feelings of safety . The intervention was associated with improvements in attitudes around rites of passage and identified social supports . Additionally , the intervention showed a decrease in reported child marriage among girls who were married at baseline . Conclusion While the intervention impacted key markers along the causal pathway to violence reduction , further research and programmatic adaptations are needed to prevent violence towards adolescents in humanitarian context s. Trial registration NCT02506543 PURPOSE This article examines gender differences in attitudes toward sexual risk-taking behaviors of acquired immune deficiency syndrome (AIDS)-orphaned youth participating in a r and omized control trial testing an economic empowerment intervention in rural Ug and a. METHODS Adolescents ( average age 13.7 years ) who had lost one or both parents to AIDS from 15 comparable schools were r and omly assigned to either an experimental ( n=135 ) or a control condition ( n=142 ) . Adolescents in the experimental condition , in addition to usual care , also received support and incentives to save money toward secondary education . RESULTS Findings indicate that although adolescent boys and girls within the experimental condition saved comparable amounts , the intervention appears to have benefited girls , in regard to the attitudes toward sexual risk-taking behavior , in a different way and to a lesser extent than boys . CONCLUSIONS Future research should investigate the possibility that adolescent girls might be able to develop equally large improvements in protective attitudes toward sexual risk taking through additional components that address gendered social norms |
14,072 | 27,610,712 | The generalisability of the review is low as most of the RCTs included neither elderly people nor participants with comorbidities , who are more prone to complications as compared to others with biliary colic .
The beneficial effect of NSAIDs compared with placebo on pain relief was confirmed when we applied Trial Sequential Analysis .The quality of evidence according to GRADE criteria was moderate for the comparison of NSAIDs versus placebo regarding the outcome lack of pain relief and low or very low for the other outcomes and comparisons . | BACKGROUND Cholelithiasis refers to the presence of gallstones , which are concretions that form in the biliary tract , usually in the gallbladder .
Cholelithiasis is one of the most common surgical problems worldwide and is particularly prevalent in most Western countries .
Biliary colic is the term used for gallbladder pain experienced by a person with gallstones and without overt infection around the gallbladder .
It is the most common manifestation of cholelithiasis , observed in over one-third of people with gallstones over the course of 10 or more years .
Non-steroid anti-inflammatory drugs ( NSAIDs ) have been widely used to relieve biliary colic pain , but their role needs further elucidation .
They may decrease the frequency of short-term complications , such as mild form of acute cholecystitis , jaundice , cholangitis , and acute pancreatitis , but they may also increase the occurrence of more severe and possibly life-threatening adverse events such as gastrointestinal bleeding , renal function impairment , cardiovascular events , or milder events such as abdominal pain , drowsiness , headache , dizziness , or cutaneous manifestations .
OBJECTIVES To assess the benefits and harms of NSAIDs in people with biliary colic . | AIMS To investigate the incidence , risk factors and natural history of gallstone disease , a r and om sample of females belonging to a rural population was enrolled in a ten-year longitudinal study . METHODS The study has been performed in a small town on the hills south of Rome . In 1985 , a r and om sample of 426 females , aged 20 - 69 years , was screened by real-time ultrasonography for gallstones and previous cholecystectomy . Screening methods included anthropometry , collection of a blood sample and a question naire on the occurrence of abdominal symptoms . During 1995 , all these subjects were invited for a 10-year follow-up examination . RESULTS The overall 10-year incidence of gallstone disease was 6.3 % ( 5.5 % of new gallstones and 0.8 % of cholecystectomies ) . Only 23.1 % of the women with gallstones were aware of their condition . More than three quarters ( 76.9 % ) had not suffered biliary pain . Univariate and multivariate analyses demonstrated a positive independent association of new gallstone disease with body mass index and parity . Out of the initially asymptomatic gallstone women , 15.4 % experienced at least one episode of biliary pain , 23.1 % were su bmi tted to elective cholecystectomy and 61.5 % remained asymptomatic . CONCLUSIONS The study demonstrates a high incidence of gallstone disease in women belonging to a rural free-living population in Italy and suggests body mass index and parity as possible true risk factors . Moreover , it confirms that a remarkable proportion of asymptomatic patients become symptomatic and eventually undergo cholecystectomy BACKGROUND Rofecoxib is a selective cyclooxygenase-2 inhibitor indicated for the treatment of acute pain , with similar analgesic efficacy to ibuprofen and naproxen sodium . Diclofenac sodium is the most commonly prescribed nonsteroidal anti-inflammatory drug worldwide ; it is effective for the treatment of pain as well as the signs and symptoms associated with the painful conditions of osteoarthritis and rheumatoid arthritis . OBJECTIVE The aim of this study was to compare the analgesic efficacy and tolerability of a single dose of rofecoxib 50 mg , 3 doses of enteric-coated diclofenac sodium 50 mg , and placebo over 8-hour and 24-hour periods in patients with moderate to severe pain after oral surgery . METHODS In this double-blind , placebo- and active comparator-controlled , parallel-group study , patients experiencing moderate to severe pain after the surgical extraction of > or = 2 third molars were r and omized to receive a single dose of rofecoxib 50 mg , 3 doses of enteric-coated diclofenac sodium 50 mg ( 50 mg given every 8 hours ) , or placebo . Patients rated pain intensity , pain relief , and global assessment s at prespecified times throughout the 24-hour period after initial dosing . Overall analgesic efficacy was determined by total pain relief over 8 hours ( TOPAR8 ) and 24 hours ( TOPAR24 ) and patient global assessment s at 8 and 24 hours . Onset of analgesic effect was determined by using the 2-stopwatch method for confirmed perceptible pain relief . Peak analgesic effect was the maximum pain relief attained during the first 8 hours . The duration of analgesic effect was determined by median time to rescue analgesia use . RESULTS A total of 305 patients were r and omized to treatment : 121 received rofecoxib , 121 received diclofenac sodium , and 63 received placebo . The baseline demographics were similar among the groups . Overall , 61.3 % experienced moderate pain and 38.7 % experienced severe pain ; 53.1 % were female ; and the mean age was 23.4 years . The overall analgesic efficacy , as assessed by TOPAR8 , of a single dose of rofecoxib 50 mg was significantly greater than a single dose of enteric-coated diclofenac sodium 50 mg ( 20.5 vs 8.2 ) and placebo ( 20.5 vs 5.9 ) . Patient global assessment at 8 hours was also significantly better for rofecoxib compared with enteric-coated diclofenac sodium and placebo . TOPAR24 was significantly greater for a single dose of rofecoxib 50 mg compared with 3 doses of enteric-coated diclofenac sodium 50 mg ( 64.1 vs 25.1 ) and placebo ( 64.1 vs 19.2 ) . At 24 hours , the patient global assessment for rofecoxib was significantly better than that achieved with enteric-coated diclofenac sodium and placebo . The onset of analgesic effect was significantly more rapid for rofecoxib than for enteric-coated diclofenac sodium and placebo ( median times : 31 minutes , > 4 hours , and > 4 hours , respectively ) . The peak analgesic effect was significantly greater for rofecoxib compared with enteric-coated diclofenac sodium ( 3.2 vs 1.5 ) and placebo ( 3.2 vs 1.1 ) . The duration of analgesia was significantly longer for rofecoxib than enteric-coated diclofenac sodium ( median times : > 24 hours vs 1 hour and 37 minutes ) and placebo ( > 24 hours vs 1 hour and 37 minutes ) . Enteric-coated diclofenac sodium was numerically greater than placebo for the key end points measuring overall efficacy ( total pain relief and patient global assessment ) , but diclofenac sodium did not provide as much analgesic effect as expected for a drug effective for pain , osteoarthritis , and rheumatoid arthritis and did not differ significantly from placebo . Overall , both rofecoxib and enteric-coated diclofenac sodium were generally well tolerated , although the rofecoxib group had a significantly lower incidence of clinical and drug-related adverse events than the enteric-coated diclofenac sodium group . CONCLUSIONS A single 50-mg dose of rofecoxib provided greater overall analgesic efficacy over 8 hours , more rapid onset of analgesia , greater maximum analgesic effect , and longer duration of effect than a single 50-mg dose of enteric-coated diclofenac sodium in patients with moderate to severe pain associated with oral surgery . Compared with 3 doses of enteric-coated diclofenac sodium 50 mg ( 50 mg every 8 hours ) , a single dose of rofecoxib 50 mg provided greater overall analgesic efficacy over 24 hours In the GRADE approach , r and omized trials start as high- quality evidence and observational studies as low- quality evidence , but both can be rated down if most of the relevant evidence comes from studies that suffer from a high risk of bias . Well-established limitations of r and omized trials include failure to conceal allocation , failure to blind , loss to follow-up , and failure to appropriately consider the intention-to-treat principle . More recently recognized limitations include stopping early for apparent benefit and selective reporting of outcomes according to the results . Key limitations of observational studies include use of inappropriate controls and failure to adequately adjust for prognostic imbalance . Risk of bias may vary across outcomes ( e.g. , loss to follow-up may be far less for all-cause mortality than for quality of life ) , a consideration that many systematic review s ignore . In deciding whether to rate down for risk of bias -- whether for r and omized trials or observational studies -- authors should not take an approach that averages across studies . Rather , for any individual outcome , when there are some studies with a high risk , and some with a low risk of bias , they should consider including only the studies with a lower risk of bias OBJECTIVES To analyze sources search ed in Cochrane review s , to determine the proportion of trials included in review s that are indexed in major data bases , and to compare the quality of these trials with those from other sources . METHODS All new systematic review s in the Cochrane Library , Issue1 2001 , that were restricted to r and omized controlled trials ( RCTs ) or quasi- RCTs were selected . The sources search ed in the review s were recorded , and the trials included were checked to see whether they were indexed in four major data bases . Trials not indexed were checked to determine how they could be identified . The quality of trials found in major data bases was compared with those found from other sources . RESULTS The range in the number of data bases search ed per review ranged between one and twenty-seven . The proportion of the trials in the four data bases were Cochrane Controlled Trials Register = 78.5 % , MEDLINE = 68.8 % , Embase = 65.0 % , and Science/Social Sciences Citation Index = 60.7 % . Search ing another twenty-six data bases after Cochrane Controlled Trials Register ( CCTR ) , MEDLINE , and Embase only found 2.4 % additional trials . There was no significant difference between trials found in the CCTR , MEDLINE , and Embase compared with other trials , with respect to adequate allocation concealment or sample size . CONCLUSIONS There was a large variation between review s in the exhaustiveness of the literature search es . CCTR was the single best source of RCTs . Additional data base search ing retrieved only a small percentage of extra trials . Contacting authors and manufacturers to find unpublished trials appeared to be a more effective method of obtaining the additional better quality trials Sixty patients were treated in the emergency ward for biliary colic . Cholelithiasis was proven by ultrasonography . Twenty patients ( group I ) were treated by placebo . Twenty patients ( group II ) were treated by papaverine , and 20 patients were treated by diclofenac sodium ( Voltaren ) ( group III ) . Twenty more patients ( group IV ) with low back pain ( LBP ) were treated with diclofenac sodium ( Voltaren ) as a control to assess the analgesic effect of Voltaren . Two interesting observations were made : Voltaren was proven more efficient for pain relief ( P<0.002 ) , and none of the patients treated with Voltaren were in need of hospitalization and immediate surgery . In comparison , nine patients of the other two groups progressed to acute cholecystitis and needed surgical intervention . The possible anticolic and anti-biliary inflammation properties and the indications for use of Voltaren are discussed In this double blind , prospect i ve study , the relative efficacy of Diclofenac + Pitofenone + Fenpiverinium ( Manyana ) and Analgin + Pitofenone + Fenpiverinium ( Baralgan ) in 200 patients of biliary , ureteric and intestinal colic was evaluated . Patients were given these coded drugs thrice daily for five days starting from day 0 to day 5 . The results of the present clinical evaluation demonstrated that Manyana appeared to be superior to Baralgan in biliary and ureteric colic while it was therapeutically equivalent to Baralgan in reducing the pain intensity in intestinal colic . Both the medications were tolerated well and there were no side-effects reported OBJECTIVES Patients presenting to the emergency department ( ED ) with suspected biliary colic often require intravenous ( IV ) analgesia . The choice of IV analgesia typically includes opioids and ketorolac . Although ultrasound ( US ) is the initial diagnostic study in these patients , nondiagnostic scans and a high clinical suspicion may require the patient to undergo hepatobiliary scintigraphy ( HIDA ) . Opioids such as morphine interfere with the HIDA scan and thus may limit its value as an analgesic in the ED for these patients . Analgesics that do not interfere with HIDA scanning include ketorolac and butorphanol , an opioid agonist-antagonist . This study evaluates the efficacy of IV ketorolac compared to butorphanol for the treatment of biliary colic pain in the ED . METHODS Between June 2005 and February 2007 , a convenience sample of patients presenting to the ED with abdominal pain suspected to be biliary colic were r and omized to receive either 30 mg of IV ketorolac or 1 mg of IV butorphanol . Pain level was assessed using a 1 to 10 " faces " visual analog pain scale initially , as well as 15 and 30 minutes after medication infusion . Side effect profiles and the need for rescue analgesia were also assessed . Patients and clinicians were blinded to the study drug given . RESULTS Forty-six patients were enrolled in the study . Both groups had similar demographics and baseline pain scores . The mean ( + /-st and ard deviation [ SD ] ) pain score in the butorphanol group decreased from 7.1 ( + /-1.7 ) to 2.1 ( + /-2.2 ) after 30 minutes . The mean ( + /-SD ) pain score in the ketorolac group decreased from 7.4 ( + /-2.0 ) to 3.1 ( + /-3.3 ) after 30 minutes . Both groups had similar needs for rescue analgesia . Side effects included dizziness and sedation with butorphanol and nausea with ketorolac . CONCLUSIONS Although limited by small sample size and convenience sample , this study demonstrates that both ketorolac and butorphanol provide pain relief in biliary colic . Both agents should be considered reasonable options in the ED treatment of biliary colic , especially in patients that may undergo HIDA Methods for combining data from several studies exist and appear to be quite useful . None satisfactorily addresses the question of what studies should be combined . This issue is the most serious method ological limitation . Even studies with statistically significant interaction might still be combined if the effect were in the same direction . Thus , substantial scientific input is required as to what criteria must be met by each potential study . Much can be learned from combining or pooling data but it must be done cautiously . Pooling exercises do not replace well design ed prospect i ve clinical trials . Efforts for establishing basic design criteria to allow for multicentre and multicountry trials to be more easily combined might be useful . During the cross-sectional studies ( February 1981 to July 1984 ) performed by the Group for Epidemiology and Prevention of Cholelithiasis ( GREPCO ) in Rome , Italy , 161 subjects were identified as having gallstones . Ten subjects did not participate in the prospect i ve follow-up . At entry , 33 of the 151 remaining subjects were symptomatic , and 118 were asymptomatic . Data on incidence of biliary colics , complications , cholecystectomy , and death were collected at least every 2 years . In the initially asymptomatic group , the cumulative probability ( % + /- SE ) of developing biliary colic was 11.9 + /- 3.0 at 2 years , 16.5 + /- 3.5 at 4 years , and 25.8 + /- 4.6 at 10 years . None of the variables considered as possible modifiers of the natural history were found to be associated with an increased risk of developing biliary colic . The cumulative probability ( % + /- SE ) of developing complications after 10 years was 3.0 + /- 1.8 in the initially asymptomatic group and 6.5 + /- 4.4 in the symptomatic group ( P = NS ) . Incidence of cholecystectomy was higher in the initially symptomatic than in the asymptomatic group ( log-rank test = 2.27 ; P = .02 ) . Fifteen ( 53.6 % ) of the 28 operated in the initially asymptomatic group were su bmi tted to cholecystectomy , although specific symptoms did not occur . Twelve ( 10.2 % ) and 2 ( 6.1 % ) of the initially asymptomatic and symptomatic subjects died during the follow-up . One patient in the former group died at age 64 of a histologically proven adenocarcinoma of the gallbladder . In conclusion , this study demonstrates that the natural history of gallstones is less benign than is generally considered In a double-blind trial , 60 patients with biliary colic were allocated at r and om to receive 200 mg ketoprofen , 1.8 g lysine acetylsalicylate or placebo by intravenous bolus . The patients were asked to rate their pain at intervals within 3 hours of injection and to indicate their overall pain experience on a visual analogue scale . Both ketoprofen and lysine acetylsalicylate proved significantly more effective than placebo in relieving pain , with no significant difference between them . A good analgesic response , reflected by complete or almost complete relief of pain within 30 minutes of injection , was recorded in 4 , 17 , and 16 patients , respectively , in the placebo , ketoprofen , and lysine acetylsalicylate treatment groups . All drugs were well tolerated . It is concluded that the results provide further evidence for a useful therapeutic role of prostagl and in inhibitors in the treatment of biliary colic Background : Although non‐steroidal anti‐inflammatory drugs ( NSAID ) and spasmolytics have been used to relieve biliary colic , the role of these drugs in the natural history of biliary colic has not been clarified . The objective of the present study is to compare the efficacy of intramuscular diclofenac with intramuscular hyoscine in the treatment of pain of acute biliary colic , and to study their role in the natural history of biliary colic and in the prevention of cholelithiasis‐related complications Ketorolac is a nonsteroidal anti-inflammatory medication that is used widely for pain management . Its effects are mediated through the inhibition of prostagl and ins , which makes it uniquely different from opioids in relieving pain . We conducted a r and omized , prospect i ve , double blind study of patients presenting to our Emergency Department ( ED ) with a diagnosis of acute biliary colic . Study patients were r and omized into one of two treatment groups , meperidine 1.5 mg/kg with a maximum dose of 100 mg or ketorolac 60 mg given intramuscularly ( i.m . ) . The patients rated their pain before and 30 min after medication on a scale of 1 to 10 using a Visual Analog Pain Scale . Overall pain relief was compared between the two groups using a two- sample t test . Thirty patients were enrolled in the study , 16 in the ketorolac group and 14 in the meperidine group . Patients ranged in age from 18 to 71 years and 6 ( 20 % ) were male . The average pain score at time 0 was 7.6 for the ketorolac group and 7.3 for the meperidine group . Pain relief at time 30 min was 3.8 in the ketorolac group and 3.9 in the meperidine group , which was not statistically different . The mean global pain score and need for an emergency cholecystectomy were similar in the two groups . Rescue medication for additional analgesia at 30 min was needed in 4 patients in the meperidine group and in 2 patients in the ketorolac group ( 28.6 % versus 12.5 % , respectively ; NS ) . In this study of patients with acute biliary colic there was no significant difference in the pain relief achieved by using either ketorolac or meperidine Indomethacin was recently shown to have a potent analgesic effect on biliary pain . The underlying mechanism is not fully clear , although reduction of increased gallbladder pressure by inhibition of prostagl and in synthesis had been suggested . For further clarification of this mechanism , the effect of intravenous indomethacin on the intraluminal gallbladder pressure was investigated in patients undergoing operation for acute cholecystitis . After laparotomy , gallbladder pressure was measured continuously during 25 min in 20 patients , 10 of whom received 100 mg indomethacin intravenously , while 10 were untreated controls . High intraluminal gallbladder pressure was found in all patients . Indomethacin reduced the average pressure by 11 % in 20 min , whereas the corresponding pressure in the controls was constant . The results indicate that acute cholecystitis is associated with substantially raised intraluminal pressure , and that the analgesic action of indomethacin on biliary pain may be attributable to a local effect on gallbladder function , result ing in reduction of intraluminal pressure The inhibition of prostagl and in synthesis by nonsteroidal anti-inflammatory drugs can alleviate the pain and inflammation associated with a variety of disorders . Nonsteroidal anti-inflammatory drugs have a role , therefore , in the treatment of nonrheumatic conditions as well as in the treatment of rheumatic diseases , an area in which these agents have been used and studied more extensively . In clinical conditions marked by acute or chronic pain and inflammation , such as oral surgery , dysmenorrhea , low back pain , renal colic , and biliary colic , as well as in post-traumatic and postoperative conditions , diclofenac sodium , a nonsteroidal anti-inflammatory drug with potent prostagl and in synthetase inhibition , has been shown to be an effective analgesic agent . In the current studies , diclofenac was given orally or by intramuscular injection in doses ranging from 50 to 75 mg daily , or up to 150 mg per day for longer-term use . When compared with placebo , diclofenac provided consistently superior relief of symptoms . Comparisons with other nonsteroidal anti-inflammatory drugs or with opioids , such as pentazocine or Spasmofen , demonstrate that symptom relief with diclofenac was either comparable to or better than that obtained with these agents This was conducted to evaluate the analgesic effect of intravenous tenoxicam ( non-steroidal anti-inflammatory drug ) in the treatment of biliary colic pain and compared with spasmolytics . Thirtytwo patients ( 26 women , 6 men , mean age 47 , range 38 - 55 years ) with acute biliary colic were entered for study . They were allocated r and omly to receive either tenoxicam 20 mg i.v . or hyoscine N-butylbromide 20 mg i.v . The patients recorded their pain severity on 5 point scale . The results showed that tenoxicam caused significant pain relief in 10 out of 16 patients at 30 min ( mean pain score decreased from 2.75 + /- 0.93 to 0.49 + /- 0.51 , p < 0.05 ) and in other 4 patients at 60 min ( mean pain score decreased to 0.58 + 5.7 , p < 0.05 ) . None of these patients developed acute cholecystitis or pain relapse over a period of 24 h follow up . With use of hyoscine N-butylbromide , 7 out 16 patients had significant pain relief at 30 min ( mean pain score decreased from 2.62 + /- 1.01 to 0.57 + /- 0.53 , p < 0.05 ) and 3 other patients relieved at 60 min ( mean pain score decreased to 0.66 + /- 0.57 , p < 0.05 ) . Four patients showed pain relapse within 24 h and needed pethidine-rescue treatment , two of them developed acute cholecystitis . Three out of 6 patients who showed no response to hyoscine N-butylbropmide and treated with 100 mg pethidine progressed to acute cholecystitis . We concluded that intravenous tenoxicam has rapid and prolong analgesic effects in the treatment of acute biliary colic as compared to hyoscine N-butylbroimde and it prevents the progression to acute cholecystitis BACKGROUND & AIMS Nonsteroidal anti-inflammatory drugs ( NSAIDs ) have been used to relieve biliary colic . Follow-up was limited in previous studies , and the role of NSAIDs in the natural history of biliary colic has not been clarified . The purpose of this study was to evaluate the efficacy of diclofenac , a potent NSAID , in the the immediate symptomatic relief of biliary colic and the prevention of cholelithiasis-related complications . METHODS Fifty-three patients with cholelithiasis and biliary colic were enrolled in this r and omized , double-blind , placebo-controlled study . They received a single 75-mg ( 3 mL ) intramuscular injection of diclofenac ( n = 27 ) or similarly administered 3 mL of saline ( n = 26 ) . All patients were followed up for at least 3 days . The effect of either treatment was assessed by changes in the severity of pain and the development of cholelithiasis-related complications . RESULTS Complete relief of pain was obtained in 21 diclofenac and in 7 placebo patients ; progression to acute cholecystitis was observed in 4 and 11 patients , respectively . Fewer overall complications were observed in the diclofenac group . CONCLUSIONS In patients with cholelithiasis who present with biliary colic , a single 75-mg intramuscular dose of diclofenac can provide satisfactory pain relief and decrease substantially the rate of progression to acute cholecystitis In the GRADE approach , r and omized trials are classified as high quality evidence and observational studies as low quality evidence but both can be rated down if a body of evidence is associated with a high risk of publication bias . Even when individual studies included in best- evidence summaries have a low risk of bias , publication bias can result in substantial overestimates of effect . Authors should suspect publication bias when available evidence comes from a number of small studies most of which have been commercially funded . A number of approaches based on examination of the pattern of data are available to help assess publication bias . The most popular of these is the funnel plot ; all , however , have substantial limitations . Publication bias is likely frequent , and caution in the face of early results , particularly with small sample size and number of events , is warranted To compare the analgesic efficacy and tolerability of intravenous ( IV ) ketorolac tromethamine with IV meperidine in the treatment of biliary colic , a prospect i ve , r and omized , double blind study was carried out upon a convenience sample of patients at a large inner city facility . Patients between the ages of 18 and 65 years of age with a history and physical examination consistent with biliary colic were enrolled over a 2-year period . Patients were r and omly assigned to receive ketorolac 30 mg IV or meperidine 50 mg IV . Pain was quantified using a 4-point verbal rating system ( VRS ) as well as a visual analog scale ( VAS ) . Patients were queried about their pain at times 0 , 12 h , 1 h , and 2 h after administration of the study medication . Adverse effects were also recorded . A total of 324 patients completed the study protocol with 175 patients receiving ketorolac and 149 receiving meperidine . Patient demographics were similar for both groups with mean age for the ketorolac group of 36.1 years and for the meperidine group of 34.6 years . Both groups were predominantly Latino and over 80 % of patients in both groups were female . No significant difference in pain control was found between ketorolac and meperidine in either the VAS or VRS for any time interval studied . The mean change in the VAS at time 2 h was 6.2 cm + /- 3.6 cm for the ketorolac group , compared with 6.7 cm + /- 3.6 cm for the meperidine group ( p = 0.25 ) . Although no significant difference was found in overall drug tolerability , patients receiving meperidine reported higher incidences of nausea and of dizziness than those receiving ketorolac ( p = 0.009 and 0.003 , respectively ) . Ketorolac tromethamine is a well-tolerated , effective medication in the treatment of acute biliary colic . It showed similar efficacy to meperidine with a decreased number of adverse effects OBJECTIVE We evaluated the inter-rater reliability ( IRR ) of assessing the quality of evidence ( QoE ) using the Grading of Recommendations , Assessment , Development , and Evaluation ( GRADE ) approach . STUDY DESIGN AND SETTING On completing two training exercises , participants worked independently as individual raters to assess the QoE of 16 outcomes . After recording their initial impression using a global rating , raters grade d the QoE following the GRADE approach . Subsequently , r and omly paired raters su bmi tted a consensus rating . RESULTS The IRR without using the GRADE approach for two individual raters was 0.31 ( 95 % confidence interval [ 95 % CI ] = 0.21 - 0.42 ) among Health Research Methodology students ( n = 10 ) and 0.27 ( 95 % CI = 0.19 - 0.37 ) among the GRADE working group members ( n = 15 ) . The corresponding IRR of the GRADE approach in assessing the QoE was significantly higher , that is , 0.66 ( 95 % CI = 0.56 - 0.75 ) and 0.72 ( 95 % CI = 0.61 - 0.79 ) , respectively . The IRR further increased for three ( 0.80 [ 95 % CI = 0.73 - 0.86 ] and 0.74 [ 95 % CI = 0.65 - 0.81 ] ) or four raters ( 0.84 [ 95 % CI = 0.78 - 0.89 ] and 0.79 [ 95 % CI = 0.71 - 0.85 ] ) . The IRR did not improve when QoE was assessed through a consensus rating . CONCLUSION Our findings suggest that trained individuals using the GRADE approach improves reliability in comparison to intuitive judgments about the QoE and that two individual raters can reliably assess the QoE using the GRADE system Published evidence suggests that aspects of trial design lead to biased intervention effect estimates , but findings from different studies are inconsistent . This study combined data from 7 meta-epidemiologic studies and removed overlaps to derive a final data set of 234 unique meta-analyses containing 1973 trials . Outcome measures were classified as " mortality , " " other objective , " " or subjective , " and Bayesian hierarchical models were used to estimate associations of trial characteristics with average bias and between-trial heterogeneity . Intervention effect estimates seemed to be exaggerated in trials with inadequate or unclear ( vs. adequate ) r and om-sequence generation ( ratio of odds ratios , 0.89 [ 95 % credible interval { CrI } , 0.82 to 0.96 ] ) and with inadequate or unclear ( vs. adequate ) allocation concealment ( ratio of odds ratios , 0.93 [ CrI , 0.87 to 0.99 ] ) . Lack of or unclear double-blinding ( vs. double-blinding ) was associated with an average of 13 % exaggeration of intervention effects ( ratio of odds ratios , 0.87 [ CrI , 0.79 to 0.96 ] ) , and between-trial heterogeneity was increased for such studies ( SD increase in heterogeneity , 0.14 [ CrI , 0.02 to 0.30 ] ) . For each characteristic , average bias and increases in between-trial heterogeneity were driven primarily by trials with subjective outcomes , with little evidence of bias in trials with objective and mortality outcomes . This study is limited by incomplete trial reporting , and findings may be confounded by other study design characteristics . Bias associated with study design characteristics may lead to exaggeration of intervention effect estimates and increases in between-trial heterogeneity in trials reporting subjectively assessed outcomes |
14,073 | 16,390,512 | Most studies reported overall positive results and found that IT-based interventions improved health care utilization , behaviors , attitudes , knowledge , and skills .
CONCLUSIONS : There is growing evidence that emerging IT may improve diabetes care . | BACKGROUND : Excellent diabetes care and self-management depends heavily on the flow of timely , accurate information to patients and providers .
Recent developments in information technology ( IT ) may , therefore , hold great promise .
OBJECTIVE : To determine , in a systematic review , how emerging interactive IT has been used to enhance care for adults with type 2 diabetes . | Computerized management of diabetes is the use of information technology to improve diabetic patient outcomes . The computer can be used to provide educational information to patients and facilitate the storage and transmittal of clinical data between patients and clinicians . The objective of this paper was to evaluate computerized management of diabetes in changing the health outcomes . Clinical trial reports were identified through systematic electronic data base and manual search es . Four eligibility criteria were applied : diabetes clinical area ; prospect i ve , contemporaneously controlled clinical trial with r and om assignment of the intervention ; computer generated information for patients in the intervention group and no similar intervention in the control group ; and measurement of effect on the outcome of care ( health status , social functioning , patient/family satisfaction ) . Data were abstract ed using a st and ardized abstract ion form and the quality of methodology was scored . Of 15 eligible clinical trials , 12 ( 80 % ) reported positive outcomes or significant benefits . A total of 48 outcome measures were reported , an average of 3.2/ study . Significantly improved clinical outcomes included Hemoglobin A1c ( HbA1c ) , blood glucose , and hypoglycemic events . Patient-computer interaction appears to be a valuable supplement to interaction with clinicians . Considering the need to enhance patient participation in the care of chronic illnesses , initial evidence indicates computers can play a more significant role in the future Sustained improvement in blood glucose control is the only treatment outcome which will reduce or eliminate the long term complications of diabetes mellitus . We have design ed and evaluated an electronic information system which facilitates this task . The system is voice-interactive , physician directed and affords , to remote patients , 24 h access via touch-tone telephone . Accordingly , patients access the system each day to report self-measured blood glucose levels or hypoglycaemic symptoms together with dietary changes , planned exercise , stress , illness or other lifestyle events . In turn they receive immediate advice with respect to medication dosing changes , and other pertinent feedback . Preliminary system beta-testing for safety and efficacy was performed for one year in an open study of 204 patients derived from two independent , health-care environments . Among the two testing centres , over 60,000 telephone cells were received by the computer systems during the start-up year . Safety and efficacy expectations were met . In addition , prevalence of diabetes related crises ( hyperglycaemia or hypoglycaemia ) fell approximately 3-fold . Glycated haemoglobin fell significantly ( 1.0 - 1.3 % ) in patients actively using the system . In control groups of patients not actively using the system , there were no improvements in metabolic control while body weights were stable in all groups . The new system was safe and effective in our h and s and empowered our health professionals to provide improved diabetes care This paper describes the development and evaluation of a computer-aided learning ( CAL ) program . The program was tested in a trial that involved 36 people with diabetes ; 20 received CAL lessons in diabetes management and 16 attended conventional diabetes classes conducted by diabetes educators . When measurements taken before and three months after the education were compared , both groups showed significant improvement in their knowledge ; the blood glucose levels of the CAL group were significantly lower but those of the conventional education group were higher . This means that the CAL program was as effective as conventional education in imparting knowledge but it was more likely to motivate people to control their glucose levels . The CAL program allows diabetes educators to spend less time on education in basic knowledge and to concentrate more on motivational and social factors that are important determinants of patient compliance . It can also benefit people with diabetes whose access to health professionals and /or conventional diabetes education is restricted Objectives .The objective of this work was to evaluate the reach , effectiveness , adoption , and implementation of a brief behavioral dietary intervention and 2 supplemental components of diabetes self-management support : telephone follow-up calls and community re sources enhancement . Design and Subjects . This was a 2 × 2 r and omized , controlled trial investigating the incremental effects of telephone follow-up and community re sources enhancement with 320 adult type 2 diabetes out patients . Methods .Key outcomes included behavioral ( dietary patterns , fat intake ) , physiologic ( HbA1C , lipids ) , and quality -of-life/patient satisfaction measures and were collected at baseline and 3- and 6-month follow-up . Results .Despite high reach ( 76 % patient participation ) , excellent adoption ( all 12 primary care practice s approached participated ) , and good implementation , there were few outcome differences among treatment conditions . There was significant improvement across conditions in most outcomes in each category at both follow-ups . Conclusions .A brief , computer-assisted , dietary goal – setting intervention basic treatment condition was moderately successful in producing dietary improvements but less so in producing biologic or quality -of-life outcomes . Additions of follow-up phone calls or a community re sources enhancement component did not produce incremental improvements over this basic intervention Disease-specific st and ards for directing patient management are becoming increasingly important . These st and ards , however , are often not followed because they are not sufficiently integrated into the clinical care setting . In this study we describe the development and evaluation of a Computer-Assisted Management Protocol ( CAMP ) of care guidelines for diabetes mellitus . While other studies have shown improved compliance with rule-based reminders , the CAMP customizes disease-specific care guidelines to individual patients over time . We evaluated the effect of the CAMP on compliance with guidelines in a prospect i ve , r and omized controlled study . The study was performed at a family practice clinic where much of the patient record is maintained electronically on The Medical Record ( TMR ) . The management protocol was developed from st and ards published by the American Diabetes Association . Fifty-eight providers were r and omized to either receive or not receive the CAMP for diabetes . Compliance with st and ards was assessed by chart audits of all encounters with diabetic patients during the study interval . The following conclusion was made : the Computer-Assisted Management Protocol result ed in a statistically significant improvement in compliance with diabetes care st and ards OBJECTIVE There is a pressing need for brief practical interventions that address diabetes management . Using a r and omized design , we evaluated a medical office-based intervention focused on behavioral issues relevant to dietary self-management . RESEARCH DESIGN AND METHODS There were 206 adult diabetes patients r and omized to usual care or brief intervention , which consisted of touchscreen computer-assisted assessment to provide immediate feedback on key barriers to dietary self-management , and goal setting and problem-solving counseling for patients . Follow-up components to the single session intervention included phone calls and interactive video or videotape instruction as needed . RESULTS Multivariate analyses of covariance revealed that the brief intervention produced greater improvements than usual care on a number of measures of dietary behavior ( e.g. , fewer calories from saturated fat , fewer high-fat eating habits and behaviors ) at the 3-month follow-up . There were also significant differences favoring intervention on changes in serum cholesterol levels and patient satisfaction but not on glycosylated hemoglobin . The intervention effects were relatively robust across a variety of patient characteristics , the two participating physicians , and intervention staff members . CONCLUSIONS If the long-term results are equally positive and generalize to other setting , this intervention could provide a prototype for a feasible cost-effective way to integrate patient views and behavioral management into office-based care for diabetes OBJECTIVE To determine whether diabetes education can be provided as effectively through telemedicine technology as through in-person encounters with diabetes nurse and nutrition educators . RESEARCH DESIGN AND METHODS A total of 56 adults with diabetes were r and omized to receive diabetes education in person ( control group ) or via telemedicine ( telemedicine group ) and were followed prospect ively . The education consisted of three consultative visits with diabetes nurse and nutrition educators . The in-person and telemedicine groups were compared using measures of glycemic control ( HbA(1c ) ) and question naires to assess patient satisfaction and psychosocial functioning as related to diabetes . Outcome measures were obtained at baseline , immediately after the completion of diabetes education , and 3 months after the third educational visit . RESULTS Patient satisfaction was high in the telemedicine group . Problem Areas in Diabetes scale scores improved significantly with diabetes education ( adjusted P < 0.05 , before vs. immediately after education and 3 months after education ) , and the attainment of behavior-change goals did not differ between groups . With diabetes education , HbA(1c ) improved from 8.6 + /- 1.8 % at baseline to 7.8 + /- 1.5 % immediately after education and 7.8 + /- 1.8 % 3 months after the third educational visit ( unadjusted P < 0.001 , P = 0.089 adjusted for BMI and age ) , with similar changes observed in the telemedicine and in-person groups . CONCLUSIONS Diabetes education via telemedicine and in person was equally effective in improving glycemic control , and both methods were well accepted by patients . Reduced diabetes-related stress was observed in both groups . These data suggest that telemedicine can be successfully used to provide diabetes education to patients OBJECTIVE We evaluated automated telephone disease management ( ATDM ) with telephone nurse follow-up as a strategy for improving diabetes treatment processes and outcomes in Department of Veterans Affairs ( VA ) clinics . We also compared the results with those of a prior ATDM trial conducted in a county health care system . RESEARCH DESIGN AND METHODS A total of 272 VA patients with diabetes using hypoglycemic medications were r and omized . During the 1-year study period , intervention patients received biweekly ATDM health assessment and self-care education calls , and a nurse educator followed up with patients based on their ATDM assessment reports . Telephone surveys were used to measure patients ' self-care , symptoms , and satisfaction with care . Outpatient service use was evaluated using electronic data bases and self-reports , and glycemic control was measured by HbA1c and serum glucose testing . RESULTS At 12 months , intervention patients reported more frequent glucose self-monitoring and foot inspections than patients receiving usual care and were more likely to be seen in podiatry and diabetes specialty clinics . Intervention patients also were more likely than control patients to have had a cholesterol test . Among patients with baseline HbA1c levels > or = 8 % , mean end-point values were lower among intervention patients than control patients ( 8.7 vs. 9.2 % , respectively ; P = 0.04 ) . Among intervention and control patients with baseline values > or = 9 % , mean end-point values were 9.1 and 10.2 % , respectively ( P = 0.04 ) . At follow-up , intervention patients reported fewer symptoms of poor glycemic control than control patients and greater satisfaction with their health care . CONCLUSIONS This intervention improved the quality of VA diabetes care . Intervention effects for most end points replicated findings from the prior county clinic trial , although intervention-control differences in the current study were smaller because of the relatively good self-care and health status among the current study 's enrollees OBJECTIVE Because of other competing priorities , physical activity ( PA ) is seldom addressed in a consistent way in either primary care or diabetes education . This 8-week pilot study evaluated the short-term benefits of an Internet-based supplement to usual care that focused on providing support for sedentary patients with type 2 diabetes to increase their PA levels . RESEARCH DESIGN AND METHODS A total of 78 type 2 diabetic patients ( 53 % female , average age 52.3 years ) were r and omized to the Diabetes Network ( D-Net ) Active Lives PA Intervention or an Internet information-only condition . The intervention condition received goal - setting and personalized feedback , identified and developed strategies to overcome barriers , received and could post messages to an on-line " personal coach , " and were invited to participate in peer group support areas . Key outcomes included minutes of PA per week and depressive symptomatology . RESULTS There was an overall moderate improvement in PA levels within both intervention and control conditions , but there was no significant improvement in regard to condition effects . There was substantial variability in both site use and outcomes within the intervention and control conditions . Internal analyses revealed that among intervention participants , those who used the site more regularly derived significantly greater benefits , whereas those in the control condition derived no similar benefits with increased program use . CONCLUSIONS Internet-based self-management interventions for PA and other regimen areas have great potential to enhance the care of diabetes and other chronic conditions . We conclude that greater attention should be focused on methods to sustain involvement with Internet-based intervention health promotion programs over time OBJECTIVE The Mayo Health System Diabetes Translation Project sought to assess models of community-based diabetes care and use of a diabetes electronic management system ( DEMS ) . Planned care is a re design ed model of chronic disease care that involves guideline implementation , support of self-management , and use of clinical information systems . RESEARCH DESIGN AND METHODS We studied adult diabetic patients attending three primary care practice sites in Wisconsin and Minnesota . We implemented planned care at all sites and DEMS in the practice of 16 primary care providers . We assessed quality of diabetes care using st and ard indicators for 200 patients r and omly selected from each site at baseline and at 24 months of implementation . We used multivariable analyses to estimate the association between planned care and DEMS and each quality indicator . RESULTS Planned care was associated with improvements in measurement of HbA(1c ) ( odds ratio 7.0 [ 95 % CI 4.2 - 11.6 ] ) , HDL cholesterol ( 5.6 [ 4.1 - 7.5 ] ) , and microalbuminuria ( 5.3 [ 3.5 - 8.0 ] ) , as well as the provision of tobacco advice ( 6.9 [ 4.7 - 10.1 ] ) , among other performance measures . DEMS use was associated with improvements in all indicators , including microalbuminuria ( 3.2 [ 1.9 - 5.2 ] ) , retinal examination ( 2.4 [ 1.5 - 3.9 ] ) , foot examinations ( 2.3 [ 1.2 - 4.4 ] ) , and self-management support ( 2.6 [ 1.7 - 3.8 ] ) . Although planned care was associated with improvements in metabolic control , we observed no additional metabolic benefit when providers used DEMS . CONCLUSIONS Planned care was associated with improved performance and metabolic outcomes in primary care . DEMS use augmented the impact of planned care on performance outcomes but not on metabolic outcomes . Optimal identification of the best translation of evidence to diabetes practice will require longer follow-up or new care-delivery models BACKGROUND A prerequisite to translating research findings into practice is information on consistency of implementation , maintenance of results , and generalization of effects . This follow-up report is one of the few experimental studies to provide such information on Internet-based health education . METHODS We present follow-up data 10 months following r and omization on the " Diabetes Network ( D-Net ) " Internet-based self-management project , a r and omized trial evaluating the incremental effects of adding ( 1 ) tailored self-management training or ( 2 ) peer support components to a basic Internet-based , information-focused comparison intervention . Participants were 320 adult type 2 diabetes patients from participating primary care offices , mean age 59 ( SD = 9.2 ) , who were relatively novice Internet users . RESULTS All intervention components were consistently implemented by staff , but participant website usage decreased over time . All conditions were significantly improved from baseline on behavioral , psychosocial , and some biological outcomes ; and there were few differences between conditions . Results were robust across on-line coaches , patient characteristics , and participating clinics . CONCLUSIONS The basic D-Net intervention was implemented well and improvements were observed across a variety of patients , interventionists , and clinics . There were , however , difficulties in maintaining usage over time and additions of tailored self-management and peer support components generally did not significantly improve results OBJECTIVE We evaluated the impact of automated telephone disease management ( ATDM ) calls with telephone nurse follow-up as a strategy for improving outcomes such as mental health , self-efficacy , satisfaction with care , and health-related quality of life ( HRQL ) among low-income patients with diabetes mellitus . RESEARCH DESIGN This was a r and omized , controlled trial . SUBJECTS Two hundred forty-eight primarily English- and Spanish-speaking adults with diabetes enrolled at the time of visits to a county health care system . INTERVENTION In addition to usual care , intervention patients received biweekly ATDM calls with telephone follow-up by a diabetes nurse educator . Patients used the ATDM calls to report information about their health and self-care and to access self-care education . The nurse used patients ' ATDM reports to allocate her time according to their needs . MEASURES Patient-centered outcomes were measured at 12 months via telephone interview . RESULTS Compared with patients receiving usual care , intervention patients at follow-up reported fewer symptoms of depression ( P = 0.023 ) , greater self-efficacy to conduct self-care activities ( P = 0.006 ) , and fewer days in bed because of illness ( P = 0.026 ) . Among English-speaking patients , those receiving the intervention reported greater satisfaction with their health care overall and with the technical quality of the services they received , their choice of providers and continuity of care , their communication with providers , and the quality of their health outcomes ( all P < 0.042 ) . Intervention and control patients had roughly equivalent scores for established measures of anxiety , diabetes-specific HRQL , and general HRQL . CONCLUSIONS This intervention had several positive effects on patient-centered outcomes of care but no measurable effects on anxiety or HRQL OBJECTIVE The public is increasingly aware of the importance of HbA(1c ) testing , yet the vast majority of patients with diabetes do not know their HbA(1c ) status or goal . We set forth to evaluate the impact of a system that provides uniquely formatted and personalized reports of diabetes status and goals on changes in HbA(1c ) levels . RESEARCH DESIGN AND METHODS A total of 150 patients with diabetes were r and omized to receive either st and ard care or intervention inclusive of a computer-generated 11 " x 17 " color poster depicting an individual 's HbA(1c ) status and goals along with personalized steps to aid in goal achievement . All patients enrolled received diabetes education during the 3 months before enrollment . HbA(1c ) was performed at baseline and 6 months . RESULTS At baseline , there were no significant differences between patient groups in terms of age , sex , education level , race , and HbA(1c ) or lipid levels . Among patients with baseline HbA(1c ) > or = 7.0 % , there was an 8.6 % ( 0.77 % absolute ) reduction in HbA(1c ) among control subjects compared with a 17.0 % ( 1.69 % absolute ) decline in the intervention group ( P = 0.032 ) . There were no differences between the control and intervention groups with respect to the frequency of patients experiencing any decline in HbA(1c ) ( 63 vs. 69 % , P = 0.87 ) ; among these patients experiencing a decline , the most substantial reductions were seen with the control group , which had a 13.3 % ( 1.15 % absolute ) decline compared with the intervention patients , who reduced their HbA(1c ) by 24.2 % ( 2.26 % absolute reduction ; P = 0.0048 ) . At study close , 77 % of the patients had their poster displayed on their refrigerator . CONCLUSIONS This unique and personalized computer-generated intervention result ed in HbA(1c ) lowering comparable to that of hypoglycemic agents PURPOSE We sought to evaluate the effect of automated telephone assessment and self-care education calls with nurse follow-up on the management of diabetes . SUBJECTS AND METHODS We enrolled 280 English- or Spanish-speaking adults with diabetes who were using hypoglycemic medications and who were treated in a county health care system . Patients were r and omly assigned to usual care or to receive an intervention that consisted of usual care plus bi-weekly automated assessment and self-care education calls with telephone follow-up by a nurse educator . Outcomes measured at 12 months included survey-reported self-care , perceived glycemic control , and symptoms , as well as glycosylated hemoglobin ( Hb A1c ) and serum glucose levels . RESULTS We collected follow-up data for 89 % of enrollees ( 248 patients ) . Compared with usual care patients , intervention patients reported more frequent glucose monitoring , foot inspection , and weight monitoring , and fewer problems with medication adherence ( all P -0.03 ) . Follow-up Hb A , , levels were 0.3 % lower in the intervention group ( P = 0.1 ) , and about twice as many intervention patients had Hb A1c levels within the normal range ( P = 0.04 ) . Serum glucose levels were 41 mg/dL lower among intervention patients than usual care patients ( P = 0.002 ) . Intervention patients also reported better glycemic control ( P = 0.005 ) and fewer diabetic symptoms ( P < 0.0001 ) , including fewer symptoms of hyperglycemia and hypoglycemia . CONCLUSIONS Automated calls with telephone nurse follow-up may be an effective strategy for improving self-care behavior and glycemic control , and for decreasing symptoms among vulnerable patients with diabetes Effective control of diabetes is known to delay or prevent the end-organ complications of this disease . Can telemedicine improve a patient 's ability to self-manage diabetes ? Twenty-eight patients entered a study comparing home telemedicine consultation with st and ard outpatient care . A nurse case manager contacted the telemedicine group once a week under the direction of a primary care physician , who contacted the telemedicine group once a month . Laboratory studies and total body weight were measured at the beginning and at the end of the 3-month study . The hemoglobin A1c ( HbA1c ) and total body weight improved significantly in the intervention ( telemedicine ) group , as shown by a 16 % reduction in mean HbA1c level ( from 9.5 to 8.2 % ) and a 4 % mean weight reduction ( from 214.3 to 206.7 pounds ) . Based on our experience , we present a functionally based telemedicine classification system to improve the application of electronic medicine in future studies OBJECTIVE To compare the compliance with diabetes care performance indicators by diabetes specialists using a diabetes electronic management system ( DEMS ) and by those using the traditional paper medical record . RESEARCH DESIGN AND METHODS A DEMS has been gradually introduced into our subspecialty practice for diabetes care . To assess the value of this DEMS as a disease management tool , we completed a retrospective review of the medical records of 82 r and omly selected patients attending a subspecialty diabetes clinic ( DC ) during the first quarter of 1996 . Eligible patients were defined by the suggested criteria from the American Diabetes Association Provider Recognition Program . During the first quarter of 1996 , ∼ one half of the providers began using the DEMS for some but not all of their patient encounters . Neither abstract ors nor providers were aware of the intent to examine performance in relationship to use of the DEMS . RESULTS Several measures were positively influenced when providers used the DEMS . The number of foot examinations , the number of blood pressure readings , and a weighted criterion score were greater ( P < 0.01 ) for providers using the DEMS . There was evidence , although not statistically significant , for lower mean diastolic blood pressures ( P = 0.043 ) in patients and for number of glycated hemoglobins documented ( P = 0.018 ) by users of the DEMS . CONCLUSIONS Performance and documentation of the process of care for patients with diabetes in a subspecialty clinic are greater with the use of a DEMS than with the traditional paper record |
14,074 | 25,913,874 | Method ological and reporting quality of diagnostic accuracy studies of perimetry is sub-optimal and appears not to have improved substantially following the development of the STARD reporting guidance .
This observation is consistent with previous studies in ophthalmology and in other medical specialities | PURPOSE To evaluate method ological and reporting quality of diagnostic accuracy studies of perimetry in glaucoma and to determine whether there had been any improvement since the publication of the St and ards for Reporting of Diagnostic Accuracy ( STARD ) guidelines . | PURPOSE To assess the screening efficacy and practical use of two portable devices to detect moderate to severe visual field loss rapidly in population screening . METHODS Henson visual field analysis and Damato campimetry for glaucoma were performed in a healthy adult population , to determine false-positive rates ; in established glaucoma patients and suspects , to determine false-negative rates ; and in a general adult population , to assess practical use in actual screenings . RESULTS There were no false-positive test failures among the 82 normal subjects who completed the Henson two-step screening . Eighty of 83 normal subjects passed Damato campimetry , result ing in a false-positive rate of 3.6 % . Among 83 glaucoma suspects and patients , the Henson test identified 49 ( 84 % ) of 58 subjects whose full-threshold fields from Humphrey perimetry were abnormal , 38 ( 97 % ) of 39 of whom had moderate to severe visual field loss . The Damato campimeter detected 55 ( 81 % ) of 68 subjects with any pathologic loss on full-threshold visual fields , 44 ( 92 % ) of 48 of whom had moderate to severe visual field loss . Among 1,278 subjects tested in general population screenings , 55 subjects ( 4.3 % ) failed either or both tests . CONCLUSIONS The Henson visual field analyzer can discriminate moderately to severely diseased from normal visual fields with high sensitivity and specificity . The Damato campimeter can reliably detect moderate to severe visual field loss with a tolerably low false-positive rate . To overcome the weakness of glaucoma screening by tonometry alone , some forms of visual field testing may be acceptably brief ( cost effective ) and accurate ( sensitive and specific ) OBJECTIVE To determine if motion automated perimetry can identify early glaucomatous visual field defects in patients with suspected glaucoma ( by disc ) , those with ocular hypertension , and those with primary open-angle glaucoma . METHODS Motion automated perimetry , a foveally centered motion test , and st and ard visual field tests were conducted on one r and omly selected eye of normal patients ( n = 38 ) , patients with suspected glaucoma ( by disc ) ( n = 28 ) , patients with ocular hypertension ( n = 18 ) , and patients with primary open-angle glaucoma ( n = 21 ) . Subjects ' performance on both motion tests were compared with their performance on st and ard perimetry . RESULTS Perimetric motion thresholds significantly distinguished the groups ( P < or = .001 ) , while the foveally centered motion test was unable to separate them ( P < or = .32 ) . Of the total patients , 90.5 % of those with glaucoma , 39.3 % of those with suspected glaucoma , 27.8 % of those with ocular hypertension , and 5.3 % of the normal subjects had abnormal results on motion automated perimetry testing . Perimetric motion thresholds were significantly correlated with st and ard visual field thresholds ( P < or = .001 ) . CONCLUSION Motion automated perimetry identifies visual field defects in patients who already show st and ard visual field loss as well as in a moderate percentage of those with suspected glaucoma and ocular hypertension , indicating that the testing of discrete locations might be necessary for increased diagnostic utility PURPOSE Scanning laser tomography with the Heidelberg retina tomograph ( HRT ; Heidelberg Engineering , Heidelberg , Germany ) has been proposed as a useful diagnostic test for glaucoma . This study was conducted to evaluate the quality of reporting of published studies using the HRT for diagnosing glaucoma . METHODS A vali date d Medline and h and search of English- language articles reporting on measures of diagnostic accuracy of the HRT for glaucoma was performed . Two review ers selected and appraised the papers independently . The St and ards for Reporting of Diagnostic Accuracy ( STARD ) checklist was used to evaluate the quality of each publication . RESULTS A total of 29 articles were included . Interobserver rating agreement was observed in 83 % of items ( kappa=0.76 ) . The number of STARD items properly reported ranged from 5 to 18 . Less than a third of studies ( 7/29 ) explicitly reported more than half of the STARD items . Descriptions of key aspects of the methodology were frequently missing . For example , the design of the study ( prospect i ve or retrospective ) was reported in 6 of 29 studies , and details of participant sampling ( e.g. , consecutive or r and om selection ) were described in 5 of 29 publications . The commonest description of diagnostic accuracy was sensitivity and specificity ( 25/29 ) followed by area under the ROC curve ( 13/29 ) , with 9 of 29 publications reporting both . CONCLUSIONS The quality of reporting of diagnostic accuracy tests for glaucoma with HRT is suboptimal . The STARD initiative may be a useful tool for appraising the strengths and weaknesses of diagnostic accuracy studies The purpose of this study was to evaluate the efficacy of three screening tests in detecting glaucoma in its early stage : the Tendency Oriented Perimetry ( TOP ) and Frequency Doubling Perimetry ( FDP ) visual field tests , and the Glaucoma Diagnostic ( GDx ) nerve fibre layer analyser . Eighteen patients with glaucoma who showed an early defect on HFA c 24 - 2 and twenty normals underwent the three tests . TOP showed a sensitivity of 94.4 % and a specificity of 75 % , FDP showed a sensitivity of 72.2 % and a specificity of 100 % , and GDx a sensitivity of 77.7 % and a specificity of 60 % PURPOSE To report the performance of glaucoma mass screening with only a visual field test utilizing frequency- doubling technology ( FDT ) perimetry in general population s. DESIGN Hospital and population -based cross-sectional study . METHODS This study took place in a multicenter setting . One hundred three consecutive glaucomatous patients and 14,814 persons were r and omly selected . We had created a glaucoma screening protocol ( GSP ) using FDT perimetry ( FDT-GSP ) . Frequency-doubling technology-glaucoma screening protocol was tested on consecutive glaucoma patients diagnosed with Humphrey visual field analyzer ( 30 - 2 SITA st and ard ) , and then FDT-GSP was applied to general population s. Frequency-doubling technology-glaucoma screening protocol positive subjects were ophthalmologically diagnosed . Detection ability of FDT-GSP was determined in consecutive patients , and the positive predictive value ( PPV ) of FDT-GSP to detect definitive glaucoma was estimated in general population s. RESULTS Frequency-doubling technique-glaucoma screening protocol detected 83.3 % and 100 % of definitive glaucoma patients with an early ( mean deviation [ MD ] > -6 dB ) and more advanced stage ( MD < or = -6 dB ) , respectively . In the population -based screening , there were 660 ( 4.5 % ) subjects who had positive FDT-GSP , including 512 in whom no visual field abnormalities ( VFA ) had been pointed out previously . Of them , 370 subjects underwent ophthalmologic diagnosis . Then , 266 ( 71.9 % , 266/370 ) subjects had a glaucomatous disk and 167 had definitive glaucomatous VFA . Fifty-five ( 14.9 % ) and 39 ( 10.5 % ) subjects were diagnosed as having other diseases and as normal , respectively . The PPV of FDT-GSP ranged from 32.6 % (167/512)-45.1 % ( 167/370 ) . CONCLUSIONS Frequency-doubling technology-based screening with only a visual field test showed reasonable performance on mass screening for detection of definitive glaucoma in this study population , considering the glaucoma prevalence OBJECTIVE To evaluate the performance of frequency-doubling technology ( FDT ) perimetry in a population -based glaucoma prevalence survey . DESIGN Population -based cross-sectional study . PARTICIPANTS Participants older than 40 years r and omly selected from the population of Tajimi City . METHODS Each participant underwent screening ophthalmic examinations including a visual field test using FDT with the C-20 - 1 screening protocol . A diagnosis of glaucoma was determined by glaucoma specialists with another detailed visual field test using Humphrey Field Analyzer ( HFA ; Humphrey Instruments , San Le and ro , CA ) with the 30 - 2 Swedish interactive threshold algorithm st and ard protocol and stereoscopic disc photographs . MAIN OUTCOME MEASURES The ratios of reliable FDT results and the sensitivity and specificity for detecting glaucoma in a general population . RESULTS Of 5784 eyes of 2892 participants ( age range , 40 - 92 years ; refractive error , -23 to 11 diopters ) in whom FDT was performed in both eyes , reliable results ( < or = 33 % fixation loss and < or = 33 % false-positive errors ) were obtained in 5707 eyes ( 98.7 % ) , including 2871 right eyes ( 99.3 % ) and 2836 left eyes ( 98.1 % ) with a significant bilateral difference ( P<0.001 , chi-square test ) . The rate of reliable FDT results did not differ between men and women ( P = 0.81 ) but decreased with age . In 5582 eyes with reliable FDT results , FDT showed 1 or more abnormal points in the visual field in 502 eyes ( 9.0 % ) , including 388 ( 7.3 % ) of 5295 normal eyes , 19 ( 16.4 % ) of 116 eyes of glaucoma suspects , and 95 ( 55.6 % ) of 171 eyes with definite glaucoma . The sensitivity and specificity values for detecting definite glaucoma were 55.6 % and 92.7 % , respectively . The positive and negative predictive values were 18.9 % and 98.5 % , respectively . In further analyses stratified with the mean deviation ( MD ) of the HFA , the sensitivities were 32.1 % , 48.4 % , 73.7 % , and 96.6 % for detecting definite glaucoma with an MD of more than -2 dB , an MD of -2 dB or less and more than -5 dB , an MD of -5 dB or less and more than -8 dB , and an MD of -8 dB or less , respectively . CONCLUSIONS In a population -based glaucoma screening study , FDT perimetry with the C-20 - 1 screening protocol was reliably performed in more than 98 % of participants . The sensitivity for detecting glaucomatous visual field damages , especially early damage , was not sufficiently high , whereas the specificity was high PURPOSE To investigate the ability of three diagnostic tests : frequency-doubling technology ( FDT ) , scanning laser polarimetry ( GDx ) , and nerve fiber layer ( NFL ) photographs to distinguish normal from glaucomatous eyes . METHODS Data were obtained in a cross-sectional , hospital clinic-based study , including one eye from each of 253 persons older than 40 years ( 68 normal , 94 glaucoma suspects and 91 glaucoma patients ) . We performed a comprehensive ocular examination , as well as static automated perimetry ( Humphrey 24 - 2 ) , screening FDT , GDx , optic nerve stereoscopic photographs and high-contrast NFL photographs . RESULTS The following were significantly different for glaucomatous patients compared with suspects and normals : mean values of mean deviation ( MD , Humphrey 24 - 2 ) and corrected pattern st and ard deviation ( CPSD ) , 11 GDx indices , mean FDT testing time and missed points , and NFL grade d defects ( ANOVA , Mantel-Haenszel test ; p = 0.0001 ) . Using Humphrey 24 - 2 test results and clinical assessment as the defining features of glaucoma , we found that the optimal mix of sensitivity and specificity values were 84 % and 100 % for FDT ( presence of any defect ) ; 62 % and 96 % for GDx ( The Number , cut-off value of 27 ) ; and , 95 % and 82 % for NFL photographs ( presence of any abnormality ) . FDT testing took the least time to be administered . CONCLUSIONS The FDT had the best diagnostic performance . Neural network analysis of GDx data outperformed other elements of its software Purpose : To evaluate the ability of frequency-doubling technology ( FDT ) perimetry in detecting glaucoma with N-30 and C-20 screening programs . Methods : Eighty eyes of 80 patients were enrolled ( 40 glaucomatous , 40 controls ) . Humphrey achromatic perimetry ( st and ard automated perimetry , SAP ) was considered as the “ gold st and ard ” for diagnosis . To assess whether N-30 screening program could detect more initial glaucomatous defects than C-20 , glaucomatous patients included 20 cases with nasal step at SAP ( pre-selected by medical chart inspection ) . Patients underwent two SAP examinations to confirm diagnosis ; then two N-30 and two C-20 screening tests with frequency-doubling technology were performed in a r and omized sequence . Finally , a frequency-doubling technology N-30 full-threshold examination was performed . Several criteria to define abnormality at frequency-doubling technology screening programs were evaluated . Results : For both C-20 and N-30 screening programs , the best parameter to detect glaucoma was the presence of at least 1 point with P < 5 % ( sensitivity = 87.5 % for both tests and specificity of 90 % and 95 % for C-20 and N-30 , respectively ) . Both screening procedures obtained a lower sensitivity ( 75 % ) in patients with a nasal step , whereas frequency-doubling technology full-threshold program was able to detect the initial defects in all cases . Conclusions : N-30 and C-20 screening procedures obtained similar results in well-defined glaucoma patients in terms of sensitivity and specificity . In the presence of a st and ard automated perimetry nasal step , diagnostic ability with both frequency-doubling technology screening strategies decreased and one quarter of nasal steps went undetected PURPOSE The aim of this study was to evaluate the diagnostic usefulness of the combined use of frequency-doubling technology ( FDT ) perimetry and polarimetry of the retinal nerve fiber layer . DESIGN Cross-sectional study . METHODS Seventy ocular hypertensive patients ( normal optic disk and st and ard perimetry , elevated intraocular pressure [ > 21 mm Hg ] ) , 59 patients with " preperimetric " open-angle glaucoma ( glaucomatous optic disk atrophy , elevated intraocular pressure [ > 21 mm Hg ] , no visual field defect in st and ard perimetry ) , 105 patients with " perimetric " open-angle glaucoma ( glaucomatous optic disk atrophy and clearly marked visual field defect ) , and 73 control subjects had FDT screening ( protocol : C-20 - 5 ) and polarimetric measurements ( GDx ) . Criteria for exclusion : optic disks larger than 4 mm(2 ) , media opacities , patients younger than 33 years or older than 66 years . None of the subjects had earlier FDT perimetry . One eye of each patient and control subject entered the statistical evaluation . Data base and statistical software were used for case-wise recalculation of all missed localized probability levels to create a FDT screening score . RESULTS At a predefined specificity of 94.5 % in control eyes , discrimination between " perimetric " glaucoma and normal subjects is superior using the FDT perimetry ( sensitivity = 84.8 % ) in comparison to polarimetry ( sensitivity = 63.8 % ) , whereas sensitivity is similar with both methods in " preperimetric " patients ( GDx , FDT : 25.4 % ) . In several cases , patients classified as glaucomatous by the GDx are not the same patients as identified by the FDT perimetry . Therefore , a two-dimensional discrimination analysis can increase correct positive classification . Using a linear combination of the present FDT screening score and polarimetry ( " the number " ) , 92.4 % of " perimetric " glaucoma eyes and 44.1 % of " preperimetric " glaucoma eyes have been classified as glaucomatous . CONCLUSION Joint usage of polarimetry and FDT perimetry indicate that a combination of different techniques which can uncover different glaucoma properties , might be helpful in early glaucoma detection PURPOSE To assess the ability of Pulsar perimetry ( Pulsar ) in detecting early glaucomatous visual field ( VF ) damage in comparison with Frequency Doubling Technology ( FDT ) , Scanning Laser Polarimetry ( SLP , GDx VCC ) , and Heidelberg Retina Tomography ( HRT ) . DESIGN Prospect i ve observational cross-sectional case study . METHODS This multicenter study included : 87 ocular hypertensives ( OHT ) ; 67 glaucomatous optic neuropathy ( GON ) patients ; 75 primary open-angle glaucoma ( POAG ) patients ; and 90 normals . All patients underwent st and ard automated perimetry ( SAP ) HFA 30 - 2 , Pulsar T30W , FDT N-30 , HRT II , and GDx VCC . Area under Receiver Operating Characteristic Curves ( AROCs ) for discriminating between healthy and glaucomatous eyes and agreement among instruments were determined . RESULTS The best parameters for Pulsar , FDT , HRT , and GDx were , respectively : loss variance square root ; no. of areas with P < 5 % ; Cup-Shape-Measure ; and Nerve Fiber Indicator ( NFI ) . In detecting POAG eyes , Pulsar ( AROC , 0.90 ) appeared comparable with FDT ( 0.89 ) and significantly better than HRT ( 0.82 ) and GDx ( 0.79 ) . For GON , Pulsar ability ( 0.74 ) was higher than GDx ( 0.69 ) and lower than FDT ( 0.80 ) and HRT ( 0.83 ) . The agreement among instruments ranged from 0.12 to 0.56 . Pulsar test duration was significantly shorter than SAP and FDT ( P < .001 ) . CONCLUSIONS Pulsar T30W test is a rapid and easy perimetric method , showing higher sensitivity than SAP in detecting early glaucomatous VF loss . Its diagnostic ability is good for detecting early perimetric POAG eyes and fair for GON eyes . Pulsar performance was comparable with FDT , HRT , and GDx , even if the agreement between instruments was poor to fair PURPOSE To evaluate the sensitivity and specificity of the screening mode of the Humphrey-Welch Allyn frequency-doubling technology ( FDT ) , Octopus tendency-oriented perimetry ( TOP ) , and the Humphrey Swedish Interactive Threshold Algorithm (SITA)-fast ( HSF ) in patients with glaucoma . DESIGN A comparative consecutive case series . METHODS This was a prospect i ve study which took place in the glaucoma unit of an academic department of ophthalmology . One eye of 70 consecutive glaucoma patients and 28 age-matched normal subjects was studied . Eyes were examined with the program C-20 of FDT , G1-TOP , and 24 - 2 HSF in one visit and in r and om order . The gold st and ard for glaucoma was presence of a typical glaucomatous optic disk appearance on stereoscopic examination , which was judged by a glaucoma expert . The sensitivity and specificity , positive and negative predictive value , and receiver operating characteristic ( ROC ) curves of two algorithms for the FDT screening test , two algorithms for TOP , and three algorithms for HSF , as defined before the start of this study , were evaluated . The time required for each test was also analyzed . RESULTS Values for area under the ROC curve ranged from 82.5%-93.9 % . The largest area ( 93.9 % ) under the ROC curve was obtained with the FDT criteria , defining abnormality as presence of at least one abnormal location . Mean test time was 1.08 + /- 0.28 minutes , 2.31 + /- 0.28 minutes , and 4.14 + /- 0.57 minutes for the FDT , TOP , and HSF , respectively . The difference in testing time was statistically significant ( P < .0001 ) . CONCLUSIONS The C-20 FDT , G1-TOP , and 24 - 2 HSF appear to be useful tools to diagnose glaucoma . The test C-20 FDT and G1-TOP take approximately 1/4 and 1/2 of the time taken by 24 to 2 HSF Purpose To compare the ability of frequency-doubling technology ( FDT ) , rarebit perimetry ( RBP ) , and pulsar perimetry ( PP ) in detecting early glaucomatous functional damage . Methods This prospect i ve observational cross-sectional case study included 52 patients with early primary open-angle glaucoma ( mean deviation −2.3±1.1 dB ; pattern st and ard deviation 3.0±1.2 dB ) and 53 healthy controls . Visual field ( VF ) testing included st and ard automated perimetry ( SAP ) Humphrey Field Analyzer 30–2 , FDT N-30 , RBP ( version 4.0 ) , and PP T30W . One eye per patient was considered . Sensitivity at fixed specificities and area under the receiver operating characteristic curve ( AROC ) for discriminating between healthy and glaucomatous eyes were calculated and compared . Results The parameters associated with the largest AROC , which were not statistically different ( Hanley – McNeil method , P0.42–0.71 ) were as follows : number of locations in the pattern deviation probability ( PDP ) plot with P<5 % for FDT ( 0.93 ) ; mean hit rate for RBP ( 0.95 ) ; and mean defect for PP ( 0.94 ) . PP test duration was significantly shorter than FDT and RBP ( P<0.002 ) . Conclusions FDT , PP , and RBP are useful non-conventional VF methods in detecting early glaucomatous VF defects with similar AROCs . The methods were rapid and easy , and PP took less than half the time than SAP . These non-conventional testing may prove to be useful in providing additional information in the diagnosis of glaucoma suspect with normal SAP results , in the therapeutic decision-making process of early glaucomatous patients , and in subjects unable to perform VF testing with SAP PURPOSE To evaluate the clinical use of a test battery of short-wavelength automated perimetry ( SWAP ) , frequency-doubling technology ( FDT ) perimetry , and pattern-electroretinography ( PERG ) in patients with definite primary open-angle glaucoma ( POAG ) but normal results on st and ard automated perimetry ( SAP ) . STUDY DESIGN Prospect i ve , comparative , observational case series . PARTICIPANTS Thirty-six patients with POAG with st and ard visual field defects in one eye and normal st and ard visual fields in the contralateral eye and 36 normal controls were enrolled . MAIN OUTCOME MEASURES SWAP , PERG , FDT , and SAP were performed in all eyes , and global indices and amplitudes were used for statistical analysis . RESULTS When contralateral POAG eyes with asymmetric glaucomatous damage was compared , a paired t test showed significant differences in SAP mean deviation ( MD ) ( P < 0.0001 ) , SWAP-MD ( P = 0.0003 ) , FDT-MD ( P = 0.0008 ) , and PERG amplitudes ( P < 0.0001 ) . When comparing between POAG eyes with normal results on SAP and normal controls , Student 's t test showed significant differences for SWAP-MD ( P < 0.0001 ) , FDT-MD ( P = 0.0006 ) , PERG N1P1-amplitude ( P = 0.0486 ) and P1N2-amplitude ( P < 0.0001 ) ; receiver operating characteristic analysis revealed promising accuracy for SWAP-MD of 73.6 % ( P < 0.0001 ) . SWAP-MD ( P < 0.0001 ) and FDT-MD ( P < 0.0001 ) correlated significantly with SAP-MD and with each other ( range , P < 0.0001 to P = 0.0020 ) . Regression analysis revealed that PERG P1N2-amplitude could improve the power of SWAP-MD from 73.6 % to detect early POAG in eyes with normal results on SAP to an accuracy of 81.9 % . CONCLUSIONS A test battery of SWAP-MD and PERG P1N2-amplitude could detect glaucomatous optic neuropathy in POAG eyes with normal st and ard visual fields , whereas FDT-MD and SWAP-MD significantly correlated with each other and with SAP-MD . All tests were able to detect the eye with the more severe glaucomatous optic neuropathy in patients with asymmetric POAG ABSTRACT Purpose : To assess methods used for glaucoma screening in the Student Sight Savers Program ( SSSP ) , an initiative of the Friends of the Congressional Glaucoma Caucus Foundation that has screened individuals for glaucoma in the United States since 2001 . Methods : This was a prospect i ve , case-control , clinic-based study ( total N = 70 ) . Patients with primary open-angle glaucoma and age- and sex-matched controls with no evidence of glaucoma or other ocular disease were evaluated with the SSSP screening method . Primary outcome measures were sensitivity , specificity , and positive predictive power for both low- and high-prevalence population s. Results : Sensitivity and specificity values of the individual tests were 48.6 % and 68.6 % for family history of glaucoma , 22.1 % and 78.6 % for intraocular pressure ( IOP ) , and 58.1 % and 98.6 % for frequency doubling technology ( FDT ) visual field ( P = 0.03 , chi-square ) . Specificity of FDT was significantly better than IOP ( P < 0.001 ) and the question naire ( P < 0.01 ) by z-test . When analyzing the overall screening criteria ( positive screen was ≥ 1 positive in the three tests ) , the sensitivity increased to 88.6 % with reduction in specificity to 57.1 % . The positive predictive power ( PPP ) for high-prevalence population was low for the overall screening criteria ( 15.4 % ) and highest for FDT as an individual ( 34.0 % ) or combined ( 41.0 % to 45.3 % ) test . The medical student education and community awareness aspects of the program were not assessed . Conclusions : Of different methods used in the SSSP , FDT was the best single screening test , demonstrating high specificity but only moderate sensitivity . Use of multiple screening criteria result ed in slightly increased sensitivity and PPP over FDT , but decreased specificity PURPOSE To compare the ability of short-wavelength automated perimetry ( SWAP ) and frequency doubling perimetry ( FDP ) to detect early glaucoma damage . DESIGN Prospect i ve case-control study using a comparative case series . PARTICIPANTS Forty-two patients with preperimetric glaucomatous optic nerve damage and a normal st and ard achromatic perimetry ( SAP ) in 1 eye , but with contralateral SAP abnormalities , and 35 normals . METHODS Forty-two patients and 35 normals underwent SWAP and FDP ( Humphrey 24 - 2 ; Carl Zeiss Meditec , Inc. , Dublin , CA ) . Correlations of mean deviation ( MD ) and pattern st and ard deviation ( PSD ) of the 2 groups were calculated . The number of defects at P<0.05 and P<0.01 on total deviation ( TD ) and pattern deviation ( PD ) plots were compared . Diagnostic precision and agreement on location of abnormalities were determined . MAIN OUTCOME MEASURES Correlations and comparisons of global indices between SWAP and FDP : MD , PSD , TD , and PD abnormal number of points . RESULTS Significant correlations in the glaucoma group were found between SWAP and FDP for MD ( r = 0.54 ; P<0.008 ) and PSD ( r = 0.49 ; P<0.001 ) . Defects on the TD and PD plots were detected more frequently by FDP in the glaucoma group , although they were significant only for PD at P<0.01 ( P = 0.024 ) . Areas under receiver operator characteristic curves for MD of SWAP and PSD of FDP were 0.74 and 0.67 , respectively ( P = 0.37 ) . Using defined defect criteria , FDP had a significantly higher sensitivity ( 72 % vs. 54 % ; P = 0.02 ) and similar specificity ( 53 % vs. 44 % ; P = 0.12 ) compared with SWAP . Agreement on defect location was moderate ( kappa , 0.46 ) . Testing time for SWAP was longer than for FDP in both glaucomatous and normal eyes ( P<0.001 ) . CONCLUSIONS Short-wavelength automated perimetry and FDP showed similar ability to detect visual dysfunction in patients with preperimetric glaucoma . Long-term follow-up is required to define their role in predicting subsequent SAP defects Aim : To evaluate the performance of the frequency doubling technology ( FDT ) 24 - 2 - 5 screening test by comparison with the established N-30 - 5 FDT screening test for detection of glaucoma . Method : A prospect i ve r and om sample of individuals referred for possible glaucoma were tested with FDT screening tests 24 - 2 - 5 and N-30 - 5 using the Humphrey Matrix perimeter in addition to st and ard clinical examination relevant to glaucoma detection . Discriminatory power , reliability and test time of these tests were assessed and compared . The case definition for glaucoma was made by patient according to the established clinical diagnosis . Results : Of 63 referred eligible individuals , 53 ( 84 % ) were recruited . Sensitivity and specificity for the N-30 - 5 screening test was 78 and 85 % respectively , compared with 83 % and 75 % for the 24 - 2 - 5 with areas under a receiver operator characteristic curve being 0.87 and 0.92 . Differences between these indices were not statistically significant . For a specificity of 95 % , sensitivity values were 76 % and 56 % for the 24 - 2 - 5 and N-30 - 5 respectively . Mean ( st and ard deviation ) test duration for the FDT 24 - 2 - 5 and N-30 - 5 screening tests were 111 ( 13 ) and 39 ( 10 ) seconds respectively ( p<0.001 ) . A total of 19 subjects ( 36 % ) produced unreliable test results in one or both eyes when tested with the 24 - 2 - 5 screening test compared with 5 subjects ( 9 % ) with the N-30 - 5 ( p<0.0005 ) . Conclusion : Minimal discriminatory power differences existed between the two screening tests evaluated , with both screening tests exhibiting high discriminatory power for detection of individuals with glaucoma . More individuals produced unreliable results on the 24 - 2 - 5 screening , which also took longer to perform PURPOSE To determine the accuracy of glaucoma detection by frequency-doubling perimetry . METHODS Stereoview optic nerve photographs , visual field examination , intraocular pressure measurements , medical and ocular history , and a screening and full threshold frequency-doubling perimetry examination were performed in a prospect i ve study of consecutive subjects . Inclusion criteria included age of 45 years or older , absence of ocular disease other than glaucoma , cataract , or mild drusen , and Snellen visual acuity of 20/60 or better . A total of 125 eyes in 102 glaucoma subjects and 95 eyes of 95 normal subjects were included . Each eye was classified as " normal , " " glaucoma , " or " uncertain " by each of three ophthalmologists on the basis of all available clinical information with the exception of frequency-doubling perimetry results . Those in the glaucoma group were subclassified as having early ( n = 51 ) , moderate ( n = 42 ) , or severe ( n = 32 ) glaucoma on the basis of automated Humphrey visual field criteria . In the glaucoma group , two eyes from a subject were allowed to be included ( 23 of 102 subjects ) if they differed in level of damage because they were never analyzed within the same statistical analysis . RESULTS Several diagnostic algorithms were evaluated . Algorithms based on the most depressed single point , pair of adjacent points , and cluster of three points performed nearly identically . For the screening test , if any abnormality was identified , specificity was 95 % , whereas sensitivity was 39 % , 86 % , and 100 % for early , moderate , and severe glaucoma , respectively . For the full threshold test , with at least one point depressed to the P < 0.5 % level , specificity measured 91 % , whereas sensitivity was 35 % , 88 % , and 100 % for early , moderate , and severe glaucoma , respectively . The two global indices , mean deviation and pattern st and ard deviation , were also evaluated and were generally less accurate . CONCLUSION Frequency-doubling perimetry , which is rapid and easily administered , is effective at detecting moderate and severe disease and appears well suited for glaucoma screening PURPOSE To evaluate visual function with a novel multichannel functional test named the ATD Multichannel Functional Test . METHODS This multicenter study had a prospect i ve and cross-sectional design . A total of 186 eyes were included : 42 with glaucoma , 14 glaucoma suspects due to optic nerve characteristics , 25 ocular hypertensives , and 105 normal eyes . All patients performed st and ard visual fields ( Humphrey 24 - 2 ) and ATD with eight stimuli configurations : four achromatic ( A ) , two red-green ( T ) , and two blue-yellow ( D ) . To derive main outcome measures , mean sensitivity , mean defect ( MD ) , and pattern st and ard deviation ( PSD ) were calculated and compared among groups and types of stimuli with the Kruskal-Wallis test . The percentage of cases outside normal limits ( ONL ) was calculated . RESULTS MD and PSD were significantly different in glaucoma eyes than in normal subjects for all types of stimuli except D-0.5 cycles per degree (cpd)/12Hz . PSD was also lower for normals than for all pathologic groups with A-4cpd/2Hz , A-4cpd/12Hz , D-0.5cpd/2Hz , and T-0.5cpd/2Hz . The highest percentage of ONL cases was obtained with the two low-spatial-frequency chromatic stimuli , with D-0.5cpd/2Hz and T-0.5cpd/2Hz using PSD , which classified as ONL 81.6 % and 86.7 % of glaucoma eyes , 51.8 % and 44.5 % of hypertensives , and 72.2 % and 41.2 % of optic disc suspects , respectively . CONCLUSIONS ATD assessed different aspects of visual function , and the most sensitive tests to detect glaucomatous damage were the low-temporal-frequency chromatic tests Purpose To evaluate the usefulness of non-mydriatic fundus camera ( NMFu-camera ) and frequency doubling perimeter ( FDP ) for detecting glaucoma in a general population . Methods This prospect i ve observational multicenter study consisted in screening for glaucoma in the population s of three Belgian cities . Intraocular pressure ( IOP ) was measured with non-contact pneumo-tonometer ( NCT ) and applanation tonometry ( AT ) if NCT IOP was ≥17 mmHg . Visual field was screened with FDP ( C-20 - 5 ) and digitized optic disc photographs ( ODPs ) were taken with NMFu-camera . FDP was considered abnormal if at least one defective point was found . ODPs were grade d as normal or glaucomatous by consensus of three glaucoma specialists . Optic disc and visual field results were matched per eye . Subjects with known ocular hypertension and /or treated primary open angle glaucoma were excluded from the analysis . Results A total of 1620 subjects were included in the study . Their mean age was 63.2 years . AT IOP was > 21 mmHg in 8.2 % . A total of 98.1 % of ODPs could be interpreted . Glaucomatous optic discs were detected in 3.5 % of the subjects . In this group only 24 % had an AT IOP ≥22 mmHg . FDP was abnormal in 44.5 % . The sensitivity and specificity of FDP to identify patients with an optic disc grade d as glaucomatous were 58.6 % and 64.3 % respectively . Conclusions The combined use of the NMFu-camera and the FDP is a feasible method for an initial glaucoma mass screening . NMFu-camera may be a useful and quick method to screen for glaucomatous damage in a community . FDP in screening strategy was revealed to be not sensitive enough when setting the cut-off value at one defective test location . IOP measurements were confirmed to be a poor tool to detect glaucomatous damage PURPOSE To compare second generation frequency-doubling perimetry ( FDP ) with st and ard automated perimetry ( SAP ) to detect glaucomatous visual field abnormalities . DESIGN Prospect i ve , cross-sectional , controlled observational study . METHODS Fifty eyes of 50 patients with glaucoma with confirmed SAP visual field abnormalities and 42 eyes from 42 normal control subjects were studied . Swedish Interactive Thresholding Algorithm ( SITA ) st and ard 24 - 2 SAP and FDP visual fields were performed . The correlation of global indices and the number of defects on total deviation ( TD ) and pattern deviation ( PD ) plots were compared . The spatial concordance of FDP and SAP defect locations was determined . RESULTS In patients with glaucoma , significant correlations of mean deviation ( MD ) and pattern st and ard deviation ( PSD ) were found between SAP and FDP ( P < .001 for MD and P < .001 for PSD ) , but not in the normal group . FDP had significantly greater defect scores than SAP on total deviation and PD plots in the glaucoma group ( P = .028 and P = .01 , respectively ) . In comparison with SAP , sensitivity and specificity of FDP were 92 % and 98 % with glaucoma hemifield test criteria and 98 % and 93 % with PSD < 5 % criteria , respectively . Similarly high diagnostic precision was found with MD and PSD ( at 95 % specificity ; MD and PSD sensitivity was 82 % and 90 % , respectively ) . The location of defects within 12 hemifield clusters found with FDP agreed moderately well with those detected with SAP ( kappa = .48 ) . CONCLUSIONS FDP and SAP perform similarly in their ability to detect visual field defects in early to moderate glaucoma . Larger and deeper defects detected with FDP suggests the possibility of earlier detection at high specificity Purpose To develop a diagnostic setup with classification rules for combined analysis of morphology [ Heidelberg Retina Tomograph ( HRT ) ] and function [ frequency doubling technology ( FDT ) perimetry ] measurements . Methods We used 2 independent case-control studies from the Erlangen eye department as learning and test data for automated classification using r and om forests . One eye of 334 open angle glaucoma patients and 254 controls entered the study . All individuals underwent HRT scanning tomography of the optic disc , FDT screening , conventional perimetry , and evaluation of fundus photographs . R and om forests were learned on individuals of the Erlangen glaucoma registry ( 102 preperimetric patients , 130 perimetric patients , 161 controls ) . The classification performances of r and om forests and built-in classifiers were examined by receiver operator characteristic analysis on an independent second cohort of individuals ( 47 preperimetric patients , 55 perimetric patients , 93 controls ) . Results HRT measurements had a higher diagnostic power for early glaucomas and FDT perimetry for glaucoma patients with visual field loss . A combination of all parameters using automated classification was superior to single tests in comparison to the diagnostic instrument with the higher diagnostic power in the respective group . Highest sensitivities at a fixed specificity ( 95 % ) in the patients of the present test population were : HRT=32 % , FDT=19 % , combined analysis = 47 % in preperimetric patients and HRT=76 % , FDT=89 % , combined analysis = 96 % in perimetric patients . Conclusions The feasibility of machine learning for medical diagnostic assistance could be demonstrated in patients from 2 independent study population s. A predictive model using automated classification is able to combine the advantages of morphology and function , result ing in a higher diagnostic power for glaucoma detection PURPOSE To evaluate the sensitivity and specificity of the screening modes of frequency-doubling technology ( FDT ) , tendency-oriented perimetry ( TOP ) , SITA St and ard ( SS ) and SITA Fast ( SF ) in perimetrically inexperienced individuals . METHODS One eye of 64 glaucoma patients and 53 normal subjects who had never undergone automated perimetry were tested with programs C-20 - 5 ( FDT ) , G1 ( TOP ) and 24 - 2 ( SS and SF ) . The gold st and ard for glaucoma was the presence of a typical glaucomatous optic disc appearance on stereoscopic examination ( judged by a glaucoma expert ) , and intraocular pressure ( IOP ) > 21 mmHg . The test order among strategies was r and omized for each subject . To define an abnormal visual field , we applied three criteria for SS and SF and two criteria for TOP and FDT , all of which have been previously described in the literature . Sensitivities and specificities among the different criteria were compared using the Cochran test . RESULTS Frequency-doubling technology showed the shortest mean test duration , followed by TOP , SF and SS ( p < 0.05 ) . Sensitivity ranges were 87.5 - 89.1 % for SS , 92.2 - 93.8 % for SF , 87.5 - 89.1 % for TOP , and 82.8 - 85.9 % for FDT ( p = 0.34 ) . Specificity ranges were 73.6 - 83 % for FDT , 56.6 - 62.3 % for TOP , 60.4 - 69.8 % for SF and 66.0 - 71.7 % for SS . The specificity obtained with criterion 2 for FDT ( based on the presence of two or more abnormal locations regardless of the severity of abnormal points ) was higher than those measured with the other strategies ( p < 0.01 ) . CONCLUSION When testing individuals with no perimetric experience , moderate sensitivities and specificities should be expected , regardless of the strategy chosen |
14,075 | 28,385,441 | These articles provided evidence that a mean complication rate was impossible to determine because of the multiplicity of contributing factors .
No clear identification of the causes of mechanical complications was found , nor was there any clear evidence of superiority of one implant and /or attachment design over another .
Prosthetic complications with IODs are unavoidable .
However , they can be reduced to an expected level if a close follow‐up protocol is implemented aim ing at anticipating risks of unexpected complications . | Different factors can affect prosthetic maintenance requirements for m and ibular implant overdentures ( IODs ) .
However , the literature shows a high level of disagreement concerning the effect of each factor on maintenance needs .
The purpose of this systematic review was to address the focus question : “ In the clinical studies published since 2004 of adult patients with totally edentulous m and ibles treated by IODs with a variable number of implants and different design s , what were the maintenance types , frequencies , and complications ? ” | PURPOSE This r and omized clinical trial tested hypotheses that there are no differences in patient satisfaction , component costs , or treatment and maintenance times when m and ibular overdentures are retained by one or two implants . MATERIAL S AND METHODS Subjects wearing conventional complete dentures were r and omized to receive either one midline or two bilateral m and ibular implants followed by a m and ibular denture reline to incorporate implant retention . They indicated on a visual analog scale satisfaction with their dentures before implants and at 2 months and 1 year after implant retention . Satisfaction outcomes between the two groups were compared using the Wilcoxon/Mann-Whitney nonparametric rank test , while changes within each group were analyzed using signed-rank tests . Component costs and times for surgery , prosthodontic treatment , and maintenance were compared using nonparametric and t tests . RESULTS Eighty-six subjects enrolled in this study and 85 completed the 1-year follow-up , at which median satisfaction was 93 ( maximum 100 ) in the single-implant group and 94 in the two-implant group ( P > .5 ) . Within each group , median improvement in satisfaction was similarly dramatic ( approximately 44 ) and significant ( P < .001 ) . Prosthodontic maintenance time was similar for both groups ( P > .37 ) , but the single-implant group had significantly lower component costs ( P < .001 ) and lower times for surgery ( P = .002 ) , postsurgical denture maintenance ( P = .021 ) , and denture reline ( P < .001 ) . Five implants failed in four subjects , all in the two-implant group and all before denture reline . CONCLUSION Lower component costs and treatment times , with comparable satisfaction and maintenance time over the first year , indicate that a m and ibular overdenture retained by a single midline implant may be an alternative to the customary two-implant overdenture for maladaptive denture patients The hypothesis of this 5-y r and omized clinical trial was that there would be no significant difference in the satisfaction of edentulous participants with removable complete overdentures attached to 1 or 2 m and ibular implants . Secondary aims were to test changes in satisfaction between and within the groups from baseline to 5 y and differences between the groups in implant survival and prosthodontic maintenance over 5 y. Each of the 86 participants ( mean age , 67 y ) was r and omly allocated to receive either 1 implant in the midline ( group 1 ) or 2 implants in the canine areas ( group 2 ) attached to a m and ibular overdenture opposing a maxillary complete denture . Satisfaction was self-assessed by participants on a visual analog scale at baseline prior to implants , as well as at 2 mo and 1 , 3 , and 5 y with implant overdentures , whereas implant survival and prosthodontic maintenance were assessed by clinical examination . After 5 y , 29 participants in group 1 and 33 in group 2 were available , with most dropouts due to death . Satisfaction with the implant denture after 5 y was significantly ( P < 0.001 ) higher than at baseline in both groups and remained with no significant difference ( P = 0.32 ) between the groups . No implants failed in group 1 but 5 failed before loading in 4 participants in group 2 . Most participants required maintenance or occasionally denture replacement , and although differences between the groups were not statistically significant , group 1 experienced almost twice as many fractured dentures usually adjacent to the implant attachment . We conclude that there were no significant differences after 5 y in satisfaction or survival of implants with m and ibular overdentures retained by 1 implant or 2 implants . Additional research is required to confirm long-term treatment effectiveness of single-implant dentures and the implication s of prosthetic maintenance with implant overdentures ( Clinical Trials.gov : NCT02117856 ) PURPOSE The aim of this systematic review is to address treatment outcomes of M and ibular implant overdentures relative to implant survival rate , maintenance and complications , and patient satisfaction . MATERIAL S AND METHODS A systematic literature search was conducted by a PubMed search strategy and h and - search ing of relevant journals from included studies . R and omized Clinical Trials ( RCT ) and comparative clinical trial studies on m and ibular implant overdentures until August , 2010 were selected . Eleven studies from 1098 studies were finally selected and data were analyzed relative to number of implants . RESULTS Six studies presented the data of the implant survival rate which ranged from 95 % to 100 % for 2 and 4 implant group and from 81.8 % to 96.1 % for 1 and 2 implant group . One study , which statistically compared implant survival rate showed no significant differences relative to the number of implants . The most common type of prosthetic maintenance and complications were replacement or reattaching of loose clips for 2 and 4 implant group , and denture repair due to the fracture around an implant for 1 and 2 implant groups . Most studies showed no significant differences in the rate of prosthetic maintenance and complication , and patient satisfaction regardless the number of implants . CONCLUSION The implant survival rate of m and ibular overdentures is high regardless of the number of implants . Denture maintenance is likely not inflenced substantially by the number of implants and patient satisfaction is typically high again regardless os the number of implants PURPOSE The purpose of this study was to determine the prosthodontic outcomes of one-piece zirconia implants and their attachment systems in edentulous participants with maxillary and m and ibular overdentures after 1 year of a r and omized controlled trial . MATERIAL S AND METHODS R and om allocation of 24 edentulous participants ( age range : 45 to 86 years ) into titanium ( control ) or zirconia ( test ) groups using onepiece implants and a planned unsplinted prosthodontic design was performed . Four maxillary implants ( one midpalatal ; three anterior crestal ) and three m and ibular implants ( one midsymphyseal ; two bilateral distal ) were conventionally loaded with the overdentures . Similar attachment systems were used throughout : ball abutment-type patrices ( diameter : 2.25 to 3.1 mm as part of the one-piece implants ) and custommade plastic matrices ( with or without metal housings depending on the patrix size ) . Prosthodontic outcomes were documented during the first year of the clinical trial . RESULTS Following three deaths and two dropouts , there were 19 participants who were available at the 1-year recall . Of these participants , 3 had early maxillary implant failure and had to be converted to conventional maxillary complete dentures opposing m and ibular implant overdentures . There were 79 maintenance events , 34 in the titanium ( control ) group and 45 in the zirconia ( test ) group . Patrix loss occurred as a result of three zirconia implant fractures ( one m and ibular and two crestal maxillary implants ) . Maintenance events were principally the replacement of matrices and overdenture fracture . Although relines and replacement overdentures also occurred , overall there were no significant differences in prosthodontic maintenance between the control and test groups . A six-field prosthodontic-success analysis table showed no statistically significant difference between the two groups ; however , 50 % of participants in each group were allocated to the retreatment ( repair ) field , which produced a low prosthodontic success rate . CONCLUSIONS Removable overdentures can be used on both one-piece titanium and zirconia implants with these attachment systems , due to no difference in prosthodontic maintenance and success . Before recommending routine use of a " metal-free " overdenture treatment option in clinical practice , consideration must be given to the success of the implants themselves OBJECTIVE The aim of this long-term study was to compare the need for prosthetic aftercare of direct vs. indirect attachment incorporation techniques to m and ibular implant-supported overdenture . MATERIAL S AND METHODS Forty-five consecutive patients were included ( 130 implants were placed ) . Treatment was r and omly allocated , result ing in 22 patients ( group A ) to be treated with direct ball attachment incorporation and 23 patients ( group B ) to be treated with indirect ball attachment incorporation . All patients were treated by experienced oral-maxillofacial surgeons/periodontists and experienced prosthodontists/residents . From the first day that the patients visited the clinic up to 20 years after the first treatment session , all surgical or prosthetic therapeutic interventions were recorded . The recorded data for the present study included the number of aftercare visits and dental treatment received ( pressure sores relieve , liner changes due to loss of retention and attachment replacement due to wear ) . RESULTS The mean follow-up was 93±57 months . No implants were lost . Statistical analysis revealed a statistically significantly ( P<0.001 ) greater need for prosthetic interventions in group B vs. group A. The mean number of visits dedicated to - pressure sores relieve ( 7.04±1.4 vs. 3.63±0.84 ) ; liner exchange due to loss of retention ( 3.6±1.3 vs. 1.09±1.06 ) was significantly higher in group B. Attachment replacement due to wear occurred only in group B ( 11/23 - 47.8 % ) . CONCLUSION The direct technique for attachment incorporation in m and ibular implant-supported overdentures using ball attachments is superior to the indirect technique from the aftercare perspective during a long-term evaluation period The CONSORT ( Consoli date d St and ards of Reporting Trials ) statement is used worldwide to improve the reporting of r and omized , controlled trials . Schulz and colleagues describe the latest version , CONSORT 2010 , which up date s the reporting guideline based on new method ological evidence and accumulating experience . PURPOSE The present study evaluated implant and peri-implant outcomes as well as prosthodontic maintenance efforts for implant/bar-supported m and ibular prostheses with different prosthesis anchorage systems . MATERIAL S AND METHODS Seventy-six patients who received two or four interforaminal implants were assigned to one of three different bar design s and subsequently to different prosthesis supporting systems . Forty-nine patients received implants and a mucosa-supported implant-retained overdenture ( OD ) with an ovoid bar ( two implants ; design 1 ) or multiple ovoid bars ( four implants ; design 2 ) . Twenty-seven patients received four implants and a rigid implant-supported prosthesis ( ISP ) with a milled bar ( design 3 ) . Implant survival , peri-implant parameters ( marginal bone resorption , pocket depth , and plaque , bleeding , gingival , and calculus indices ) , and postinsertion prosthodontic maintenance were followed over a 5-year period and compared among the different retention modalities . At the most recent follow-up examination , subjective patient satisfaction was additionally evaluated using a simplified scoring system ( ranging from 1 = not satisfactory to 5 = excellent ) . RESULTS Implant survival rates ( 100 % ) and all peri-implant parameters evaluated showed no differences among the three design s used for implant prosthesis anchorage . Prosthodontic maintenance did not differ between the different ODs ( OD design 1 : average of 1.04 maintenance visits/year/patient ; OD design 2 : 1.2 maintenance visits/year/patient ) , but it was significantly lower for the dentures that were rigidly stabilized with milled bars ( ISP : 0.37 maintenance visits/year/patient ) . A high subjective satisfaction rate ( range : 4.5 to 5.0 ) was registered at the final examination , without any differences among the design s used . CONCLUSIONS Rigid anchorage with milled bars on four-implant prostheses combined with a metal-reinforced framework showed a lower extent of prosthodontic maintenance issues than round bars on two- or four-implant overdentures with resilient denture stabilization . Nevertheless , implants and peri-implant structures were not negatively affected by either resilient or rigid anchorage mechanisms Prosthetic outcome and patient satisfaction were evaluated in order to investigate whether there is a need or advantage to splint two implants in the m and ible retaining a hinging overdenture . This study included 36 fully edentulous patients r and omly divided into three groups according to the attachment system they received : magnets , ball attachments or straight bars ( reference group ) . None of the implants failed during the whole observation period in any of the groups . After 5 years of observation , the Bar group presented the highest retention capacity and the least prosthetic complications but revealed more mucositis and gingival hyperplasia . Patient satisfaction rated similar for all groups although the Magnet group showed lower retention forces . All patients would repeat the same treatment even though the majority of the Magnet group would prefer a more retentive solution because of limited denture stability PURPOSE Few long-term studies on overdentures report both implant and prosthodontic outcomes . The aim of this prospect i ve study was to report long-term prosthodontic- and implant-related treatment outcomes of patients treated with design -specific implant-supported overdentures . MATERIAL S AND METHODS Between 1982 and 1992 , 45 consecutively treated patients received a total of 47 overdentures ( 42 m and ibular and 5 maxillary ) supported by Brånemark implants . Prospect i ve clinical and radiographic data were collected over the observation period ; this study presents the most recent treatment outcomes . RESULTS Thirty patients ( mean age 70 years ) with 32 prostheses attended the final recall visit , with 67 % of patients followed for 15.53 years ( range 10 to 19 years ) . Six implants failed , and the prosthetic plan and implant cumulative survival rates were both in excess of 90 % . Mean marginal bone loss around implants after the first year of loading was small ( 0.05 mm/year ) , although the individual variation was high . Linear regression analysis of bone loss indicated that gender , bicortical stabilization , bone quality , and healing time were predictors of bone loss for the first year of loading but not for the ensuing years . Prosthetic maintenance included fractured components , denture relining , and replacement of prostheses . On average , the longevity of overdenture prostheses was 12 years , and laboratory relining was necessary every 4 years . CONCLUSION This study confirmed the long-term outcome success of patients treated with design -specific overdenture prostheses supported by Brånemark implants . However , prosthetic maintenance was required , a fact that should be discussed with patients prior to treatment PURPOSE This study aim ed to compare the prosthetic aspects and patient satisfaction with prosthetic care in two-implant-retained m and ibular overdentures , whether implants were splinted with a bar or left with magnets or ball attachments . MATERIAL S AND METHODS Thirty-six completely edentulous patients had two Brånemark implants placed in the m and ibular canine area . A r and omized procedure allocated patients into three groups of equal size , each with a different attachment system : bars , magnets , or balls . Prosthesis retention and mechanical as well as soft tissue complications were recorded in addition to patient satisfaction . A linear mixed model was fitted with attachment type and time as classification variables and adjusted by Turkey 's multiple range test . RESULTS Ball-retained overdentures showed at year 10 the greatest vertical retention force ( 1,327 g ) , followed by bars ( 1,067 g ) and magnets ( 219 g ) . In the ball group , need for tightening of abutment screws was the most common mechanical complication ; in the magnet and bar groups , respectively , the most common complications were wear and corrosion , and the need for clip activation . Prosthesis stability and chewing comfort for the overdenture were rated significantly lower for the magnet group compared to the ball and bar groups . Prosthesis stability of the maxillary denture was rated significantly lower in the bar group compared to ball and magnet groups . CONCLUSION The ball group scored best in relation to retention of the overdenture , soft tissue complications , and patient satisfaction at year 10 . The bar group scored lower for comfort and stability of the maxillary denture . Magnets offered patients the least comfort PURPOSE The aim of the present study was to evaluate the prosthodontic maintenance required for m and ibular overdentures supported by 4 implants and splinted with either a round bar and resilient overdenture anchorage or a milled bar with rigid anchorage over a 5-year period . MATERIAL S AND METHODS In a r and omized prospect i ve trial , 51 edentulous patients received 4 m and ibular interforaminal implants to support an overdenture and maxillary complete dentures . For the implant-supported overdentures ( IODs ) , bar architecture and denture stabilization were chosen r and omly ; 25 patients received round bars ( group 1 ) and resilient anchorage and 26 patients received milled bars ( group 2 ) and rigid anchorage . The prosthodontic maintenance required for the IODs and opposing dentures were evaluated during a 5-year follow-up period and compared between the 2 retention modalities used for IODs . RESULTS Forty-six patients ( 22 in group 1 , 24 in group 2 ) were available for a 5-year follow-up ( dropout rate : 9.8 % ) . Prosthodontic maintenance efforts were significantly greater ( P < .01 ) with the round bar design ( group 1 ) than with the overdentures stabilized with milled bars ( group 2 ) . In group 1 , prosthodontic maintenance efforts were more frequent in the early phase of use ( 1 to 2 years ) , as compared with an evenly distributed incidence over the 5-year period with the rigid milled bar system . Major prosthetic complications ( IOD remaking , bar fracture ) were only seen in cases without metal-reinforced frameworks ( group 1 ) . CONCLUSION When 4 interforaminal implants are used to anchor m and ibular overdentures , the design of the anchorage system will significantly affect prosthodontic maintenance efforts and complication rates . Rigid anchorage using milled bars and a metal-reinforced denture framework required less prosthodontic maintenance , ie , for clip activation/fracture , than resilient denture stabilization using multiple round bars without a rigid denture framework PURPOSE The aim of this study was to compare , prospect ively , treatment with implant-retained m and ibular overdentures versus conventional complete dentures . MATERIAL S AND METHODS Part 2 of this paper reports on the outcome after 7 years of denture use , using additional question naires . RESULTS Patients with implant-stabilized overdentures continued to be more satisfied with their m and ibular dentures and their diet than those using conventional complete dentures . About 50 % of the implant group who completed the question naire had had their dentures remade . The other 50 % remained satisfied with their original dentures and were still using them at the 7-year review . The average chairside time spent on them was 467 minutes . CONCLUSIONS M and ibular overdentures with two endosseous implants permit better function than conventional complete dentures PURPOSE The aim of this research was to determine the long-term prosthodontic maintenance requirements of m and ibular two-implant overdentures using different loading protocol s and attachment systems . MATERIAL S AND METHODS A total of 106 participants were allocated r and omly to one of four different implant systems ( Steri-Oss , Southern , Straumann , or Branemark ) . Three different loading protocol s ( 2 , 6 , and 12 weeks ) were used with six different ball abutment patrices and their respective matrices ( Steri-Oss rubber , Straumann gold , Straumann titanium , Branemark gold , Southern plastic , and Southern gold/platinum ) . Prosthodontic maintenance events were documented prospect ively from baseline until the 8-year recall according to predefined categories . RESULTS After 6 years , 90 participants attended recall and , thereafter , 68 participants were followed for 8 years . No significant differences were found between the number of prosthodontic maintenance events and the loading protocol used . Steri-Oss rubber matrices had the highest mean number of maintenance events at 32.2 ± 14.5 events , followed by the Branemark gold matrices at 28.8 ± 12.6 events . The Southern plastic matrices had a significantly lower mean number of maintenance events ( 8.7 ± 4.2 ) when compared with all other groups . Over a 6-year period , the matrices with the best longevity were Straumann gold at 3.9 ± 2.1 years . Straumann gold matrices also lasted significantly longer than all other matrices ( P < .05 ) . Southern gold/platinum , Branemark gold , and Southern plastic matrices all lasted significantly longer than the Straumann titanium and Steri-Oss matrices ( P < .05 ) . The mean time to reline for overdentures was 3.37 ± 2.06 years ; remaking of overdentures peaked by year 7 , with a mean time to remake of 5.81 ± 2.04 years . CONCLUSION Early loading protocol s do not influence long-term prosthodontic maintenance requirements of unsplinted m and ibular two-implant overdentures . By contrast , attachment systems do influence prosthodontic maintenance , particularly with regard to the type of matrices used PURPOSE To determine patient satisfaction and preference for implant-supported m and ibular overdentures ( IOD ) retained with ball or Locator attachments . In addition , peri-implant conditions and prosthodontic maintenance efforts for the final attachments were evaluated after 1 year of function . MATERIAL AND METHODS In this crossover clinical trial , 20 edentulous patients were recruited to receive two m and ibular implants in the canine region and were provided with implant-retained m and ibular overdentures and new complete maxillary dentures . Implant-retained m and ibular overdentures were stabilized with either ball attachments or Locator attachments , in r and om order . After 3 months of function , the attachments in the existing denture were changed . Question naires on satisfaction/complaints with the prostheses were administered at baseline ( with the old dentures ) and after 3 months of function with each attachment , thus providing for an intraindividual comparison . The decision for the final attachment chosen was based on the patient 's preference . For the definitive attachment , peri-implant conditions ( peri-implant marginal bone resorption , pocket depth , and Plaque Index , Gingival Index , and Bleeding Index ) as well as prosthodontic maintenance efforts and satisfaction score were evaluated after an insertion period of 1 year . RESULTS Nineteen ( 95 % ) patients completed the study ( 1 dropout ) . Patient satisfaction improved significantly ( P<.05 ) from baseline ( old dentures ) to the new prostheses retained with each of the two attachment types for all domains of satisfaction . However , there were no differences between ball or Locator attachment for any items of satisfaction evaluated and neither attachment had a significant patient preference . No differences for peri-implant parameters or for patient satisfaction were noted between the definitive attachments ( ball , n=10 ; Locator , n=9 ) after 1 year . Although the overall incidence rate of prosthodontic maintenance did not significantly differ between both retention modalities , the Locator attachment required more postinsertion aftercare ( activation of retention ) than the ball anchors OBJECTIVES The aim of this study was to establish the treatment outcome of full denture treatment with or without implant support , in which the outcome assessment focuses on the patient 's subjective evaluation ( ' denture-satisfaction ' ) . DESIGN A multicenter r and omized clinical trial . SUBJECTS Thirty-two men and 118 women ( mean age 56 + /- 9 , range 35 - 84 years ) participated in the study . The mean height of the m and ible was 13 + /- 2 mm , measured on a lateral cephalometric radiograph . The patients were r and omly assigned to either a group treated with implant-retained m and ibular overdentures and a new maxillary denture , or to a control group treated with a new set of complete dentures . MAIN OUTCOME MEASURES Denture satisfaction was assessed using question naires focusing on denture-related complaints and ' a general satisfaction rate ' . RESULTS Based on the baseline data , from the ' denture complaints ' question naire six interpretable factors could be extracted . One factor did not vary following treatment and was excluded from the outcome analysis . At the 1-year evaluation three out of five factors showed significantly better scores for the group treated with implants than for the control-group . The same was found for the general satisfaction rate . CONCLUSION For patients with a severely resorbed m and ible , overdentures retained by dental implants appear to provide a more satisfactory solution to their denture-related problems The aim of this prospect i ve r and omized controlled clinical trial was to evaluate the clinical outcomes and prosthetic aftercare of edentulous patients with a m and ibular overdenture retained by two IMZ implants or two Brånemark implants during a 10-year period . Patients were allocated to the IMZ group ( n=29 ) or the Brånemark group ( n=32 ) by a computerized balancing method . In the IMZ group , four implants were lost during the 10-year follow-up ( survival rate : 93 % ) . In the Brånemark group , nine implants were lost ( survival rate : 86 % ) . All patients were re-operated successfully . Multiple prosthetic revisions were necessary in both groups ; especially the precision attachment system in the overdenture ( 23 % of the total number of revisions ) and the denture base and teeth ( 26 % of the total number of revisions ) were subject to frequent fracture . From this study , it can be concluded that both the IMZ implant and the Brånemark implant systems supporting an overdenture are functioning well after 10 years of follow-up . There are no indications of a worsening of clinical or radiographical state after 10 years OBJECTIVE The objective is to compare , in a prospect i ve r and omized clinical trial , three types of attachment systems for m and ibular implant overdenture , focusing on costs , maintenance requirements and complications from baseline to the end of 5-year follow-up period . MATERIAL S AND METHODS Sixty-nine fully m and ibular and fully/partially maxillary edentulous patients received two screw-type Straumann implants , in the m and ibular canine region . New overdentures with three types of attachment systems were inserted according to an early-loading protocol : Group B ( balls , divided into Subgroup B.1 - retentive anchor with gold matrix and Subgroup B.2 - retentive anchor with titanium matrix ) ( n = 23 ) , Group M ( magnets ) ( n = 23 ) and Group L ( locator ) ( n = 23 ) . RESULTS The highest maintenance event number ( 195 ) was observed in Group B vs. 31 in Group L and 15 in Group M. Significantly more complications were recorded in Subgroup B.1 than in Subgroup B.2 , Group M and Group L ( P < 0.05 ) . Group M registered the highest prosthetic success ( 82.6 % ) in the 5 years , followed by Group L ( 78.2 % ) . Subgroup B.1 had the lowest success rate ( 50 % ) . The magnet group recorded statistically significant higher costs , comparing with the other two groups ( P < 0.05 ) . CONCLUSIONS The three attachment systems functioned well after 5 years . The magnets had a low maintenance requirement and high success rate , despite the relatively increased initial costs . Retentive anchor with titanium matrix and locator may be a better choice from a financial point of view , taking into consideration the initial low cost of the components and also the reduced number of complications PURPOSE This report aim ed to compare prosthetic aspects and patient satisfaction during a 3-year r and omized clinical trial of bar- and implant-retained m and ibular overdentures attached with either resilient liners or clips . MATERIAL S AND METHODS Thirty edentulous male patients ( mean age : 62.5 years ) received two implants in the anterior m and ible after being allocated into two equal groups ( according to attachment type received ) using balanced r and omization . After 3 months , implants were connected with resilient bars . New maxillary complete dentures were then constructed , and m and ibular overdentures were retained to the bars with either clips ( group I ) or silicone resilient liners ( group II ) . Subjects indicated satisfaction with their prostheses using a question naire and visual analog scale . Patient satisfaction and prosthetic complications were recorded for both attachments at 6 months and 1 and 3 years after overdenture insertion . RESULTS Comfort and stability with the maxillary denture and ease of hygiene procedures were rated higher in group II , while ease of h and ling the dentures was rated higher in group I. No significant differences in other parameters of patient satisfaction between groups were noted after 3 years . The mean number of prosthetic adjustments and repairs in group I ( 11.9 ) was significantly higher ( P = .00 ) compared to that in group II ( 4.8 ) . The most common complication in group I was clip wear , while separation of the resilient liner from the denture base was the most common problem in group II . Hyperplasia under the bar and flabby ridge in the maxilla occurred significantly more often in group I compared to group II . CONCLUSIONS Resilient liner-retained m and ibular overdentures had comparable patient satisfaction , less prosthetic maintenance and costs , and less soft tissue complications when compared to clip-retained ones after 3 years BACKGROUND Documentation of early loading of m and ibular overdentures supported by different implant systems is scarce . PURPOSE This study aim ed to compare the biologic and prosthetic outcome of m and ibular overdentures supported by unsplinted early-loaded one- and two-stage oral implants after 5 years of function . MATERIAL S AND METHODS Twenty-eight consecutive patients were screened following an inclusion and exclusion criteria , and r and omly allocated to treatment groups . Ball-retained m and ibular overdentures were fabricated on two unsplinted Straumann ( Institut Straumann AG , Basel , Switzerl and ) and Brånemark ( Nobel Biocare AB , Göteborg , Sweden ) dental implants and subjected to an early-loading protocol . During the 5-year period , prosthetic complications were recorded . At 5-years of function , plaque , peri-implant inflammation , bleeding , and calculus index scores were recorded , and st and ard periapical radiographs were obtained from each implant for measurement of marginal bone loss . RESULTS All implants survived during the observation period . The peri-implant inflammation , bleeding , and calculus index scores around Straumann and Brånemark implants were similar ( p > .05 ) . The marginal bone loss around Brånemark implants ( 1.21 + /- 0.1 ) was higher than Straumann implants ( 0.73 + /- 0.06 ) at 5 years of function ( p = .002 ) . Kaplan-Meier tests revealed that 1- and 5-year survival of overdentures on Straumann and Brånemark implants were similar ( p = .85 ) . Wear of the ball abutment in the Brånemark group was higher than in the Straumann group ( p < .05 ) . Complications regarding the retainer and the need for occlusal adjustments were higher in the Straumann group ( p < .05 ) . Chi-square test revealed that the frequency of retightening of the retainer was higher in the Straumann group than in the Brånemark group ( p < .05 ) . CONCLUSIONS M and ibular overdentures supported by unsplinted early-loaded Straumann and Brånemark implants lead to similar peri-implant soft tissue and prosthetic outcomes , although higher marginal bone loss could be observed around Brånemark implants after 5 years BACKGROUND There is evidence for the superiority of two-implant overdentures over complete dentures in the m and ible . Various anchorage devices were used to provide stability to overdentures . The aim of the present study was to compare two design s of a rigid bar connecting two m and ibular implants . MATERIAL S AND METHODS Completely edentulous patients received a new denture in the maxilla and an implant-supported overdenture in the m and ible . They were r and omly allocated to two groups ( A or B ) with regard to the bar design . A st and ard U-shaped bar ( Dolder bar ) was used connecting the two implants in a straight line . For comparison , precision attachments were soldered distal to the bar copings . Group A started the study with the st and ard bar ( S-bar ) , while group B started with the attachment-bar ( A-bar ) . After 3 months , they had to answer a question naire ( visual analogue scale [ VAS ] ) ; then the bar design was changed in both groups . After a period of another 3 months , the patients had to answer the same questions ; then they had the choice to keep their preferred bar . Now the study period was extended to another year of observation , and the patients answered again the same question naire . In vivo force measurements were carried out with both bar types at the end of the test periods . The prosthetic maintenance service carried out during the 6-month period was recorded for both bar types in both groups . Statistical analysis as performed with the SPSS statistical package ( SPSS Inc. , Chicago , IL , USA ) . RESULTS Satisfaction was high in both groups . Group B , who had entered the study with the attachment bar , gave slightly better ratings to this type for four items , while in group A , no differences were found . At the end of the 6-month comparison period , all but one patient wished to continue to wear the attachment bar . Prosthetic service was equal in groups A and B , but the total number of interventions is significantly higher in the attachment bar . Force patterns of maximum biting were similar in both bar design s , but exhibited significantly higher axial forces in the attachment bar . CONCLUSIONS Both bar design s provide good retention and functional comfort . High stability appears to be an important factor for the patients ' satisfaction and oral comfort . Rigid retention results in a higher force impact and appears to evoke the need for the retightening of occlusal screws , result ing in more maintenance service |
14,076 | 20,464,765 | The trials assessing the impact on errors found that caffeine significantly reduced the number of errors compared to placebo .
Based on the current evidence , there is no reason for healthy individuals who already use caffeine within recommended levels to improve their alertness to stop doing so . | BACKGROUND Sleepiness leads to a deterioration in performance and attention , and is associated with an increased risk of injury .
Jet lag and shift work disorder are circadian rhythm sleep disorders which result in sleepiness and can elevate injury risk .
They create a need for individuals to operate at times which are different to those dictated by their circadian rhythms .
Consequently there is also a need for interventions to help ensure that these persons can do so safely .
Caffeine has a potential role in promoting alertness during times of desired wakefulness in persons with jet lag or shift work disorder , however its effects on injury and error are unclear .
OBJECTIVES To assess the effects of caffeine for preventing injuries caused by impaired alertness in persons with jet lag or shift work disorder . | Thirty healthy volunteers were r and omly assigned to either a caffeine or a placebo group to investigate the alerting effects of caffeine at night . Subjects adhered to a simulated night-shift schedule for 5 consecutive nights . On the first 3 nights , 2 mg/kg caffeine was added to decaffeinated coffee at 2220 and 0120 hours for the caffeine group . On nights 4 and 5 both groups received placebo . Each night , subjects completed five 60-minute sessions of a computerized simulated assembly line performance task ( SALT ) , a multiple sleep latency test ( MSLT ) and question naires . Daytime sleep was recorded in the laboratory between 0900 and 1700 hours each day following nighttime testing . Caffeine decreased physiological sleep tendency on the night shift compared with placebo ; however , the two groups performed at equivalent levels on the SALT . On nights 4 and 5 , when both groups received placebo , there were no differences between the groups on the MSLT , suggesting the absence of a discontinuation effect . There were no differences on daytime polysomnograms between the groups STUDY OBJECTIVES To evaluate the effects of napping , caffeine , and napping plus caffeine on performance and alertness in both laboratory and field setting s. DESIGN ( 1 ) Laboratory Study : parallel-groups design with r and om assignment to 1 of 4 experimental conditions . ( 2 ) Field Study : crossover design . SETTING Sleep laboratory and field setting s. PARTICIPANTS ( 1 ) Laboratory Study : 68 healthy individuals ; ( 2 ) Field Study : 53 shiftworkers who worked nights or rotating shifts . INTERVENTIONS ( 1 ) Laboratory Study : an evening nap opportunity before the first 2 of 4 consecutive simulated night shifts plus placebo taken all 4 nights , caffeine taken nightly , the combination of the nap and caffeine conditions , or placebo . ( 2 ) Field Study : an evening nap on the first 2 of 4 consecutive night shifts plus caffeine taken nightly versus placebo taken nightly without naps . MEASUREMENTS AND RESULTS ( 1 ) Laboratory Study : Napping , caffeine , and their combination all improved alertness and performance as measured by Maintenance of Wakefulness Test and Psychomotor Vigilance Task , but the combination of napping and caffeine was best in improving alertness . ( 2 ) Field Study : Napping plus caffeine improved performance as measured by Psychomotor Vigilance Test and decreased subjective sleepiness in individuals working the night shift . CONCLUSIONS Napping plus caffeine helps improve performance and alertness of night-shift workers Chewing has been shown to alleviate feelings of sleepiness and improve cognitive performance during the day . This study investigated the effect of chewing on alertness and cognitive performance across one night without sleep as well as the possible mediating role of cardiac autonomic activity . Fourteen adults participated in a r and omized , counterbalanced protocol employing a chewing , placebo and caffeine condition . Participants completed tasks assessing psychomotor vigilance , tracking , grammatical reasoning , alertness and sleepiness each hour across the night . All participants received either placebo or caffeine ( 200 mg ) , while the chewing condition also chewed on a tasteless and odorless substance for 15 min each hour . Heart rate ( HR ) , root mean square of the successive differences in R-R intervals on the ECG ( RMSSD ) , and preejection period ( PEP ) were simultaneously recorded . Alertness and cognitive performance amongst the chewing condition did not differ or were in fact worse when compared with placebo . Similarly , measures of HR and RMSSD remained the same between these two conditions ; however , PEP was reduced in the later part of the night in the chewing condition compared with a relative increase for placebo . Caffeine led to improved speed and accuracy on cognitive tasks and increased alertness when compared with chewing . Relative increases in RMSSD and reductions in HR were demonstrated following caffeine ; however , no change in PEP was seen . Strong associations between cardiac parasympathetic activity and complex cognitive tasks , as well as between subjective alertness and simpler cognitive tasks , suggest a differential process mediating complex versus simple cognitive performance during sleep deprivation We measured the effects of slow-release caffeine ( SRC ) and melatonin ( Mlt ) on sleep and daytime sleepiness after a seven-time zone eastbound flight . In a double-blind , r and omized , placebo-controlled study , each of three groups of nine subjects was given either 300 mg SRC on recovery day 1 ( D1 ) to D5 ( 0800 ) or 5 mg Mlt on preflight D-1 ( 1700 ) , flight day D0 ( 1600 ) , and from D1 to D3 ( 2300 ) , or placebo ( Pbo ) at the same times . Nighttime sleep was evaluated by polysomnography and daytime sleepiness from measurements of sleep latencies and continuous wrist actigraphy . Compared with baseline , we found a significant rebound of slow-wave sleep on night 1 ( N1 ) to N2 under Pbo and Mlt and a significant decrease in rapid eye movement sleep on N1 ( Pbo ) and N1-N3 ( Mlt ) . Sleepiness was objective ly increased under Pbo ( D1-D6 ) and Mlt ( D1-D3 ) . SRC reduced sleepiness but also tended to affect sleep quality until the last drug day . In conclusion , both drugs have positive effects on some jet lag symptoms after an eastbound flight : SRC on daytime sleepiness , and Mlt on sleep Abstract . The aim of this work was to investigate the potential chronobiotic properties of slow-release caffeine , in comparison with melatonin , on resynchronization of endogenous melatonin and cortisol secretions after an eastbound flight by jet incurring a time loss of 7 h. A group of 27 reservists of the US Air Force received either slow-release caffeine ( 300 mg ) , melatonin ( 5 mg ) or placebo before , during and /or after the transmeridian flight . Saliva and urine were sample d before the flight in the United States ( from day –2 to day 0 ) and after the flight in France ( from day 1 to day 10 ) . Saliva was collected once a day on waking to determine saliva melatonin and cortisol concentrations . In addition , concentrations of caffeine in saliva were determined three times a day and of 6-sulphatoxymelatonin in urine collected overnight to check that the treatment regimes had been complied with . From day 3 to day 5 , post-flight saliva melatonin concentrations were significantly different from control values in the placebo group only . During treatment with melatonin , the mean urinary 6-sulphatoxymelatonin concentration in the melatonin group was more than twice as high as in the two other groups . In the slow-release caffeine group and the melatonin group , mean saliva cortisol concentrations were significantly lower than control from day 2 to day 5 , whereas the placebo group had a mean saliva cortisol concentration significantly lower than the control value from day 2 to day 9 . In conclusion , these results indicate that administration of slow-release caffeine , as well as of melatonin , allows a faster resynchronization of hormone rhythms during the 4 days following an eastbound flight incurring the loss of 7 The effect on performance overnight of a 1 h nap taken at 0200 h was studied in six young female subjects . The subjects completed three schedules , including one with a nap and two without a nap , during which either a placebo or 300 mg caffeine was ingested at 2315 h. Performance was measured from 1700 h in the evening until 1030 h the next morning . Caffeine improved performance overnight on almost all tasks compared with placebo . The nap had some limited beneficial effect compared with placebo , but most tasks remained impaired INTRODUCTION Interventions to maintain performance are necessary to meet dem and ing mission requirements during sustained and surge aviation operations . Tube foods are the only foods that can be consumed during a U-2 mission due to the confining and encapsulating nature of required support equipment . Caffeine is a safe and effective strategy to enhance cognitive performance and is an ingredient in some tube foods . The objective of this study was to determine whether moderate doses of caffeinated tube foods would enhance performance in a simulated U-2 mission . METHODS Volunteers were 12 healthy USAF male pilots . The study used a double blind , placebo-controlled , two-factor , repeated- measures ( five iterations per night ) design . Caffeinated ( 200 mg each ) or placebo tube food was consumed at 00:00 and 04:00 . Dependent measures assessed included st and ardized tests of cognitive performance , vigilance , and mood design ed to simulate the dem and s of a nighttime U-2 mission . RESULTS Statistically significant ( p < 0.05 ) improvements in performance due to caffeine administration compared with placebo were present in all five cognitive tasks either as main effects , interactions , or absence of significant degradation in the caffeine treatment condition compared with the placebo condition . A majority of sleep deprivation-induced performance decrements were attenuated by 200 mg of caffeine in tube food consumed every 4 h , and in some cases , performance was improved beyond baseline levels . CONCLUSIONS Caffeinated tube food maintained cognitive performance representative of U-2 long- duration mission tasks at or near baseline levels for a 9-h overnight period in qualified USAF pilots . Side effects were minor and did not differ between placebo and caffeine conditions CONTEXT In their first year of postgraduate training , interns commonly work shifts that are longer than 24 hours . Extended- duration work shifts are associated with increased risks of automobile crash , particularly during a commute from work . Interns may be at risk for other occupation-related injuries . OBJECTIVE To assess the relationship between extended work duration and rates of percutaneous injuries in a diverse population of interns in the United States . DESIGN , SETTING , AND PARTICIPANTS National prospect i ve cohort study of 2737 of the estimated 18,447 interns in US postgraduate residency programs from July 2002 through May 2003 . Each month , comprehensive Web-based surveys that asked about work schedules and the occurrence of percutaneous injuries in the previous month were sent to all participants . Case-crossover within-subjects analyses were performed . MAIN OUTCOME MEASURES Comparisons of rates of percutaneous injuries during day work ( 6:30 am to 5:30 pm ) after working overnight ( extended work ) vs day work that was not preceded by working overnight ( nonextended work ) . We also compared injuries during the nighttime ( 11:30 pm to 7:30 am ) vs the daytime ( 7:30 am to 3:30 pm ) . RESULTS From a total of 17,003 monthly surveys , 498 percutaneous injuries were reported ( 0.029/intern-month ) . In 448 injuries , at least 1 contributing factor was reported . Lapse in concentration and fatigue were the 2 most commonly reported contributing factors ( 64 % and 31 % of injuries , respectively ) . Percutaneous injuries were more frequent during extended work compared with nonextended work ( 1.31/1000 opportunities vs 0.76/1000 opportunities , respectively ; odds ratio [ OR ] , 1.61 ; 95 % confidence interval [ CI ] , 1.46 - 1.78 ) . Extended work injuries occurred after a mean of 29.1 consecutive work hours ; nonextended work injuries occurred after a mean of 6.1 consecutive work hours . Injuries were more frequent during the nighttime than during the daytime ( 1.48/1000 opportunities vs 0.70/1000 opportunities , respectively ; OR , 2.04 ; 95 % CI , 1.98 - 2.11 ) . CONCLUSION Extended work duration and night work were associated with an increased risk of percutaneous injuries in this study population of physicians during their first year of clinical training Abstract Objectives To examine the association between self assessed driving while sleepy and the risk of serious road traffic accidents ( RTAs ) . Design Prospect i ve cohort study . Setting France . Participants 13 299 of the 19 894 living members of the GAZEL cohort , workers and recent retirees of a French national utility company followed up since 1989 . Main outcome measures Frequency of driving while sleepy in the previous 12 months , reported in 2001 ; rate ratios for serious RTAs in 2001 - 3 , estimated by using generalised linear Poisson regression models with time dependent covariates . Results The risk of serious RTAs increased proportionally with the frequency of self reported driving while sleepy . After adjustment for sociodemographic characteristics , driving behaviour variables , work conditions , retirement , medical conditions and treatments , depressive symptoms , and sleep disorders , the adjusted rate ratios of serious RTAs for participants who reported driving while sleepy in the previous 12 months “ a few times ” or “ once a month or more often ” were 1.5 ( 95 % confidence interval 1.2 to 2.0 ) and 2.9 ( 1.3 to 6.3 ) respectively compared with those who reported not driving while sleepy over the same period . These associations were not explained by any reported sleep disorders . Conclusions Self assessed driving while sleepy was a powerful predictor of serious RTAs , suggesting that drivers ' awareness of their sleepiness while driving is not sufficient to prevent them from having RTAs . Messages on prevention should therefore focus on convincing sleepy drivers to stop driving and sleep before resuming their journey Context The effectiveness of coffee drinking and napping to maintain alertness during nighttime driving is unknown . Contribution Twelve healthy young men drove 125 miles on a straight highway in 4 sessions : 1 session during daylight and 3 sessions from 2:00 a.m. to 3:30 a.m. An hour before the nighttime driving sessions , participants drank decaffeinated coffee ( placebo ) or caffeinated coffee or took a 30-minute nap . The principal outcome was crossing the line between the lanes . The proportion of participants with no or 1 line crossing was 13 % , 66 % , and 75 % after placebo , nap , and caffeinated coffee , respectively . Implication s Drinking coffee or napping reduces impaired nighttime driving . The Editors Sleep-related accidents represent up to 20 % of all traffic accidents in industrial societies ( 1 - 3 ) . Although sleepiness at the wheel is a well-known risk factor for traffic accidents , many people drive at night ( 4 , 5 ) when alertness is at its lowest level . Connor and colleagues ( 3 ) have shown that driving between 2:00 a.m. and 5:00 a.m. increases the risk for traffic accidents by 5.6 times . Many people repeat this dangerous behavior because of economic rewards for professional drivers ( 6 ) or because of sociocultural factors ( 5 , 7 ) . The age group that is most often involved in sleep-related accidents is 18 years to 25 years ( 1 , 8) . Nurses or physicians who often must stay awake for very long hours face the same risk ( 9 , 10 ) . Traffic accidents occurring between the workplace and home are a major cause of injury and death among workers ( 11 , 12 ) , and medical interns are particularly exposed ( 13 ) . Because of the conflicts between physiologic needs and social or professional activities ( 13 - 15 ) , developing safe and affordable counter measures to sleepiness at the wheel is a key issue in accident prevention . These counter measures include sleeping ( or napping ) and the use of awakening agents , such as caffeine . Caffeine is a widely used awakening substance . Adults in western societies are estimated to have an average all- source daily caffeine intake of about 200 mg to 300 mg ( 16 ) . Within and above this dose range , caffeine increases alertness and reduces sleep propensity . Some studies have tested the effects of caffeine on daytime driving in simulators by young sleep-deprived participants using caffeine pills , caffeinated beverages , or energy drinks ( 17 , 18 ) . Other studies have compared daytime naps with caffeine in driving simulators ( 19 ) . However , no studies to date have tested the effects of coffee or napping on nighttime driving performances in a real-life environment . A recent study comparing performances in real driving and driving simulators showed that sleepiness and performances are significantly more affected by sleep deprivation in a simulated environment than in the real world ( 20 ) . This questions the validity of driving simulator studies , at least in the amplitude of effect of sleep deprivation or effect of counter measures . A real-life environment ( such as a freeway rest area ) may also affect napping . A laboratory near a driving simulator after a night of sleep deprivation is an optimal place to fall asleep , even in the daytime . In real life , sleeping in a car at a highway rest area may not be so easy . On the other h and , the implication s of real driving may reactivate the participants and could defer the effects of sleepiness at the wheel compared with the safe and boring environment of a driving simulator , which we have shown in a recent study ( 20 ) . Another very important point is the timing of the test : A combination of homeostatic and chronobiological factors explains the driving impairment . Epidemiologic studies show that sleep-related accidents occur most frequently in the middle of the night ( 3 , 8) . Testing counter measures at that time is therefore crucial , combining extended wakefulness and chronobiological pressure . Other studies ( 19 , 21 ) have tested the effect of caffeine , naps , or both on simulated driving , but the driving sessions were performed during the day or the early morning . For these reasons , we design ed a controlled , crossover study of real driving at night to study the effects of coffee or napping on nighttime driving performance . Methods Participants We recruited 12 healthy men ( mean age , 21.3 years [ SD , 1.8 ] ; range , 20 to 25 years ) . All participants provided written informed consent , and the local ethics committee ( consultative committee for the protection of persons participating in biomedical research [ CCPPRB Bordeaux A ] ) approved the study . All participants completed an Epworth Sleepiness Scale ( ESS ) ( 22 ) , a Symptom Checklist 90 ( SCL-90 ) ( 23 ) , a HorneOstberg question naire ( 24 ) , and a Basic Nordic Sleep Question naire ( BNSQ ) ( 25 ) . We excluded participants who reported a sleep disorder , such as sleep apnea , insomnia ( BNSQ score > 3 ) , or excessive daytime somnolence ( ESS score > 9 ) . We excluded participants with preexisting sleep disorders ( diagnosed by clinical interview ) , organic disorders affecting sleep , or poor sleep hygiene and participants who were night or shift workers . Aside from the psychological profile evaluated by the SCL-90 , we asked questions about substance abuse ( caffeine , drug , or alcohol ) during the clinical interview . We excluded participants who reported drug or alcohol abuse ( more than 21 units per week ) or who had an SCL-90 score greater than 59 . All recruited participants were intermediate according to the HorneOstberg question naire . Participants were not professional drivers , had had their driving license for at least 2 years , and drove between 10000 km and 20000 km per year . Sleep Variables Volunteers had to have normal usual sleep patterns as determined from an interview with a sleep specialist and 7 days ' monitoring with actimeters ( Actiwatch , Cambridge Neurotechnology , Cambridge , United Kingdom ) ( 26 ) showing at least 85 % mean sleep efficiency ( 27 ) over a week . Study Design This was a r and omized , partly blinded , crossover study . All participants performed 4 driving sessions : 1 session from 6:00 p.m. to 7:30 p.m. in the daytime ( reference condition ) and 3 sessions from 2:00 a.m. to 3:30 a.m. ( coffee , decaffeinated coffee , or nap condition ) , with at least 1 week between sessions . All participants started with the reference condition ( Table ) . We r and omly attributed the order of nocturnal driving sessions ( nap , decaffeinated coffee , or coffee ) to each participant in a balanced design by using a r and om permutations sequence . Table . Line Crossings per Participant and Driving Session Sleep Schedules and Sleep Recordings We instructed the participants to maintain a regular sleepwake schedule and monitored them by actimetry during the 3 days before each experimental session to verify the absence of sleep deprivation . We report only the last night 's sleep duration in the Results section . We did not allow stimulants of any kind during the study . For the nocturnal testing periods , the participants came to the laboratory at 8:00 p.m. and were equipped with an ambulatory polysomnograph ( Deltamed , Paris , France ) . Participants were not allowed to sleep before the driving sessions or the nap . We performed electroencephalography , electromyography , and electrooculography during the nap , the driving session , and the rest of the night after driving . All participants slept in a research room in the laboratory after the driving session . We calculated sleep latency from the time of lights out to the first epoch of stage 1 sleep . We calculated sleep efficiency by dividing the time in bed by the total sleep time from lights out to lights on . Coffee and Placebo We prepared coffee and placebo from 2 single packs of instant coffee ( normal or decaffeinated ) provided by Nestl ( Nestl France , Noisiel , France ) . Coffee contained 4.25 % of caffeine , and placebo ( decaffeinated coffee ) contained less than 0.3 % of caffeine . Placebo and coffee were not distinguishable by taste or aspect . Each participant drank 125 mL of instant coffee ( about half a cup of coffee containing 200 mg of caffeine ) or 125 mL of placebo ( containing 15 mg of caffeine ) 30 minutes before the nighttime driving session . Napping During the naps , the driver 's seat was fully reclined , the participants were covered with a blanket , and an electrical heating system , which was installed in the car , maintained a constant temperature ( 19 C ) . The car was parked in a quiet rest area and was guarded by the copilot so that no one disturbed the driver . The 30-minute nap started at 1:00 a.m. , 1 hour before the driving session . Driving Sessions All participants drove 200 km ( 125 miles ) on the same highway in separate lanes ( 100 km [ 62.5 miles ] one way and 100 km [ 62.5 miles ] the other way ) for all conditions . The nighttime driving session started 30 minutes after ingestion of coffee or placebo or 30 minutes after awakening from the nap . Driving conditions were a straight highway on weekdays with usually light traffic conditions , in fair weather . All drivers were exposed to the same or very similar conditions . During a training session , participants were instructed to maintain a constant speed ( 130 kph [ 80 mph ] ) , to drive in the center of the lane , and to not cross the painted lines separating the lanes except to pass a slower vehicle . During the whole experiment , a professional driving instructor monitored the driving speed and noted the number of line crossings . The instructor was ready to take control of the car ( which was equipped with dual controls ) if needed . If a participant could no longer drive during a session , the participant was driven back to the rest area . The car used for the experiment was equipped with a video camera , which filmed and recorded the road , as described elsewhere ( 28 , 29 ) . Sleepiness and Fatigue Immediately before each driving session , we asked participants to rate their instantaneous fatigue ( Describe how fatigued you are now ) on a 100-mm visual analogue scale . Scores ranged from 0 ( not at all tired ) to 100 ( very PURPOSE The purpose of this study was to evaluate physical performance ( static and dynamic ) of U.S. Air Force reservists after an eastbound air travel across seven time zones and to estimate the pharmacological aids slow-release caffeine and melatonin versus placebo in attempt to overcome the decline in performance . METHODS 27 American volunteers were r and omly divided into three groups : caffeine 300 mg , melatonin 5 mg , and placebo ( lactose capsules ) . Two days before the flight and 10 d after , three tests were performed : h and grip strength test ( static performance ) , squat jump test ( maximal height ) , and multiple jump test ( power and endurance ) . All measures were repeated twice a day : morning and afternoon . RESULTS In placebo conditions , the static performance of the dominant h and decreased significantly during the first three mornings and tended to decrease the fourth morning . Simultaneously , the caffeine group 's static performance increased significantly , whereas the melatonin group maintained its levels . No significant differences were observed the afternoons . No statistical differences appeared for the nondominant h and in the mornings or afternoons . Dynamic capacities presented no significant degradation after the travel . In the placebo group , for the squat jump test , performance increased from the fourth day . No real explanation can be given about this result . CONCLUSIONS We demonstrated that slow-release caffeine and melatonin might be used to compensate for jet-lag troubles and particularly for the static physical performance decrease . The slow-release caffeine seems to be the best treatment , but its effects are only demonstrated on previously damaged performance . These preliminary results need further investigation , but we are the first to report a beneficial effect of slow-release caffeine and melatonin on physical performances after jet-lag BACKGROUND The impact of the separate and combined effects of a 1-h exposure to bright light ( approximately 3000 lx ) and a 200-mg dose of caffeine on nocturnal performance was studied during a simulated shift-work schedule beginning 1730 in the evening and ending 1000 the next morning . HYPOTHESIS Light and caffeine exposure were expected to improve nocturnal fatigue degradation . METHODS There were 11 subjects tested under 4 treatment conditions : 1 ) 1 h Dim Light-Placebo ; 2 ) 1 h Bright Light-Placebo ; 3 ) 1 h Dim Light-Caffeine ; 4 ) 1 h Bright Light-Caffeine . Exposure to the light occurred between 0130 and 0230 hours . Caffeine or placebo was administered at 0140 hours . RESULTS Choice Reaction Time ( RT ) recorded during the four post-treatment sessions were shorter for the Bright Light-Caffeine , Bright Light-Placebo , and Dim Light-Caffeine conditions than for the Dim Light-Placebo condition . During the sessions beginning 0430 and 0830 hours , the shortest RT was recorded for the Bright Light-Caffeine treatment . The largest number of trials without false alarms per session for the working memory task ( letter cancellation ) was found for the Bright Light-Caffeine condition . Exposure for 1 h to 3000 lx reduced melatonin concentration between 42 - 47 % from 0230 to 0410 hours . A 200-mg dose of caffeine also reduced melatonin levels , although to a lesser degree than 1 h exposure to 3000 lx . CONCLUSION Although 1 h exposure to bright light at 0130 hours combined with a 200-mg dose of caffeine maintains performance throughout the remainder of the night/early morning , a 1-h exposure to bright light without the caffeine may actually de grade performance After a normal baseline night of sleep and a morning of baseline test performance , 24 young adult male subjects returned to bed from 16:00 - 20:00 prior to a 24 h period of sleep loss . Twelve subjects received caffeine 200 mg at 01:30 and 07:30 . Performance tests ( correctly completed addition problems , vigilance sensitivity , and logical reasoning correct responses ) all indicated maintenance of baseline performance levels in the caffeine group after administration of caffeine while performance declined in the placebo group . Similar results were found for the Multiple Sleep Latency Test and Oral Temperature , which both remained near baseline levels throughout the observation period in subjects receiving caffeine . The results indicated that the combination of a prophylactic nap and caffeine was more effective in maintaining nocturnal alertness and performance than was the nap alone . Of more interest was the fact that the group which was given the combination of nap and caffeine was able to maintain alertness and performance at very close to baseline levels throughout a 24 h period without sleep Cognitive performance at night exhibits a substantial drop , typically before dawn . One of the means of dealing with this phenomenon , as well as with the accompanying sleepiness during sustained wakefulness , is the administration of stimulants . The most widely used and well‐documented stimulants are caffeine , amphetamines , and modafinil . Of these , amphetamines are the least recommended , as they may severely affect behavior . Caffeine and modafinil seem to produce relatively milder side effects and usually only at high doses . Previous comparison studies have revealed equal efficacy of both the stimulants in maintaining alertness and performance during sustained wakefulness . However , these studies used relatively high , and thus not completely safe , doses of these drugs ( 600 mg caffeine and 400 mg modafinil ) . Therefore , the aim of the present study was to assess the efficacy of a low and medically safe dose of caffeine ( 200 mg ) and modafinil ( 200 mg ) in maintaining cognitive performance during sustained wakefulness . A flight simulation task was chosen for the assessment of the stimulants in a counter‐balanced , within‐subject design under four different conditions : baseline ( no drugs ) , placebo , caffeine ( 200 mg ) , and modafinil ( 200 mg ) . The equal effectiveness of both drugs in abolishing the nocturnal drop in cognitive performance , as well as of oral temperature and blood pressure , supported the use of low doses of caffeine and modafinil for the maintenance of alertness in healthy subjects during sustained wakefulness STUDY OBJECTIVES Although there are considerable data demonstrating the impact of shift work on sleep and alertness , little research has examined the prevalence and consequences of shift work sleep disorder in comparison to the difficulties with insomnia and excessive sleepiness experienced by day workers . The present study was design ed to determine the relative prevalence and negative consequences associated with shift work sleep disorder in a representative sample drawn from the working population of metropolitan Detroit . DESIGN R and om-digit dialing techniques were used to assess individuals regarding their current work schedules and a variety of sleep- and non-sleep-related outcomes . SETTING Detroit tricounty population . PARTICIPANTS A total of 2,570 individuals aged 18 to 65 years from a representative community-based sample including 360 people working rotating shifts , 174 people working nights , and 2036 working days . MEASUREMENTS AND RESULTS Using st and ardized techniques , individuals were assessed for the presence of insomnia and excessive sleepiness , based on DSM-IV and ICSD criteria . Those individuals with either insomnia or excessive sleepiness and who were currently working rotating or night schedules were classified as having shift work sleep disorder . Occupational , behavioral , and health-related outcomes were also measured . Individuals who met criteria for shift work sleep disorder had significantly higher rates of ulcers ( odds ratio = 4.18 , 95 % confidence interval = 2.00 - 8.72 ) , sleepiness-related accidents , absenteeism , depression , and missed family and social activities more frequently compared to those shift workers who did not meet criteria ( P < .05 ) . Importantly , in most cases , the morbidity associated with shift work sleep disorder was significantly greater than that experienced by day workers with identical symptoms . CONCLUSION These findings suggest that individuals with shift work sleep disorder are at risk for significant behavioral and health-related morbidity associated with their sleep-wake symptomatology . Further , it suggests that the prevalence of shift work sleep disorder is approximately 10 % of the night and rotating shift work population Historical accounts of sleep loss studies have described changes in the content and patterns of speech , although to date these cl aims have not been systematic ally studied . We examined the effects of sleep loss on the spontaneous generation of words during a verbal word fluency task and the articulation of speech during a vocalized reading task . Nine subjects underwent two counterbalanced 36-hour trials involving sleep deprivation ( SD ) and no sleep deprivation ( NSD ) . After SD , there was a significant deterioration in word generation and a tendency for subjects to become fixated within a semantic category . There was a significant reduction in the subjects ' use of appropriate intonation in the voice after SD , with subjects displaying more monotonic or flattened voices . These findings are discussed in light of neuropsychological evidence concerning the functions of sleep in relation to the frontal cortex and in light of the implication s for interpersonal communication in the event of sleep loss The mortality risk associated with different sleeping patterns was assessed by use of the 1965 Human Population Laboratory survey of a r and om sample of 6928 adults in Alameda County , CA and a subsequent 9-year mortality follow-up . The analysis indicates that mortality rates from ischemic heart disease , cancer , stroke , and all causes combined were lowest for individuals sleeping 7 or 8 h per night . Men sleeping 6 h or less or 9 h or more had 1.7 times the total age-adjusted death rate of men sleeping 7 or 8 h per night . The comparable relative risk for women was 1.6 . The association between sleeping patterns and all causes of mortality was found to be independent of self-reported trouble sleeping and self-reported physical health status at the time of the 1965 survey . Simultaneous adjustment for age , sex , race , socioeconomic status , physical health status , smoking history , physical inactivity , alcohol consumption , weight status , use of health services , social networks , and life satisfaction reduced the relative mortality risk associated with sleeping patterns to 1.3 ( p less than or equal to 0.04 ) Past research has indicated that caffeinated ' functional energy drinks ' ( FEDs ) are effective in counteracting sleepiness . It is not known however , what impact FEDs have on sleep itself . FEDs contain several active ingredients , including caffeine . They may therefore impact negatively on sleep and hence subsequent performance , deeming their use counterproductive . In a r and omised cross-over design , 15 young adults participated in a simulated first night-shift protocol with 2 conditions , Functional Energy Drink ( FED ) and Non Functional Energy Drink ( NonFED ) . Both involved a period of extended wakefulness ( 0700 - 0730 h-24.5 h ) followed by an 8-h daytime ' recovery ' sleep ( 0730 - 1530 h ) . During the FED condition , a commercially available FED was administered twice during the night . Sleepiness was assessed during the period of extended wakefulness and for a further 6h after waking . Sleep periods were recorded using a st and ard 5 channel polysomnogram . Comparison of the sleep periods showed that sleep onset latency remained unchanged as did stage 2 and slow wave sleep . Total sleep time however , was 29.1 min shorter ( p<.05 ) in the FED condition . Sleep efficiency was also significantly reduced from 91.8+/-.9 % to 84.7+/-2.7 % ( p<.05 ) . It is evident that the residual effects of the FED 's active ingredients impact on some aspects of daytime sleep following a simulated night-shift . Subsequent performance however was unaffected . The results deem FEDs to be effective for a single night-shift and warrant investigation into their use over successive night-shifts The capacity to maintain vigilance generally falls with time on task . However , it has been suggested that , for example , the effects of sleep loss need a rather long time on task to become evident . The present experiment examined when significant deterioration of performance occurred in a 34-min visual vigilance task ( with 32 signals ) given to twelve subjects every 3 h across 64 h without sleep . Results from the whole test , the first eight signals , and even the first signal varied significantly across the experiment and were significantly lower than baseline after 24 h awake . The rate of decline over time on task was similar across the experiment . Less than half the misses could be attributed to electrophysiologically defined sleepiness . It was concluded that there is no " safe " duration of a monotonous task if the situation is undem and ing and boring , but that the effect may become immediately evident . This may have practical implication s in terms of safety OBJECTIVE To investigate whether the effectiveness of a novel high-frequency low-dose caffeine regimen in counteracting the deterioration of performance during extended wakefulness is related to its interaction with homeostatic or circadian signals modulating performance and sleep propensity . DESIGN Double-blind , placebo-controlled , parallel-group design in a 29-day forced desynchrony paradigm in which the period of the sleep-wake cycle was scheduled to be 42.85 hours , i.e. , far removed from the circadian range . This design allowed for separate estimation of the sleep homeostatic , circadian , and caffeine contributions to performance deficits or improvements . SETTING Private suite of a general clinical research center , in the absence of time of day information . PARTICIPANTS Sixteen healthy normal-sleeping men ( aged 18 - 30 years ) INTERVENTIONS Caffeine ( 0.3 mg per kg per hour ) or placebo was administered hourly during the 28.57-hour wake episodes . RESULTS Plasma caffeine concentrations rose in an exponential saturating manner during wakefulness . Rising caffeine levels markedly attenuated wake-dependent deterioration of a number of measures of cognitive performance , particularly at the circadian performance nadir . Moreover , caffeine enhanced the ability of subjects to remain consistently awake for extended periods , holding subjects back from completing the full transition to sleep , but at the expense of increasing subjective sleepiness . CONCLUSIONS High-frequency low-dose caffeine administration is effective in countering the detrimental performance effects of extended wakefulness . These data are in accordance with the hypothesis that adenosine is a mediator of performance decrements associated with extended wakefulness and may lead to new strategies to use caffeine in situations in which neurobehavioral functioning is affected by sleep loss Aims : To determine whether fatigue and need for recovery are risk factors for being injured in an occupational accident . Methods : These associations were investigated within the Maastricht Cohort Study of “ Fatigue at Work ” , a prospect i ve cohort study of employees from a wide range of companies and organisations . For 7051 employees information was available on fatigue as measured with the Checklist Individual Strength ( CIS ) , need for recovery as measured with the VBBA , and possible confounding factors such as age , smoking , alcohol consumption , educational level , shift work , and work environment . Information on the risk factors was collected in May 1999 and January 2000 , before the occurrence of the occupational accidents . The incidence of being injured in an occupational accident was inventoried over the year 2000 . A total of 108 employees reported having been injured in an occupational accident in 2000 . Results : For the highest CIS fatigue score tertile a for age , gender , educational level , smoking , shift work , and work environment , adjusted relative risk for being injured in an occupational accident of 1.29 ( 95 % CI : 1.03 to 2.78 ) was found compared to the lowest tertile , and for the highest tertile of need for recovery a relative risk of 2.28 ( 95 % CI : 1.41 to 3.66 ) was found . Conclusions : Fatigue and need for recovery were found to be independent risk factors for being injured in an occupational accident . This means that in the push back of occupational accidents , fatigue , and even more importantly need for recovery , need special attention BACKGROUND Resident work hours may impact patient care . We hypothesized that " call-associated " acute sleep deprivation has no effect on technical dexterity as measured on a minimally invasive surgery trainer , virtual reality ( MIST VR ) surgical simulator . METHODS Thirty-five surgical residents were prospect ively evaluated pre-call ( rested ) , on-call ( rested ) , and post-call ( acutely sleep deprived ) . Participants completed question naires regarding sleep hours and level of fatigue . Technical skill was assessed using the MIST VR . Speed , errors , and economy of motion were automatically recorded by the MIST VR computer simulator . Data were analyzed by paired Student t test and analysis of variance . RESULTS Estimated hours of sleep and subjective indicators of fatigue were different between rested and sleep-deprived residents . The number of errors and time to complete all tasks increased at the post-call assessment . CONCLUSIONS Resident work schedules lead to sleep deprivation and fatigue . Call-associated sleep deprivation and fatigue are associated with increased technical errors in the performance of simulated laparoscopic surgical skills This pilot study examined the relationships between the effects of sleep deprivation on subjective and objective measures of sleepiness and affect , and psychomotor vigilance performance . Following an adaptation night in the laboratory , healthy young adults were r and omly assigned to either a night of total sleep deprivation ( SD group ; n = 15 ) or to a night of normal sleep ( non-SD group ; n = 14 ) under controlled laboratory conditions . The following day , subjective reports of mood and sleepiness , objective sleepiness ( Multiple Sleep Latency Test and spontaneous oscillations in pupil diameter , PUI ) , affective reactivity/regulation ( pupil dilation responses to emotional pictures ) , and psychomotor vigilance performance ( PVT ) were measured . Sleep deprivation had a significant impact on all three domains ( affect , sleepiness , and vigilance ) , with significant group differences for eight of the nine outcome measures . Exploratory factor analyses performed across the entire sample and within the SD group alone revealed that the outcomes clustered on three orthogonal dimensions reflecting the method of measurement : physiological measures of sleepiness and affective reactivity/regulation , subjective measures of sleepiness and mood , and vigilance performance . Sleepiness and affective responses to sleep deprivation were associated ( although separately for objective and subjective measures ) . PVT performance was also independent of the sleepiness and affect outcomes . These findings suggest that objective and subjective measures represent distinct entities that should not be assumed to be equivalent . By including affective outcomes in experimental sleep deprivation research , the impact of sleep loss on affective function and their relationship to other neurobehavioral domains can be assessed Caffeine produces mild psychostimulant effects that may be particularly evident in individuals whose mood or performance is impaired by sleep restriction or caffeine withdrawal . Caffeinated energy drinks have been shown to improve energy and cognition but expectancy effects can not be ruled out in these studies . Very few studies have examined the effects of caffeine-containing energy capsules upon behavioral and subjective measures . This study compared the effects of a caffeine-containing ( 200 mg ) supplement ( CAF ) or placebo in capsule form after prolonged wakefulness , in participants who varied in their level of habitual caffeine use . Thirty-five healthy volunteers ( 16 male , 19 female ) participated in two experimental sessions in which they remained awake between 5 p.m. and 5 a.m. At 3:30 a.m. they consumed CAF or placebo in r and om order under double-blind conditions . Participants completed subjective effects question naires and performed computerized attention tasks before and after consuming capsules . Heart rate and blood pressure were monitored at regular intervals . Compared to measures at 5 p.m. , participants reported more tiredness and mood disturbance at 3 a.m. , and exhibited longer reaction times and more attentional lapses . Heavier caffeine consumers exhibited the greatest decreases in Profile of Mood States ( POMS ) Vigor . CAF produced stimulant-like effects and significantly improved mood and reaction times upon the tasks . These effects did not vary with level of habitual caffeine consumption . These findings indicate that consumption of a caffeine-containing food supplement improves subjective state and cognitive performance in fatigued individuals that is likely a result of its caffeine content |
14,077 | 18,626,051 | Findings showed that poor outcomes were associated with initial drug resistance and that treatment was not based on susceptibility testing . | Context Identifying strategies to optimize tuberculosis treatment outcomes is important in light of the increasing occurrence of drug-resistant tuberculosis .
The Editors Resistance to antituberculosis drugs was first described soon after the introduction of streptomycin ( 1 ) and is currently one of the most important threats to global tuberculosis control ( 2 ) .
In 2004 , the World Health Organization estimated that among patients who had never received treatment before ( new cases ) , the prevalence of drug resistance to any of the st and ard first-line tuberculosis drugs ranged from less than 5 % to more than 30 % in different countries ( 3 ) .
The threat of drug resistance has been underscored by recent reports of extensively drug-resistant strains ( 5 ) .
Drug-resistant strains cause much higher rates of mortality , failure , and relapse ( 6 ) , and treatment is more toxic , expensive , and lengthy ( 7 ) .
Therefore , we planned a systematic review and meta- analysis ( if appropriate ) among previously untreated patients ( new cases ) with active pulmonary tuberculosis to determine the association among tuberculosis treatment outcomes ( failure , relapse , and acquired drug resistance ) and initial drug resistance ( that is , before treatment ) ; duration of rifampin therapy ; use of pyrazinamide ; use of streptomycin ; and the number of drugs used in therapy . | A controlled clinical trial of three short-course chemotherapy regimens was undertaken in patients with newly diagnosed bacteriologically positive pulmonary tuberculosis . The patients were r and omly allocated to receive one of three regimens : rifampicin , streptomycin , isoniazid and pyrazinamide daily for 2 months , followed by streptomycin , isoniazid and pyrazinamide twice weekly for 3 months ( R/5 ) or for 5 months ( R/7 ) , or the same regimen as R/7 but without rifampicin ( Z/7 ) . A bacteriological relapse requiring retreatment occurred by 5 years in 7.1 % of 126 R/5 , 4.0 % of 124 R/7 and 6.7 % of 253 Z/7 patients with organisms initially sensitive to streptomycin and isoniazid ; none of these differences is statistically significant . Of the 31 relapses , 16 occurred within 2 years of the completion of chemotherapy and the remaining 15 between 2 and 5 years . Among 65 patients with initial drug resistance to streptomycin or isoniazid or both , there were six bacteriological relapses requiring retreatment BACKGROUND Rifapentine is a cyclopentyl-substituted rifamycin whose serum half-life is five times that of rifampin . The US Public Health Service Study 22 compared a once-weekly regimen of isoniazid and rifapentine with twice weekly isoniazid and rifampin in the continuation phase ( the last 4 months ) of treatment for pulmonary tuberculosis in HIV-seropositive and HIV-seronegative patients . This report concerns only the HIV-seropositive part of the trial , which has ended . The HIV-seronegative part will stop follow-up in 2001 . METHODS Adults with culture-positive , drug-susceptible pulmonary tuberculosis who completed 2 months of four-drug ( isoniazid , rifampin , pyrazinamide , ethambutol ) treatment ( induction phase ) were r and omly assigned 900 mg isoniazid and 600 mg rifapentine once weekly , or 900 mg isoniazid and 600 mg rifampin twice weekly . All therapy was directly observed . Statistical analysis used univariate , Kaplan-Meier , and logistic and proportional hazards regression methods . FINDINGS 71 HIV-seropositive patients were enrolled : 61 completed therapy and were assessed for relapse . Five of 30 patients in the once-weekly isoniazid/rifapentine group relapsed , compared with three of 31 patients in the twice-weekly isoniazid/rifampin group ( log rank chi2=0.69 , p=0.41 ) . However , four of five relapses in the once-weekly isoniazid/rifapentine group had monoresistance to rifamycin , compared with none of three in the rifampin group ( p=0.05 ) . Patients who relapsed with rifamycin monoresistance were younger ( median age 29 vs 41 years ) , had lower baseline CD4 cell counts ( median 16 vs 144 microL ) , and were more likely to have extrapulmonary involvement ( 75 % vs 18 % , p=0.03 ) and concomitant therapy with antifungal agents ( 75 % vs 9 % , p=0.006 ) . No rifamycin monoresistant relapse has occurred among 1004 HIV-seronegative patients enrolled to date . INTERPRETATION Relapse with rifamycin monoresistant tuberculosis occurred among HIV-seropositive tuberculosis patients treated with a once-weekly isoniazid/rifapentine continuation-phase regimen . Until more effective regimens have been identified and assessed in clinical trials , HIV-seropositive people with tuberculosis should not be treated with a once-weekly isoniazid/rifapentine regimen The time is now right for r and omized trials of MDR-TB , say the authors , as the expansion of MDR-TB programs provides the setting in which trials can be implemented . In a study in Singapore 310 patients with sputum smear-positive pulmonary tuberculosis were allocated at r and om to daily chemotherapy with streptomycin , isoniazid , rifampin , and pyrazinamide ( 1 ) for 2 months ( 2SHRZ ) , ( 2 ) for 1 month ( 1SHRZ ) , or ( 3 ) for 2 months without streptomycin ( 2HRZ ) . This was followed for all patients by three times weekly isoniazid and rifampin to a total duration of 6 months . During the initial period of daily chemotherapy the patients were also allocated at r and om to be given their HRZ either as a combined formulation ( Rifater ) , each tablet containing 50 mg isoniazid , 120 mg rifampin , and 300 mg pyrazinamide , or as three separate drugs . During the Rifater versus separate drugs comparison the most common spontaneous complaints were of nausea and vomiting , reported by 8 % of 155 patients receiving Rifater and 7 % of 155 separate drugs . Other adverse effects were also reported in similar proportions in the two series . Among 271 patients with drug-susceptible strains of tubercle bacilli pretreatment there were no bacteriologic failures during chemotherapy . During 18 months of subsequent follow-up bacteriologic relapse occurred in 3 ( 7 % ) of 46 2SHRZ , 2 ( 5 % ) of 42 1SHRZ , and 3 ( 8 % ) of 40 2HRZ patients allocated to Rifater and in 0 of 47 2SHRZ , 1 ( 2 % ) of 46 1SHRZ , and 1 ( 2 % ) of 44 2HRZ patients allocated to separate drugs . There was no evidence of therapeutic benefit from continuing SHRZ administration beyond 1 month or from adding streptomycin to HRZ . The relapse rates were slightly higher in the Rifater series ( p = 0.04 ) . Further follow-up and results from other studies are therefore needed fully to assess the combined preparation The purpose of this study was to evaluate the impact of human immunodeficiency virus ( HIV ) infection on treatment for tuberculosis ( TB ) . The study population comprised 28,522 black Southern African gold miners . Patients with sputum culture-positive new or recurrent pulmonary TB diagnosed in 1995 were prospect ively enrolled in the cohort . Directly observed therapy ( DOT ) was practice d and outcomes were assessed at 6 mo after treatment was begun . There were 376 cases of TB ( incidence 1,318 per 100,000 ) , of which 190 ( 50 % ) were HIV positive and 82 ( 22 % ) had recurrent TB . There was no association between HIV status and history of previous TB or drug resistance . Neither the treatment interruption rate ( 2 % ) nor the rate at which patients transferred out of the treatment program ( 1.6 % ) were associated with HIV status . Excluding deaths , cure rates were similar for HIV-positive and HIV-negative patients ( 89 % versus 88 % ) , but significantly lower in those with recurrent than in those with new TB ( 77 % versus 92 % ) . Mortality was 0.5 % in HIV-negative patients versus 13.7 % in HIV-positive patients , and in the latter group was associated with CD4(+ ) lymphocyte depletion . Autopsy examination showed that in HIV-positive patients , early mortality was due to TB whereas late deaths were most commonly due to cryptococcal pneumonia . The study showed that a well-run TB control program can result in acceptable cure rates even in a population with a very high incidence of TB and HIV infection . Particular vigilance is needed for concurrent infections , which may contribute significantly to mortality during treatment of TB in HIV-positive patients The bacteriological relapse rates up to 30 months after the start of chemotherapy have been compared for 4 daily short-course regimens for pulmonary tuberculosis . All 4 had the same initial 2-month intensive phase of streptomycin , isoniazid , rifampicin and pyrazinamide ( SHRZ ) followed by isoniazid plus rifampicin for 4 months ( 4HR ) , or isoniazid plus pyrazinamide for 4 months ( 4HZ ) , or isoniazid alone for 4 months ( 4H ) , or isoniazid alone for 6 months ( 6H ) . In patients with fully sensitive strains pretreatment , the 6-month regimen with rifampicin throughout ( 4HR ) was highly effective , only 2 % of 166 patients relapsing bacteriologically in 24 months of follow-up after stopping chemotherapy . This regimen was significantly better than the 4H regimen which had a relapse rate of 10 % in 156 patients ( P less than 0.02 ) and the 4HZ regimen which had a relapse rate of 8 % in 164 patients ( P = 0.05 ) . The 6H regimen was also highly effective , only 3 % of the 123 patients relapsing , compared with 10 % of the 156 on the 4H regimen ( P = 0.06 ) . The relapse rate of the regimen with pyrazinamide throughout ( 4HZ ) , was not significantly different from that of either of the regimens with isoniazid alone in the continuation phase . All except 3 ( 1 4HR , 1 4HZ , 1 4H ) of the 36 relapses were with fully drug-sensitive strains . In patients with strains resistant to isoniazid alone pretreatment none of the 23 on the 4HR or 4HZ regimens had an unfavourable bacteriological status at the end of chemotherapy compared with 8 of the 17 patients ( P less than 0.005 ) on 4H or 6H regimens . Of the patients assessed , 3 of 20 receiving rifampicin or pyrazinamide throughout relapsed compared with 2 of 8 who did not A controlled study of three short-course regimens was undertaken in South Indian patients with newly diagnosed , sputum-positive pulmonary tuberculosis . The patients were allocated at r and om to one of three regimens : a ) Rifampicin , streptomycin , isoniazid and pyrazinamide daily for 3 months ( R3 ) ; b ) the same regimen as above but followed by streptomycin , isoniazid and pyrazinamide twice-weekly for a further period of 2 months ( R5 ) ; c ) the same as R5 but without rifampicin ( Z5 ) . A bacteriological relapse requiring treatment occurred by 5 years in 16.8 % of 113 R3 , 5.2 % of 97 R5 , and 20.0 % of 115 Z5 patients with organisms sensitive to streptomycin and isoniazid initially . The differences in the relapse rates between the R3 and R5 regimens and the R5 and Z5 regimens were statistically significant ( p less than 0.01 for both ) . Considering patients with organisms initially resistant to streptomycin or isoniazid or both , 7 of 52 patients ( 4 R3 , 2 R5 , 1 Z5 ) had a bacteriological relapse requiring retreatment In a previous study , we have shown that a 6-month regimen consisting of 2 months of isoniazid , rifampin , pyrazinamide , and streptomycin administered daily ( 2IRSZ ) followed by 4 months of isoniazid and rifampin administered twice weekly ( 4I2R2 ) yielded no relapses after 30 months of follow-up . In order to assess the contribution of streptomycin to this treatment regimen , 213 patients with newly detected smear-positive pulmonary tuberculosis were r and omly assigned to the following two 6-month treatment regimens : 2IRZ/4I2R2 and 2IRSZ/4I2R2 . One hundred seventy-two of the 213 patients ( 81 % ) completed therapy , i.e. , 116 of 135 patients ( 86 % ) treated with 2IRZ/4I2R2 and 56 of 78 patients ( 72 % ) treated with 2IRSZ/4I2R2 . Adverse reactions requiring withdrawal of drugs for 7 days or longer were observed in 4.2 % of patients ( 3.7 % receiving the 2IRZ/4I2R2 regimen and 5.1 % receiving the 2IRSZ/4I2R2 regimen ) . At the end of treatment , all patients in the 2IRZ/I2R2 series had negative smears and cultures . Two of the 116 patients ( 1.7 % ) in the 2IRZ/I2R2 series developed isoniazid resistance in the fourth month of treatment and remained sputum positive at the end of treatment . In the follow-up period , 4 patients ( 3.4 % ) treated with 2IRZ/4I2R2 relapsed and 1 ( 1.8 % ) treated with 2IRSZ/4I2R2 relapsed . The only significant difference between the 2 regimens was the higher dropout rate among those assigned to the 2IRSZ/4I2R2 regimen OBJECTIVE --To examine the relation between damp and mould growth and symptomatic ill health . DESIGN --Cross-sectional study of r and om sample of households containing children ; separate and independent assessment s of housing conditions ( by surveyor ) and health ( structured interview by trained research er ) . SETTING --Subjects ' homes ( in selected areas of public housing in Glasgow , Edinburgh , and London ) . SUBJECTS -- Adult respondents ( 94 % women ) and 1169 children living in 597 households . END POINTS -- Specific health symptoms and general evaluation of health among respondents and children over two weeks before interview ; and score on general health question naire ( only respondents ) . MEASUREMENTS AND MAIN RESULTS --Damp was found in 184 ( 30.8 % ) dwellings and actual mould growth in 274 ( 45.9 % ) . Adult respondents living in damp and mouldy dwellings were likely to report more symptoms overall , including nausea and vomiting , blocked nose , breathlessness , backache , fainting , and bad nerves , than respondents in dry dwellings . Children living in damp and mouldy dwellings had a greater prevalence of respiratory symptoms ( wheeze , sore throat , runny nose ) and headaches and fever compared with those living in dry dwellings . The mean number of symptoms was higher in damp and mouldy houses and positively associated with increasing severity of dampness and mould ( dose response relation ) . All these differences persisted after controlling for possible confounding factors such as household income , cigarette smoking , unemployment , and overcrowding . Other possible sources of bias that might invali date the assumption of a causal link between housing conditions and ill health -- namely , investigator bias , respondent bias , and selection bias -- were also considered and ruled out . CONCLUSION --Damp and mouldy living conditions have an adverse effect on symptomatic health , particularly among children In a study in Singapore , patients of Chinese , Malay , and Indian ethnic origin with sputum-smear-positive pulmonary tuberculosis were allocated at r and om to daily treatment with streptomycin , isoniazid , rifampin , and pyrazinamide for 2 months ( 2SHRZ ) , for 1 month ( 1SHRZ ) , or for 2 months without streptomycin ( 2HRZ ) , followed , for all patients , by 3-times-weekly isoniazid and rifampin ( H3 R3 ) up to 6 months . As previously reported , all except 1 of 319 patients with drug-susceptible tubercle bacilli pretreatment had a favorable bacteriologic status at the end of chemotherapy , and among the 300 patients assessed up to 30 months ( 24 months after the end of chemotherapy ) , there was only 1 bacteriologic relapse in each series , giving an overall therapeutic failure rate of only 1.3 % . Follow-up has been continued at 6-month intervals up to 5 yr . During the 5 yr , the total relapse rate for patients with drug-susceptible strains pretreatment was 2.4 % of 297 patients ( 95 % confidence limits , 1.0 to 4.8 % ) . Among the 31 patients with strains resistant to isoniazid , streptomycin , or both drugs pretreatment , there were no failures during chemotherapy and 4 ( 13 % ) subsequent relapses OBJECTIVE To evaluate the efficacy of split-drug regimens for treatment of patients with sputum smear-positive pulmonary tuberculosis in south India . DESIGN R and omized controlled clinical trial where eligible patients were r and omly allocated to : ( i ) 2RE(3)HZ(3)(alt)/4RH(2 ) ( split I ) : rifampicin plus ethambutol given on one day and isoniazid plus pyrazinamide the next day for first 2 months followed by rifampicin plus isoniazid twice weekly for 4 months , or ( ii ) 3RE(3)HZ(3)(alt)/3RH(2 ) ( split II ) : similar to regimen 1 , except duration was 3 months in each phase , or ( iii ) 2REHZ(3)/4RH(2 ) ( control ) : rifampicin , isoniazid , ethambutol and pyrazinamide , given thrice weekly for 2 months followed by isoniazid and rifampicin twice weekly for 4 months . All patients were followed up clinical ly and bacteriologically every month up to 2 years and every 6 months for up to 5 years . RESULTS A favourable response ( cultures negative for Mycobacterium tuberculosis during the last 2 months of treatment ) was observed in 91 % of 407 patients in split I , 94 % of 415 in split II and 89 % of 418 in the control regimen . Ninety-one per cent of 370 patients in split I , 93 % of 389 in split II and 90 % of 370 in control regimens had quiescent disease at the end of 60 months . Gastrointestinal symptoms were more frequent under the control regimen ( P = 0.01 ) . CONCLUSION Split-drug regimens were as effective as the control regimen in terms of favourable response at the end of treatment and quiescent disease at 5 years , and caused fewer gastrointestinal side-effects |
14,078 | 20,802,947 | INTRODUCTION Chronic hepatitis B is one of the most frequent infectious disease in the world and represents a serious problem of public health METHODS A systematic review of r and omized clinical trials was conducted to evaluate the efficacy of the nucleoside/nucleotide analogues ( adefovir , entecavir and telbivudine ) used for the treatment of chronic hepatitis B. The data bases PubMed and LILACS were consulted , among others RESULTS Twenty nine articles published between January/1970 to December/2009 were selected CONCLUSIONS All nucleoside/nucleotide analogues demonstrate upper or similar efficacy to lamivudine .
The entecavir can be appropriate for patients with chronic hepatitis B , HBeAg positive and negative treatment-naive as alternative to lamivudine , considering its low potential of viral resistance .
The addition of adefovir to lamivudine presented good results in lamivudine resistant patients .
The use of entecavir and telbivudine in those patients presents risk of crossed resistance .
Adverse events of nucleoside/nucleotide analogues were similar in characteristics , gravity and incidence when compared to the lamivudina and placebo | TBV is one of the most recent antivirals available , but antiviral resistance already documented represents limitation to its use as therapeutic option to LAM . | BACKGROUND Entecavir is a potent and selective guanosine analogue with significant activity against hepatitis B virus ( HBV ) . METHODS In this phase 3 , double-blind trial , we r and omly assigned 715 patients with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B who had not previously received a nucleoside analogue to receive either 0.5 mg of entecavir or 100 mg of lamivudine once daily for a minimum of 52 weeks . The primary efficacy end point was histologic improvement ( a decrease by at least two points in the Knodell necroinflammatory score , without worsening of fibrosis ) at week 48 . Secondary end points included a reduction in the serum HBV DNA level , HBeAg loss and seroconversion , and normalization of the alanine aminotransferase level . RESULTS Histologic improvement after 48 weeks occurred in 226 of 314 patients in the entecavir group ( 72 percent ) and 195 of 314 patients in the lamivudine group ( 62 percent , P=0.009 ) . More patients in the entecavir group than in the lamivudine group had undetectable serum HBV DNA levels according to a polymerase-chain-reaction assay ( 67 percent vs. 36 percent , P<0.001 ) and normalization of alanine aminotransferase levels ( 68 percent vs. 60 percent , P=0.02 ) . The mean reduction in serum HBV DNA from baseline to week 48 was greater with entecavir than with lamivudine ( 6.9 vs. 5.4 log [ on a base-10 scale ] copies per milliliter , P<0.001 ) . HBeAg seroconversion occurred in 21 percent of entecavir-treated patients and 18 percent of those treated with lamivudine ( P=0.33 ) . No viral resistance to entecavir was detected . Safety was similar in the two groups . CONCLUSIONS Among patients with HBeAg-positive chronic hepatitis B , the rates of histologic , virologic , and biochemical improvement are significantly higher with entecavir than with lamivudine . The safety profile of the two agents is similar , and there is no evidence of viral resistance to entecavir . ( Clinical Trials.gov number , NCT00035633 . ) BACKGROUND Entecavir is a potent and selective antiviral agent that has demonstrated efficacy in phase 2 studies in patients with hepatitis B e antigen (HBeAg)-negative chronic hepatitis B. METHODS In this phase 3 , double-blind trial , we r and omly assigned 648 patients with HBeAg-negative chronic hepatitis B who had not previously been treated with a nucleoside analogue to receive 0.5 mg of entecavir or 100 mg of lamivudine once daily for a minimum of 52 weeks . The primary efficacy end point was histologic improvement ( a decrease by at least two points in the Knodell necroinflammatory score , without worsening of fibrosis ) . RESULTS Histologic improvement after 48 weeks of treatment occurred in 208 of 296 patients in the entecavir group who had adequate baseline liver-biopsy specimens that could be evaluated ( 70 percent ) , as compared with 174 of 287 such patients in the lamivudine group ( 61 percent , P=0.01 ) . More patients in the entecavir group than in the lamivudine group had undetectable serum hepatitis B virus ( HBV ) DNA levels according to a polymerase-chain-reaction assay ( 90 percent vs. 72 percent , P<0.001 ) and normalization of alanine aminotransferase levels ( 78 percent vs. 71 percent , P=0.045 ) . The mean reduction in serum HBV DNA levels from baseline to week 48 was greater with entecavir than with lamivudine ( 5.0 vs. 4.5 log [ on a base-10 scale ] copies per milliliter , P<0.001 ) . There was no evidence of resistance to entecavir . Safety and adverse-event profiles were similar in the two groups . CONCLUSIONS Among patients with HBeAg-negative chronic hepatitis B who had not previously been treated with a nucleoside analogue , the rates of histologic improvement , virologic response , and normalization of alanine aminotransferase levels were significantly higher at 48 weeks with entecavir than with lamivudine . The safety profile of the two agents was similar , and there was no evidence of viral resistance to entecavir . ( Clinical Trials.gov number , NCT00035789 . ) Entecavir is an oral antiviral drug with selective activity against hepatitis B virus ( HBV ) . We conducted a r and omized , placebo-controlled , dose-escalating study in patients with chronic hepatitis B infection in which we evaluated the efficacy and safety of entecavir given for 28 days . Follow-up was 24 weeks . All doses of entecavir ( 0.05 mg , 0.1 mg , 0.5 mg , and 1.0 mg ) showed a pronounced suppression of replication of the HBV with a 2.21 , 2.29 , 2.81 , and 2.55 mean log(10 ) reduction of viral load , respectively . Approximately 25 % of patients on entecavir showed a decline of HBV DNA below the limit of detection of the Chiron HBV-DNA assay ( < 0.7 MEq/mL ) . In the postdosing follow-up period patients who were treated with 0.5 and 1.0 mg of entecavir showed a considerably slower return in their HBV DNA levels to baseline compared with those patients treated with lower dosages ( P < .05 ) . All doses of entecavir were well tolerated with no significant difference between treated patients and those receiving placebo . No significant changes in alanine transaminase ( ALT ) levels within the dose groups and the placebo group between baseline and the end of treatment were observed . Three patients ( 9 % ) ( 1 each in the 0.05- , 0.1- , and 0.5-mg groups ) experienced asymptomatic hepatitis flares 16 weeks ( 2 patients ) and 24 weeks ( 1 patient ) after withdrawal of entecavir . In conclusion , in this 28-day study of entecavir a pronounced decrease of HBV DNA was observed and there were no significant side effects in entecavir patients in comparison with placebo-treated patients BACKGROUND & AIMS Entecavir demonstrated superior benefit to lamivudine at 48 weeks in nucleoside-naive patients with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B ( CHB ) . We evaluated continued entecavir and lamivudine treatment through 96 weeks . METHODS 709 HBeAg-positive CHB patients were r and omized to entecavir 0.5 mg ( n = 354 ) or lamivudine 100 mg ( n = 355 ) once daily . At week 52 , protocol -defined virologic responders could continue blinded treatment for up to 96 weeks . Patients continuing in year 2 ( entecavir , n = 243 ; lamivudine , n = 164 ) were assessed for serum hepatitis B virus ( HBV ) DNA , alanine aminotransferase ( ALT ) normalization , HBeAg seroconversion , and safety . Cumulative confirmed proportions of all treated patients who achieved these responses were also analyzed . RESULTS Among patients treated in year 2 , 74 % of entecavir-treated versus 37 % of lamivudine-treated patients achieved HBV DNA < 300 copies/mL by polymerase chain reaction ( PCR ) , and 79 % of entecavir-treated versus 68 % of lamivudine-treated patients normalized ALT levels . Similar proportions of entecavir-treated and lamivudine-treated patients achieved HBeAg seroconversion ( 11 % vs 12 % , respectively ) . Higher proportions of entecavir-treated than lamivudine-treated patients achieved cumulative confirmed HBV DNA < 300 copies/mL by PCR ( 80 % vs 39 % ; P < .0001 ) and ALT normalization ( 87 % vs 79 % ; P = .0056 ) through 96 weeks . Cumulative confirmed HBeAg seroconversion occurred in 31 % of entecavir-treated versus 25 % of lamivudine-treated patients ( P = NS ) . Through 96 weeks , no patient experienced virologic breakthrough due to entecavir resistance . The safety profile was comparable in both groups . CONCLUSIONS Entecavir treatment through 96 weeks results in continued benefit for patients with HBeAg-positive CHB Current therapy for chronic hepatitis B is suboptimal as a result of limited durable response rates , cumulative viral resistance , and /or poor tolerability . Telbivudine has potent antiviral activity against hepatitis B virus ( HBV ) in vitro and in the woodchuck model and has a promising pre clinical safety profile . In this first clinical study of telbivudine , safety , antiviral activity , and pharmacokinetics were assessed in 43 adults with hepatitis B e antigen-positive chronic hepatitis B. This placebo-controlled dose-escalation trial investigated 6 telbivudine daily dosing levels ( 25 , 50 , 100 , 200 , 400 , and 800 mg/d ) ; treatment was given for 4 weeks , with 12 weeks ' follow-up . Serum HBV DNA levels were monitored via quantitative polymerase chain reaction . The results indicate that telbivudine was well tolerated at all dosing levels , with no dose-related or treatment-related clinical or laboratory adverse events . telbivudine plasma pharmacokinetics were dose-proportional within the studied dose range . Marked dose-related antiviral activity was evident , with a maximum at telbivudine doses of 400 mg/d or more . In the 800 mg/d cohort , the mean HBV DNA reduction was 3.75 log10 copies/mL at week 4 , comprising a 99.98 % reduction in serum viral load . Correspondingly , posttreatment return of viral load was slowest in the high-dose groups . Viral dynamic analyses suggested a high degree of efficiency of inhibition of HBV replication by telbivudine and helped refine selection of the optimal dose . In conclusion , these results support exp and ed clinical studies of this new agent for the treatment of hepatitis BACKGROUND / AIMS We aim ed to evaluate nucleoside/nucleotide combination therapy in treatment-naïve HBeAg-positive patients with chronic hepatitis B ( CHB ) . METHODS One hundred and fifteen HBeAg-positive patients received lamivudine 100 mg daily plus placebo ( monotherapy ) or lamivudine 100 mg plus adefovir dipoxil 10 mg daily ( combination therapy ) for 104 weeks in a r and omized double-blind study . RESULTS Time-weighted average change in serum HBV DNA from baseline up to week 16 was -4.20 log(10)copies/mL for both groups ( p=0.936 ) . At week 104 , median serum HBV DNA change from baseline ( log(10)copies/mL ) for monotherapy and combination therapy was -3.41 versus -5.22 , respectively . HBV DNA breakthrough was detected in 44 % of monotherapy and 19 % of combination therapy patients . The M204V/I mutation was detected in 43 % ( 15/35 ) and 15 % ( 6/41 ) of each group , respectively . ALT normalization at week 100 and 104 was 34 % ( 19/56 ) in the monotherapy group and 45 % ( 23/51 ) in the combination therapy group ( p=0.018 ) . By week 104 , HBeAg seroconversion occurred in 20 % of monotherapy and 13 % of combination therapy patients . Both regimens were well tolerated . CONCLUSIONS Lower rates of resistance to lamivudine , lower serum HBV DNA levels and higher rates of ALT normalization were seen in the combination therapy group after two years . However , serological outcomes were similar Adefovir dipivoxil ( bis-POM PMEA ) is an adenine nucleotide analogue with activity against retroviruses and herpesviruses , and in vitro activity against hepatitis B virus ( HBV ) . This study was conducted to evaluate its safety and antiviral activity in patients with chronic HBV infection . Twenty patients ( 13 co-infected with human immunodeficiency virus , HIV ) were r and omized in a phase I/II , double-blind , placebo-controlled study . Patients who had been hepatitis B surface antigen (HBsAg)/hepatitis B e antigen ( HBeAg ) positive for > or = 6 months , with elevated hepatic transaminases and serum HBV DNA > or = 50 pg ml-1 , were r and omized to adefovir dipivoxil 125 mg ( n = 15 ) or placebo ( n = 5 ) as a single , daily , oral dose for 28 days . Antiviral activity was assessed by changes in serum HBV DNA ( using the Digene Hybrid Capture assay ) and HBeAg/hepatitis B e antibody ( HBeAb ) status . HBV DNA levels fell rapidly by > 1 log10 in all active drug recipients ( median fall 1.8 log10 pg ml-1 ) but increased by 0.01 log10 pg ml-1 in controls ( P = 0.002 ) . Reductions were sustained during treatment . HBV DNA returned to baseline over 1 - 6 weeks following discontinuation of active drug . HBeAg became transiently undetectable in one patient on treatment and , in another , sustained seroconversion to HBeAb occurred 12 weeks after treatment ended . Liver transaminase elevations > 300 U l-1 were observed in three patients during therapy ( leading to protocol -specified treatment discontinuation or dose reduction ) and in four patients during follow-up . On-treatment transaminase elevations were associated with HIV status , occurring in three of six HIV-uninfected patients compared with none of nine who were HIV infected . In addition , a slower return to baseline of serum HBV DNA levels was observed in the non-HIV-infected patients . Treatment for chronic hepatitis B as a once-daily oral dose was well tolerated and associated with significant and sustained reductions in serum HBV DNA levels during treatment . Transaminase elevations , which may be related to the therapeutic effect , were observed during and after treatment . Further studies are warranted to investigate the safety , and optimum dose and duration , of adefovir dipivoxil treatment for chronic hepatitis BACKGROUND Adefovir dipivoxil , a nucleotide analogue , demonstrated clinical ly significant antiviral activity in patients with chronic hepatitis B in phase 1 and 2 clinical trials . METHODS We r and omly assigned 185 patients with chronic hepatitis B who were negative for hepatitis B e antigen ( HBeAg ) to receive either 10 mg of adefovir dipivoxil or placebo once daily for 48 weeks in a 2:1 ratio and a double-blind manner . The primary end point was histologic improvement . RESULTS At week 48 , 64 percent of patients who had base-line liver-biopsy specimens available in the adefovir dipivoxil group had improvement in histologic liver abnormalities ( 77 of 121 ) , as compared with 33 percent of patients in the placebo group ( 19 of 57 , P<0.001 ) . Serum hepatitis B virus ( HBV ) DNA levels were reduced to fewer than 400 copies per milliliter in 51 percent of patients in the adefovir dipivoxil group ( 63 of 123 ) and in 0 percent of those in the placebo group ( 0 of 61 , P<0.001 ) . The median decrease in log-transformed HBV DNA levels was greater with adefovir dipivoxil treatment than with placebo ( 3.91 vs. 1.35 log copies per milliliter , P<0.001 ) . Alanine aminotransferase levels had normalized at week 48 in 72 percent of patients receiving adefovir dipivoxil ( 84 of 116 ) , as compared with 29 percent of those receiving placebo ( 17 of 59 , P<0.001 ) . No HBV polymerase mutations associated with resistance to adefovir were identified . The safety profile of adefovir dipivoxil was similar to that of placebo . CONCLUSIONS In patients with HBeAg-negative chronic hepatitis B , 48 weeks of adefovir dipivoxil treatment result ed in significant histologic , virologic , and biochemical improvement , with an adverse-event profile similar to that of placebo . There was no evidence of the emergence of adefovir-resistant HBV polymerase mutations BACKGROUND & AIMS Entecavir is a nucleoside analogue with potent in vitro activity against lamivudine-resistant hepatitis B virus ( HBV ) . This r and omized , dose-ranging , phase 2 study compared the efficacy and safety of entecavir with lamivudine in lamivudine-refractory patients . METHODS Hepatitis B e antigen (HBeAg)-positive and -negative patients ( n = 182 ) , viremic despite lamivudine treatment for > or = 24 weeks or having documented lamivudine resistance substitutions , were switched directly to entecavir ( 1.0 , 0.5 , or 0.1 mg daily ) or continued on lamivudine ( 100 mg daily ) for up to 76 weeks . RESULTS At week 24 , significantly more patients receiving entecavir 1.0 mg ( 79 % ) or 0.5 mg ( 51 % ) had undetectable HBV DNA levels by branched chain DNA assay compared with lamivudine ( 13 % ; P < .0001 ) . Entecavir 1.0 mg was superior to entecavir 0.5 mg for this end point ( P < .01 ) . After 48 weeks , mean reductions in HBV DNA levels were 5.06 , 4.46 , and 2.85 log(10 ) copies/mL on entecavir 1.0 , 0.5 , and 0.1 mg , respectively , significantly higher than 1.37 log(10 ) copies/mL on lamivudine . Significantly higher proportions of patients achieved normalization of alanine aminotransferase levels on entecavir 1.0 , 0.5 , and 0.1 mg ( 68 % , 59 % , and 47 % , respectively ) than on lamivudine ( 6 % ) . One virologic rebound due to resistance occurred ( in the 0.5-mg group ) . CONCLUSIONS In HBeAg-positive and HBeAg-negative lamivudine-refractory patients , treatment with entecavir 1.0 and 0.5 mg daily was well tolerated and result ed in significant reductions in HBV DNA levels and normalization of alanine aminotransferase levels . One milligram of entecavir was more effective than 0.5 mg in this population Entecavir is a potent inhibitor of hepatitis B virus ( HBV ) polymerase . The efficacy and safety of entecavir in nucleoside-naïve patients with hepatitis B virus e antigen (HBeAg)-positive chronic hepatitis B was established in a large , international , double-dummy study ( ETV-022 ) where patients were r and omized to entecavir 0.5 mg/day ( n = 354 ) or lamivudine 100 mg/day ( n = 355 ) once daily . ETV-022 had a 52-week blinded treatment phase , followed by an extended blinded treatment phase for up to 44 additional weeks ( 96 weeks total ) . Treatment was discontinued for patients achieving a protocol -defined response as determined by patient management criteria that intended to test the possibility of finite therapy , which has not previously been studied for entecavir or other anti-HBV agents in a large trial . Early results from this study have been previously presented/published separately . This paper compiles the results of up to 2 years of treatment for protocol -defined responders , virologic responders and nonresponders . For responders who discontinued therapy ( per protocol ) , 24-week off-treatment evaluation is presented to provide a more ' complete picture ' of what clinicians can expect when treating nucleoside-naïve HBeAg-positive patients with chronic hepatitis B. For patients who discontinued therapy because of nonresponse ( nonresponders ) and subsequently entered the rollover study ETV-901 , follow-up results , including resistance profile , are provided AIM To evaluate the efficacy and safety of entecavir ( ETV ) in hepatitis Be antigen (HBeAg)-positive chronic hepatitis B ( CHB ) patients who had not received a nucleoside analogue and who had failed in lamivudine ( LVD ) therapy . METHODS Sixty-one patients were divided into three groups . Forty-two patients who had not received a nucleoside analogue were r and omized into two groups : group A ( n = 21 ) received LVD 100 mg/d and group B ( n = 21 ) received ETV 0.5 mg/d . The remaing 19 patients treated with LVD ( n = 19 ) , who switched to ETV 1.0 mg/d served as group C. All patients were treated for 48 wk . HBV DNA levels were measured with polimerase-chain-reaction ( PCR ) analysis . Liver function tests , HBV serology and safety assessment s were also conducted . RESULTS Significantly more patients in group B ( 52.1 % and 71.4 % ) had undetectable HBV DNA levels than in groups A ( 35.8 % and 38 % ; P < 0.0001 ) and C ( 10.6 % and 21.1 % , P < 0.0001 ) at wk 24 and 48 , respectively . At wk 48 , ALT levels were normalized in more patients in group B ( 85.7 % ) than in groups A ( 76.2 % ) and C ( 74 % ) . CONCLUSION ETV had a significantly higher response rate than LVD in patients with HBeAg-positive CHB who had not previously received a nucleoside analogue ; ETV can effectively inhibit the replication of HBV DNA and normalize the levels of ALT in refractory CHB patients treated with LVD ; and ETV is safe in clinical application BACKGROUND The efficacy of nucleoside and nucleotide analogues for hepatitis B has been linked to the magnitude and durability of hepatitis B virus ( HBV ) suppression . OBJECTIVE To compare the antiviral efficacy of telbivudine and adefovir dipivoxil , and the effects of switching from adefovir to telbivudine , in hepatitis B e antigen (HBeAg)-positive patients with chronic hepatitis B. DESIGN R and omized , controlled , open-label trial . SETTING 16 outpatient clinics . PATIENTS 135 treatment-naive , HBeAg-positive adults with chronic hepatitis B. INTERVENTION Patients were r and omly assigned in a 1:1:1 ratio to 52 weeks of telbivudine ( group A ) or adefovir ( group B ) , or 24 weeks of adefovir and then telbivudine for the remaining 28 weeks ( group C ) . One hundred thirty-one patients completed 52 weeks of treatment . MEASUREMENTS The primary efficacy comparison was serum HBV DNA reduction at week 24 , with a secondary comparison at week 52 . RESULTS At week 24 , mean HBV DNA reduction was greater in group A than in pooled groups B and C ( -6.30 vs. -4.97 log10 copies/mL ; difference , -1.33 log10 copies/mL [ 95 % CI , -1.99 to -0.66 log(10 ) copies/mL ] ; P < 0.001 ) , and more patients in group A were polymerase chain reaction-negative ( 39 % vs. 12 % ; odds ratio , 4.46 [ CI , 1.86 to 10.72 ] ; P = 0.001 ) . At week 52 , the mean residual HBV DNA level was lower in group A and group C than in group B ( 3.01 log10 copies/mL [ group A ] and 3.02 log10 copies/mL [ group C ] vs. 4.00 log10 copies/mL [ group B ] ; difference , -0.99 log10 copies/mL [ CI , -1.67 to -0.32 log10 copies/mL ] and -0.98 log10 copies/mL [ CI , -1.64 to -0.32 log10 copies/mL ] ; P = 0.004 ) . Adverse events were similar across groups ; the most common were upper respiratory symptoms , headache , back pain , and diarrhea . LIMITATIONS The trial was open-label and was not of sufficient size or duration to compare clinical outcomes and long-term efficacy . CONCLUSION Telbivudine demonstrated greater and more consistent HBV DNA suppression than adefovir after 24 weeks of treatment . After 52 weeks , HBV DNA suppression was greater in patients who had received continuous telbivudine or were switched to telbivudine after 24 weeks than in those who received continuous adefovir Purpose A r and omized , double-blind , multicenter study ( ETV-047 ) was conducted to evaluate the dose – response relationship of entecavir and compare its antiviral activity and safety with lamivudine in Japanese patients with chronic hepatitis B ( CHB ) . Methods One hundred thirty-seven nucleoside-naive adult patients with CHB were r and omized to once-daily oral doses of entecavir 0.01 , 0.1 , or 0.5 mg or lamivudine 100 mg for 24 weeks . The primary efficacy end point used to evaluate the dose – response relationship was mean change from baseline in serum hepatitis B virus ( HBV ) DNA level at week 22 , as determined by polymerase chain reaction assay . Results Entecavir demonstrated a clear dose – response relationship , with mean change from baseline in serum HBV DNA level of −3.11 , −4.77 , and −5.16 log10 copies/ml with entecavir 0.01 , 0.1 , and 0.5 mg , respectively . Entecavir 0.5 mg was superior to lamivudine 100 mg for the mean change in HBV DNA level ( −5.16 vs. −4.29 log10 copies/ml ; P = 0.007 ) . The overall incidence of adverse events was comparable between treatment groups . Two patients discontinued treatment because of adverse events ( one with liver cirrhosis [ entecavir 0.5 mg ] and one with grade 4 serum alanine aminotransferase ( ALT ) elevation , nausea , and malaise [ lamivudine 100 mg ] ) . Serum ALT flares were observed in four patients ; flares were associated with 2 log10 reductions or more in HBV DNA level and resolved without dose interruption . Conclusion Entecavir 0.01–0.5 mg is well tolerated and produces a dose-dependent reduction in viral load in nucleoside-naive Japanese patients with CHB . Compared with lamivudine 100 mg , entecavir 0.1 mg demonstrated noninferiority and entecavir 0.5 mg was superior in this population BACKGROUND & AIMS Entecavir is a novel and selective nucleoside analogue with potent activity against hepatitis B virus ( HBV ) . METHODS In a 24-week , double-blind , r and omized , multicenter , phase II clinical trial , the safety and efficacy of entecavir ( 0.01 mg/day , 0.1 mg/day , or 0.5 mg/day orally ) were compared with lamivudine ( 100 mg/day orally ) . Patients ( n = 169 ) chronically infected with HBV ( hepatitis B e antigen [HBeAg]-positive and -negative ) were evaluated for efficacy . RESULTS Compared with lamivudine , entecavir reduced HBV DNA by an additional 0.97 log(10 ) at the 0.1-mg/day dose and an additional 1.28 log(10 ) at the 0.5-mg/day dose ( P < 0.0001 ) . A clear dose-response relationship was observed for entecavir with the higher doses showing significantly greater viral suppression . In patients treated with entecavir 0.5 mg/day , 83.7 % had an HBV-DNA level below the lower limit of detection of the Quantiplex branched DNA ( bDNA ) assay ( Bayer-Versant Diagnostics , formerly Chiron Diagnostics , Emeryville , CA ) , compared with 57.5 % treated with 100 mg/day lamivudine ( P = 0.008 ) . In both treatment arms , very few patients achieved HBeAg loss and /or seroconversion by week 22 . More patients treated with the 0.1-mg/day and 0.5-mg/day doses of entecavir had normalization of alanine transaminase ( ALT ) levels at week 22 compared with lamivudine ( P = not significant ) . Entecavir was well tolerated ; most adverse events were mild to moderate , transient , and comparable in all study arms . CONCLUSIONS This study showed that entecavir has potent antiviral activity against HBV at 0.1-mg/day and 0.5-mg/day doses , both of which were superior to lamivudine in chronically infected HBV patients BACKGROUND AND AIMS Adefovir dipivoxil possesses potent in vitro and in vivo antiviral activity in wild-type hepatitis B. This study assessed the safety and efficacy of adefovir dipivoxil alone and in combination with lamivudine compared with ongoing lamivudine therapy in patients with chronic hepatitis B with compensated liver disease and lamivudine-resistant hepatitis B virus ( HBV ) . METHODS Fifty-nine hepatitis B e antigen (HBeAg)-positive patients with genotypic evidence of lamivudine-resistant HBV , serum alanine aminotransferase ( ALT ) level > or = 1.2 times the upper limit of normal , and serum HBV DNA level > or = 6 log(10 ) copies/mL despite ongoing treatment with lamivudine were r and omized to adefovir dipivoxil 10 mg , lamivudine 100 mg , or addition of adefovir dipivoxil to ongoing lamivudine daily . The primary end point was the time-weighted average change from baseline in serum HBV DNA level ( DAVG ) up to week 16 . RESULTS Rapid reductions in serum HBV DNA level were seen by 4 weeks in all recipients of adefovir dipivoxil ; DAVG(16 ) was -0.07 in the lamivudine group compared with -2.45 and -2.46 log(10 ) copies/mL in the adefovir dipivoxil/lamivudine and adefovir dipivoxil monotherapy groups , respectively ( P < 0.001 ) . Median change from baseline in serum HBV DNA level at week 48 was 0.0 , -3.59 , and -4.04 log(10 ) copies/mL in the lamivudine , adefovir dipivoxil/lamivudine , and adefovir dipivoxil groups , respectively . ALT level normalized in 10 of 19 ( 53 % ) and 9 of 18 ( 47 % ) recipients of adefovir dipivoxil/lamivudine and adefovir dipivoxil , respectively , compared with 1 of 19 ( 5 % ) recipients of lamivudine . Three patients receiving adefovir dipivoxil or adefovir dipivoxil/lamivudine and none receiving lamivudine monotherapy were HBeAg negative at week 48 and one became hepatitis B surface antigen negative . CONCLUSIONS These data , limited to patients with compensated liver disease , indicate that adefovir dipivoxil alone or in combination with ongoing lamivudine therapy provides effective antiviral therapy in patients with lamivudine-resistant HBV BACKGROUND In pre clinical and phase 2 studies , adefovir dipivoxil demonstrated potent activity against hepatitis B virus ( HBV ) , including lamivudine-resistant strains . METHODS We r and omly assigned 515 patients with chronic hepatitis B who were positive for hepatitis B e antigen ( HBeAg ) to receive 10 mg of adefovir dipivoxil ( 172 patients ) , 30 mg of adefovir dipivoxil ( 173 ) , or placebo ( 170 ) daily for 48 weeks . The primary end point was histologic improvement in the 10-mg group as compared with the placebo group . RESULTS After 48 weeks of treatment , significantly more patients who received 10 mg or 30 mg of adefovir dipivoxil per day than who received placebo had histologic improvement ( 53 percent [ P<0.001 ] , 59 percent [ P<0.001 ] , and 25 percent , respectively ) , a reduction in serum HBV DNA levels ( by a median of 3.52 [ P<0.001 ] , 4.76 [ P<0.001 ] , and 0.55 log copies per milliliter , respectively ) , undetectable levels ( fewer than 400 copies per milliliter ) of serum HBV DNA ( 21 percent [ P<0.001 ] , 39 percent [ P<0.001 ] , and 0 percent , respectively ) , normalization of alanine aminotransferase levels ( 48 percent [ P<0.001 ] , 55 percent [ P<0.001 ] , and 16 percent , respectively ) , and HBeAg seroconversion ( 12 percent [ P=0.049 ] , 14 percent [ P=0.01 ] , and 6 percent , respectively ) . No adefovir-associated resistance mutations were identified in the HBV DNA polymerase gene . The safety profile of the 10-mg dose of adefovir dipivoxil was similar to that of placebo ; however , there was a higher frequency of adverse events and renal laboratory abnormalities in the group given 30 mg of adefovir dipivoxil per day . CONCLUSIONS In patients with HBeAg-positive chronic hepatitis B , 48 weeks of 10 mg or 30 mg of adefovir dipivoxil per day result ed in histologic liver improvement , reduced serum HBV DNA and alanine aminotransferase levels , and increased the rates of HBeAg seroconversion . The 10-mg dose has a favorable risk-benefit profile for long-term treatment . No adefovir-associated resistance mutations were identified in the HBV DNA polymerase gene BACKGROUND AND AIMS Prolonged lamivudine therapy is associated with treatment-resistant YMDD mutant hepatitis B virus ( HBV ) . We evaluated the efficacy and safety of adding adefovir dipivoxil to lamivudine in 135 patients with chronic hepatitis B ( CHB ) and YMDD mutant HBV . METHODS Ninety-five patients with compensated CHB ( group A ) were r and omized to adefovir 10 mg daily ( n = 46 ) or placebo ( n = 49 ) for 52 weeks while continuing treatment with lamivudine . Forty patients with decompensated hepatitis B or post-liver transplantation ( group B ) received adefovir and lamivudine . The primary end point was a decline in serum HBV DNA level to 10(5 ) copies/mL or a > 2 log(10 ) reduction from baseline at weeks 48 and 52 . RESULTS HBV DNA response occurred in 85 % of patients ( 39 of 46 ) in group A given combined therapy versus 11 % ( 5 of 46 ) receiving lamivudine alone ( P < 0.001 ) , with a significant change in HBV DNA level from baseline ( P < 0.001 ) between treatment groups ( median , -4.6 vs. + 0.3 log(10 ) copies/mL , respectively ) . Normalization of alanine aminotransferase levels occurred in 31 % of patients ( 14 of 45 ) receiving combined therapy versus 6 % ( 3 of 48 ) receiving lamivudine alone ( P = 0.002 ) . Ninety-two percent of patients ( 36 of 39 ) in group B had an HBV DNA response ( median change of -4.6 log(10 ) copies/mL ) and improved liver chemistries ( P < or = 0.001 ) . Both treatment regimens were well tolerated , and renal function abnormalities were not observed in either group . CONCLUSIONS The addition of adefovir dipivoxil to lamivudine in patients with CHB with compensated or decompensated liver disease due to YMDD mutant HBV is associated with virologic and biochemical improvement during 52 weeks of treatment and is well tolerated BACKGROUND & AIMS A previous 4-week trial of telbivudine in patients with chronic hepatitis B indicated marked antiviral effects with good tolerability , leading to the present 1-year phase 2b trial . METHODS This r and omized , double-blind , multicenter trial evaluated the efficacy and safety of telbivudine 400 or 600 mg/day and telbivudine 400 or 600 mg/day plus lamivudine 100 mg/day ( Comb400 and Comb600 ) compared with lamivudine 100 mg/day in hepatitis B e antigen (HBeAg)-positive adults with compensated chronic hepatitis B. RESULTS A total of 104 patients were r and omized 1:1:1:1:1 among the 5 groups . Median reductions in serum hepatitis B virus ( HBV ) DNA levels at week 52 ( log(10 ) copies/mL ) were as follows : lamivudine , 4.66 ; telbivudine 400 mg , 6.43 ; telbivudine 600 mg , 6.09 ; Comb400 , 6.40 ; and Comb600 , 6.05 . At week 52 , telbivudine monotherapy showed a significantly greater mean reduction in HBV DNA levels ( 6.01 vs 4.57 log(10 ) copies/mL ; P < .05 ) , clearance of polymerase chain reaction-detectable HBV DNA ( 61 % vs 32 % ; P < .05 ) , and normalization of alanine aminotransferase levels ( 86 % vs 63 % ; P < .05 ) compared with lamivudine monotherapy , with proportionally greater HBeAg seroconversion ( 31 % vs 22 % ) and less viral breakthrough ( 4.5 % vs 15.8 % ) ( P = NS for both ) . Combination treatment was not better than telbivudine alone . All treatments were well tolerated . In exploratory scientific analyses , clinical efficacy at 1 year appeared related to reduction in HBV DNA levels in the first 6 months of treatment . CONCLUSIONS Patients with chronic hepatitis B treated with telbivudine exhibited significantly greater virologic and biochemical responses compared with lamivudine . Results with the combination regimens were similar to those obtained with telbivudine alone . These data support the ongoing phase 3 evaluation of telbivudine for treatment of patients with chronic hepatitis Four hundred and eighty Chinese subjects with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B ( CHB ) were enrolled in a multicenter , double-blind , r and omized , placebo-controlled study of adefovir dipivoxil ( ADV ) 10 mg once daily . There was a significant difference in reduction of serum hepatitis B virus ( HBV ) DNA after 12 weeks between subjects who received ADV and those who received the placebo ( 3.4 and 0.1 log10 copies/mL , respectively , P < .001 ) . Further reductions in serum HBV DNA and increases in the proportion of subjects with an HBV DNA level of at most 10(5 ) copies/mL , with HBV DNA undetectable , and with ALT normalization were observed in ADV-treated subjects at week 52 ( median HBV DNA reduction of 4.5 log(10 ) copies/mL , 67 % with HBV DNA < or= 10(5 ) copies/mL , 28 % with HBV DNA undetectable , and 79 % with ALT normalization ) . Subjects who initially received ADV lost some treatment benefit after being rer and omized to the placebo in week 40 . Subjects with YMDD mutant HBV at baseline had virological , biochemical , and serological responses to treatment that were similar to those of subjects with wild-type HBV . The incidence of clinical ly adverse events was similar in nature and severity between the treatment groups , and there was no evidence of renal toxicity . No adefovir-related HBV mutations were identified . In conclusion , treatment with ADV 10 mg daily over 52 weeks was safe and effective in Chinese subjects with HBeAg-positive CHB and did not lead to the emergence of drug resistance . The study is continuing for an additional 4 years with all subjects on open-label ADV 10 mg daily BACKGROUND & AIMS Lamivudine treatment is associated with frequent development of resistant hepatitis B virus ( HBV ) and loss of treatment benefit . In pre clinical and phase II studies , entecavir demonstrated potent antiviral activity against lamivudine-resistant HBV . METHODS In this phase III , double-blind trial , hepatitis B e antigen-positive patients who were refractory to lamivudine therapy ( persistent viremia or documented YMDD mutations while receiving lamivudine ) were r and omized to switch to entecavir 1 mg daily ( n = 141 ) or continue lamivudine 100 mg daily ( n = 145 ) for a minimum of 52 weeks . Two co primary end points were assessed at 48 weeks : histologic improvement and a composite end point ( HBV branched DNA < 0.7 MEq/mL and alanine aminotransferase [ ALT ] < 1.25 times the upper limit of normal ) . RESULTS Histologic improvement occurred in 55 % ( 68/124 ) of entecavir-treated vs 28 % ( 32/116 ) of lamivudine-treated patients ( P < .0001 ) . More patients on entecavir than lamivudine achieved the composite end point : 55 % ( 77/141 ) vs 4 % ( 6/145 ) , respectively ( P < .0001 ) . Mean change from baseline in HBV DNA was -5.11 log(10 ) copies/mL for entecavir-treated patients and -0.48 log(10 ) copies/mL for lamivudine-treated patients ( P < .0001 ) . Virologic rebound because of entecavir resistance substitutions occurred in 2 of 141 of entecavir-treated patients , and genotypic evidence of resistance was detected in 10 patients . The safety profile of entecavir was comparable to lamivudine with fewer ALT flares on treatment . CONCLUSIONS In patients with lamivudine-refractory chronic hepatitis B , switching to entecavir provides superior histologic improvement , viral load reduction , and ALT normalization compared with continuing lamivudine , with a comparable adverse event profile BACKGROUND AND AIM Adefovir dipivoxil ( ADV ) is effective in lamivudine (LAM)-resistant hepatitis B e antigen-negative ( HBeAg(- ) ) chronic hepatitis B ( CHB ) . However , it is unclear whether LAM treatment should be continued in these patients . We aim ed to compare the long-term efficacy of adding ADV to ongoing LAM treatment versus switching to ADV monotherapy in LAM-resistant HBeAg(- ) CHB . METHODS Sixty LAM-resistant patients with HBeAg(- ) CHB were r and omly assigned ( 3:1 ) to combination therapy ( 10 mg ADV once daily plus ongoing LAM at 100 mg once daily [ n = 45 ] ) or 10 mg ADV monotherapy once daily ( n = 15 ) . Virological and biochemical responses were defined as hepatitis B virus (HBV)-DNA < 400 copies/mL and as normalization of alanine aminotransferase levels , respectively . RESULTS The median follow-up time was 53 months ( range 20 - 60 months ) . A virological response was observed in 38/45 ( 84.4 % ) and 11/15 ( 73.3 % ) patients in the ADV/LAM and ADV monotherapy groups , respectively ( P = 0.56 ) . Biochemical response rates were higher in the ADV/LAM group than in the ADV monotherapy group ( 90.9 % vs 57.1 % , respectively ; P = 0.01 ) . In the ADV/LAM group , serum HBV-DNA remained undetectable in all patients who achieved a virological response ( n = 38 ) . In the ADV monotherapy group , virological breakthrough occurred in four of the 11 patients who achieved a virological response ( 36.4 % ; P < 0.001 vs the ADV/LAM group , log-rank test ) . In addition , two patients in each group who did not achieve a virological response eventually developed ADV resistance . CONCLUSIONS Adding ADV to LAM is more effective than switching to ADV monotherapy in LAM-resistant patients with HBeAg(- ) CHB Chronic hepatitis B virus ( HBV ) infection is an important cause of morbidity and mortality in subjects coinfected with HIV . Tenofovir disoproxil fumarate ( TDF ) and adefovir dipivoxil ( ADV ) are licensed for the treatment of HIV‐1 and HBV infection , respectively , but both have in vivo and in vitro activity against HBV . This study evaluated the anti‐HBV activity of TDF compared to ADV in HIV/HBV‐coinfected subjects . ACTG A5127 was a prospect i ve r and omized , double‐blind , placebo‐controlled trial of daily 10 mg of ADV versus 300 mg of TDF in subjects with HBV and HIV coinfection on stable ART , with serum HBV DNA ≥ 100,000 copies/mL , and plasma HIV‐1 RNA ≤ 10,000 copies/mL. This study closed early based on results of a prespecified interim review , as the primary noninferiority end point had been met without safety issues . Fifty‐two subjects were r and omized . At baseline , 73 % of subjects had a plasma HIV‐1 RNA < 50 copies/mL , 86 % were HBeAg positive , 94 % were 3TC resistant , median serum ALT was 52 IU/L , and 98 % had compensated liver disease . The mean time‐weighted average change in serum HBV DNA from baseline to week 48 ( DAVG48 ) was −4.44 log10 copies/mL for TDF and −3.21 log10 copies/mL for ADV . There was no difference in toxicity between the 2 treatment arms , with 11 subjects ( 5 ADV and 6 TDF ) experiencing elevations of serum ALT on treatment . In conclusion , over 48 weeks , treatment with either ADV or TDF result ed in clinical ly important suppression of serum HBV DNA . Both drugs are safe and efficacious for patients coinfected with HBV and HIV . ( HEPATOLOGY 2006;44:1110–1116 . This study was undertaken to compare the early antiviral activity and viral kinetic profiles of entecavir ( ETV ) versus adefovir ( ADV ) in hepatitis B e antigen positive nucleoside‐naïve adults with chronic hepatitis B ( CHB ) . Sixty‐nine nucleoside‐naïve CHB patients with baseline HBV DNA of 108 copies/mL or more were r and omized 1:1 to open‐label treatment with entecavir 0.5 mg/day or adefovir 10 mg/day for a minimum of 52 weeks . The primary efficacy analysis compared mean reduction in HBV DNA at week 12 adjusted for baseline levels using linear regression . Entecavir was superior to adefovir for mean change from baseline in HBV DNA at week 12 ( −6.23 log10 copies/mL versus −4.42 log10 copies/mL , respectively ; mean difference −1.58 log10 copies/mL ; P < 0.0001 ) . Both drugs demonstrated biphasic viral kinetics , with a first phase of rapid decline lasting 10 days . A significant difference favoring ETV was reached at day 10 ( day 10 ETV−ADV difference estimate : −0.66 log10 copies/mL ; 95 % CI [ −0.30 , −0.01 ] ) . Early virological response was found to be predictive of subsequent virological response , with those having lower HBV DNA levels at day 10 being more likely to achieve HBV DNA of less than 300 copies/mL at week 48 . In addition , there was considerably less variability in the extent of HBV DNA reductions in patients treated with entecavir versus adefovir . Both the mean decrease in serum HBV DNA and the proportion of patients achieving HBV DNA less than 300 copies/mL were greater in entecavir‐treated than adefovir‐treated patients at weeks 2 , 4 , 8 , 12 , 24 , and 48 . At week 48 , one ( 3 % ) ETV‐treated versus 15 ( 47 % ) ADV‐treated patients had HBV DNA of 105 copies/mL or more . Both antivirals were well tolerated . Conclusion : Entecavir therapy result ed in earlier and superior reduction in HBV DNA compared with adefovir in nucleoside‐naïve HBeAg‐positive patients with CHB . ( HEPATOLOGY 2009;49:72‐79 . Background : Prolonged use of lamivudine in patients coinfected with HIV and hepatitis B virus ( HBV ) leads to an increasing risk of lamivudine resistance in both diseases . We investigated the addition of entecavir , a potent inhibitor of HBV polymerase , to lamivudine-containing highly active antiretroviral therapy ( HAART ) in patients who experienced rebound in HBV viremia while maintaining suppression of plasma HIV RNA less than 400 copies/ml . Methods : Sixty-eight patients were r and omized to entecavir 1 mg ( n = 51 ) or placebo ( n = 17 ) once daily for 24 weeks ; 65 patients continued the study with entecavir for an additional 24 weeks . Lamivudine-containing HAART was continued throughout . Results : At week 24 , the mean HBV DNA in entecavir-treated patients was 5.52 log10 copies/ml versus 9.27 log10 copies/ml for placebo , and at week 48 , it was 4.79 log10 copies/ml versus 5.63 log10 copies/ml , respectively . The mean HBV DNA change from baseline for entecavir was −3.65 log10 copies/ml ( versus + 0.11 for placebo , P < 0.0001 ) and alanine aminotransferase normalization in 34 % of patients ( versus 8 % for placebo , P = 0.08 ) . At 48 weeks , mean change in HBV DNA reached −4.20 log10 copies/ml in patients who received entecavir for the entire 48 weeks . The frequency of adverse events with entecavir and placebo was comparable . Through 48 weeks , no clinical ly relevant changes in HIV viremia or CD4 cell counts were identified . Conclusion : In this study , entecavir was associated with rapid , clinical ly significant reductions in HBV DNA , with maintenance of HIV viremia suppression , in HIV/HBV coinfected patients with HBV viremia while on lamivudine treatment |
14,079 | 30,247,198 | Discussion : Results indicate that pain-free participants show a larger OA response when rating pain continuously compared with individuals with chronic pain | Objective : Offset analgesia ( OA ) is a test paradigm increasingly used to estimate endogenous pain modulation characterized by a disproportionally profound analgesia after a small decrease of a heat stimulus .
This systematic review and meta- analysis examined the magnitude and difference of OA in healthy participants and chronic pain patients . | Background Offset analgesia is a disproportionate decrease of pain perception following a slight decrease of noxious thermal stimulus and attenuated in patients with neuropathic pain . We examined offset analgesia in patients with heterogeneous chronic pain disorders and used functional magnetic resonance imaging to explore modification of cerebral analgesic responses in comparison with healthy controls . Results We recruited seventeen patients with chronic pain and seventeen age- , sex-matched healthy controls . We gave a noxious thermal stimulation paradigm including offset analgesia and control stimuli on the left volar forearm , while we obtained a real-time continuous pain rating and a whole-brain functional magnetic resonance imaging . Baseline , first plateau ( 5 s ) , increment ( 5 s ) , and second plateau ( 20 s ) temperatures of offset analgesia stimulus were set at 32 ° C , 46 ° C , 47 ° C , and 46 ° C , respectively . Control stimulus included 30-s 46 ° C stimulus or only the first 10 s of offset analgesia stimulus . We evaluated magnitude of offset analgesia , analyzed cerebral activation by thermal stimulation , and further compared offset analgesia-related activation between the groups . Magnitude of offset analgesia was larger in controls than in patients ( median : 28.9 % ( interquartile range : 11.0–56.0 % ) vs. 19.0 % ( 4.2–48.7 % ) , p = 0.047 ) . During the second plateau , controls showed a larger blood oxygenation level-dependent activation than patients at the putamen , anterior cingulate , dorsolateral prefrontal cortices , nucleus accumbens , brainstem , and medial prefrontal cortex ( p < 0.05 ) , which are known to mediate either of descending pain modulation or reward responses . Offset analgesia-related activity at the anterior cingulate cortex was negatively correlated with neuropathic component of pain in patients with chronic pain ( p = 0.004 ) . Conclusions Attenuation of offset analgesia was associated with suppressed activation of the descending pain modulatory and reward systems in patients with chronic pain , at least in the studied cohort . The present findings might implicate both behavioral and cerebral plastic alterations contributing to chronification of pain . Clinical trial registry : The Japanese clinical trials registry ( UMIN-CTR , No. UMIN000011253 ; http://www.umin.ac.jp/ctr/ OBJECTIVE . The α2-agonist clonidine is an analgesic agent , whose yet uncertain action may involve either increase in pain modulation efficiency , change in autonomic function , and /or decrease in anxiety level . The present study aim ed to examine the effect of oral clonidine on pain perception in healthy subjects in order to reveal its mode of action . DESIGN . R and omized , double-blind , placebo-controlled study . SUBJECTS . Forty healthy subjects . METHODS . Subjects received either 0.15 mg oral clonidine or placebo . We measured pain parameters of heat pain thresholds , tonic heat stimulus , mechanical temporal summation , offset analgesia ( OA ) and conditioned pain modulation ( CPM ) ; autonomic parameters of deep breathing ratio and heart rate variability indices obtained before , during , and after tonic heat stimulus ; and psychological parameters of anxiety and pain catastrophizing . RESULTS . Clonidine decreased systolic blood pressure ( P = 0.022 ) and heart rate ( P = 0.004 ) and increased rMSSD ( P = 0.020 ) , though no effect was observed on pain perception , pain modulation , and psychological parameters . Autonomic changes were correlated with pain modulation capacity ; for OA , the separate slope model was significant ( P = 0.008 ) ; in the clonidine group , more efficient OA was associated with lower heart rate ( r = 0.633 , P = 0.005 ) , unlike in the placebo group . CONCLUSIONS . The change in autonomic function that was related to the increase in pain modulation capacity , and the lack of change in anxiety , suggest a combined modulatory-autonomic mode of analgesic action for clonidine & NA ; Inhibitory and facilitatory descending pathways , originating at higher central nervous system sites , modulate activity of dorsal horn nociceptive neurons , and thereby influence pain perception . Dysfunction of inhibitory pain pathways or a shift in the balance between pain facilitation and pain inhibition has been associated with the development of chronic pain . The N‐methyl‐d‐aspartate receptor antagonist ketamine has a prolonged analgesic effect in chronic pain patients . This effect is due to desensitization of sensitized N‐methyl‐d‐aspartate receptors . Additionally , ketamine may modulate or enhance endogenous inhibitory control of pain perception . Diffuse noxious inhibitory control ( DNIC ) and offset analgesia ( OA ) are 2 mechanisms involved in descending inhibition . The present study investigates the effect of a ketamine infusion on subsequent DNIC and OA responses to determine whether ketamine has an influence on descending pain control . Ten healthy subjects ( 4 men/6 women ) received a 1‐hour placebo or S(+)‐ketamine ( 40 mg per 70 kg ) infusion on 2 separate occasions in r and om order . Upon the termination of the infusion , DNIC and OA responses were obtained . After placebo treatment , significant descending inhibition of pain responses was present for DNIC and OA . In contrast , after ketamine infusion , no DNIC was observed , but rather a significant facilitatory pain response ( P < 0.01 ) ; the OA response remained unchanged . These findings suggest that the balance between pain inhibition and pain facilitation was shifted by ketamine towards pain facilitation . The absence of an effect of ketamine on OA indicates differences in the mechanisms and neurotransmitter influences between OA and DNIC . Diffuse noxious inhibitory control responses following a 1‐hour low‐dose ketamine treatment displayed facilitation of pain in response to experimental noxious thermal stimulation Background There is evidence for augmented processing of pain and impaired endogenous pain inhibition in Fibromyalgia syndrome ( FM ) . In order to fully underst and the mechanisms involved in FM pathology , there is a need for closer investigation of endogenous pain modulation . In the present study , we compared the functional connectivity of the descending pain inhibitory network in age-matched FM patients and healthy controls (HC).We performed functional magnetic resonance imaging ( fMRI ) in 42 subjects ; 14 healthy and 28 age-matched FM patients ( 2 patients per HC ) , during r and omly presented , subjectively calibrated pressure pain stimuli . A seed-based functional connectivity analysis of brain activity was performed . The seed coordinates were based on the findings from our previous study , comparing the fMRI signal during calibrated pressure pain in FM and HC : the rostral anterior cingulate cortex ( rACC ) and thalamus . Results FM patients required significantly less pressure ( kPa ) to reach calibrated pain at 50 mm on a 0–100 visual analogue scale ( p < .001 , two-tailed ) . During fMRI scanning , the rACC displayed significantly higher connectivity to the amygdala , hippocampus , and brainstem in healthy controls , compared to FM patients . There were no regions where FM patients showed higher rACC connectivity . Thalamus showed significantly higher connectivity to the orbitofrontal cortex in healthy controls but no regions showed higher thalamic connectivity in FM patients . Conclusion Patients with FM displayed less connectivity within the brain ’s pain inhibitory network during calibrated pressure pain , compared to healthy controls . The present study provides brain-imaging evidence on how brain regions involved in homeostatic control of pain are less connected in FM patients . It is possible that the dysfunction of the descending pain modulatory network plays an important role in maintenance of FM pain and our results may translate into clinical implication s by using the functional connectivity of the pain modulatory network as an objective measure of pain dysregulation The endogenous analgesia ( EA ) system is psychophysically evaluated using various paradigms , including conditioned pain modulation ( CPM ) and offset analgesia ( OA ) testing , respectively , the spatial and temporal filtering processes of noxious information . Though both paradigms assess the function of the EA system , it is still unknown whether they reflect the same aspects of EA and consequently whether they provide additive or equivalent data . Twenty-nine healthy volunteers ( 15 males ) underwent 5 trials of different stimulation conditions in r and om order including : ( 1 ) the classic OA three-temperature stimulus train ( ‘ OA ’ ) ; ( 2 ) a three-temperature stimulus train as control for the OA ( ‘ OAcon ’ ) ; ( 3 ) a constant temperature stimulus ( ‘ constant ’ ) ; ( 4 ) the classic parallel CPM ( ‘ CPM ’ ) ; and ( 5 ) a combination of OA and CPM ( ‘ OA + CPM ’ ) . We found that in males , the pain reduction during the OA + CPM condition was greater than during the OA ( P = 0.003 ) and CPM ( P = 0.07 ) conditions . Furthermore , a correlation was found between OA and CPM ( r = 0.62 , P = 0.01 ) at the time of maximum OA effect . The additive effect found suggests that the two paradigms represent at least partially different aspects of EA . The moderate association between the CPM and OA magnitudes indicates , on the other h and , some commonality of their underlying mechanisms BACKGROUND Tapentadol is an analgesic agent for treatment of acute and chronic pain that activates the µ-opioid receptor combined with inhibition of neuronal norepinephrine reuptake . Both mechanisms are implicated in activation of descending inhibitory pain pathways . In this study , we investigated the influence of tapentadol on conditioned pain modulation ( CPM , an experimental measure of endogenous pain inhibition that gates incoming pain signals as a consequence of a preceding tonic painful stimulus ) and offset analgesia ( OA , a test in which a disproportionally large amount of analgesia becomes apparent upon a slight decrease in noxious heat stimulation ) . METHODS Twenty-four patients with diabetic polyneuropathy ( DPN ) were r and omized to receive daily treatment with tapentadol sustained-release ( SR ) [ average daily dose 433 ( 31 ) mg ] or placebo for 4 weeks . CPM and OA were measured before and on the last day of treatment . RESULTS Before treatment , none of the patients had significant CPM or OA responses . At week 4 of treatment , CPM was significantly activated by tapentadol SR and coincided with significant analgesic responses . CPM increased from 9.1 (5.4)% ( baseline ) to 14.3 (7.2)% ( placebo ) and 24.2 (7.7)% ( tapentadol SR , P<0.001 vs placebo ) ; relief of DPN pain was also greater in patients treated with tapentadol than placebo ( P=0.028 ) . Neither placebo nor tapentadol SR treatment had an effect on the magnitude of the OA responses ( P=0.78 ) . CONCLUSIONS Tapentadol 's analgesic effect in chronic pain patients with DPN is dependent on activation of descending inhibitory pain pathways as observed by CPM responses . CLINICAL TRIAL REGISTRATION The study was registered at trialregister.nl under number NTR2716 OBJECTIVE : To test the feasibility of creating a valid and reliable checklist with the following features : appropriate for assessing both r and omised and non-r and omised studies ; provision of both an overall score for study quality and a profile of scores not only for the quality of reporting , internal validity ( bias and confounding ) and power , but also for external validity . DESIGN : A pilot version was first developed , based on epidemiological principles , review s , and existing checklists for r and omised studies . Face and content validity were assessed by three experienced review ers and reliability was determined using two raters assessing 10 r and omised and 10 non-r and omised studies . Using different raters , the checklist was revised and tested for internal consistency ( Kuder-Richardson 20 ) , test-retest and inter-rater reliability ( Spearman correlation coefficient and sign rank test ; kappa statistics ) , criterion validity , and respondent burden . MAIN RESULTS : The performance of the checklist improved considerably after revision of a pilot version . The Quality Index had high internal consistency ( KR-20 : 0.89 ) as did the subscales apart from external validity ( KR-20 : 0.54 ) . Test-retest ( r 0.88 ) and inter-rater ( r 0.75 ) reliability of the Quality Index were good . Reliability of the subscales varied from good ( bias ) to poor ( external validity ) . The Quality Index correlated highly with an existing , established instrument for assessing r and omised studies ( r 0.90 ) . There was little difference between its performance with non-r and omised and with r and omised studies . Raters took about 20 minutes to assess each paper ( range 10 to 45 minutes ) . CONCLUSIONS : This study has shown that it is feasible to develop a checklist that can be used to assess the method ological quality not only of r and omised controlled trials but also non-r and omised studies . It has also shown that it is possible to produce a checklist that provides a profile of the paper , alerting review ers to its particular method ological strengths and weaknesses . Further work is required to improve the checklist and the training of raters in the assessment of external validity Summary The magnitude of offset analgesia is not altered by naloxone administration , by remifentanil analgesia , or during opioid‐induced hypersensitivity . Offset analgesia is therefore subserved by nonopioid mechanisms . ABSTRACT The mechanisms supporting temporal processing of pain remain poorly understood . To determine the involvement of opioid mechanisms in temporal processing of pain , responses to dynamic noxious thermal stimuli and offset analgesia were assessed after administration of naloxone , a μ‐opioid antagonist , and on a separate day , during and after intravenous administration of remifentanil , a μ‐opioid agonist , in 19 healthy human volunteers . Multiple end points were sample d from real‐time computerized visual analog scale ratings ( VAS , 1 to 10 ) to assess thermal sensitivity , magnitude and duration of offset analgesia , and painful after sensations . It was hypothesized that the magnitude of offset analgesia would be reduced by direct opioid antagonism and during states of acute opioid‐induced hypersensitivity ( OIH ) , as well as diminished by the presence of exogenous opioids . Surprisingly , the magnitude of offset analgesia was not altered after naloxone administration , during remifentanil infusion , or after the termination of remifentanil infusion . Because thermal hyperalgesia was observed after both drugs , 8 of the original 19 subjects returned for an additional session without drug administration . Thermal hyperalgesia and increased magnitude of offset analgesia were observed across conditions of remifentanil , naloxone , and no drug within this subset analysis , indicating that repeated heat testing induced thermal hyperalgesia , which potentiated the magnitude of offset analgesia . Thus , it is concluded that the mechanisms subserving temporal processing of nociceptive information are largely opioid‐independent , but that offset analgesia may be potentiated by heat‐induced thermal hyperalgesia in a proportion of individuals OBJECTIVE Conditioned pain modulation ( CPM ) and offset analgesia ( OA ) are considered to represent paradigms of descending inhibitory pain modulation in humans . This study tested the effects of hydromorphone therapy on descending inhibitory pain modulation , as measured by changes from baseline in the magnitudes of CPM and OA . DESIGN Prospect i ve evaluation . SETTING Institute of Pain Medicine , Rambam Health Care Campus . SUBJECTS Patients with chronic radicular pain . METHODS Thirty patients received 4 weeks of oral hydromorphone treatment at an individually titrated dose ( mean ± st and ard deviation dose of 11.6 ± 4.8 mg/day ) . CPM and OA were assessed before and after hydromorphone treatment . CPM was assessed by subtracting the response to a painful phasic heat stimulus administered simultaneously with a conditioning cold pain stimulus , from the response to the same heat stimulus administered alone . The OA paradigm consisted of a three-temperature stimuli train ( T1 = 49 ° C [ 5 seconds ] , T2 = 50 ° C [ 5 seconds ] , and T3 = 49 ° C [ 20 seconds ] ) . The magnitude of OA was quantified by subtracting minimal pain scores obtained during T3 from the maximal pain scores obtained during T2 . RESULTS CPM scores changed from a baseline of 17.7 ± 20.6 to 21 ± 20.4 following treatment , and OA scores changed from 7.8 ± 20.5 to 9.7 ± 14.6 . Wilcoxon signed rank test indicated that these changes were not significant ( CPM : P = 0.22 ; OA : P = 0.44 ) . McNemar test revealed that the percentage of patients who exhibited a change in the direction of CPM or OA in response to hydromorphone treatment was not significant ( CPM : P = 0.37 ; OA : P = 0.48 ) . CONCLUSIONS These results suggest that the descending inhibitory pain modulation , as manifested in humans by CPM and OA , is unlikely to be mediated by hydromorphone therapy |
14,080 | 30,363,010 | Compared with placebo , all vaginal estrogens demonstrated superiority in objective endpoints and subjective endpoints of GSM , whereas some trials demonstrated superiority versus placebo in urogenital symptoms .
No significant difference was observed between various dosages and dosage forms of vaginal estrogen products .
Vaginal estrogen showed superiority over vaginal lubricants and moisturizers for the improvement of objective clinical endpoints of vulvovaginal atrophy but not for subjective endpoints .
Unopposed vaginal estrogens seemed safe , although studies were not powered to detect a long-term estrogenic side effect .
Conclusion : Estrogen products were found to be clinical ly effective for the treatment of GSM with doses as low as 4 & mgr;g .
Vaginal estrogen products seem to be safe with few adverse effects , although there is a lack of long-term controlled clinical trial safety data . | Objective : We up date d a systematic review to evaluate the totality of evidence available for the efficacy and safety of vaginal estrogen products for the treatment of genitourinary syndrome of menopause ( GSM ) based on published r and omized controlled trials .
This review supports the use of commercially available vaginal estrogen therapies as an effective and safe first-line therapy for the treatment of moderate-to-severe GSM | Silicone vaginal rings for the continuous release of 17 beta-oestradiol ( E2 ) with 2 constant in vitro release rates were used for the treatment of symptoms of urogenital atrophy in 2 groups of postmenopausal women . The very low dose of 7 micrograms/24 h was found to alleviate atrophic symptoms effectively and to induce significant maturation of vaginal and urethral epithelium . After a brief initial peak , the serum levels of E2 over 3 mth of treatment remained close to the detection limit . The ' undetectable ' E2 release pattern was reflected only in increased levels of oestrone sulphate . There was no evidence of a systemic metabolic response and patient acceptance of the method was excellent . Continuous low-dose release of E2 via vaginal rings consequently offers an alternative means of administering local oestrogen therapy which may be particularly suitable for geriatric patients The objective of the study was to assess the effects of low-dose vaginal treatment with oestradiol before vaginal operation . In a double-blind r and omized study including 43 postmenopausal women scheduled for vaginal repair operation for genital descensus , it was found that 7 patients suffered from concomitant urinary stress incontinence . Vagifem ( 25 micrograms oestradiol ) or placebo was administered as vaginal pessaries daily , 3 weeks prior to surgery and the clinical effects evaluated . One month postoperatively the prevalence of bacteriuria ( > 100,000 CFU/ml urine ) was significantly lower when using oestradiol than in the placebo group . At follow-up 3 years later 40 women ( 93 % ) answered the question naires . None received hormone replacement therapy . Nineteen percent in the preoperative oestradiol group and 11 % in the preoperative placebo group had had more than two episodes of cystitis treated with antibiotics . This difference is not statistically significant ( p > 0.05 ) . Recurrent cystitis was not correlated to bacteriuria postoperatively . Seventy-nine percent of the women with genital prolapse but only 29 % of the women with concomitant urinary stress incontinence were cured ( p < 0.05 ) . Neither preoperative oestradiol treatment nor body weight had any influence on relapse . Preoperative low-dose vaginal oestradiol treatment may reduce the incidence of bacteriuria in the immediate postoperative period but no long-lasting effects on recurrent cystitis or relapse were seen . Longer-lasting hormone replacement therapy may be necessary to achieve lasting effects Importance Nearly half of postmenopausal women report bothersome vulvovaginal symptoms , but few data support the efficacy of 2 commonly recommended treatments . Objective To compare the efficacy of a low-dose vaginal estradiol tablet and a vaginal moisturizer , each vs placebo , for treatment of moderate-to-severe postmenopausal vulvovaginal symptoms . Design , Setting , and Participants This 12-week multicenter r and omized clinical trial enrolled postmenopausal women with moderate to severe symptoms of vulvovaginal itching , pain , dryness , irritation , or pain with penetration . Interventions Vaginal 10-&mgr;g estradiol tablet ( daily for 2 weeks , then twice weekly ) plus placebo gel ( 3 times a week ) ( n = 102 ) vs placebo tablet plus vaginal moisturizer ( n = 100 ) vs dual placebo ( n = 100 ) . Main Outcomes and Measures The main outcome was decrease in severity ( 0 - 3 ) of most bothersome symptom ( MBS ) between enrollment and 12 weeks . Additional measures included a composite vaginal symptom score , Female Sexual Function Index ( FSFI ) score ( 2 - 36 ) , modified Female Sexual Distress Score – Revised item 1 , treatment satisfaction and meaningful benefit , Vaginal Maturation Index , and vaginal pH. Results The 302 women had a mean ( SD ) age of 61 ( 4 ) years and were primarily white ( 267 [ 88 % ] ) , college educated ( 200 [ 66 % ] ) , and sexually active ( 245 [ 81 % ] ) . Most women ( 294 [ 97 % ] ) provided data for the primary analysis . The most commonly reported MBS was pain with vaginal penetration ( 182 [ 60 % ] ) , followed by vulvovaginal dryness ( 63 [ 21 % ] ) . Mean baseline MBS severity was similar between treatment groups : estradiol , 2.4 ( 95 % CI , 2.3 to 2.6 ) ; moisturizer , 2.5 ( 95 % CI , 2.3 to 2.6 ) ; placebo , 2.5 ( 95 % CI , 2.4 to 2.6 ) . All treatment groups had similar mean reductions in MBS severity over 12 weeks : estradiol , −1.4 ( 95 % CI , −1.6 to −1.2 ) ; moisturizer , −1.2 ( 95 % CI , −1.4 to −1.0 ) ; and placebo , −1.3 ( 95 % CI , −1.5 to −1.1 ) . No significant differences were seen between estradiol ( P = .25 ) or moisturizer ( P = .31 ) compared with placebo . Mean total FSFI improvement was similar between estradiol ( 5.4 ; 95 % CI , 4.0 to 6.9 ) and placebo ( 4.5 ; 95 % CI , 2.8 to 6.1 ) ( P = .64 ) , and between moisturizer ( 3.1 ; 95 % CI , 1.7 to 4.5 ) and placebo ( P = .17 ) . Conclusions and Relevance Our results suggest that neither prescribed vaginal estradiol tablet nor over-the-counter vaginal moisturizer provides additional benefit over placebo vaginal tablet and gel in reducing postmenopausal vulvovaginal symptoms . Trial Registration clinical trials.gov Identifier : OBJECTIVE : To evaluate the efficacy of two vaginal doses of estradiol ( E2 ) compared with placebo in the treatment of atrophic vaginitis . METHODS : In a multi-center , r and omized , double-blind , parallel-group study , 230 postmenopausal women received treatment with 25 mcg or 10 mcg E2 or placebo for 12 weeks . Efficacy was measured through composite score of three vaginal symptoms and grading of vaginal health . Additional analyses included maturation of vaginal and urethral mucosa . Safety assessment s included endometrial biopsy , adverse events , changes in laboratory tests , and physical examinations . After 12 weeks of treatment , all patients were switched to the open-label extension and received treatment with 25 mcg E2 up to week 52 . RESULTS : Vaginal tablets with 25 mcg and 10 mcg E2 showed significant ( P<.001 ) improvement in composite score of vaginal health . Other results with 10 mcg E2 were not entirely consistent with those for 25 mcg E2 . Over 12 weeks , both active treatments result ed in greater decreases in vaginal pH than placebo . There were no significant differences between the 25 mcg and 10 mcg E2 groups in terms of improvements in maturation value or composite score of three vaginal symptoms . The efficacy was maintained to week 52 with 25 mcg E2 . CONCLUSION : Vaginal tablets with 25 mcg and 10 mcg E2 provided relief of vaginal symptoms , improved urogenital atrophy , decreased vaginal pH , and increased maturation of the vaginal and urethral epithelium . Those improvements were greater with 25 mcg than with 10 mcg E2 . Both doses were effective in the treatment of atrophic vaginitis . CLINICAL TRIAL REGISTRATION : Clinical Trials.gov , www . clinical trials.gov , NCT00465192 and NCT00464971 LEVEL OF EVIDENCE : Objective : The aim of this study was to evaluate the efficacy and safety of low-dose conjugated estrogens ( CE ) cream for treatment of atrophic vaginitis . Methods : Postmenopausal women ( N = 423 ) with moderate-to-severe vaginal atrophy were r and omized to CE cream 0.3 mg or placebo once daily ( 21 days on/7 days off ) or twice weekly for 12 weeks , followed by open-label treatment with CE cream for 40 weeks consistent with their prior regimen . Primary endpoints were changes in vaginal maturation index ( VMI ; percentage of superficial cells ) , vaginal pH , and severity of participant-reported most bothersome symptom ( vaginal dryness , itching , burning , or dyspareunia ) at week 12 . Endometrial safety was assessed by transvaginal ultrasound and endometrial biopsy for 52 weeks . Results : At week 12 , improvements in VMI with daily and twice-weekly use of low-dose CE cream ( 27.9 % and 25.8 % , respectively ) were significantly greater compared with placebo ( 3.0 % and 1.0 % , respectively ; P < 0.001 ) . Improvements in vaginal pH with daily and twice-weekly CE cream ( −1.6 for both ) were also significantly greater relative to placebo ( −0.4 and −0.3 , respectively ; P < 0.001 ) . VMI and vaginal pH responses were sustained through 52 weeks . Both CE cream regimens significantly reduced most bothersome symptom scores compared with placebo ( P ≤ 0.001 ) , including those for dyspareunia ( P ≤ 0.01 ) . There was no report of endometrial hyperplasia or carcinoma . Adverse events occurred with similar frequency among the active and placebo groups during the double-blind phase . Conclusions : Daily and twice-weekly use of low-dose CE cream was equally effective in relieving symptoms of vulvovaginal atrophy . Both regimens showed endometrial safety and sustained efficacy during 1 year of therapy PURPOSE To evaluate the clinical efficacy and safety of intravaginal application of 25 microg micronized oestradiol in postmenopausal women from the Greek population suffering from symptoms related to vaginal atrophy . MATERIAL S AND METHODS 91 women suffering from vaginal dryness , vaginal itching and dyspareunea were treated with 25 microg 17beta-oestradiol vaginal tablets . The duration of treatment was 12 weeks . During the first two weeks the women inserted one vaginal tablet intravaginally once daily . Thereafter , the women inserted one tablet twice per week with at least a 3-day interval between treatments to maintain therapeutic response for ten weeks . Efficacy was evaluated by the relief of vaginal symptoms and safety by the concentrations of serum oestradiol ( E2 ) and follicular-stimulating hormone ( FSH ) . Pretreatment and post-treatment findings were compared and each patient served as her own control . RESULTS The rates of symptoms of vaginal dryness , vaginal itching and dyspareunea showed statistically significant differences over the course of the trial ( Cochran Q test , p < 0.001 ) . No one complained of vaginal dryness and vaginal itching after four and six weeks of treatment respectively , while in one patient the sensation of dyspareunea remained constant after the fourth week of treatment . Despite the statistically significant increase in blood oestradiol levels in relation to baseline values ( ANOVA model of repeated measures , p < 0.001 ) , these levels were within the normal range for postmenopausal women . Also , serum FSH levels were statistically significantly reduced from 47.4 mIU/ml at entry into the study to 45.5 mIU/ml after two weeks of treatment ( dependent sample s t-test , p < 0.003 ) , but were clearly within the postmenopausal range . CONCLUSIONS The twice-weekly local single treatment with vaginal tablets containing 25 microg of 17beta-oestradiol was effective and safe for the relief of symptoms related to atrophic vaginitis in postmenopausal women from the Greek population Background : Vaginal atrophy is a common complication in menopause which does not improve with time and , if untreated , can affect the quality of life for women . The aim of this study was to compare the effectiveness of the vaginal cream of hyaluronic acid and conjugated estrogen ( Premarin ) in treatment of vaginal atrophy . Methods : This study was a r and omized controlled clinical trial on 56 menopausal women with symptoms of vaginal atrophy ; they were r and omly allocated to two groups ( recipient conjugated estrogen and hyaluronic acid ) . The severity of each sign of atrophy was evaluated by visual analog signals ( VAS ) and on the basis of a four point scale . Also to recognize the cellular maturation with pap smear and the maturation degree were calculated according to the formula and scores 0 - 100 . As to the vaginal PH , we used PH marker b and , the rate of which was divided into 4 degrees . Data were analyzed using SPSS , version 20 , and P≤0.05 was considered as significant . Results : The results of this study showed that the symptoms of vaginal atrophy compared with the baseline level were relieved significantly in both groups . Dryness , itching , maturation index , PH and composite score of the vaginal symptoms were relieved significantly in both groups ( P<0.001 ) . Dyspareunia in Premarin ( P<0.05 ) and hyaluronic acid ( P<0.001 ) decreased compared with pre-treatment . Urinary incontinence only showed improvement in the hyaluronic acid group ( P<0.05 ) . Improvement in urinary incontinence , dryness , maturation index ( P<0.05 ) and composite score of vaginal symptoms ( P<0.001 ) in the hyaluronic acid group was better than those in the Premarin group . Conclusion : According to the results of the present study , hyaluronic acid and conjugated estrogen improved the symptoms of vaginal atrophy . But hyaluronic acid was more effective and this drug is suggested for those who do not want to or can not take local hormone treatment . Trial Registration Number : I RCT Fifty-one post-menopausal women suffering from symptoms of oestrogen deficiency-derived atrophic vaginitis were treated intravaginally with two therapeutic regimens based on doses of 25 micrograms 17 beta-oestradiol ( E2 ) in an open , controlled study . All the patients received treatment daily for 2 weeks by way of induction therapy . They were then r and omly allocated to either once-weekly ( 17 patients ) or twice-weekly ( 34 patients ) vaginal administration for a further 50 weeks as maintenance treatment . Endometrial histopathology was evaluated before and after 1 year of treatment . The effects on symptoms and oestrogen/gonadotrophin levels were determined before and after 2 , 12 , 24 , 36 and 52 weeks of therapy . Nine women continued twice-weekly treatment for a further year , meaning that they underwent treatment for a total period of 2 years . Endometrial biopsies were obtained after 2 years of treatment . All the pretreatment endometrial biopsies indicated an atrophic endometrium . One patient out of the 14 who completed 1 year of therapy in the group treated once weekly showed weak proliferation of the endometrium , while the other 13 had an atrophic endometrium . In the group treated twice weekly , 2 out of the 31 patients who completed the study showed weak proliferation of the endometrium . The other 29 had an atrophic endometrium . All 9 women who received treatment for 2 years had an atrophic endometrium at the end of the treatment period . The twice-weekly dosage regimen gave complete relief of symptoms in almost all patients , whereas the majority of the patients in the group treated once weekly still had mild symptoms . No adverse effects were reported . ( ABSTRACT TRUNCATED AT 250 WORDS CONTEXT Pelvic organ prolapse ( POP ) increases in prevalence with age ; recurrence after surgical repair is common . OBJECTIVE The objective of the study was to determine the effects of local estrogen treatment on connective tissue synthesis and breakdown in the vaginal wall of postmenopausal women planning surgical repair of POP . DESIGN This was a r and omized trial . SETTING The study was conducted at an academic tertiary medical center . PATIENTS OR OTHER PARTICIPANTS Postmenopausal women with a uterus and symptomatic anterior and /or apical prolapse at stage 2 or greater participated in the study . INTERVENTION Estrogen ( Premarin ) or placebo cream for 6 weeks preoperatively was the intervention . MAIN OUTCOME MEASURES Full-thickness anterior apical vaginal wall biopsies were obtained at the time of hysterectomy and analyzed for mucosa and muscularis thickness , connective tissue synthesis , and degradation . Serum levels of estrone and 17β-estradiol were analyzed at baseline and the day of surgery using highly sensitive liquid chromatography-t and em mass spectrometry . RESULTS Fifteen women per group ( n = 30 total ) were r and omized ; 13 per group underwent surgery . Among drug-adherent participants ( n = 8 estrogen , n = 13 placebo ) , epithelial and muscularis thickness was increased 1.8- and 2.7-fold ( P = .002 and P = .088 , respectively ) by estrogen . Collagen types 1α1 and 1α2 mRNA increased 6.0- and 1.8-fold in the vaginal muscularis ( P < .05 for both ) ; collagen type Ia protein increased 9-fold in the muscularis ( P = .012 ) , whereas collagen III was not changed significantly . MMP-12 ( human macrophage elastase ) mRNA was suppressed in the vaginal mucosa from estrogen-treated participants ( P = .011 ) , and matrix metalloprotease-9 activity was decreased 6-fold in the mucosa and 4-fold in the muscularis ( P = .02 ) . Consistent with menopausal norms , serum estrone and 17β-estradiol were low and did not differ among the two groups . CONCLUSIONS Vaginal estrogen application for 6 weeks preoperatively increased synthesis of mature collagen , decreased degradative enzyme activity , and increased thickness of the vaginal wall , suggesting this intervention improves both the substrate for suture placement at the time of surgical repair and maintenance of connective tissue integrity of the pelvic floor OBJECTIVE To assess the efficacy , tolerability , and acceptance of a vaginal ring delivering the equivalent of 50 or 100 microg per day of estradiol ( E2 ) , compared with placebo , for relief of moderate to severe vasomotor symptoms and urogenital symptoms in postmenopausal women . METHODS Women with moderate to severe vasomotor symptoms ( seven or more per day or 56 per week average ) received 13 weeks of treatment with a vaginal ring delivering 50 microg per day E2 ( n = 113 ) or 100 microg per day E2 ( n = 112 ) , or a placebo vaginal ring ( n = 108 ) . Severity of vasomotor symptoms was assessed by a daily diary card and the Greene Climacteric Scale . Urogenital signs and symptoms were evaluated via patient and physician assessment and vaginal cytology . Participant satisfaction with the vaginal ring was evaluated via question naire . RESULTS Vasomotor symptoms significantly improved in both treatment groups , compared with placebo ( P < .05 ) . There was a trend toward greater improvement in patient assessment of urogenital signs with active rings compared with placebo . For women with vaginal atrophy at baseline ( n = 60 ) , the maturation index improved significantly in both treatment groups compared with placebo . Total Greene Climacteric Scale scores significantly improved for both E2 vaginal ring groups ( P < .05 ) compared with placebo . The vaginal rings were well tolerated . Most adverse events were mild or moderate and consistent with estrogen therapy . CONCLUSION A novel vaginal ring delivering the equivalent of 50 or 100 microg per day of E2 significantly reduced the number and severity of vasomotor symptoms and improved urogenital symptoms , compared with placebo . The E2 vaginal ring was well tolerated Vaginal atrophy can be reversed for most women through systemic hormones . Those women who can not take systemic hormones can get relief of symptoms with local estrogen therapy , which ideally should be locally effective without significant systemic absorption and without endometrial stimulation . An estradiol-releasing vaginal ring was therefore tested for efficacy , safety and patient acceptability in a 15-week open-label , r and omized parallel group trial with blinded evaluations of the cytological response data . Conjugated estrogen vaginal cream was used as a reference control . The primary objectives of the study were to evaluate whether the two treatments were equivalent regarding improvement in urogenital atrophy , improvement in physicians 's overall evaluation of product performance on urinary and /or vaginal changes , and improvement in patient 's assessment of urinary and /or vaginal symptoms . A secondary objective was to assess frequency of endometrial overstimulation during estrogen replacement therapy , to be measured by a progestogen challenge test . The ring and cream treatment produced an equivalent effect on the vaginal mucosa , and equivalence was also found in physician 's and patient 's assessment s of both vaginal and urinary symptomatology . Both treatments were equally effective in improving the vaginal pH toward levels normally seen in fertile women ( < 5.0 ) . With regard to endometrial stimulation , significantly more patients had bleedings at progestogen challenge test after 3 months of treatment with cream than with the ring . The ring , however , was given significantly better overall product acceptability ratings by the patients . It can therefore be seen as an equally effective , but significantly more acceptable , new administration form for treatment of urogenital disorders due to estrogen deficiency , with a more favourable safety profile than vaginal cream OBJECTIVE To compare the effects of oral and vaginal estrogen therapy ( ET ) on the lower urinary tract in postmenopausal women with prior hysterectomy . DESIGN R and omized , prospect i ve study . SETTING Tertiary teaching hospital . PATIENT(S ) Fifty-seven hysterectomized , postmenopausal women . INTERVENTION(S ) Patients were r and omized to receive either oral ( 0.625 mg of conjugated equine E per tablet ; n = 27 ) or topical ( 0.625 mg conjugated equine E per 1 g vaginal cream ; n = 30 ) E , administered once daily . MAIN OUTCOME MEASURE(S ) All subjects had E2 measurements , urinalysis , pelvic examination , introital color Doppler ultrasonographies , and personal interviews with the Bristol Female Lower Urinary Tract Symptoms Question naires before and 3 months after ET . RESULT ( S ) A higher serum level of E2 was noted in the oral group compared with the topical group after ET . The post-ET pulsatility index of periurethral vessels and bladder neck revealed statistically significant decreases in both groups . The incidences of urinary frequency and nocturia were significantly decreased after 3 months of ET in both groups . Changes in the incidence of other symptoms , including stress incontinence and urge incontinence , were not statistically significant . However , subjective improvement of stress incontinence was found in 72.7 % of the oral group and 60 % of the topical group . CONCLUSION ( S ) The results suggest that ET alone , by an oral or vaginal route , could increase the blood flow around the bladder neck and mid-urethra and relieve the symptoms of overactive bladder and stress incontinence in postmenopausal women with prior hysterectomy . In addition , vaginal preparations are as effective as systemic therapy at the lower serum level of E2 Estrogen and progesterone receptors in the cytosol ( ERc , PRc ) and estrogen receptors in the nuclear compartment ( ERn ) were measured in the endometrium , myometrium and vagina of 29 postmenopausal women who underwent hysterectomy . The effects of vaginal estriol ( 0.5 mg daily ) compared to 17 beta-estradiol ( 0.05 mg daily ) therapy on these receptor levels were studied . In addition , the endometrium was examined by light microscopy for estrogenic stimulation . We found biochemical and histological signs of estrogenic stimulation in all three tissues after estradiol as well as estriol therapy . In the vagina the effect of both estrogens on the ERc concentration was different from that in the endometrium and myometrium . The effects of estradiol and estriol on the ERn were comparable in all three tissues . The PRc levels increased significantly in all tissues after estrogen therapy ; in the myometrium it was significantly higher after estriol than after estradiol applications . In conclusion , there were no clear differences between vaginal estradiol and estriol medication with regard to the effects on receptor levels in vaginal and uterine tissues . In the histological studies at the light microscopy level similar signs of estrogen stimulation of the endometrium were found following estradiol and estriol medication Objectives To assess the efficacy of an oestradiol‐releasing vaginal ring and oestriol pessaries in the alleviation of lower urinary tract symptoms occurring after the menopause OBJECTIVE To disclose a clinical and histopathological effect of local low-dose oestradiol treatment on the vagina . DESIGN A r and omised , double-blind trial . SETTING Two gynaecological departments at University Hospitals . SUBJECTS Forty-eight postmenopausal women scheduled for surgery because of genital prolapse . INTERVENTION 25 micrograms oestradiol or placebo , administered as vaginal pessaries daily , 3 weeks prior to surgery . MAIN OUTCOME MEASURES Cytological , histological and clinical changes of the vaginal mucosa . RESULTS The thickness of the vaginal wall increased as did the oestrogenic index . No clinical effect was seen apart from decreased incidence of recurrent cystitis postoperatively . CONCLUSIONS Preoperative oestrogen treatment has been shown to reduce the incidence of recurrent cystitis and may be needed for stimulation of vaginal mucosa ; the short-term clinical effect is not convincing , however OBJECTIVE Our purpose was to study the efficacy , safety , and acceptability of a new estradiol-releasing ( 6.5 to 9.5 micrograms per 24 hours ) silicone rubber vaginal ring compared with Ovesterin 0.5 mg estriol vaginal pessaries . STUDY DESIGN Gynecologic clinical status , vaginal pH , cytologic characteristics , and occurrence of bacteriuria were determined before starting and after 3 and 12 weeks of treatment in 146 postmenopausal women . RESULTS Both treatments alleviated the subjective and objective symptoms of estrogen deficiency excellently , and both were equally effective at restoring the vaginal pH to levels normally seen in fertile women ( < 5.5 ) . Vaginal cytologic studies showed a significant difference in maturation value in favor of the estradiol-releasing silicone rubber vaginal ring , as measured by the pathologist 's assessment of the proliferation of the vaginal mucosa . A total of 77 % of users were classified as responders , compared with 39 % in the pessary group . Both treatments were well accepted . The administration of the pessary was associated with a significantly higher ( p < 0.001 ) incidence of discomfort than that of the ring , which was given better ( p < 0.001 ) rating by the patients at the 12-week visit . A strong preference ( p < 0.001 ) for the ring was shown by patients with previous experience with pessaries . CONCLUSION Treatment of urogenital symptoms in postmenopausal women with an estradiol-releasing vaginal ring is shown to be an effective and safe method , exhibiting advantages over treatment with estriol vaginal pessaries A prospect i ve r and omised double-blind placebo-controlled trial of 17-beta oestradiol 25-mg vaginal tablets or placebo daily for 12 weeks was undertaken in 110 postmenopausal women with urinary frequency , urgency and /or urge incontinence recruited from a tertiary referral urogynaecology clinic . After 3 months the only statistically significant difference was a greater reduction in urinary urgency in those women with sensory urgency treated with 17-beta oestradiol compared to placebo . This may be due to the effective treatment of local vaginal atrophy by low-dose oestrogen rather than any effect on the lower urinary tract Background : Atrophic vaginitis is a disease , which affects up to 50 % of postmenopausal women . This study compared the effectiveness and user-friendliness of Vagifem ( an estradiol vaginal tablet ) and vaginal estrogen cream in the treatment of atrophic vaginitis . Material s and Methods : One hundred and sixty postmenopausal women with symptoms of atrophic vaginitis were r and omly divided into two groups of treatment with Vagifem or with vaginal estrogen cream for 12 weeks . Patients used the medication daily for the first 2 weeks of the study , and twice weekly . Severity of vaginal atrophy and four main symptoms of atrophic vaginitis including dysuria , dyspareunia , vaginal itching , and dryness were evaluated and compared before and after treatment . In addition , patients were asked regarding user-friendliness and hygienic issues of medications . Results : Both vaginal estrogen cream and Vagifem significantly improved symptoms of atrophic vaginitis but in terms of effectiveness for the treatment symptoms of atrophic vaginitis , there was no significant difference between the two medications . Vagifem compared to estrogen cream result ed in significantly lower rate of hygienic problems ( 0 % versus 23 % , P < 0.001 ) , and was reported by the patients as a significantly easier method of treatment ( 90 % versus 55 % , P < 0.0001 ) . Conclusion : This investigation showed that Vagifem is an appropriate medication for the treatment of atrophic vaginitis , which is as effective as vaginal estrogen creams and is more user-friendly Objective : To evaluate the safety and efficacy of TX-004HR vaginal estradiol soft-gel capsules for moderate-to-severe dyspareunia associated with postmenopausal vulvar and vaginal atrophy . Methods : In this r and omized , double-blind , placebo-controlled , phase 3 study , postmenopausal women with a self-identified most bothersome symptom of dyspareunia received 4 , 10 , or 25 & mgr;g TX-004HR or placebo for 12 weeks . Four co- primary efficacy endpoints were change from baseline to week 12 in percentages of superficial and parabasal cells , vaginal pH , and severity of dyspareunia . Secondary endpoints included severity of vaginal dryness and vulvar and /or vaginal itching or irritation . Endometrial histology and adverse events ( AEs ) were included in the safety endpoints . Results : In all , 764 women were r and omized ( modified intent-to-treat population , n = 747 ; mean age 59 y ) . Compared with placebo , all three doses of TX-004HR significantly improved the four co- primary endpoints ( P < 0.0001 for all , except dyspareunia with 4 & mgr;g , P = 0.0149 ) . Changes in cytology , pH , and dyspareunia were also significant at weeks 2 , 6 , and 8 . Vaginal dryness and vaginal itching/irritation improved . Sex hormone binding globulin concentrations did not change with treatment . TX-004HR was well-tolerated , with no clinical ly meaningful differences in treatment-emergent AEs versus placebo , and no treatment-related serious AEs or deaths . Conclusions : TX-004HR ( 4 , 10 , and 25 & mgr;g ) was safe , well-tolerated , and effective for treating moderate-to-severe dyspareunia within 2 weeks with minimal systemic estrogen exposure . This novel product may be a potential new treatment option for women experiencing postmenopausal vulvar and vaginal atrophy To determine whether the combined contraceptive pill used intravaginally was as effective as the st and ard conjugated estrogen cream for the treatment of urogenital symptoms in postmenopausal Thai women In a double‐blind parallel study daily intravaginal administration of conjugated estrogen cream and estradiol cream for 14 days relieved vasomotor and vaginal postmenopausal symptoms in 29 postmenopausal women . By day 14 , therapy with the estradiol vaginal cream result ed in plasma estrone and estradiol levels closer to those in premenopausal women than therapy with the conjugated estrogen cream . The extent of improvement and final estradiol plasma levels in the estradiol vaginal‐cream group correlated . There was no correlation with severity of symptoms or estradiol plasma level at baseline . The metabolism of the conjugated estrogen cream might account for absence of correlation between improvement and final estradiol plasma levels in the conjugated vaginal‐cream group Objective To evaluate the use and effect of early administration of vaginal estrogen via a continuous low-dose estradiol vaginal ring placed immediately after pelvic reconstructive surgery . Methods This was a r and omized controlled trial of 65 postmenopausal women undergoing vaginal reconstructive surgery . The subjects were r and omly assigned to receive an estradiol-releasing vaginal ring , placebo vaginal ring , or control without vaginal ring for 12 weeks immediately after vaginal reconstructive surgery . The primary outcome was tissue quality based on vaginal maturation 3 months postoperatively . Secondary outcome measures were subjective and objective signs of atrophy ; vaginal pH ; the presence of granulation tissue , microscopic inflammation , and major healing abnormalities ; and the ability to tolerate an intravaginal ring . Results At 12 weeks , the estradiol ring group had a significantly improved maturation value ( P<0.01 ) and objective atrophy assessment ( P<0.01 ) compared with the placebo ring and control arms . Granulation tissue was increased in the placebo ring arm ( P<0.01 ) . Subjective atrophy scores did not differ among the groups ( P=0.39 ) . Conclusions Early administration of vaginal estrogen after vaginal surgery via an estradiol-releasing ring is feasible and results in improved markers of tissue quality postoperatively compared to placebo and controls Abstract : Local estrogen substitution has been shown to be more appropriate than any systemic application for the treatment of urogenital symptoms of hormone defiency . The efficacy , safety and acceptability of a new low-dose drug delivery system consisting of an estradiol-releasing silicone vaginal ring was studied in two multicenter trials . In an open-label comparative trial a total of 219 postmenopausal women were r and omized to the estradiol-releasing vaginal ring or to estriol suppositories . In terms of efficacy both treatment arms were shown to be equivalent ; however , significantly higher rates of acceptability were found for the vaginal ring . In a double-blinded placebo-controlled study a total of 84 patients were r and omized to either treatment arm for a period of 24 weeks . The statistically significant improvement of the vaginal epithelial pH and maturation values demonstrated the efficacy of the estradiol-releasing vaginal ring compared to the placebo ring Twenty-four postmenopausal women with vaginal atrophy due to oestrogen deficiency were treated with 17 beta-oestradiol administered as vaginal tablets containing 10 and 25 micrograms , respectively , in a slow-release system ( Vagifem , Novo Nordisk , Denmark ) . All the women were treated for 2 weeks with each dose in a double-blind , cross-over study . Plasma concentrations of unconjugated oestradiol and unconjugated oestrone were measured at regular intervals for 24 h on days 1 and 14 of each treatment regimen . Cytological and clinical evaluations of the vaginal and urethral epithelium were also carried out . Initially , when the epithelium was still atrophic , dose-dependent absorption of oestradiol was demonstrated . After 14 days of treatment maturation of the vaginal epithelium was seen with both regimens and the absorption of oestradiol then declined significantly on both the 10 and the 25 micrograms dose . Oestrone levels remained unchanged and gonadotrophin levels were unaffected during treatment . Vaginal cytology showed maturation on both the 10 and the 25 micrograms dose , whereas urethral cytology showed a reduction in parabasal cells that was significant only on 25 micrograms . Clinical and subjective improvement was apparent on both doses and acceptance of treatment was good OBJECTIVES Determination of the efficacy and safety of vaginally administered low dose ( 25 microg ) micronized 17beta-estradiol in the management of patients with urogenital symptoms . METHODS A total of 1612 patients with urogenital complaints were r and omized to receive 25 microg of micronized 17beta-estradiol ( n=828 ) or placebo ( n=784 ) in a multicenter double-blind placebo-controlled study running for 12 months . Female patients were treated once a day over a period of 2 weeks , and then twice a week for the remaining of the 12 months with an active or placebo tablet . The assessment included full history- question naire , micturition diary , gynecologic and cystometric examination , transvaginal ultrasound , and serum 17beta-estradiol level determination . It was carried out at the beginning , and after 4 and 12 months of treatment . RESULTS The overall success rate of micronized 17beta-estradiol and placebo on subjective and objective symptoms of postmenopausal women with vaginal atrophy was 85.5 % , and 41.4 % , respectively . A significant improvement of urinary atrophy symptoms was determined in vaginal ERT group as compared with the beginning of the study ( 51.9 % vs. 15.5 % , P=0.001 ) . The maximal cystometric capacity ( 290 ml vs. 200 ml , P=0.023 ) , the volume of the urinary bladder at which patients first felt urgency ( 180 vs. 140 , P=0.048 ) , and strong desire to void ( 170 ml vs. 130 ml , P=0.045 ) were significantly increased subsequent to the micronized 17beta-estradiol treatment . The number of patients with uninhibited bladder contractions significantly decreased following micronized 17beta-estradiol as compared with pretreatment values ( 17/30 , P=0.013 ) . Side effects were observed in 61 ( 7.8 % ) patients treated with low dose micronized 17beta-estradiol . Therapy with 25 microg of micronized 17beta-estradiol did not raise serum estrogen level nor stimulated endometrial growth . CONCLUSIONS Local administration of 25 microg of micronized 17beta-estradiol is an effective and a safe treatment option in the management of women with urogenital complaints Objective : To compare the effects of oral and vaginal estrogen therapy ( ET ) on the vaginal blood flow and sexual function in postmenopausal women with previous hysterectomy . Design : Fifty-seven women were r and omized to receive either oral ( 0.625 mg of conjugated equine estrogens per tablet ; n = 27 ) or topical ( 0.625 mg conjugated equine estrogens per 1 g vaginal cream ; n = 30 ) estrogen administered once daily . All women underwent estradiol measurements , urinalysis , pelvic examination , introital color Doppler ultrasonographies , and personal interviews for sexual symptoms using a vali date d question naire before and 3 months after ET . Results : A higher serum level of estradiol was noted in the oral group compared with the topical group after 3 months of ET . There were significant increases in the number of vaginal vessels and the minimum diastole ( P < 0.01 ) , and marked decreases of pulsatility index values ( P < 0.01 ) in both groups after ET . Regarding the systolic peak , we found a significant decrease only in the topical group ( P < 0.05 ) . Although the post-ET prevalence of anorgasmia decreased significantly in both groups ( P < 0.05 ) , changes in other domains , including the rates of low libido and coital frequency , were not statistically significant ( P > 0.05 ) . In the topical group , ET improved sexual function on the vaginal dryness and dyspareunia domains in a statistically significant manner ( P < 0.05 ) , but this was not the case in the oral group ( P > 0.05 ) . However , the efficacy of oral ET for vaginal dryness and dyspareunia reached 80 % and 70.6 % , respectively . The corresponding figures of the topical ET were 79.2 % and 75 % . Conclusions : The results of our study suggest that ET alone in hysterectomized postmenopausal women increases the vaginal blood flow and improves some domains of sexual function , but it may not have an impact on diminished sexual desire or activity . Compared with systemic therapy , topical vaginal preparations are found to correlate with better symptom relief despite the lower serum level of estradiol Twenty ( 20 ) post-menopausal women , mean age 62.4 yr , presenting with symptoms associated with urogenital atrophy were treated intravaginally with daily doses of 25 and 50 micrograms oestradiol ( E2 ) in a double-blind , cross-over study . After r and omization , the patients started daily treatment with pessaries containing either 25 or 50 micrograms E2 for 3 wk , followed by a maintenance period of 6 wk during which the pessaries were used only twice a week . A 4-wk wash-out period was followed by another treatment period of 9 wk . The effects on the karyopyknotic index ( KPI ) and on endometrial histopathology were assessed before and after 3 , 9 , 16 and 22 wk of treatment . In the case of the 25 micrograms dose the mean KPI values were 34.7 and 20.9 % after 3 and 9 weeks of treatment , respectively , the corresponding figures after treatment with 50 micrograms E2 being 39.2 and 22.7 % . No dose-effect relationship was apparent from the vaginal cytology findings . Endometrial biopsies could not be taken systematic ally in all patients . Weak proliferation of the endometrium was observed in 1 woman after 3 wk of daily treatment with the 50 micrograms dose . No endometrial stimulation was detected in any of the patients after treatment with 25 micrograms daily . Beneficial clinical and cytological effects were obtained with both dosage regimens . Daily intravaginal administration of 25 micrograms E2 can accordingly be advocated for the treatment of urogenital symptoms attributable to oestrogen deficiency in post-menopausal women Objective To determine the potential interaction of oral raloxifene 60 mg/day on the efficacy of a low-dose , estradiol-releasing vaginal ring used to treat signs and symptoms of vaginal atrophy in postmenopausal women . Design R and omized , double-blind , placebo-controlled , parallel treatment trial of raloxifene and placebo with open-label 17&bgr;-estradiol ring . At 10 sites in the United States , 91 postmenopausal women with at least two signs of vaginal atrophy were treated with a 17&bgr;-estradiol ring and r and omized to receive concomitant raloxifene 60 mg/day or placebo for 6 months . Efficacy of treatments was evaluated by comparing investigator assessment s of genitourinary atrophic signs , vaginal maturation value , and participant assessment s of vaginal symptoms at 6 months . Other measures included rate and severity of hot flashes and assessment of sexual function . Uterine safety was assessed by endometrial biopsy and transvaginal ultrasound . Results In women treated with a 17&bgr;-estradiol ring , both the raloxifene and placebo treatment groups showed improvements in signs and symptoms of vaginal atrophy at 6 months , with no significant differences in degree of improvement between groups . There were no signs of endometrial proliferation in either group . Conclusions Concomitant administration of raloxifene does not alter the effects of the 17&bgr;-estradiol ring on alleviating signs and symptoms of genitourinary atrophy in postmenopausal women Objective To compare the effectiveness of the vaginal tablets of hyaluronic acid and estrodiol for the treatment of atrophic vaginitis . Material s and methods Forty-two postmenopausal women with symptoms of atrophic vaginitis were r and omized to take vaginal tablets of 25 μg estradiol ( n = 21 ) ( group I ) or 5 mg hyaluronic acid sodium salt ( n = 21 ) ( group II ) for 8 weeks . The symptoms of atrophic vaginitis were evaluated by a self-assessed 4-point scale of composite score and the degree of epithelial atrophy was determined as , none , mild , moderate and severe . Vaginal pH and maturation index were measured and compared in both the groups . Results The symptoms were relieved significantly in both the groups ( P < 0.001 ) . The relief of symptoms was significantly superior in group I compared with group II ( P < 0.05 ) . A significant decrease in epithelial atrophy and vaginal pH were detected in both the groups ( P < 0.01 ) after treatment . The vaginal maturation values were also significantly improved at both study groups ( P < 0.001 ) . The mean maturation value was significantly higher in group I when compared with group II ( P < 0.001 ) . Conclusion Both treatments provided relief of vaginal symptoms , improved epithelial atrophy , decreased vaginal pH , and increased maturation of the vaginal epithelium . Those improvements were greater in group I. Hyaluronic acid vaginal tablets can be used in patients with atrophic vaginitis who do not want to or can not take local estrogen treatment Objective : To compare serum 17&bgr;-estradiol ( E2 ) , estrone ( E1 ) , estrone sulfate , follicle-stimulating hormone , luteinizing hormone , sex hormone-binding globulin , vaginal pH , and the vaginal maturation indices in women using a low-dose transdermal patch releasing 14 & mgr;g of E2 per day and a vaginal ring releasing 7.5 & mgr;g of E2 per day . Design : Twenty-four postmenopausal women were r and omly assigned to either the patch ( n = 12 ) or the ring ( n = 12 ) for a 12-week study period . Serum E2 , E1 , estrone sulfate , follicle-stimulating hormone , luteinizing hormone , and sex hormone-binding globulin were measured by immunoassay at baseline and 6 and 12 weeks . Vaginal pH was determined at baseline and 6 and 12 weeks . Vaginal cytologic examinations for vaginal maturation index were done at baseline and 12 weeks . Results : Twenty women completed the study . The patch significantly increased serum E1 and E2 levels at 6 and 12 weeks ( P < 0.01 ) ; there was no significant increase in serum E1 and E2 levels with the ring . Both the patch and the ring significantly reduced vaginal pH at 6 ( P < 0.001 ) and 12 ( P < 0.001 ) weeks and significantly reduced the percentage of vaginal parabasal cells at 12 weeks with no significant difference between the two groups . Both preparations increased the proportion of superficial cells ; the increase was significant only with the patch ( P = 0.04 ) . Conclusions : A transdermal E2 skin patch releasing 14 & mgr;g of E2 per day had an effect on vaginal pH and vaginal maturation indices similar to that of a vaginal E2 ring releasing 7.5 & mgr;g of E2 per day . Therefore , this patch is likely to relieve symptoms of vulvovaginal atrophy The aim of the study was to investigate the effect of 25 micrograms 17 beta-estradiol administered as a small vaginal tablet ( Vagifem , Novo Nordisk A/S ) on the symptoms of the vagina related to atrophy . The study was design ed as a double-blind r and omized placebo controlled study running for 12 weeks . The women were treated once daily for 2 weeks with the active or the placebo tablet . During the subsequent 10 weeks the women were treated twice a week . One hundred and sixty-four women were included . Ten dropped out for minor reasons , most of these due to lack of effect in the placebo group . In the Vagifem group 78.8 % were suffering from moderate to severe atrophy of the vagina , compared with 81.9 % in the placebo group . After 2 weeks the percentages were 14.3 and 35.3 , respectively . After 12 weeks of treatment , 10.7 % in the Vagifem group compared with 29.9 % in the placebo group had moderate to severe atrophy ( P less than 0.0001 ) . A substantial part of the women complained about subjective symptoms such as vaginal dryness and dyspareunia . After 12 weeks of treatment , a significant improvement was found in the Vagifem group ( P less than 0.002 ) . Before treatment 53.1 % in the treatment group and 41.0 % in the placebo group were suffering from urological symptoms . After 2 weeks , 60.5 % of the women in the Vagifem group underwent a change for the better compared to 35.3 % in the placebo group . After 12 weeks of treatment the percentages in the two groups feeling an improvement were 62.8 % and 32.4 % . In this study local low-dose treatment with 25 micrograms 17 beta-estradiol was found to have a significant effect on the postmenopausal urogenital symptoms related to atrophy Background . Atrophic vaginitis is a common condition . This study compared the usefulness of estradiol vaginal tablets ( EVT ) and estriol vagitories ( EV ) in treatment of atrophic vaginitis Aims The major aims of the study were to compare the safety of a continuous low-dose estradiol-releasing vaginal ring ( ESTring ) to that of a vaginal estradiol tablet ( Vagifem ® ) on the endometrium and the relief of subjective symptoms and signs of urogenital estrogen deficiency . Quality of life and acceptability of treatment delivery were also assessed . Study design A prospect i ve , r and omized study in which women were assigned in a 2 : 1 ratio to ESTring and Vagifem and followed for 12 months . The primary endpoint was endometrial safety , based on the results of ultrasound measurement of endometrial thickness and a progestogen challenge test at baseline and week 48 . Efficacy was determined by subjective assessment of urogenital estrogen deficiency symptoms at baseline and weeks 3 , 12 , 24 , 36 and 48 and assessment of signs of vaginal epithelial atrophy by the clinician at baseline , 12 and 48 weeks . In addition , pelvic floor strength , vaginal cytological evaluation and pH , bacteruria and patient acceptability were assessed . Quality of life was assessed using a menopause-specific quality -of-life question naire and a 2-day bladder diary at baseline and 12 and 48 weeks . The comparability of the two groups was assessed using ANOVA , χ2 or Fisher 's exact tests . Results A total of 126 women were r and omized to ESTring and 59 to Vagifem . There was no statistical difference between the groups in the alleviation of symptoms and signs of urogenital estrogen deficiency . Maturation indices increased in both groups , from generally atrophic at baseline to proliferative or highly proliferative at 48 weeks . After 48 weeks of treatment , there was no statistically significant difference in endometrial thickness between the two groups . A statistically smaller proportion of bleeding/spotting occurred in the ESTring group ( n = 0 ) compared to the Vagifem users ( n = 4 ) . Estradiol and total estrone serum levels increased during treatment in both groups but remained within the normal postmenopausal range . General health status in both groups was unchanged but the urogenital component of health burden was significantly improved in both groups . Bladder diary variables showed no differences between treatment groups . Conclusion Equivalent endometrial safety and efficacy in the relief of the symptoms and signs of urogenital estrogen deficiency were demonstrated for the 12 months ' use of a low-dose estradiol-releasing vaginal ring and a vaginal estradiol tablet OBJECTIVES To determine if the efficacy of continuous low dose estradiol released from a vaginal ring is equivalent to estriol vaginal cream regarding improvement of the patient 's subjective feeling of vaginal dryness and to determine if there is a preference for either of the two study treatments . METHODS Open-label r and omized parallel group trial with active control with a blind evaluation of vaginal cytology and with a cross-over ( change-over ) phase for preference comparison . One hundred and sixty five postmenopausal women with symptoms of vaginal dryness and signs of vaginal atrophy were r and omized to an estradiol ring ( Estring ) or estriol cream ( Synapause ) . The duration of each treatment period was 12 weeks . RESULTS Both study treatments were equally effective regarding the ability to alleviate the symptom feeling of vaginal dryness and the signs of vaginal atrophy . Both treatments were efficient in restoring the vaginal mucosa , recorded as higher maturation values and as decreased vaginal pH. Estring was superior to estriol cream regarding preference of treatment . Both treatments were equivalent for the occurrence of adverse events , including bleeding . CONCLUSION data from this change-over study confirm efficacy and safety of both the vaginal ring and cream in the treatment of postmenopausal women with urogenital atrophy symptoms and signs . The patients had a strong preference for the vaginal ring OBJECTIVE : To evaluate the efficacy of ultra – low-dose 10-microgram 17&bgr;-estradiol ( E2 ) vaginal tablets for treatment of vaginal atrophy . METHODS : Postmenopausal women ( N=309 ) were r and omly assigned to 10-microgram E2 or placebo vaginal tablets for 52 weeks in a multicenter , double-blind study . Primary efficacy endpoints included change from baseline to week 12 in vaginal cytology , vaginal pH , and most bothersome urogenital symptoms score . Grading of vaginal health was a secondary efficacy assessment . Safety assessment s included endometrial biopsy , physical and gynecologic examinations , and recording adverse events . RESULTS : At week 12 , the change from baseline for 10 micrograms E2 compared with placebo demonstrated significant improvement in vaginal Maturation Index ( proportion of parabasal cells : –37 % compared with –9 % ; superficial cells : 13 % compared with 4 % ; intermediate cells : 24 % compared with 5 % ; P<.001 for each ) , Maturation Value ( 25.0 compared with 6.5 , P<.001 ) , grading of vaginal health ( –0.91 compared with –0.51 , P<.001 ) , vaginal pH grade ( –1.3 compared with –0.4 , P<.001 ) , and most bothersome symptoms score ( –1.23 compared with –0.87 , P=.003 ) . For each component of vaginal Maturation Index , vaginal Maturation Value , grading of vaginal health , and vaginal pH , treatment effects were statistically different from placebo after 2 weeks of treatment . For most bothersome symptoms , treatment effect became apparent after 4 weeks and reached statistical significance at week 8 of therapy . All treatment effects were statistically significant at week 52 . There were no major safety findings regarding physical , gynecologic , or laboratory assessment s. CONCLUSION : After 12 weeks of treatment , an ultra – low-dose 10-microgram E2 vaginal tablet , compared with placebo , demonstrated significant improvement for the primary endpoints : vaginal cytology and pH and most bothersome urogenital symptoms score . CLINICAL TRIAL REGISTRATION : Clinical Trials.gov , http:// clinical trials.gov , NCT00108849 LEVEL OF EVIDENCE : Forty post-menopausal women with urogenital disorders who were in patients in the same geriatric hospital were treated with oestriol ( E3 ) for 6 weeks . For the first 2 weeks 0.5 mg E3 ( Leo AB , Sweden ) was administered intravaginally every day . Over the following 4 weeks the patients received the same quantity either once or twice weekly as a maintenance dose . Oestrogen influence on the vaginal and urethral epithelium was assessed by means of the karyopyknotic index ( KPI ) , while the degree of maturation of the vaginal epithelium was estimated visually . Urinary bacteria were cultivated . A pronounced and progressive rise in KPI was seen in both the vaginal and the urethral epithelium following daily E3 treatment . However , neither of the two maintenance dosages was sufficient to sustain the initial maturation of the vaginal and urethral epithelium induced by E3 , since the KPI returned to pretreatment values within 4 weeks . The effect of E3 administration on the vaginal epithelium was overestimated by the visual assessment method . No changes were seen in urinary bacteria . Medroxyprogesterone acetate was given before and after E3 treatment . None of the women suffered from withdrawal bleeding The treatment of postmenopausal symptoms was studied in 26 healthy women using a new synthetic rubber ( Kraton D 2109 ) vaginal ring containing 53 mg of 17 beta-oestradiol . All women were postmenopausal , at least 6 months after the last vaginal bleeding and suffering from daily hot flushes . The study was conducted in a double-blind placebo-controlled intrapatient cross-over fashion , and the study period was 6 months . The rings used give an initial in vitro release rate of 0.4 mg/E2 per day . The in vitro release rate decreases to about 0.2 mg/day after 20 days and levels off asymptotically to about 0.1 mg/day after 50 days . Serum E2 levels equivalent to the follicular phase of the normal menstrual cycle were measured after 1 month 's use , and serum E2 level stayed above postmenopausal levels throughout the study period . FSH was suppressed during use of the E2-releasing vaginal ring , while LH showed no statistically significant suppression in continued use . Postmenopausal complaints were recorded by Visual Analogue Scales ( VAS ) as judged by both the patient and the examining doctor ; all complaints had favourable outcomes during use of the E2-releasing vaginal ring without deterioration of symptoms during use of the placebo ring . No serious side-effects were encountered , and the possibility of managing all postmenopausal complaints with intravaginal oestrogen treatment is discussed Objectives : The efficacy and safety of 25‐μg 17&bgr;‐estradiol vaginal tablets ( Vagifem ) were assessed and compared with 1.25‐mg conjugated equine estrogen vaginal cream ( Premarin Vaginal Cream ) for the relief of menopausal‐derived atrophic vaginitis , result ing from estrogen deficiency . Design : In a multicenter , open‐label , r and omized , parallel‐group study , 159 menopausal women were treated for 24 weeks with either vaginal tablets or vaginal cream . Efficacy was evaluated by relief of vaginal symptoms and concentrations of serum estradiol and follicle‐stimulating hormone . Safety was monitored by the incidence of adverse events , evaluation of endometrial biopsies , and clinical laboratory results . Patients also assessed the acceptability of the study medications . Results : Composite scores of vaginal symptoms ( dryness , soreness , and irritation ) demonstrated that both treatments provided equivalent relief of the symptoms of atrophic vaginitis . At weeks 2 , 12 , and 24 , increases in serum estradiol concentrations and suppression of follicle‐stimulating hormone were observed in significantly more patients who were using the vaginal cream than in those who were using the vaginal tablets ( p < 0.001 ) . Fewer patients who were using the vaginal tablets experienced endometrial proliferation or hyperplasia compared with patients who were using the vaginal cream . Significantly more patients who were using the vaginal tablets rated their medication favorably than did patients who were using the vaginal cream ( p ≤ 0.001 ) . Patients who were receiving the vaginal tablets also had a lower incidence of patient withdrawal ( 10 % versus 32 % ) . Conclusions : Treatment regimens with 25‐μg 17&bgr;‐estradiol vaginal tablets and with 1.25‐mg conjugated equine estrogen vaginal cream were equivalent in relieving symptoms of atrophic vaginitis . The vaginal tablets demonstrated a localized effect without appreciable systemic estradiol increases or estrogenic side effects . Vaginal tablet therapy result ed in greater patient acceptance and lower withdrawal rates compared with vaginal cream therapy . ( Menopause 2000;7:156‐161 . © 2000 , The North American Menopause Society . OBJECTIVES To compare the effects of estradiol vaginal tablet with conjugated estrogen cream on urogenital symptoms , vaginal health index , vaginal cytology , endometrial thickness , and plasma estradiol level in postmenopausal women . METHODS Fifty-three women with urogenital symptoms were r and omized to local vaginal treatment of 25 microg estradiol tablet or 1 g of conjugated estrogen cream for 12 weeks . They were assessed for urogenital symptoms , vaginal health index , vaginal cytology , endometrial thickness and estradiol level . RESULTS Forty-eight women completed the treatment . Both groups showed improvement of urogenital symptoms , vaginal health index , and vaginal cytology after the first 4 weeks of treatment . Conjugated estrogen cream showed superior efficacy in alleviating vaginal dryness and dyspareunia . Two cases of endometrial proliferation were noted . CONCLUSIONS Estradiol vaginal tablet and conjugated estrogen cream were effective in treating urogenital symptoms , the restoration of normal vaginal epithelium and reduction of vaginal pH in postmenopausal women . However , 2 cases of endometrial proliferation were noted This was an open-label study comparing effects of a nonhormonal drug-free bioadhesive vaginal moisturizer to a local estrogen therapy in the treatment of vaginal dryness symptoms . There were 15 women evaluated in each treatment group during a 12-week period . Results indicated that the bioadhesive vaginal moisturizer was a safe and effective alternative to estrogen vaginal cream , with both therapies exhibiting statistically significant increases in vaginal moisture , vaginal fluid volume , and vaginal elasticity with a return of the premenopausal pH state Objective : Vulvovaginal atrophy ( VVA ) is characterized by vaginal changes , dyspareunia , and itching/irritation . Efficacy and safety of a lower-dose estradiol vaginal cream ( 0.003 % ) were evaluated in postmenopausal women with VVA-related dyspareunia . Methods : This was a phase 3 , r and omized , double-blind , placebo-controlled study . Sexually active postmenopausal women with moderate – severe dyspareunia as the most bothersome symptom , ⩽5 % vaginal superficial cells , and vaginal pH > 5.0 were r and omized ( 1:1 ) to 0.003 % estradiol vaginal cream ( 15 & mgr;g estradiol ; 0.5 g cream ) or placebo ( 0.5 g cream ) applied daily for 2 weeks followed by three applications/week for 10 weeks . Co primary outcomes were changes in dyspareunia severity , vaginal cytology , and vaginal pH from baseline to final assessment . Additional efficacy outcomes and safety were assessed . Results : A total of 550 participants ( average age , 58 y ) were r and omized . Compared with placebo , estradiol reduced dyspareunia severity ( mean change from baseline ± SD : −1.5 ± 1.0 estradiol vs −1.2 ± 0.9 placebo ) , decreased vaginal pH ( −1.36 ± 0.89 vs −0.53 ± 0.92 ) , and improved vaginal cytology ( percentage superficial and parabasal cells 10.1 ± 16.7 vs 1.4 ± 6.1 and −48.5 ± 45.1 vs −14.6 ± 39.6 ; P < 0.001 , all ) at the final assessment . In addition , estradiol decreased dyspareunia severity at weeks 8 and 12 , vaginal/vulvar irritation/itching at weeks 4 and 12 , and dryness at week 12 versus placebo ( P < 0.01 , all ) . VVA severity , pH , and cytology improved at week 12 with estradiol versus placebo ( P < 0.001 , all ) . Vulvovaginal mycotic infections were more frequent with estradiol . One serious event leading to discontinuation occurred with estradiol . No deaths occurred . Conclusions : Lower-dose estradiol vaginal cream ( 0.003 % ) dosed three applications/week is an effective and well-tolerated treatment for VVA-related dyspareunia Objective : The aim of this study was to evaluate low-dose synthetic conjugated estrogens A ( SCE-A ) cream administered twice weekly for the treatment of moderate to severe vulvovaginal atrophy ( VVA ) in a symptomatic postmenopausal population . Methods : In a multicenter , double-blind , r and omized , placebo-controlled study , 305 women with symptoms of VVA were treated with either 1 g SCE-A cream ( n = 150 ) or matching placebo ( n = 155 ) for a period of up to 12 weeks . Participants had to have a vaginal pH of greater than 5 , less than or equal to 5 % superficial cells on a vaginal smear , and at least one of five symptoms of VVA ( dryness , soreness , irritation , pain with intercourse , and bleeding after intercourse ) that was moderate or severe in intensity . Women had to select one moderate or severe symptom as the most bothersome . Results : Efficacy was assessed at 2 , 3 , 4 , 8 , and 12 weeks and included the change from baseline in the severity of the most bothersome symptom ( MBS ) , maturation index , and pH. Most women identified vaginal dryness as the MBS ( 48 % ) followed by pain with intercourse ( 31.3 % ) . A statistically significant increase in the maturation index and significant decreases in pH and severity of the MBS were observed for those treated with SCE-A vaginal cream compared with placebo . Conclusions : A low dose ( 1 g = 0.625 mg ) of SCE-A vaginal cream administered twice weekly was shown to be effective compared with placebo in treating VVA in postmenopausal women for the three co primary efficacy measures of maturation index , pH , and severity of the MBS INTRODUCTION A significant number of postmenopausal women suffer from distressing problems because of urogenital atrophy secondary to the decline in circulating estrogen levels . Treatment with topical hormones may provide relief in such women when used judiciously . AIM To study the effects of local estrogen with or without local testosterone on urogenital and sexual health in postmenopausal women . METHODS Seventy-five postmenopausal women symptomatic for urogenital atrophy and sexual dysfunction were r and omly divided into two study groups and one control group . The women in study group 1 received local estrogen cream ; study group 2 received local estrogen and testosterone cream ; the control group received nonhormonal lubricant KY gel for 12 weeks . The urogenital and sexuality score , along with the vaginal health index and the vaginal maturation index ( VMI ) , was calculated at the beginning of therapy and 12 weeks later . MAIN OUTCOME MEASURES Changes in the urogenital and sexuality score along with vaginal health index and VMI . RESULTS After 12 weeks of therapy , there was a significant improvement in all the four study parameters , which correlated well with the improvement in symptoms of urogenital atrophy and sexual dysfunction in both the study groups as compared with the control group . Improvement in sexuality score was greatest with combined estrogen- and rogen therapy . There were no adverse effects and the therapies were well accepted without any compliance issue . CONCLUSION Local estrogen either alone or with and rogen is highly effective in relieving symptoms of urogenital atrophy and in improving sexual function in symptomatic postmenopausal women |
14,081 | 17,943,921 | Lumiracoxib 400 mg given as a single oral dose , is an effective analgesic for acute postoperative pain | BACKGROUND Lumiracoxib is a novel selective cyclooxygenase-2 ( COX-2 ) inhibitor .
COX-2 inhibitors have been developed to avoid COX-1 related gastrointestinal ( GI ) problems .
Lumiracoxib has analgesic and anti-inflammatory activity comparable with traditional non-steroidal anti-inflammatory drugs ( tNSAIDs ) in the management of post-operative pain , but with the advantage of better GI tolerability .
OBJECTIVES To review the analgesic efficacy , duration of analgesia , and adverse effects of a single oral dose of lumiracoxib for moderate to severe postoperative pain in adults and compare it with established analgesics . | Abstract Variability in patients ' response to interventions in pain and other clinical setting s is large . Many explanations such as trial methods , environment or culture have been proposed , but this paper sets out to show that the main cause of the variability may be r and om chance , and that if trials are small their estimate of magnitude of effect may be incorrect , simply because of the r and om play of chance . This is highly relevant to the questions of ‘ How large do trials have to be for statistical accuracy ? ’ and ‘ How large do trials have to be for their results to be clinical ly valid ? ’ The true underlying control event rate ( CER ) and experimental event rate ( EER ) were determined from single‐dose acute pain analgesic trials in over 5000 patients . Trial group size required to obtain statistically significant and clinical ly relevant ( 0.95 probability of number‐needed‐to‐treat within ±0.5 of its true value ) results were computed using these values . Ten thous and trials using these CER and EER values were simulated using varying group sizes to investigate the variation due to r and om chance alone . Most common analgesics have EERs in the range 0.4–0.6 and CER of about 0.19 . With such efficacy , to have a 90 % chance of obtaining a statistically significant result in the correct direction requires group sizes in the range 30–60 . For clinical relevance nearly 500 patients are required in each group . Only with an extremely effective drug ( EER>0.8 ) will we be reasonably sure of obtaining a clinical ly relevant NNT with commonly used group sizes of around 40 patients per treatment arm . The simulated trials showed substantial variation in CER and EER , with the probability of obtaining the correct values improving as group size increased . We contend that much of the variability in control and experimental event rates is due to r and om chance alone . Single small trials are unlikely to be correct . If we want to be sure of getting correct ( clinical ly relevant ) results in clinical trials we must study more patients . Credible estimates of clinical efficacy are only likely to come from large trials or from pooling multiple trials of conventional ( small ) size We studied the effects of various nonmorphine pain medications as well as rheumatoid arthritis and osteoarthritis on fracture risk in a nationwide case-control study . Cases were all subjects with any fracture sustained during the year 2000 ( n = 124,655 ) in Denmark . For each case , three controls ( n = 373,962 ) matched on age and gender were r and omly drawn from the background population . The primary exposure variables were use of acetaminophen , nonsteroidal anti-inflammatory drugs ( NSAIDs ) , or acetylsalicylic acid ( ASA ) . Adjustments were made for several confounders . The effect of dose was examined by stratifying for cumulated dose ( defined daily dose , DDD ) . For acetaminophen , a small increase in overall fracture risk was observed with use within the last year ( odds ratio [ OR ] = 1.45 , 95 % confidence interval [ CI ] 1.41–1.49 ) . For ASA , no increase in overall fracture risk was present with recent use . Significant heterogeneity was present for the NSAIDs ; e.g. , ibuprofen was associated with an increased overall fracture risk ( OR = 2.09 , 95 % CI 2.00–2.18 for < 20 DDD ) , while celecoxib was not ( OR = 0.76 , 95 % CI 0.51–1.13 for < 20 DDD , 2P < 0.01 for comparison ) . Osteoarthritis was associated with a decreased risk of any fracture if the diagnosis had been made more than 1 year ago ( OR = 0.70 , 95 % CI 0.67–0.72 ) . Rheumatoid arthritis was associated with an increase in overall fracture risk if the diagnosis had been made within the last year ( OR = 1.86 , 95 % CI 1.68–2.07 ) . Weak analgesics may be associated with fracture risk in a varying way . The effects in most cases were small . Falls may be one reason for the increase in fracture risk with some NSAIDs Renal prostagl and in inhibition by nonsteroidal antiinflammatory drugs ( NSAIDs ) may decrease renal function , especially under conditions of low effective circulating volume . To evaluate the risk of important deterioration of renal function due to this effect , the authors performed a nested case-control study using Tennessee Medicaid enrollees aged > or = 65 years in 1987 - 1991 . Cases were patients who had been hospitalized with community-acquired acute renal failure ; they were selected on the basis of medical record review of Medicaid enrollees with selected discharge diagnoses . Information on the timing , duration , and dose of prescription NSAIDs used , demographic factors , and comorbidity was gathered from computerized Medicaid-Medicare data files . Of the 1,799 patients with acute renal failure ( 4.51 hospitalizations per 1,000 person-years ) , 18.1 % were current users of prescription NSAIDs as compared with 11.3 % of 9,899 r and omly selected population controls . After control for demographic factors and comorbidity , use of NSAIDs increased the risk of acute renal failure 58 % ( adjusted odds ratio = 1.58 ; 95 % confidence interval ( CI ) : 1.34 , 1.86 ) . For ibuprofen , which accounted for 35 % of NSAID use , odds ratios associated with dosages of < or = 1,200 mg/day , > 1,200-<2,400 mg/day , and > or = 2,400 mg/day were 0.94 ( 95 % CI : 0.58 , 1.51 ) , 1.89 ( 95 % CI : 1.34 , 2.67 ) , and 2.32 ( 95 % CI : 1.45 , 3.71 ) , respectively ( test for linear trend : p = 0.009 ) . Prescription NSAID use result ed in an estimated 25 excess hospitalizations associated with renal failure per 10,000 years of use . Thus , NSAIDs represent a relatively uncommon but avoidable cause of acute renal failure in frail elderly persons & NA ; There is uncertainty over whether the patient group in which acute pain studies are conducted ( pain model ) has any influence on the estimate of analgesic efficacy . Data from four recently up date d systematic review s of aspirin 600/650 mg , paracetamol 600/650 mg , paracetamol 1000 mg and ibuprofen 400 mg were used to investigate the influence of pain model . Area under the pain relief versus time curve equivalent to at least 50 % maximum pain relief over 6 h was used as the outcome measure . Event rates with treatment and placebo , and relative benefit ( RB ) and number needed to treat ( NNT ) were used as outputs from the meta‐analyses . The event rate with placebo was systematic ally statistically lower for dental than postsurgical pain for all four treatments . Event rates with analgesics , RB and NNT were infrequently different between the pain models . Systematic difference in the estimate of analgesic efficacy between dental and postsurgical pain models remains unproven , and , on balance , no major difference is likely BACKGROUND Cyclo-oxygenase 2 (COX2)-selective inhibitors should reduce ulcer complications compared with non-selective non-steroidal anti-inflammatory drugs , but evidence is limited , and the possibility that these inhibitors increase cardiovascular events has been raised . The Therapeutic Arthritis Research and Gastrointestinal Event Trial ( TARGET ) aim ed to assess gastrointestinal and cardiovascular safety of the COX2 inhibitor lumiracoxib compared with two non-steroidal anti-inflammatory drugs , naproxen and ibuprofen . METHODS 18325 patients age 50 years or older with osteoarthritis were r and omised to lumiracoxib 400 mg once daily ( n=9156 ) , naproxen 500 mg twice daily ( 4754 ) , or ibuprofen 800 mg three times daily ( 4415 ) for 52 weeks , in two sub studies of identical design ( lumiracoxib vs ibuprofen or naproxen ) . R and omisation was stratified for low-dose aspirin use and age . The primary endpoint was the difference in time-to-event distribution of upper gastrointestinal ulcer complications ( bleeding , perforation , or obstruction ) ; analysis was by modified intention to treat . The principle measure of adverse cardiovascular events was the Antiplatelet Trialists ' Collaboration endpoint ( myocardial infa rct ion , stroke , or cardiovascular death ) ; this analysis was intention to treat . FINDINGS 81 ( 0.44 % ) patients did not start treatment and 7120 ( 39 % ) did not complete the study . In patients not taking aspirin , the cumulative 1-year incidence of ulcer complications was 1.09 % ( 95 % CI 0.82 - 1.36 ) with non-steroidal anti-inflammatory drugs ( 64 events ) versus 0.25 % ( 95 % CI 0.12 - 0.39 ) with lumiracoxib ( 14 events ; hazard ratio 0.21 [ 95 % CI 0.12 - 0.37 ] , p<0.0001 ) . Reductions in ulcer complications were also significant in the overall population ( 0.34 [ 0.22 - 0.52 ] , p<0.0001 ) but not in those taking aspirin ( 0.79 [ 0.40 - 1.55 ] , p=0.4876 ) . In the overall population , 0.55 % ( 50/9127 ) of those on non-steroidal anti-inflammatory drugs and 0.65 % ( 59/9117 ) of those on lumiracoxib reached the cardiovascular endpoint ( 1.14 [ 0.78 - 1.66 ] , p=0.5074 ) . INTERPRETATION Lumiracoxib showed a three to four-fold reduction in ulcer complications compared with non-steroidal anti-inflammatory drugs without an increase in the rate of serious cardiovascular events , suggesting that lumiracoxib is an appropriate treatment for patients with osteoarthritis Background : Valdecoxib and its intravenous prodrug parecoxib are reported to increase thromboembolic risk after coronary artery bypass grafting . The authors conducted a r and omized trial to examine their safety and analgesic efficacy in patients recovering from major noncardiac surgical procedures . Methods : The trial was r and omized and double-blind , with 10 days of treatment and 30 days of follow-up . Patients ( n = 1,062 ) received either parenteral parecoxib for 3 days and oral valdecoxib for the rest of the treatment period or placebo medications throughout . The frequency of predefined adjudicated postr and omization adverse events , including cardiovascular thromboembolism , renal dysfunction , gastroduodenal ulceration , and wound-healing complications , was assessed in each group . Secondary efficacy endpoints included patients ' pain ratings , opioid analgesic consumption ( recorded as morphine equivalents ) , and reports of opioid-related adverse effects . Results : Predefined adjudicated adverse events had similar frequencies among patients who received parecoxib and valdecoxib ( 2.7 % ) and placebo patients ( 3.2 % ) ( P = 0.58 ) , including cardiovascular thromboembolic events ( 1.0 % in each group ; P = 1.0 ) . Placebo patients consumed more morphine equivalents ( 66.2 ± 92.4 mg ) than did patients receiving parecoxib and valdecoxib ( 43.2 ± 65.7 mg ) ( P < 0.001 ) . Placebo patients had higher mean pain ratings on each of study days 2–10 ( P < 0.01 ) and reported more opioid-related symptom distress on days 2–6 ( P < 0.01 ) . Conclusions : Parecoxib and valdecoxib are useful adjuncts to opioids for the treatment of postoperative pain in noncardiac surgical patients . Further study will be required to determine the safety profile of parecoxib and valdecoxib administered to patients with known atherosclerotic disease after noncardiac surgery Abstract A previously established relationship for deriving dichotomous from continuous information in r and omised controlled trials ( RCTs ) of analgesics has been tested using an independent data set . Individual patient information from 18 RCTs of parallel‐group design in acute postoperative pain ( after abdominal , gynaecological and oral surgery ) was used to calculate the percentage of the maximum possible pain relief score ( % maxTOTPAR ) and the proportion of patients with > 50%maxTOTPAR for the different treatments . The relationship between the measures was investigated in 85 treatments with over 3400 patients . In 80 of 85 treatments ( 94 % ) agreement between calculated and actual number of patients with > 50%maxTOTPAR was within four patients per treatment and in 72 ( 85 % ) was within three ( average of 40 patients per treatment , range 21–58 patients ) . Summing the positive and negative differences between actual and calculated numbers of patients with > 50%maxTOTPAR gave an average difference of 0.30 patients per treatment arm . Reports of RCTs of analgesics frequently describe results of studies in the form of mean derived indices , rather than using discontinuous events , such as number or proportion of patients with 50 % pain relief . Because mean data inadequately describe information with a non‐normal distribution , combining mean data in systematic review s may compromise the results . Showing that dichotomous data can reliably be derived from mean data in acute pain studies enables data published as means to be used for quantitative systematic review s which require data in dichotomous form We assessed the quality of assessment and reporting of adverse effects in r and omized , double-blind clinical trials of single-dose acetaminophen or ibuprofen compared with placebo in moderate to severe postoperative pain . Reports were identified by systematic search ing of a number of bibliographic data bases ( e.g. , MEDLINE ) . Information on adverse effect assessment , severity and reporting , patient withdrawals , and anesthetic used was extracted . Compliance with former guidelines for adverse effect reporting was noted . Fifty-two studies were included ; two made no mention of adverse effects . No method of assessment was given in 19 studies . Twenty trials failed to report the type of anesthetic used , eight made no mention of patient withdrawals , and nine did not state the severity of reported adverse effects . Only two studies described the method of assessment of adverse effect severity . When all adverse effect data were pooled , significantly more adverse effects were reported with active treatment than with placebo . For individual adverse effects , there was no difference between active ( acetaminophen 1000 mg or ibuprofen 400 mg ) and placebo ; the exception was significantly more somnolence/drowsiness with ibuprofen 400 mg . Ninety percent of trials reporting somnolence/drowsiness with ibuprofen 400 mg were in dental pain . All studies published after 1994 complied with former guidelines for adverse effect reporting . Different methods of assessing adverse effects produce different reported incidence : patient diaries yielded significantly more adverse effects than other forms of assessment . We recommend guidelines for reporting adverse effect information in clinical trials Two r and omised , multicentre , double-blind , placebo- and active-controlled , 3-way crossover studies were performed to evaluate the efficacy and tolerability of the novel COX-2 selective inhibitor lumiracoxib in the treatment of primary dysmenorrhoea . Subjects with moderate-to-severe dysmenorrhoea received lumiracoxib 400 mg once daily ( od ) , rofecoxib 50 mg od and placebo ( Study 1 ; n = 84 ) or lumiracoxib 400 mg od , naproxen 500 mg twice daily and placebo ( Study 2 ; n = 99 ) . For the primary variable , summed pain intensity difference from 0 to 8 h on day 1 ( SPID-8 ) , all active treatments were superior to placebo in each study ( p < 0.001 ) ; lumiracoxib was comparable to rofecoxib and naproxen . For PID ( categorical scale ) , all active treatments were significantly better than placebo from 2 to 12 h ; lumiracoxib was generally comparable to rofecoxib and naproxen . All treatments were well tolerated . Lumiracoxib 400 mg is effective and well tolerated in the treatment of primary dysmenorrhoea , with efficacy comparable to rofecoxib and naproxen & NA ; Reports of RCTs of analgesics frequently describe results of studies in the form of mean derived indices , rather than using discontinuous events — such as number or proportion of patients with 50 % pain relief . Because mean data inadequately describe information with a non‐normal distribution , combining mean data in systematic review s may compromise the results . Showing that dichotomous data can reliably be derived from mean data , at least in acute pain models , indicates that more meaningful overviews or meta‐ analysis may be possible . This study investigated the relationship between continuous and dichotomous analgesic measures in a set of individual patient data , and then used that relationship to derive dichotomous from continuous information in r and omised controlled trials ( RCTs ) of analgesics . Individual patient information from 13 RCTs of parallel‐group and crossover design in acute postoperative pain was used to calculate the percentage of the maximum possible pain relief score ( % maxTOTPAR ) and the proportion of patients with greater than 50 % pain relief ( > 50%maxTOTPAR ) for the different treatments . The relationship between the measures was investigated in 45 actual treatments and 10 000 treatments simulated using the underlying actual distribution ; 1283 patients had 45 separate treatments . Mean % maxTOTPAR correlated with the proportion of patients with > 50%maxTOTPAR ( r2 = 0.90 ) . The relationship calculated from all the 45 treatments predicted to within three patients the number of patients with more than 50 % pain relief in 42 of 45 treatments , and 98.8 % of 10 000 simulated treatments . For seven effective treatments , actual numbers‐needed‐to‐treat ( NNT ) to achieve > 50%maxTOTPAR compared with placebo were very similar to those derived from calculated data BACKGROUND Valdecoxib and its intravenous prodrug parecoxib are used to treat postoperative pain but may involve risk after coronary-artery bypass grafting ( CABG ) . We conducted a r and omized trial to assess the safety of these drugs after CABG . METHODS In this r and omized , double-blind study involving 10 days of treatment and 30 days of follow-up , 1671 patients were r and omly assigned to receive intravenous parecoxib for at least 3 days , followed by oral valdecoxib through day 10 ; intravenous placebo followed by oral valdecoxib ; or placebo for 10 days . All patients had access to st and ard opioid medications . The primary end point was the frequency of predefined adverse events , including cardiovascular events , renal failure or dysfunction , gastroduodenal ulceration , and wound-healing complications . RESULTS As compared with the group given placebo alone , both the group given parecoxib and valdecoxib and the group given placebo and valdecoxib had a higher proportion of patients with at least one confirmed adverse event ( 7.4 percent in each of these two groups vs. 4.0 percent in the placebo group ; risk ratio for each comparison , 1.9 ; 95 percent confidence interval , 1.1 to 3.2 ; P=0.02 for each comparison with the placebo group ) . In particular , cardiovascular events ( including myocardial infa rct ion , cardiac arrest , stroke , and pulmonary embolism ) were more frequent among the patients given parecoxib and valdecoxib than among those given placebo ( 2.0 percent vs. 0.5 percent ; risk ratio , 3.7 ; 95 percent confidence interval , 1.0 to 13.5 ; P=0.03 ) . CONCLUSIONS The use of parecoxib and valdecoxib after CABG was associated with an increased incidence of cardiovascular events , arousing serious concern about the use of these drugs in such circumstances OBJECTIVE To compare the efficacy and tolerability of the novel cyclooxygenase 2-selective inhibitor lumiracoxib with placebo and diclofenac in osteoarthritis ( OA ) . METHODS Adults ( n=583 ) with knee or hip OA were r and omized to receive for 4 weeks lumiracoxib 50 , 100 , or 200 mg twice daily or 400 mg once daily ; placebo ; or diclofenac 75 mg twice daily . Efficacy assessment s included overall joint pain intensity and Western Ontario and McMaster Universities Osteoarthritis Index subscales ; tolerability was evaluated by adverse event and physician reporting . RESULTS All lumiracoxib doses were superior to placebo in relieving pain , improving stiffness , and improving physical function after 4 weeks . At study endpoint , pain relief was comparable among all lumiracoxib dosages and similar to diclofenac . Lumiracoxib tolerability was superior to diclofenac and comparable to placebo . CONCLUSION Lumiracoxib provides predictable and sustained relief from pain , stiffness , and impaired physical function in OA . Lumiracoxib shows clinical ly comparable efficacy and superior tolerability to diclofenac OBJECTIVE To determine the upper gastrointestinal ( GI ) tolerability of celecoxib , naproxen , and placebo in patients with rheumatoid arthritis ( RA ) and osteoarthritis ( OA ) . METHODS An analysis of 5 , 12-week , r and omized , double blind , parallel group , placebo controlled clinical trials was conducted . In these trials , patients were r and omized to : naproxen 500 mg bid ( n = 1,099 ) , placebo ( n = 1,136 ) , celecoxib 50 mg bid ( n = 690 ) ( subtherapeutic dose ) , celecoxib 100 mg ( n = 1,131 ) or 200 mg bid ( n = 1,125 ) ( therapeutic dose ) , or celecoxib 400 mg bid ( n = 434 ) ( supratherapeutic dosage ) . The incidence and time until moderate to severe abdominal pain , dyspepsia , nausea , and any of the aforementioned 3 upper GI symptoms ( composite endpoint ) were determined using time-to-event analysis . RESULTS The cumulative incidences of moderate to severe abdominal pain , dyspepsia , or nausea ( composite endpoint ) were : naproxen 500 mg ( 12.0 % ; 95 % CI 9.9%-14.0 % ) , celecoxib 50 mg bid ( 7.1 % ; 95 % CI 5.0%-9.2 % ) , celecoxib 100 mg bid ( 7.8 % ; 95 % CI 6.0%-9.5 % ) , celecoxib 200 mg bid ( 8.1 % ; 95 % CI 6.4%-9.9 % ) , celecoxib 400 mg bid ( 6.0 % ; 95 % CI 3.6%-8.4 % ) , and placebo ( 8.5 % ; 95 % CI 6.5%-10.8 % ) . After controlling for independent predictors of the composite endpoint , relative risks ( RR ) for the various treatments relative to naproxen 500 mg bid were : celecoxib 50 mg ( RR 0.54 ; 95 % CI 0.37 - 0.77 ; p < 0.001 ) , celecoxib 100 mg ( RR 0.60 ; 95 % CI 0.45 - 0.80 ; p < 0.001 ) , celecoxib 200 mg bid ( RR 0.63 ; 95 % CI 0.47 - 0.83 ; p = 0.001 ) , celecoxib 400 mg bid ( RR 0.56 ; 95 % CI 0.35 - 0.89 ; p = 0.015 ) , and placebo ( RR 0.63 ; 95 % CI 0.47 - 0.85 ; p = 0.002 ) . After controlling for independent predictors of the composite endpoint , celecoxib treatment group patients did not differ from placebo patients when reporting the composite endpoint , with p values ranging from 0.40 to 0.96 . CONCLUSION The upper GI tolerability of celecoxib is superior to naproxen . A dose-response relationship between celecoxib and upper GI symptoms was not apparent This r and omised , double-blind study compared single dose lumiracoxib ( a cyclooxygenase-2 selective inhibitor ) 100 and 400 mg , ibuprofen 400 mg and placebo in patients with postoperative dental pain over 12 h. The primary efficacy variable was pain intensity difference . Lumiracoxib 400 mg and ibuprofen were superior to placebo from 1 to 12 h post dose while lumiracoxib 100 mg was superior from 1.5 to 9 h. Lumiracoxib 400 mg demonstrated the fastest median time to onset of analgesia ( 37.4 min ) followed by ibuprofen ( 41.5 ) , and lumiracoxib 100 mg ( 52.4 ; all p < or = 0.001 vs. placebo ) . Median time to rescue medication ( h ) was longer for lumiracoxib 400 mg ( > or = 12 ) , lumiracoxib 100 mg ( approximately 7 ) and ibuprofen ( approximately 8) than placebo ( approximately 2 ; all p < or = 0.001 vs. placebo ) . Patients rated lumiracoxib 400 mg superior to the other active treatments ( p < 0.05 ) ; lumiracoxib 100 mg was comparable with ibuprofen and superior to placebo ( p < 0.001 ) . Lumiracoxib provided rapid , effective and well-tolerated analgesia OBJECTIVE Inhibition of cyclooxygenase 2 provides analgesia in ambulatory patients . We prospect ively evaluated the safety and efficacy of a newly introduced cyclooxygenase 2 inhibitor in patients undergoing coronary artery bypass grafting surgery through a median sternotomy in a r and omized clinical trial . METHODS A total of 462 patients with New York Heart Association classes I to III who were less than 77 years of age and were from 58 institutions in the United States , Canada , Germany , and the United Kingdom participated in this multicenter , phase III , placebo-controlled , double-blind , r and omized , parallel-group trial . Patients were allocated at a ratio of 2:1 to parecoxib/valdecoxib or st and ard care ( control ) groups , respectively . Intravenous study drug ( 40 mg ) was administered within 30 minutes after extubation and every 12 hours for a minimum of 3 days . Subsequently , oral treatment at a dose of 40 mg every 12 hours was initiated and administered for a combined total of 14 days . Patient-controlled analgesia with morphine , oral opioids , or acetaminophen was available as required . Assessment of the analgesic efficacy of the study drug was primarily based on morphine and morphine equivalent use . Additional efficacy evaluations included daily pain intensity , patient and physician global evaluation of study medication , and pain effect on quality of life . Clinical adverse events were assessed by the principal investigator at each site from the time of the first dose through the 30-day postdosing period . RESULTS Patients in the parecoxib/valdecoxib group received significantly less morphine or morphine equivalents than patients in the control group during the 0- to 24-hour ( P = .009 ) , 24- to 48-hour ( P = .017 ) , 72- to 96-hour ( P = .002 ) , 96- to 120-hour ( P = .004 ) , and 120- to 144-hour ( P = .037 ) periods . Both patients ( P < .001 ) and physicians ( P < .001 ) evaluated the study medication as significantly better than control therapy . The modified Brief Pain Inventory question naire used in the oral dosing period detected significant improvements in the parecoxib/valdecoxib treatment group in 6 of 8 domains tested ( eg , current pain , worst pain , and mood ) beginning on day 4 and continuing for at least 4 days . Although there were no differences between the groups in overall adverse events , serious adverse events occurred twice as frequently in parecoxib/valdecoxib-treated patients ( 19.0 % , 59/311 patients ) than in control patients ( 9.9 % , 15/151 patients ; P = .015 ) . Regarding individual serious adverse events , a greater incidence in sternal wound infection was found in the parecoxib/valdecoxib patients ( 10 [ 3.2 % ] ) versus control patients ( 0 [ 0 % ] ) ( P = .035 ) . The incidences of other individual serious adverse events , including cerebrovascular complications , myocardial infa rct ion , and renal dysfunction , were proportionally greater but not significantly different between the groups . CONCLUSIONS In patients undergoing coronary artery bypass grafting surgery , the cyclooxygenase 2 inhibitor combination , parecoxib/valdecoxib , was effective for postoperative analgesia . However , the 14-day treatment regimen also was associated with an increased incidence of serious adverse events overall and sternal wound infections in particular . Therefore our study raises important concerns requiring their comprehensive evaluation in a large-scale trial before these cyclooxygenase 2 inhibitors are used in patients undergoing coronary artery bypass grafting surgery This r and omised , double-blind , placebo-controlled , parallel-group study compared the efficacy and tolerability of lumiracoxib ( a novel COX-2 selective inhibitor ) with rofecoxib , celecoxib and placebo in patients with moderate-to-severe post-operative dental pain . Following third molar extraction , patients received single oral doses of lumiracoxib 400 mg , rofecoxib 50 mg , celecoxib 200 mg or placebo ( n = 355 ) . Additional patients from a similar study , assigned to lumiracoxib , rofecoxib or placebo ( n = 155 ) , were included for analysis of the primary variable , Summed Pain Intensity Difference over the first 8 h post dose ( SPID-8 ) . For SPID-8 , lumiracoxib was superior to rofecoxib ( p < 0.05 ) , celecoxib ( p < 0.001 ) and placebo ( p < 0.001 ) . Lumiracoxib demonstrated the fastest onset of analgesia and the longest time to rescue medication use . Patient global evaluation of lumiracoxib was comparable to rofecoxib and superior to celecoxib and placebo . All treatments were well tolerated . Lumiracoxib 400 mg provides rapid , effective and sustained relief of post-operative dental pain , comparable or superior to rofecoxib Abstract Objective : To survey patients ' opinions of their experiences in hospital in order to produce data that can help managers and doctors to identify and solve problems . Design : R and om sample of 36 NHS hospitals , stratified by size of hospital ( number of beds ) , area ( north , midl and s , south east , south west ) , and type of hospital ( teaching or non-teaching , trust or directly managed ) . From each hospital a r and om sample of , on average , 143 patients was interviewed at home or the place of discharge two to four weeks after discharge by means of a structured question naire about their treatment in hospital . Subjects : 5150 r and omly chosen NHS patients recently discharged from acute hospitals in Engl and . Subjects had been patients on medical and surgical wards apart from paediatric , maternity , psychiatric , and geriatric wards . Main outcome measures : Patients ' responses to direct questions about preadmission procedures , admission , communication with staff , physical care , tests and operations , help from staff , pain management , and discharge planning . Patients ' responses to general questions about their degree of satisfaction in hospitals . Results : Problems were reported by patients , particularly with regard to communication with staff ( 56 % ( 2824/5020 ) had not been given written or printed information ) ; pain management ( 33 % ( 1042/ 3162 ) of those suffering pain were in pain all or most of the time ) ; and discharge planning ( 70 % ( 3599/ 5124 ) had not been told about warning signs and 62 % ( 3177/5119 ) had not been told when to resume normal activities ) . Hospitals failed to reach the st and ards of the Patient 's Charter — for example , in explaining the treatment proposed and giving patients the option of not taking part in student training . Answers to questions about patient satisfaction were , however , highly positive but of little use to managers . Conclusions : This survey has highlighted several problems with treatment in NHS hospitals . Asking patients direct questions about what happened rather than how satisfied they were with treatment can eluci date the problems that exist and so enable them to be solved |
14,082 | 27,021,481 | Based on low quality evidence , chemoradiotherapy appears to be at least equivalent to surgery in terms of short-term and long-term survival in people with oesophageal cancer ( squamous cell carcinoma type ) who are fit for surgery and are responsive to induction chemoradiotherapy .
However , there is uncertainty in the comparison of definitive chemoradiotherapy versus surgery for oesophageal cancer ( adenocarcinoma type ) and we can not rule out significant benefits or harms of definitive chemoradiotherapy versus surgery .
Based on very low quality evidence , radiotherapy results in less long-term survival than surgery in people with oesophageal cancer who are fit for surgery .
Early identification of responders to chemoradiotherapy and better second-line treatment for non-responders will also increase the need and acceptability of trials that compare definitive chemoradiotherapy with surgery | BACKGROUND Oesophageal cancer is the sixth most common cause of cancer-related mortality in the world .
Currently surgery is the recommended treatment modality when possible .
However , it is unclear whether non-surgical treatment options is equivalent to oesophagectomy in terms of survival .
OBJECTIVES To assess the benefits and harms of non-surgical treatment versus oesophagectomy for people with oesophageal cancer . | This retrospective study was conducted to compare the treatment results between radical surgery and definitive chemoradiotherapy for resectable squamous cell carcinoma of the esophagus . Between June 2000 and May 2005 , 82 consecutive patients were selected for this study in which 33 were treated with chemoradiotherapy and 49 with surgery . The patients in the chemoradiotherapy ( CRT ) group received 2 - 4 cycles of 5-fluorouracil ( 1000 mg/m(2)/day , day 1 - 4 , continuous ) combined with cisplatin ( 75 mg/m(2 ) , day 1 , bolus ) plus 50.4 Gy of radiation , while those in the surgery group were treated by an esophagectomy with radical node dissection . Eighteen surgical patients received postoperative chemotherapy . The baseline clinical TNM stage was similar between the two groups . With a median follow-up period of 36 months ( range : 23 - 84 months ) with 47 survivors ( 57 % ) , the 3-year overall survival rates ( P = 0.22 ) and disease-free survival rates ( P = 0.16 ) were 48 % and 44 % in the chemoradiotherapy group versus 65 % and 59 % in the surgery group , and lacked statistical significance . This non-r and omized study on patients with resectable squamous cell carcinoma of the esophagus showed that chemoradiotherapy could result in survival comparable with conventional surgery in spite of selection bias of patients . There is a trend toward improved survival with surgery versus definitive CRT Background : The optimal treatment for localised oesophageal squamous cell carcinoma ( SCC ) is uncertain . We assessed the feasibility of an RCT comparing neoadjuvant treatment and surgery with definitive chemoradiotherapy . Methods : A feasibility RCT in three centres examined incident patients and reasons for in eligibility using multi-disciplinary team meeting records . Eligible patients were offered participation in the RCT with integrated qualitative research involving audio-recorded recruitment appointments and interviews with patients to inform recruitment training for staff . Results : Of 375 patients with oesophageal SCC , 42 ( 11.2 % ) were eligible . Reasons for eligibility varied between centres , with significantly differing proportions of patients excluded because of total tumour length ( P=0.002 ) . Analyses of audio-recordings and patient interviews showed that recruiters had challenges articulating the trial design in simple terms , balancing treatment arms and explaining the need for r and omisation . Before analyses of the qualitative data and recruiter training no patients were r and omised . Following training in one centre 5 of 16 eligible patients were r and omised . Conclusions : An RCT of surgical vs non-surgical treatment for SCC of the oesophagus is not feasible in the UK alone because of the low number of incident eligible patients . A trial comparing diverse treatment approaches may be possible with investment to support the recruitment process The CONSORT ( Consoli date d St and ards of Reporting Trials ) statement is used worldwide to improve the reporting of r and omized , controlled trials . Schulz and colleagues describe the latest version , CONSORT 2010 , which up date s the reporting guideline based on new method ological evidence and accumulating experience . BACKGROUND The role of neoadjuvant chemoradiotherapy in the treatment of patients with esophageal or esophagogastric-junction cancer is not well established . We compared chemoradiotherapy followed by surgery with surgery alone in this patient population . METHODS We r and omly assigned patients with resectable tumors to receive surgery alone or weekly administration of carboplatin ( doses titrated to achieve an area under the curve of 2 mg per milliliter per minute ) and paclitaxel ( 50 mg per square meter of body-surface area ) for 5 weeks and concurrent radiotherapy ( 41.4 Gy in 23 fractions , 5 days per week ) , followed by surgery . RESULTS From March 2004 through December 2008 , we enrolled 368 patients , 366 of whom were included in the analysis : 275 ( 75 % ) had adenocarcinoma , 84 ( 23 % ) had squamous-cell carcinoma , and 7 ( 2 % ) had large-cell undifferentiated carcinoma . Of the 366 patients , 178 were r and omly assigned to chemoradiotherapy followed by surgery , and 188 to surgery alone . The most common major hematologic toxic effects in the chemoradiotherapy-surgery group were leukopenia ( 6 % ) and neutropenia ( 2 % ) ; the most common major nonhematologic toxic effects were anorexia ( 5 % ) and fatigue ( 3 % ) . Complete resection with no tumor within 1 mm of the resection margins ( R0 ) was achieved in 92 % of patients in the chemoradiotherapy-surgery group versus 69 % in the surgery group ( P<0.001 ) . A pathological complete response was achieved in 47 of 161 patients ( 29 % ) who underwent resection after chemoradiotherapy . Postoperative complications were similar in the two treatment groups , and in-hospital mortality was 4 % in both . Median overall survival was 49.4 months in the chemoradiotherapy-surgery group versus 24.0 months in the surgery group . Overall survival was significantly better in the chemoradiotherapy-surgery group ( hazard ratio , 0.657 ; 95 % confidence interval , 0.495 to 0.871 ; P=0.003 ) . CONCLUSIONS Preoperative chemoradiotherapy improved survival among patients with potentially curable esophageal or esophagogastric-junction cancer . The regimen was associated with acceptable adverse-event rates . ( Funded by the Dutch Cancer Foundation [ KWF Kankerbestrijding ] ; Netherl and s Trial Register number , NTR487 . ) Methods for combining data from several studies exist and appear to be quite useful . None satisfactorily addresses the question of what studies should be combined . This issue is the most serious method ological limitation . Even studies with statistically significant interaction might still be combined if the effect were in the same direction . Thus , substantial scientific input is required as to what criteria must be met by each potential study . Much can be learned from combining or pooling data but it must be done cautiously . Pooling exercises do not replace well design ed prospect i ve clinical trials . Efforts for establishing basic design criteria to allow for multicentre and multicountry trials to be more easily combined might be useful . PURPOSE Two separate studies were conducted , the first to evaluate the maximal tolerated dose and the second the efficacy of raltitrexed plus oxaliplatin in conjunction with preoperative chemoradiation in patients with resectable T3 rectal carcinoma . METHODS AND MATERIAL S A total of 48 patients received radiotherapy ( 50 Gy ) administered to the posterior pelvis 5 d/wk for 5 weeks . Combination raltitrexed ( 3 mg/m(2 ) ) and oxaliplatin ( 60 to 130 mg/m(2 ) ) was administered on Days 1 , 19 , and 38 . RESULTS The recommended dose of oxaliplatin is 130 mg/m(2 ) ( maximal tolerated dose not reached ) . No patients developed Grade 4 acute toxicity . Grade 3 acute toxicity occurred in 9 patients ( 18.7 % ) . It was hematologic in 1 patient and GI in 1 patient ; 7 patients had an asymptomatic increase of transaminase . Surgery was performed in 47 ( 98 % ) of 48 patients . Of the 47 patients , 42 underwent sphincter-saving surgery ; in 19 , the tumor at diagnosis was located < 30 mm from the anorectal ring . Chemoradiation in combination with raltitrexed and oxaliplatin produced high rates of tumor response . The overall tumor downstaging rate was 73 % for T and N stages . A complete pathologic tumor response ( pT0 ) or microscopic tumor foci ( pTmic ) was observed in 28 patients . The tumor regression grade ( TRG ) , using the M and ard scoring system , was TRG1 in 16 patients ( 43.2 % ) , TRG2 in 12 ( 32.4 % ) , TRG3 in 12 ( 32.4 % ) , TRG4 in 6 ( 16.2 % ) , and TRG5 in 1 patient ( 2.7 % ) . CONCLUSION Raltitrexed plus oxaliplatin combined with pelvic radiotherapy was effective and well tolerated in patients with resectable T3 rectal carcinoma BACKGROUND The aim of this study was to report on the 5-year survival outcomes of patients with resectable esophageal carcinoma who were treated by definitive chemoradiotherapy ( CRT ) or st and ard esophagectomy . PATIENTS AND METHODS Between July 2000 and December 2004 , 81 patients with resectable squamous cell carcinoma of the mid- or lower thoracic esophagus were r and omized to receive esophagectomy or definitive CRT . The primary outcome was the overall survival and secondary outcomes included disease-free survival , morbidities and mortalities . RESULTS Forty-five patients received esophagectomy and 36 patients were treated by definitive CRT . The overall 5-year survival favors CRT but the difference did not reach statistical significance ( surgery 29.4 % and CRT 50 % , P=0.147 ) . A trend to improved 5-year survival was observed for patients suffering from node-positive disease ( P=0.061 ) . The 5-year disease-free survival also showed a trend to significance favoring CRT ( P=0.068 ) , particularly for patients suffering from node-positive disease ( P=0.017 ) . Both the stage of the disease and albumin level were significant predictors to mortality and disease-free survival . CONCLUSIONS Definitive CRT for squamous esophageal carcinoma result ed in comparable long-term survival to surgery . Further large-scale studies would be required to further investigate the role of CRT in node-positive patients . Clinical trials.gov identifier : NCT01032967 4013 Background : To compare the treatment results between radical surgery and late-course accelerated hyperfractionation radiotherapy ( LCAHFR ) for patients with resectable thoracic segment esophageal cancer . METHODS From June 1998 to September 2002 , 269 patients with resectable thoracic esophageal cancer were r and omized into two groups . 135 were with surgery and 134 with late-course accelerated hyperfractionated ( LCAF ) radiotherapy . Chemotherapy only for clinical recurrence and salvage therapy . RESULTS The 1- , 3- and 5- year overall survival rate were 88.6 % , 56.2 % and 34.7 % in the surgery group and 93.3 % , 61.5 % and 36.9 % in the radiotherapy group . There was no statistical difference between the two groups ( P = 0.58 ) . Median survival was 28.5 months and 30.5 months respectively . The 1- , 3- and 5-year progression-free survival rate was 73.3 % , 39.7 % and 20.6 % in the surgery group and 75.9 % , 43.7 % and 23.1 % in the radiotherapy group ( P = 0.65 ) . There was no difference between the two groups in survival rates including different location and length ( P > 0.05 ) . The incidence of failure by hematogenous metastasis and distant lymphatic metastasis in the radiotherapy group ( 16.6 % and 13.3 % respectively ) was lower than in the surgery group ( 25.3 % and 20.3 % respectively ) , there was no significance between them . The incidence of local failure in the radiotherapy and surgery group was 57.3 % and 27.8 % respectively ( P = 0.001 ) The incidence of death by local reasons was higher than in the surgery group ( P = 0.02 ) . The incidence of death by distant metastasis was lower than in the surgery group ( P = 0.02 ) . CONCLUSION The treatment results between radical surgery and LCAHFR with conformal radiotherapy for patients with resectable thoracic esophageal cancer were comparable . No significant financial relationships to disclose PURPOSE Combined chemoradiotherapy with and without surgery are widely accepted alternatives for the curative treatment of patients with locally advanced esophageal cancer . The value of adding surgery to chemotherapy and radiotherapy is unknown . PATIENTS AND METHODS Patients with locally advanced squamous cell carcinoma ( SCC ) of the esophagus were r and omly allocated to either induction chemotherapy followed by chemoradiotherapy ( 40 Gy ) followed by surgery ( arm A ) , or the same induction chemotherapy followed by chemoradiotherapy ( at least 65 Gy ) without surgery ( arm B ) . Primary outcome was overall survival time . RESULTS The median observation time was 6 years . The analysis of 172 eligible , r and omized patients ( 86 patients per arm ) showed overall survival to be equivalent between the two treatment groups ( log-rank test for equivalence , P < .05 ) . Local progression-free survival was better in the surgery group ( 2-year progression-free survival , 64.3 % ; 95 % CI , 52.1 % to 76.5 % ) than in the chemoradiotherapy group ( 2-year progression-free survival , 40.7 % ; 95 % CI , 28.9 % to 52.5 % ; hazard ratio [ HR ] for arm B v arm A , 2.1 ; 95 % CI , 1.3 to 3.5 ; P = .003 ) . Treatment-related mortality was significantly increased in the surgery group than in the chemoradiotherapy group ( 12.8 % v 3.5 % , respectively ; P = .03 ) . Cox regression analysis revealed clinical tumor response to induction chemotherapy to be the single independent prognostic factor for overall survival ( HR , 0.30 ; 95 % CI , 0.19 to 0.47 ; P < .0001 ) . CONCLUSION Adding surgery to chemoradiotherapy improves local tumor control but does not increase survival of patients with locally advanced esophageal SCC . Tumor response to induction chemotherapy identifies a favorable prognostic group within these high-risk patients , regardless of the treatment group OBJECTIVE To compare the treatment results between radical surgery and late course accelerated hyperfractionated radiotherapy ( LCAHFR ) for patients with resectable esophageal cancer in the chest . METHODS From June 1998 to September 2002 , 269 patients with resectable esophageal cancer in the chest were r and omized into two groups : 135 in surgery group and 134 in radiotherapy . The surgery group received esophagectomy including resection of the lesion and 5 cm margin at both ends from the lesion as well as surrounding lymph nodes > or = 5 mm and fatty tissue . In the radiotherapy group : irradiation field for the lesion in the upper esophageal cancer included the gross lesion , bilateral supraclavicular nodes and 4 cm of normal esophagus from lower margin of the gross disease ; for the esophageal cancer at the middle segment , it included the gross disease with 4 cm normal esophagus from both ends of the lesion ; for the lesion in the lower esophageal cancer , it included 4 cm of normal esophagus and the gross lesion as well as the draining gastric lymph nodes . The width of the irradiation field was 5 - 6 cm . The 90 % isodose volume was covered by the entire CTV with 3 - 5 beams , in a conventionally fractionated RT at 1.8 - 2.0 Gy/d for the first two thirds of treatment course to a dose of about 50 - 50.4 Gy followed by LCAHFR using reduced fields ( 2 cm extended margin at both ends of the lesion ) , twice daily at 1.5 Gy per fraction ( with aminimal interval of 6 h between fractions ) to a dose of 18 - 21 Gy . The total dose whole radiotherapy was 68.4 - 71.0 Gy . RESULTS The 1- , 3- and 5-year overall survival rate was 93.3 % , 61.5 % and 36.9 % in the surgery group versus 88.6 % , 56.2 % and 34.7 % in the radiotherapy group without statistical difference between the two groups . The 1- , 3- and 5-year progression free survival rate was 75.9 % , 43.7 % and 23.1 % in the surgery group and 73.3 % , 39.7 % and 20.6 % , respectively , in the radiotherapy group without statistical difference between the two groups either . CONCLUSION The results treated by late course accelerated hyperfractionated conformal radiotherapy alone may be comparable to that by radical surgery for patient with resectable esophageal cancer in the chest Surgery is considered the st and ard treatment for operable esophageal carcinoma , although there is no compelling evidence that surgery can achieve better results than radiotherapy . There has previously been no direct r and omized comparison of these two modalities with survival or disease specific outcome end points BACKGROUND The aim of the study was to compare the longitudinal quality of life ( QoL ) between chemoradiation with or without surgery in patients with locally advanced squamous resectable esophageal cancer included in a r and omized multicenter phase III trial ( FFCD 9102 ) . MATERIAL S AND METHODS All patients with locally advanced resectable ( T3 - 4 N0 - 1 M0 ) epidermoid or gl and ular esophageal cancer ( n = 451 ) received induction chemoradiation . Responders ( n = 259 ) were r and omized between surgery ( arm A ) and continuation of chemoradiation ( arm B ) . The Spitzer QoL Index was scored ( 0 - 10 ) at inclusion and at each follow-up , every 3 months during 2 years . QoL at baseline and longitudinal changes were respectively compared with univariate ANOVA and mixed-model analysis of variance for repeated measurements . The time interval between the follow-up was assessed and the same analyses were performed among survivors with 2 years of follow-up . RESULTS The squamous histology was predominant in both arms . The mean QoL score decreased between baseline and the first follow-up and between the first and the second follow-ups . QoL scores at the first follow-up were comparatively worse in arm A than in arm B ( 7.52 versus 8.45 , P < 0.01 ) , whereas the longitudinal QoL study showed no difference between treatments ( adjusted P = 0.26 ) . Furthermore , the longitudinal QoL was not different ( adjusted P = 0.23 ) among survivors with 2 years of follow-up . CONCLUSIONS Among patients responding to induction chemoradiation , surgery and continuation of chemoradiation had the same impact on QoL in patients with locally advanced , resectable esophageal cancer although a significantly greater decrease in the Spitzer Index was observed in the postoperative period The objective of the trial was to determine whether there was any difference in survival rates after operable cases of squamous cell carcinoma of the oesophagus were treated by radiotherapy or surgery . It was design ed as a prospect i ve , r and omised , multicentre trial in the United Kingdom , after staging as potentially operable , and it was planned to enter 100 patients per annum for 4 years , with a minimum follow-up of 5 years , after pre-entry staging of patients under 75 years of age by barium swallow , chest radiographs , oesophagoscopy , biopsy , bronchoscopy and CT scanning . The protocol was published in July 1986 ; the trial started in January 1987 and was stopped in June 1988 when only 31 patients from 16 centres were entered , although 30 centres had ethical committees ' approval and were willing to start the trial . Interventions were to be as follows : 1 . Surgery . According to the practice of that particular surgeon and classified as ( a ) curative resection if the surgeon considered that no macroscopic tumour was left behind , and ( b ) palliative if incompletely resected . 2 . Radiotherapy . ( a ) Prescribed minimum corrected tumour dose of 5000 cGy with daily dose of 250 cGy in 20 fractions over 4 weeks . ( b ) Prescribed minimum corrected tumour dose of 6000 cGy with daily dose of 200 cGy in 30 fractions over 6 weeks . The endpoint was to be survival at 1 , 2 and 5 years . The trial was discontinued after 18 months because of lack of recruitment and thus the question whether operable squamous cell cancer of the oesophagus , staged before treatment with CT scanning , is to be treated by radiotherapy or surgical resection remains unanswered . It is unlikely that a phase III trial will ever have sufficient support from surgeons to find the answer PURPOSE Uncontrolled studies suggest that chemoradiation has similar efficacy as surgery for esophageal cancer . Therefore , a r and omized trial was carried out to compare , in responders only , chemoradiation alone with chemoradiation followed by surgery in patients with locally advanced tumors . PATIENTS AND METHODS Eligible patients had operable T3N0 - 1M0 thoracic esophageal cancer . Patients received two cycles of fluorouracil ( FU ) and cisplatin ( days 1 to 5 and 22 to 26 ) and either conventional ( 46 Gy in 4.5 weeks ) or split-course ( 15 Gy , days 1 to 5 and 22 to 26 ) concomitant radiotherapy . Patients with response and no contraindication to either treatment were r and omly assigned to surgery ( arm A ) or continuation of chemoradiation ( arm B ; three cycles of FU/cisplatin and either conventional [ 20 Gy ] or split-course [ 15 Gy ] radiotherapy ) . Chemoradiation was considered equivalent to surgery if the difference in 2-year survival rate was less than 10 % . RESULTS Of 444 eligible patients , 259 were r and omly assigned ; 230 patients ( 88.8 % ) had epidermoid cancer , and 29 ( 11.2 % ) had gl and ular carcinoma . Two-year survival rate was 34 % in arm A versus 40 % in arm B ( hazard ratio for arm B v arm A = 0.90 ; adjusted P = .44 ) . Median survival time was 17.7 months in arm A compared with 19.3 months in arm B. Two-year local control rate was 66.4 % in arm A compared with 57.0 % in arm B , and stents were less required in the surgery arm ( 5 % in arm A v 32 % in arm B ; P < .001 ) . The 3-month mortality rate was 9.3 % in arm A compared with 0.8 % in arm B ( P = .002 ) . Cumulative hospital stay was 68 days in arm A compared with 52 days in arm B ( P = .02 ) . CONCLUSION Our data suggest that , in patients with locally advanced thoracic esophageal cancers , especially epidermoid , who respond to chemoradiation , there is no benefit for the addition of surgery after chemoradiation compared with the continuation of additional chemoradiation METHODS A prospect i ve , r and omized controlled study of radiotherapy after resection of esophageal carcinoma was carried out in 130 patients . Patients were stratified according to whether the resection was curative or palliative and were then r and omized to receive postoperative radiotherapy or no additional treatment . Sixty patients underwent curative resection ; 30 each were r and omized into the radiotherapy group ( CR + R ) and the control group ( CR ) . Seventy patients underwent palliative resection ; 35 each were r and omized into the radiotherapy group ( PR + R ) and the control group ( PR ) . RESULTS No complications occurred while the patients were undergoing radiotherapy treatment . On follow-up , complications in the intrathoracic stomach occurred in 24 patients ( 37 % ) who underwent radiotherapy compared with four patients ( 6 % ) in the control group ( p < 0.0001 ) . Seventeen of these 24 patients in the radiotherapy group had gastric ulceration and there were five deaths as a result of bleeding . Local recurrence developed significantly less frequently in the PR + R group compared with the PR group ( seven patients [ 20 % ] vs 16 patients [ 46 % ] ; p = 0.04 ) ; no difference was observed between CR + R and CR groups ( 10 % and 13 % , respectively ) . Intrathoracic recurrence occurred in fewer patients in the radiotherapy groups ( CR + R and PR + R ) compared with the control groups ( CR and PR ) ( four patients vs 15 patients ; p = 0.01 ) . In patients with residual tumor in the mediastinum after resection , two ( 7 % ) of 29 patients who underwent radiotherapy died of tracheobronchial obstruction , compared with nine ( 33 % ) of 27 patients in the control groups ( p = 0.03 ) . No difference in local recurrence was observed for extrathoracic or anastomotic recurrence . Distant metastasis developed in 12 patients ( 40 % ) in the CR + R group , nine patients ( 30 % ) in the CR group ( p = 0.59 ) , 24 patients ( 69 % ) in the PR + R group , and 18 patients ( 51 % ) in the PR group ( p = 0.22 ) . The time of onset of metastasis was 5.1 months for the PR + R group , which was shorter than the 8.5 months for the PR group ( p = 0.05 ) . The time of onset of metastasis was similar for the CR + R and CR groups ( 9.9 months and 11.0 months , respectively ; p = 0.76 ) . The overall median survival of patients after postoperative radiotherapy ( CR + R and PR + R ) was 8.7 months , which was shorter than the 15.2 months for the control groups ( CR and PR ) ( p = 0.02 ) . CONCLUSIONS The shorter survival of patients who underwent postoperative radiotherapy was the result of irradiation-related death and the early appearance of metastatic diseases . The role of postoperative radiotherapy is therefore limited to a specific group of patients with residual tumor in the mediastinum after operation , for whom radiotherapy can significantly reduce the incidence of local recurrence obstructing the tracheobronchial tree We conducted a prospect i ve r and omized trial to compare the efficacy and survival outcome by chemoradiation with that by esophagectomy as a curative treatment . From July 2000 to December 2004 , 80 patients with potentially resectable squamous cell carcinoma of the mid or lower thoracic esophagus were r and omized to esophagectomy or chemoradiotherapy . A two-or three-stage esophagectomy with two-field dissection was performed . Patients treated with chemoradiotherapy received continuous 5-.uorouracil infusion ( 200 mg/m2/day ) from day 1 to 42 and cisplatin ( 60 mg/m2 ) on days 1 and 22 . The tumor and regional lymphatics were concomitantly irradiated to a total of 50–60 Gy . Tumor response was assessed by endoscopy , endoscopic ultrasonography , and computed tomography scan . Salvage esophagectomy was performed for incomplete response or recurrence . Forty-four patients received st and ard esophagectomy , whereas 36 were treated with chemoradiotherapy . Median follow-up was 16.9 months . The operative mortality was 6.8 % . The incidence of postoperative complications was 38.6 % . No difference in the early cumulative survival was found between the two groups ( RR = 0.89 ; 95 % confidence interval , 0.37 - 2.17 ; log-rank test P = 0.45 ) . There was no difference in the disease-free survival . Patients treated with surgery had a slightly higher proportion of recurrence in the mediastinum , whereas those treated with chemoradiation sustained a higher proportion of recurrence in the cervical or abdominal regions . St and ard esophagectomy or chemoradiotherapy offered similar early clinical outcome and survival for patients with squamous cell carcinoma of the esophagus . The challenge lies in the detection of residue disease after chemoradiotherapy |
14,083 | 21,892,108 | Some benefit was noted from intensive follow-up strategies . | INTRODUCTION The burden of lung cancer is high for patients and carers .
Care after treatment may have the potential to impact on this .
We review ed the published literature on follow-up strategies intended to improve survival and quality of life . | Objective : To assess the effectiveness of nurse led follow up in the management of patients with lung cancer . Design : R and omised controlled trial . Setting : Specialist cancer hospital and three cancer units in southeastern Engl and Participants : 203 patients with lung cancer who had completed their initial treatment and were expected to survive for at least 3 months . Intervention : Nurse led follow up of out patients compared with conventional medical follow up . Outcome measures : Quality of life , patients ' satisfaction , general practitioners ' satisfaction , survival , symptom-free survival , progression-free survival , use of re sources , and comparison of costs . Results : Patient acceptability of nurse led follow up was high : 75 % ( 203/271 ) of eligible patients consented to participate . Patients who received the intervention had less severe dyspnoea at 3 months ( P=0.03 ) and had better scores for emotional functioning ( P=0.03 ) and less peripheral neuropathy ( P=0.05 ) at 12 months . Intervention group patients scored significantly better in most satisfaction subscales at 3 , 6 , and 12 months ( P<0.01 for all subscales at 3 months ) . No significant differences in general practitioners ' overall satisfaction were seen between the two groups . No differences were seen in survival or rates of objective progression , although nurses recorded progression of symptoms sooner than doctors ( P=0.01 ) . Intervention patients were more likely to die at home rather than in a hospital or hospice ( P=0.04 ) , attended fewer consultations with a hospital doctor during the first 3 months ( P=0.004 ) , had fewer radiographs during the first 6 months ( P=0.04 ) , and had more radiotherapy within the first 3 months ( P=0.01 ) . No other differences were seen between the two groups in terms of the use of re sources . Conclusion : Nurse led follow up was acceptable to lung cancer patients and general practitioners and led to positive outcomes We investigated whether intensive follow-up leads to earlier diagnosis of recurrence , more effective treatment , and longer survival in patients with small cell lung cancer ( SCLC ) who had shown a complete or partial response to first-line chemotherapy . The subjects of this retrospective study were 94 patients with SCLC who had shown a complete or partial response to first-line chemotherapy . The patients were separated into two arms : an intensive follow-up arm in which patients underwent regular blood tests , chest radiography , computed tomography of the chest and upper abdomen , magnetic resonance or computed tomography of the brain , and bone scintigraphy bimonthly for 6 months and then quarterly for 1.5 years ; and a nonintensive follow-up arm in which these examinations were performed at the physician 's discretion . All patients also underwent interviews and physical examinations monthly for 2 years and bimonthly for a further 3 years . Patient characteristics did not differ significantly between the arms . Disease recurred in 55 of 62 patients of the intensive arm and 29 of 32 patients of the nonintensive arm . Asymptomatic recurrences were detected more frequently in the intensive arm than in the nonintensive arm . The response rate to salvage therapy among all patients with recurrent disease was significantly higher in the intensive arm ( 61.8 % ) than in the nonintensive arm ( 37.9 % ; p=0.04 ) . Both median postrelapse survival and overall median survival were significantly longer in the intensive arm ( 9 and 20 months , respectively , p=0.04 and p=0.001 ) than in the nonintensive arm ( 4 and 13 months , respectively ) . Intensive follow-up helps detect recurrence earlier , enhances the effectiveness of treatment , and lengthens survival in patients with SCLC . Well- design ed prospect i ve , r and omized trials including a cost-benefit analysis are needed to compare intensive and nonintensive follow-up regimens Objective To compare traditional hospital follow-up with telephone follow-up by specialist nurses after treatment for breast cancer . Design A two centre r and omised equivalence trial in which women remained in the study for a mean of 24 months . Setting Outpatient clinics in two NHS hospital trusts in the north west of Engl and Participants 374 women treated for breast cancer who were at low to moderate risk of recurrence . Interventions Participants were r and omised to traditional hospital follow-up ( consultation , clinical examination , and mammography as per hospital policy ) or telephone follow-up by specialist nurses ( consultation with structured intervention and mammography according to hospital policy ) . Main outcome measures Psychological morbidity ( state-trait anxiety inventory , general health question naire ( GHQ-12 ) ) , participants ’ needs for information , participants ’ satisfaction , clinical investigations ordered , and time to detection of recurrent disease . Results The 95 % confidence interval for difference in mean state-trait scores adjusted for treatment received ( −3.33 to 2.07 ) was within the predefined equivalence region ( −3.5 to 3.5 ) . The women in the telephone group were no more anxious as a result of foregoing clinic examinations and face-to-face consultations and reported higher levels of satisfaction than those attending hospital clinics ( intention to treat P<0.001 ) . The numbers of clinical investigations ordered did not differ between groups . Recurrences were few ( 4.5 % ) , with no differences between groups for time to detection ( median 60.5 ( range 37 - 131 ) days in hospital group v 39.0 ( 10 - 152 ) days in telephone group ; P=0.228 ) . Conclusions Telephone follow-up was well received by participants , with no physical or psychological disadvantage . It is suitable for women at low to moderate risk of recurrence and those with long travelling distances or mobility problems and decreases the burden on busy hospital clinics . Trial registration National Cancer Research Institute 1477 BACKGROUND Although a minimal follow-up with periodic clinic visits and chest radiographs is usually recommended after complete operation for non-small cell lung cancer , the ideal follow-up has not been defined yet . Objectives of this prospect i ve study were to determine the feasibility of an intensive surveillance program and to analyze its influence on patient survival . METHODS Follow-up consisted of physical examination and chest roentgenogram every 3 months and fiberoptic bronchoscopy and thoracic computed tomographic scan with sections of the liver and adrenal gl and s every 6 months . Influence of patient and recurrence characteristics on survival from recurrence was successively analyzed using the log-rank test and a Cox model adjusted for treatment . RESULTS Among the 192 eligible patients , recurrence developed in 136 patients ( 71 % ) and was asymptomatic in 36 patients ( 26 % ) . In 35 patients , recurrence was asymptomatic and detected by a scheduled procedure : thoracic computed tomographic scan in 10 ( 28 % ) patients and fiberoptic bronchoscopy in 10 . Fifteen patients ( 43 % ) had a thoracic recurrence treated with curative intent . From the date of recurrence , 3-year survival was 13 % in all patients and 31 % in asymptomatic patients whose recurrence was detected by a scheduled procedure . Asymptomatic recurrences ( p < 0.001 ) , female sex ( p < 0.001 ) , performance status 2 or less ( p = 0.01 ) , and age 61 years or younger ( p = 0.01 ) were shown to be significantly favorable prognostic factors . CONCLUSIONS This intensive follow-up is feasible and may improve survival by detecting recurrences after surgery for non-small cell lung cancer at an asymptomatic stage The aims of this study were ( a ) to estimate the prevalence of pain and eight other common symptoms in a large population of patients with advanced cancer from different palliative care centers , and ( b ) to assess the differences in prevalence of the symptoms by primary site . In 1990 - 1991 , the prevalence of eight major symptoms and performance status were assessed prospect ively among 1840 cancer patients in seven hospices in Europe , the United States , and Australia . The data were collected at each institution using structured data collection sheets from the World Health Organization 's ( WHO ) Cancer and Palliative Care Unit . The prevalence of moderate to severe pain was 51 % , ranging from 43 % in stomach cancer to 80 % in gynecological cancers . Nausea was most prevalent in gynecological ( 42 % ) and stomach ( 36 % ) cancers , and dyspnea ( 46 % ) in lung cancer . There were statistically significant differences in the prevalence of most symptoms depending on the primary site of cancer and the hospice . Population -based follow-up studies are needed to document the incidence and prevalence of symptoms throughout the course of the disease Objectives The first objective was to identify variations in patient management practice patterns after potentially curative lung cancer surgery . Patient management practice patterns were expected to range from intensive follow-up to no active surveillance . The second objective was to measure whether intensity of follow-up was related to patient outcomes . Methods An 18-month retrospective analysis was conducted of 182 patients with low TNM stage ( ≤IIIA ) lung cancer who were surgically treated with curative intent over the 11 -year period from 1982 through 1992 at the St. Louis Department of Veterans Affairs Medical Center . Results Patients were followed for a mean of 3.3 years , until death or the end of the study . Analyses of diagnostic test and outpatient visit frequency distributions and cluster analyses facilitated the identification of 62 nonintensively followed patients and 120 intensively followed patients . Both groups were comparable at baseline , and there were no significant differences in patient outcomes attributable to intensity of follow-up . Intensively followed patients did , however , live an average of 192 days longer than nonintensively followed patients . Conclusions Significant variations in follow-up practice patterns can exist within a single health care facility . In this analysis , variations in test and visit frequency did not result in statistically significant differences in patient outcomes , though the survival difference between groups suggests that some benefit might exist . Only well- design ed prospect i ve trials are likely to answer the question of what constitutes optimal follow-up after potentially curative lung cancer treatment The majority of patients with lung cancer have incurable disease from presentation and a survival measured in months . Treatments offered to these patients are aim ed at the palliation of symptoms with either radiotherapy or chemotherapy , or with supportive measures . It has been traditional to offer regular outpatient follow-up after initial palliative treatment . Further treatment options , which may be limited , are usually reserved for the recurrence of troublesome symptoms . A pilot ' open access ' lung cancer clinic has been set up . Rather than have regular follow-up at the hospital , patients who have completed initial palliative treatments are discharged to the community with follow-up by their general practitioner and Macmillan nurse . Review at the open access clinic can be arranged at short notice if requested by the patient , carers , general practitioner or Macmillan nurse . The outcomes and level of satisfaction of patients , their relatives and staff to this method of follow-up were found to be positive . Open access follow-up may be useful for many patients after the completion of initial palliative treatment BACKGROUND The aim of this study was to determine the risk of overall death in long-term survivors ( > 5 years ) after pneumonectomy for non-small cell lung cancer ( NSCLC ) , and to establish the optimal follow-up strategy for these patients . METHODS We analyzed a single-center experience with 94 long-term survivors who underwent pneumonectomy ( group A ) for NSCLC between January 1992 and December 2000 . Prospect i ve tumor registry data were compared with data for 147 long-term survivors who underwent lobectomy ( group B ) during the same period . RESULTS Clinical characteristics at the time of operation differed between the two groups with more squamous histology , larger tumor size , and more advanced stage in group A compared with group B. During follow-up , late lung cancer relapses were rare in both groups ( 2.1 % vs 1.4 % ) , and second primary malignancies were less frequent in group A ( 2.1 % vs 9.5 % , p = 0.032 ) . The overall 10-year survival rate was lower in group A than in group B ( 67.3 % vs 82.8 % ) ; however , there was no significant difference in lung cancer-specific survival ( 93.5 % vs 95.1 % ) . Intercurrent disease was the leading cause of death in group A ( 14 patients , 14.9 % ) , most commonly respiratory failure result ing from community-acquired pneumonia . CONCLUSION Late cancer relapse or second primary malignancies were rare in long-term survivors after pneumonectomy , but the overall mortality remained high as a result of intercurrent diseases . Continued surveillance should focus on prevention , early detection and aggressive management of intercurrent disease during follow-up care of these patients BACKGROUND AND PURPOSE The European Society for Therapeutic Radiology and Oncology was funded by the EU for a project on Recording providing Education , and Ameliorating the Consequences of Treatment ( REACT ) . An important aim of follow-up ( FU ) after treatment for cancer is to detect various events associated with disease recurrence or metastatic spread or severe treatment-related complications as early as possible . Each tumour type may show a specific pattern and timing of these events related to different prognostic factors . The aim of this study was to propose a way of defining an optimal timing schedule for follow-up after treatment based on the analysis of failure patterns determined from follow-up data from prospect i ve clinical trials . MATERIAL AND METHODS Cox proportional hazards model was used to identify prognostic factors associated with each failure type ( loco-regional recurrence ( LR ) , distant metastasis ( DM ) or side effects ( SE ) ) . Competing risks methods were applied to estimate the cumulative incidence functions ( CIF ) , adjusted on the significant prognostic factors . Equally spaced quantiles of the CIF were then used to estimate the corresponding optimised follow-up times depending on a pre-specified total number of visits . Follow-up data from the CHART bronchus clinical trial were used to analyse the pattern of time to first failure . RESULTS A significantly higher risk of failure was observed for males ( SE ) , stage III ( DM ) and conventional treatment ( LR ) . Overall , patients treated with CHART needed 1 fewer visit in each category of patients compared to the Conventional group . For example , stage III male patients treated with CHART would need 8 visits during the first two years at 7 , 11 , 16 , 24 , 37 , 52 , 64 and 104 weeks rather than the 9 follow-up visits planned in the protocol . Similar patients treated with Conventional radiotherapy would need 8 visits at 3 , 5 , 7 , 11 , 15 , 24 , 52 and 104 weeks . CONCLUSIONS Use of these methods would allow timing of follow-up visits to be adapted according to tumour site and prognostic factors determined previously from audit or clinical trials . Application of this approach could optimize the timing of follow-up visits by placing them closer to the times when failures are expected to occur . It does not address the wider issues of follow-up such as who should do it or what should be done for which further studies are required A r and omized clinical trial was conducted to assess the effects of home nursing care for patients with progressive lung cancer . One hundred sixty‐six patients were assigned to either an oncology home care group ( OHC ) that received care from oncology home care nurses , a st and ard home care group ( SHC ) that received care from regular home care nurses , or an office care group ( OC ) that received whatever care they needed except for home care . Patients were entered into the study 2 months after diagnosis and followed for 6 months . Patients were interviewed at 6‐week intervals across five occasions . At the end of the study , there were no differences in pain , mood disturbance , and concerns among the three groups . There were significant differences in symptom distress , enforced social dependency , and health perceptions . The two home nursing care groups had less distress and greater independence 6 weeks longer than the office care group . In addition , the two home nursing care groups steadily reported worse health perceptions over time . Thus , it was remarkable that the office care group , which indicated more symptom distress and social dependency with time , also indicated perceptions of improved health with time . These results suggest that home nursing care assists patients with forestalling distress from symptoms and maintaining their independence longer in comparison to no home nursing care . Home care may also include assisting patients in acknowledging the reality of their situation BACKGROUND The optimal follow-up strategy of non-small cell lung cancer ( NSCLC ) patients after curative intent therapy is still not established . In a recent prospect i ve study with 100 patients , we showed that a FDG-PET-CT 3 months after radiotherapy ( RT ) could identify progression amenable for curative treatment in 2 % ( 95 % confidence interval ( CI ) : 1 - 7 % ) of patients , who were all asymptomatic . Here , we report on the economic evaluation of this study . PATIENTS AND METHODS A decision-analytic Markov model was developed in which the long-term cost-effectiveness of 3 follow-up strategies was modelled with different imaging methods 3 months after therapy : a PET-CT scan ; a chest CT scan ; and conventional follow-up with a chest X-ray . A probabilistic sensitivity analysis was performed to account for uncertainty . Because the results of the prospect i ve study indicated that the advantage seems to be confined to asymptomatic patients , we additionally examined a strategy where a PET-CT was applied only in the subgroup of asymptomatic patients . Cost-effectiveness of the different follow-up strategies was expressed in incremental cost-effectiveness ratios ( ICERs ) , calculating the incremental costs per quality adjusted life year ( QALY ) gained . RESULTS Both PET-CT- and CT-based follow-up were more costly but also more effective than conventional follow-up . CT-based follow-up was only slightly more effective than conventional follow-up , result ing in an incremental cost-effectiveness ratio ( ICER ) of euro 264.033 per QALY gained . For PET-CT-based follow-up , the ICER was euro 69.086 per QALY gained compared to conventional follow-up . The strategy in which a PET-CT was only performed in the asymptomatic subgroup result ed in an ICER of euro 42.265 per QALY gained as opposed to conventional follow-up . With this strategy , given a ceiling ratio of euro 80.000 , PET-CT-based follow-up had the highest probability of being cost-effective ( 73 % ) . CONCLUSIONS This economic evaluation shows that a PET-CT scan 3 months after (chemo)radiotherapy with curative intent is a potentially cost-effective follow-up method , and is more cost-effective than CT alone . Applying a PET-CT scan only in asymptomatic patients is probably as effective and more cost-effective . It is worthwhile to perform additional research to reduce uncertainty regarding the decision concerning imaging in the follow-up of NSCLC |
14,084 | 32,250,414 | Conclusions and Relevance The findings suggest that quality -based PE interventions are associated with small increases in both student health-related physical fitness components and FMSs regardless of frequency or duration of PE lessons . | Importance Whether quality - or quantity-based physical education ( PE ) interventions are associated with improvement of health-related physical fitness outcomes and fundamental motor skills ( FMSs ) in children and adolescents is unknown .
Objective To examine the association of interventions aim ed at optimizing PE in terms of quality ( teaching strategies or fitness infusion ) or quantity ( lessons per week ) with health-related physical fitness and FMSs in children and adolescents . | Background Strategies for combating increasing childhood obesity is called for . School setting s have been pointed out as potentially effective setting s for prevention . The objective of this paper was to evaluate the effect of four additional Physical Education ( PE ) lessons/week in primary schools on body composition and weight status in children aged 8–13 . Methods Children attending 2nd to 4th grade ( n = 632 ) in 10 public schools , 6 intervention and 4 control schools , participated in this longitudinal study during 2 school years . Outcome measures : Primary : Body Mass Index ( BMI ) and Total Body Fat percentage ( TBF% ) derived from Dual Energy X ray Absorptiometry ( DXA ) . Secondary : the moderating effect of overweight/obesity ( OW/OB ) and adiposity based on TBF% cut offs for gender . Results Intervention effect on BMI and TBF% ( BMI : β -0.14 , 95 % CI : -0.33 ; 0.04 , TBF% : β -0.08 , 95 % CI:-0.65;0.49 ) was shown insignificant . However , we found significant beneficial intervention effect on prevalence of OW/OB based on BMI ( OR 0.29 , 95 % CI : 0.11;0.72 ) . The intervention effect on adiposity based on TBF% cut offs was borderline significant ( OR 0.64 , 95 % CI:0 . 39 ; 1.05 ) . Conclusion Four additional PE lessons/week at school can significantly improve the prevalence of OW/OB in primary schoolchildren . Mean BMI and TBF% improved in intervention schools , but the difference with controls was not significant . The intervention had a larger effect in children who were OW/OB or adipose at baseline The aim was to study long-term effects on motor skills and school performance of increased physical education ( PE ) . All pupils born 1990 - 1992 from one school were included in a longitudinal study over nine years . An intervention group ( n = 129 ) achieved daily PE ( 5 × 45 min/week ) and if needed one extra lesson of adapted motor training . The control group ( n = 91 ) had PE two lessons/week . Motor skills were evaluated by the Motor Skills Development as Ground for Learning observation checklist and school achievements by marks in Swedish , English , Mathematics , and PE and proportion of pupils who qualified for upper secondary school . In school year 9 there were motor skills deficits in 7 % of pupils in the intervention group compared to 47 % in the control group ( P < 0.001 ) , 96 % of the pupils in the intervention group compared to 89 % in the control group ( P < 0.05 ) qualified for upper secondary school . The sum of evaluated marks was higher among boys in the intervention group than in the control group ( P < 0.05 ) . The sum of marks was also higher in pupils with no motor skills deficit than among pupils with motor skills deficits ( P < 0.01 ) , as was the proportion of pupils who qualified for upper secondary school ( 97 % vs 81 % , P < 0.001 ) . Daily PE and adapted motor skills training during the compulsory school years is a feasible way to improve not only motor skills but also school performance and the proportion of pupils who qualify for upper secondary school Current physical activity and fitness levels among adolescents are low , increasing the risk of chronic disease . Although the efficacy of high intensity interval training ( HIIT ) for improving metabolic health is now well established , it is not known if this type of activity can be effective to improve adolescent health . The primary aim of this study is to assess the effectiveness and feasibility of embedding HIIT into the school day . A 3-arm pilot r and omized controlled trial was conducted in one secondary school in Newcastle , Australia . Participants ( n = 65 ; mean age = 15.8(0.6 ) years ) were r and omized into one of three conditions : aerobic exercise program ( AEP ) ( n = 21 ) , resistance and aerobic exercise program ( RAP ) ( n = 22 ) and control ( n = 22 ) . The 8-week intervention consisted of three HIIT sessions per week ( 8–10 min/session ) , delivered during physical education ( PE ) lessons or at lunchtime . Assessment s were conducted at baseline and post-intervention to detect changes in cardiorespiratory fitness ( multi-stage shuttle-run ) , muscular fitness ( push-up , st and ing long jump tests ) , body composition ( Body Mass Index ( BMI ) , BMI -z scores , waist circumference ) and physical activity motivation ( question naire ) , by research ers blinded to treatment allocation . Intervention effects for outcomes were examined using linear mixed models , and Cohen 's d effect sizes were reported . Participants in the AEP and RAP groups had moderate intervention effects for waist circumference ( p = 0.024 ) , BMI -z ( p = 0.037 ) and BMI ( not significant ) in comparison to the control group . A small intervention effect was also evident for cardiorespiratory fitness in the RAP group ABSTRACT Aim of this study was to evaluate the effectiveness of two different 5-month physical education ( PE ) interventions conducted by a specialist PE teacher on primary school children ’s skill- and health-related outcomes . About 230 children were r and omly assigned to one of three intervention groups : experimental_1 group , experimental_2 group or control group ( school curriculum given by the generalist teacher ) . Pre- and post-intervention tests assessed pupils ’ fitness ( pacer , curl-up , push-up , trunk lift , sit and reach tests ) and gross motor coordination ( shifting platforms , balance beam , jumping laterally , hopping on one leg over an obstacle tests ) . Both experimental groups significantly improved some fitness and coordinative tests after the intervention period when compared with control group . However , no differential changes on coordinative development were observed between the 2 experimental groups . Results of this study demonstrated that children benefitted from a well-structured PE intervention conducted and supervised by a specialist PE teacher improving their motor skills and fitness Abstract This study aims to evaluate the effectiveness of two school-based physical education ( PE ) programmes ( exercise-based and games-based ) compared with traditional PE , on health- and skill-related physical fitness components in children in Tirana , Albania . Participants were 378 first- grade ( 6.8 years ) and 389 fourth- grade ( 9.8 years ) children attending four r and omly selected schools in Tirana . Twenty-four school classes within these schools were r and omly selected ( stratified by school and school grade ) to participate as exercise group ( EG ) , games group ( GG ) and control group ( CG ) . Both EG and GG intervention programmes were taught by professional PE teachers using station/circuit teaching framework while CG referred to traditional PE school lessons by a general teacher . All programmes ran in parallel and lasted 5 months , having the same frequency ( twice weekly ) and duration ( 45 min ) . Heart rate ( HR ) monitoring showed that intensity during PE lessons was significantly higher in the intervention groups compared with control ( P < 0.001 ) . Both PE exercise- and games programmes significantly improved several health- and skill-related fitness indicators compared with traditional PE lessons ( e.g. gross motor skill summary score : 9.4 ( 95 % CI 7.9 ; 10.9 ) for exercise vs. control and 6.5 ( 95 % CI 5.1 ; 8.1 ) for games vs. control , cardiorespiratory fitness : 2.0 ml O2 · min−1 · kg−1 ( 95 % CI 1.5 ; 2.4 ) for exercise vs. control and 1.4 ml O2 · min−1 · kg−1 ( 95 % CI 1.0 ; 1.8 ) for games vs. control ) . Furthermore , compared to games-based PE , exercise-based PE showed more positive changes in some gross motor coordination skills outcomes , coordination skills outcomes and cardiorespiratory fitness . The results from this study show that exercise- and games-based PE represents a useful strategy for improving health- and skill-related physical fitness in Albanian elementary school children . In addition , the study shows that exercise-based PE was more effective than games-based PE in improving gross motor function and cardiorespiratory fitness BACKGROUND Although adolescence is a time when physical activity levels decline , few interventions have targeted high school-aged girls in the school setting . OBJECTIVE To evaluate the effects of a life skills-oriented physical activity intervention for increasing overall physical activity in high school-aged girls . DESIGN R and omized controlled trial . SETTING Baltimore magnet high school . PARTICIPANTS A total of 221 ninth- grade girls , 83.0 % of whom were African American . Intervention Participants were r and omized to an 8-month physical intervention conducted in physical education class or to a st and ard physical education class ( control ) . MAIN OUTCOME MEASURES Self-reported estimated daily energy expenditure ( physical activity ) , self-reported sedentary activities ( television viewing and computer or Internet use ) , cardiorespiratory fitness , and selected cardiovascular disease risk factors . RESULTS Intervention classes spent 46.9 % of physical education class time in moderate to vigorous activity compared with 30.5 % of time for control classes ( P<.001 ) . There were no significant between-treatment group differences for mean daily energy expenditure ( P = .93 ) , moderate-intensity energy expenditure ( P = .77 ) , or hard to very hard energy expenditure ( P = .69 ) . The proportion of participants who spent 3 or more hours viewing television during school days declined from 22.3 % to 17.0 % in the intervention group , but remained at 26.7 % for the control group ( P = .03 ) . Both groups improved their cardiorespiratory fitness ( P<.001 ) . CONCLUSION A life skills-oriented physical education curriculum may need to be combined with other approaches to increase the magnitude of effects on physical activity behavior in predominantly African American high school-aged girls The POWER PE study was an 8-mo , r and omized , controlled , school-based exercise intervention design ed to apply known principles of effective bone loading to practical opportunities to improve life-long musculoskeletal outcomes . A total of 99 adolescents ( 46 boys and 53 girls ) with a mean age of 13.8 + /- 0.4 yr ( peri- to postpubertal ) volunteered to participate . Intervention subjects performed 10 min of jumping activity in place of regular physical education ( PE ) warm up . Control subjects performed usual PE warm-up activities . Bone mass ( DXA and QUS ) was assessed at baseline and follow-up along with anthropometry , maturity , muscle power , and estimates of physical activity and dietary calcium . Geometric properties ( such as femoral neck [ FN ] moment of inertia ) were calculated from DXA measures . Boys in the intervention group experienced improvements in calcaneal broadb and ultrasound attenuation ( BUA ) ( + 5.0 % ) and fat mass ( -10.5 % ) , whereas controls did not ( + 1.4 % and -0.8 % , respectively ) . Girls in the intervention group improved FN BMC ( + 13.9 % ) and lumbar spine ( LS ) BMAD ( + 5.2 % ) more than controls ( + 4.9 % and + 1.5 % , respectively ) . Between-group comparisons of change showed intervention effects only for whole body ( WB ) BMC ( + 10.6 % versus + 6.3 % ) for boys . Boys in the intervention group gained more lean tissue mass , trochanter ( TR ) BMC , LS BMC , and WB BMC and lost more fat mass than girls in the intervention group ( p < 0.05 ) . Ten minutes of jumping activity twice a week for 8 mo during adolescence seems to improve bone accrual in a sex-specific manner . Boys increased WB bone mass and BUA , and reduced fat mass , whereas girls improved bone mass at the hip and spine BACKGROUND Physical activity is important for weight control and good health ; however , activity levels decline in the adolescent years , particularly in girls . DESIGN Group r and omized controlled trial . SETTING / PARTICIPANTS Middle school girls with English-speaking skills and no conditions to prevent participation in physical activity in 36 schools in six geographically diverse areas of the United States . R and om , cross-sectional sample s were drawn within schools : 6th grade rs in 2003 ( n=1721 ) and 8th grade rs in 2005 ( n=3504 ) and 2006 ( n=3502 ) . INTERVENTION A 2-year study -directed intervention ( fall 2003 to spring 2005 ) targeted schools , community agencies , and girls to increase opportunities , support , and incentives for increased physical activity . Components included programs linking schools and community agencies , physical education , health education , and social marketing . A third-year intervention used school and community personnel to direct intervention activities . MAIN OUTCOME MEASURES The primary outcome , daily MET-weighted minutes of moderate-to-vigorous physical activity ( MET-weighted MVPA ) , was assessed using accelerometry . Percent body fat was assessed using anthropometry . RESULTS After the staff-directed intervention ( pre-stated primary outcome ) , there were no differences ( mean= -0.4 , 95 % CI= -8.2 to 7.4 ) in adjusted MET-weighted MVPA between 8th- grade girls in schools assigned to intervention or control . Following the Program Champion-directed intervention , girls in intervention schools were more physically active than girls in control schools ( mean difference 10.9 MET-weighted minutes of MVPA , 95 % CI=0.52 - 21.2 ) . This difference is about 1.6 minutes of daily MVPA or 80 kcal per week . There were no differences in fitness or percent body fat at either 8th- grade timepoint . CONCLUSION A school-based , community-linked intervention modestly improved physical activity in girls Using a quasiexperimental design , the authors examine whether fourth- and fifth- grade students exposed to a developmental physical education ( PE ) curriculum , Michigan ’s Exemplary Physical Education Curriculum ( EPEC ) , demonstrated stronger motor skill — specific self-efficacy and perceptions of physical activity competence , physical activity levels , motor skills , and physical fitness than did students exposed to existing PE curricula . The authors conducted a multilevel regression analysis with data from 1,464 students in the fourth and fifth grade s. Data were collected using a student survey , an activity checklist , and motor and fitness assessment s. Compared to students receiving st and ard PE , students exposed to EPEC showed significantly stronger results in motor skills but not fitness outcomes . The authors found significant positive intervention effects on indicators of motor skill self-efficacy and physical activity levels among the fourth- grade cohort . EPEC was more effective than st and ard PE curricula at improving motor skill performance ( fourth- and fifth- grade cohorts ) and at increasing self-reported motor skill-specific self-efficacy and physical activity ( fourth- grade cohort ) Background School-based intervention studies promoting a healthy lifestyle have shown favorable immediate health effects . However , there is a striking paucity on long-term follow-ups . The aim of this study was therefore to assess the 3 yr-follow-up of a cluster-r and omized controlled school-based physical activity program over nine month with beneficial immediate effects on body fat , aerobic fitness and physical activity . Methods and Findings Initially , 28 classes from 15 elementary schools in Switzerl and were grouped into an intervention ( 16 classes from 9 schools , n = 297 children ) and a control arm ( 12 classes from 6 schools , n = 205 children ) after stratification for grade ( 1st and 5th grade rs ) . Three years after the end of the multi-component physical activity program of nine months including daily physical education ( i.e. two additional lessons per week on top of three regular lessons ) , short physical activity breaks during academic lessons , and daily physical activity homework , 289 ( 58 % ) participated in the follow-up . Primary outcome measures included body fat ( sum of four skinfolds ) , aerobic fitness ( shuttle run test ) , physical activity ( accelerometry ) , and quality of life ( question naires ) . After adjustment for grade , gender , baseline value and clustering within classes , children in the intervention arm compared with controls had a significantly higher average level of aerobic fitness at follow-up ( 0.373 z-score units [ 95%-CI : 0.157 to 0.59 , p = 0.001 ] corresponding to a shift from the 50th to the 65th percentile between baseline and follow-up ) , while the immediate beneficial effects on the other primary outcomes were not sustained . Conclusions Apart from aerobic fitness , beneficial effects seen after one year were not maintained when the intervention was stopped . A continuous intervention seems necessary to maintain overall beneficial health effects as reached at the end of the intervention . Trial Registration ControlledTrials.com IS RCT UNLABELLED The CAPO Kids trial was a 9-mo , controlled , school-based intervention to examine the effects of a novel , brief , high intensity exercise regime on indices of musculoskeletal and metabolic health in pre- and early-pubertal girls . METHODS A total of 151 pre- and early-pubertal girls ( 10.6±0.6years ) , recruited from two different schools consented to participate ; 76 in the exercise group ( EX ) and 75 in the control group ( CON ) . EX performed 10min bouts of thrice-weekly jumping plus capoeira ( a Brazilian sport that combines martial art with dance ) , along with usual physical education ( PE ) activities . CON continued usual PE alone . Maturity , weight , height , waist circumference , resting heart rate and blood pressure , maximal vertical jump , and aerobic capacity were determined using st and ard clinical and field measures . Calcaneal broadb and ultrasound attenuation ( BUA ) and stiffness index ( SI ) were determined from quantitative ultrasonometry . A sub sample of children also underwent DXA and pQCT measures . Prior physical activity participation and daily calcium consumption were determined from vali date d instruments . RESULTS EX girls improved BUA more than CON ( + 4.5 % vs. + 1.4 % , p=0.019 ) . Resting heart rate ( -7.2 % vs. -1.8 % , p<0.01 ) , maximal vertical jump ( + 13.4 % vs. -1.2 % , p<0.001 ) , estimated maximal oxygen consumption ( + 10.6 % vs. + 1.0 % , p<0.001 ) , and waist circumference ( + 2.7 % vs. + 5.6 % , p<0.001 ) also improved more for EX than CON . CONCLUSION Ten minutes of high intensity exercise ( capoeira and jumping ) three times a week in the primary school setting enhances musculoskeletal and metabolic outcomes in pre- and early-pubertal girls without disrupting the academic schedule . The programme , amenable to broad-scale school implementation , would confer meaningful public health benefits OBJECTIVE --To examine the effect of physical training on physical fitness and blood pressure in children aged 9 - 11 years . DESIGN -- Prospect i ve r and omised controlled intervention study of a sample of children drawn from a population survey of coronary risk factors in children . SETTING --Odense , Denmark . SUBJECTS--69 children with mean blood pressure greater than or equal to 95th centile ( hypertensive group ) and 68 with mean blood pressure less than 95th centile ( normotensive group ) , r and omly selected from a population of 1369 children . INTERVENTION--67 children were r and omised to receive three extra lessons a week of an ordinary school physical education programme for eight months . MAIN OUTCOME MEASURES --Physical fitness assessed by calculation of maximum oxygen uptake and blood pressure recorded by one unblinded observer . RESULTS --After three months neither blood pressure nor physical fitness had changed significantly . After adjustment for values in weight , height , heart rate , and the variable in question before training physical fitness rose significantly at the end of eight months ' training , by 3.7 mlO2/kg/min ( 95 % confidence interval 2.2 to 5.3 ) in the normotensive training subgroup and by 2.1 mlO2/kg/min ( 0.1 to 4.2 ) in the hypertensive training subgroup compared with that in the controls . Systolic and diastolic blood pressures in the training subgroups fell significantly by 6.5 mm Hg ( 3.2 to 9.9 ) and 4.1 mm Hg ( 1.7 to 6.6 ) respectively in the normotensive group and by 4.9 mm Hg ( 0.7 to 9.2 ) and 3.8 mm Hg ( 0.9 to 6.6 ) respectively in the hypertensive group . CONCLUSIONS --Physical training lowers blood pressure and improves physical fitness in children and might have implication s for an important non-pharmacological approach to primary prevention of essential hypertension Objective To assess the effectiveness of a school based physical activity programme during one school year on physical and psychological health in young schoolchildren . Design Cluster r and omised controlled trial . Setting 28 classes from 15 elementary schools in Switzerl and r and omly selected and assigned in a 4:3 ratio to an intervention ( n=16 ) or control arm ( n=12 ) after stratification for grade ( first and fifth grade ) , from August 2005 to June 2006 . Participants 540 children , of whom 502 consented and presented at baseline . Intervention Children in the intervention arm ( n=297 ) received a multi-component physical activity programme that included structuring the three existing physical education lessons each week and adding two additional lessons a week , daily short activity breaks , and physical activity homework . Children ( n=205 ) and parents in the control group were not informed of an intervention group . For most outcome measures , the assessors were blinded . Main outcome measures Primary outcome measures included body fat ( sum of four skinfolds ) , aerobic fitness ( shuttle run test ) , physical activity ( accelerometry ) , and quality of life ( question naires ) . Secondary outcome measures included body mass index and cardiovascular risk score ( average z score of waist circumference , mean blood pressure , blood glucose , inverted high density lipoprotein cholesterol , and triglycerides ) . Results 498 children completed the baseline and follow-up assessment s ( mean age 6.9 ( SD 0.3 ) years for first grade , 11.1 ( 0.5 ) years for fifth grade ) . After adjustment for grade , sex , baseline values , and clustering within classes , children in the intervention arm compared with controls showed more negative changes in the z score of the sum of four skinfolds ( −0.12 , 95 % confidence interval −0.21 to −0.03 ; P=0.009 ) . Likewise , their z scores for aerobic fitness increased more favourably ( 0.17 , 0.01 to 0.32 ; P=0.04 ) , as did those for moderate-vigorous physical activity in school ( 1.19 , 0.78 to 1.60 ; P<0.001 ) , all day moderate-vigorous physical activity ( 0.44 , 0.05 to 0.82 ; P=0.03 ) , and total physical activity in school ( 0.92 , 0.35 to 1.50 ; P=0.003 ) . Z scores for overall daily physical activity ( 0.21 , −0.21 to 0.63 ) and physical quality of life ( 0.42 , −1.23 to 2.06 ) as well as psychological quality of life ( 0.59 , −0.85 to 2.03 ) did not change significantly . Conclusions A school based multi-component physical activity intervention including compulsory elements improved physical activity and fitness and reduced adiposity in children . Trial registration Current Controlled Trials IS RCT N15360785 In light of the interrelation between motor and cognitive development and the predictive value of the former for the latter , the secular decline observed in motor coordination ability as early as preschool urges identification of interventions that may jointly impact motor and cognitive efficiency . The aim of this study was twofold . It ( 1 ) explored the outcomes of enriched physical education ( PE ) , centered on deliberate play and cognitively challenging variability of practice , on motor coordination and cognitive processing ; ( 2 ) examined whether motor coordination outcomes mediate intervention effects on children ’s cognition , while controlling for moderation by lifestyle factors as outdoor play habits and weight status . Four hundred and sixty children aged 5–10 years participated in a 6-month group r and omized intervention in PE , with or without playful coordinative and cognitive enrichment . The weight status and spontaneous outdoor play habits of children ( parental report of outdoor play ) were evaluated at baseline . Before and after the intervention , motor developmental level ( Movement Assessment Battery for Children ) was evaluated in all children , who were then assessed either with a test of working memory ( R and om Number Generation task ) , or with a test of attention ( from the Cognitive Assessment System ) . Children assigned to the ‘ enriched ’ intervention showed more pronounced improvements in all motor coordination assessment s ( manual dexterity , ball skills , static/dynamic balance ) . The beneficial effect on ball skills was amplified by the level of spontaneous outdoor play and weight status . Among indices of executive function and attention , only that of inhibition showed a differential effect of intervention type . Moderated mediation showed that the better outcome of the enriched PE on ball skills mediated the better inhibition outcome , but only when the enrichment intervention was paralleled by a medium-to-high level of outdoor play . Results suggest that specifically tailored physical activity ( PA ) games provide a unique form of enrichment that impacts children ’s cognitive development through motor coordination improvement , particularly object control skills , which are linked to children ’s PA habits later in life . Outdoor play appears to offer the natural ground for the stimulation by design ed PA games to take root in children ’s mind First , this study aim ed to investigate if four extra physical education ( PE ) lessons per week improved children 's development in physical fitness . Second , to investigate if the extra PE lessons improved development in physical fitness for children with lower levels of fitness at baseline . This study was a longitudinal controlled school-based study . The study population consisted of 10 Danish public schools with children in preschool to fourth grade ( cohorts 0 - 4 ) with 2.5-year follow-up . Six schools had extra PE and four schools had normal PE . In total 1247 children were included ( normal PE = 536 , extra PE = 711 ) . Development in fitness was analyzed using a composite z-score from six fitness tests . Multilevel mixed-effects linear regression was used to examine the association between school type and development in fitness . Extra PE increased the total development of composite z-score units among children enrolled in cohort 4 and borderline in cohort 3 with 1.06 ( 95 % confidence interval 0.48 - 1.65 ) and 0.52 z-score units ( -0.06 to 1.09 ) , respectively . Children in the lower 50 percentiles increased their development with 0.47 ( 0.08 - 0.85 ) z-score units . Extra PE in schools improved development in fitness for cohort 4 and borderline for cohort 3 among all children . Extra PE improved fitness development across all cohorts among children with low fitness levels Objective : Early menarche is a risk factor for breast cancer . Since body composition influences age at menarche we decided to estimate the effects of a school-based intervention for the prevention of obesity on the initiation of menses in young girls . Methods : Ten schools were r and omized to a modified curriculum or no curricular changes for 2 school-years . Data of 508 pre-menarcheal girls at baseline ( age range : 10–13 years ) were analyzed . Results : Girls attending an intervention school experienced menarche less frequently than girls attending control schools during the intervention period ( intervention schools = 54 % , control schools = 59 % ; RR = 0.76 ; 95 % CI [ 0.66 , 0.87 ] ) . Attending an intervention school was also associated with lower increase in BMI ( −0.3 kg/m2 ; p = 0.003 ) , lower gains in triceps skinfold thickness ( −1.5 mm ; p = 0.007 ) , decreased television viewing ( −0.6 h/day ; p<0.0001 ) and increased physical activity ( 3.1 MET-h/week ; p = 0.032 ) . Including these changes as predictors of menarche incidence attenuated the intervention effect ( RR = 0.94 ; 95 % CI [ 0.80 , 1.10 ] ) . Conclusions : The intervention delayed menarche in this group of girls . The delay was produced by increased physical activity , reduced television viewing and changes in BMI and fat distribution . These findings may have implication s for the primary prevention of breast cancer BACKGROUND Obesity and poor physical fitness constitute a health problem affecting an increasing number of children . Causes include a pervasive " toxic " environment that facilitates increased caloric intake and reduced physical activity . An effective strategy for prevention and treatment of childhood obesity likely includes a collaborative effort in the school setting . OBJECTIVE To determine whether a school-based fitness program can improve body composition , cardiovascular fitness level , and insulin sensitivity in overweight children . DESIGN Fifty overweight middle school children with a body mass index ( BMI ) above the 95th percentile for age were r and omized to lifestyle-focused , fitness-oriented gym classes ( treatment group ) or st and ard gym classes ( control group ) for 9 months . Children underwent evaluation of fasting insulin and glucose levels , body composition by means of dual energy absorptiometry , and maximum oxygen consumption ( V0(2)max ) treadmill testing at baseline ( before the school year ) and at end of the school year . SETTING S Rural middle school and an academic children 's hospital . MAIN OUTCOME MEASURES Baseline test results for cardiovascular fitness , body composition , and fasting insulin and glucose levels . RESULTS At baseline , there were no differences between groups before intervention ( values for age , 12 + /- 0.5 years [ all results , mean + /- SD ] ; BMI [ calculated as weight in kilograms divided by the square of height in meters ] , 31.0 + /- 3.7 ; percentage of body fat , 36.5 % + /- 4.6 % ; lean body mass , 41.4 + /- 8.6 kg ; and V0(2)max , 31.5 + /- 5.1 mL/kg per minute ) . Compared with the control group , the treatment group demonstrated a significantly greater loss of body fat ( loss , -4.1 % + /- 3.4 % vs -1.9 % + /- 2.3 % ; P = .04 ) , greater increase in cardiovascular fitness ( V0(2)max , 2.7 + /- 2.6 vs 0.4 + /- 3.3 mL/kg per minute ; P<.001 ) , and greater improvement in fasting insulin level ( insulin level , -5.1 + /- 5.2 vs 3.0 + /- 14.3 microIU/mL [ -35.4 + /- 36.1 vs 20.8 + /- 99.3 pmol/L ] ; P = .02 ) . CONCLUSIONS Children enrolled in fitness-oriented gym classes showed greater loss of body fat , increase in cardiovascular fitness , and improvement in fasting insulin levels than control subjects . The modification to the school physical education curriculum demonstrates that small but consistent changes in the amount of physical activity has beneficial effects on body composition , fitness , and insulin levels in children . Partnering with school districts should be a part of a public health approach to improving the health of overweight children This 4-year cluster r and omized controlled trial of 365 boys and 362 girls ( mean age 8.1 ± 0.3 years ) from grade 2 in 29 primary schools investigated the effects of a specialist-taught physical education ( PE ) program on bone strength and body composition . All children received 150 min/week of common practice ( CP ) PE from general classroom teachers but in 13 schools 100 min/week of CP PE was replaced by specialized-led PE ( SPE ) by teachers who emphasized more vigorous exercise/games combined with static and dynamic postural activities involving muscle strength . Outcome measures assessed in grade s 2 , 4 , and 6 included : total body bone mineral content ( BMC ) , lean mass ( LM ) , and fat mass ( FM ) by DXA , and radius and tibia ( 4 % and 66 % sites ) bone structure , volumetric density and strength , and muscle cross-sectional area ( CSA ) by pQCT . After 4-years , gains in total body BMC , FM , and muscle CSA were similar between the groups in both sexes , but girls in the SPE group experienced a greater gain in total body LM ( mean 1.0 kg ; 95 % CI , 0.2 to 1.9 kg ) . Compared to CP , girls in the SPE group also had greater gains in cortical area ( CoA ) and cortical thickness ( CoTh ) at the mid-tibia ( CoA , 5.0 % [ 95 % CI , 0.2 % to 1.9 % ] ; CoTh , 7.5 % [ 95 % CI , 2.4 % to 12.6 % ] ) and mid-radius ( CoA , 9.3 % [ 95 % CI , 3.5 % to 15.1 % ] ; CoTh , 14.4 % [ 95 % CI , 6.1 % to 22.7 % ] ) , whereas SPE boys had a 5.2 % ( 95 % CI , 0.4 % to 10.0 % ) greater gain in mid-tibia CoTh . These benefits were due to reduced endocortical expansion . There were no significant benefits of SPE on total bone area , cortical density or bone strength at the mid-shaft sites , nor any appreciable effects at the distal skeletal sites . This study indicates that a specialist-led school-based PE program improves cortical bone structure , due to reduced endocortical expansion . This finding challenges the notion that periosteal apposition is the predominant response of bone to loading during the prepubertal and early-pubertal period BACKGROUND Physical inactivity is a risk behavior for cardiovascular and other diseases . Schools can promote public health objectives by increasing physical activity among youth . METHODS The Child and Adolescent Trial for Cardiovascular Health ( CATCH ) was a multicenter , r and omized trial to test the effectiveness of a cardiovascular health promotion program in 96 public schools in four states . A major component of CATCH was an innovative , health-related physical education ( P+ ) program . For 2.5 years , r and omly assigned schools received a st and ardized PE intervention , including curriculum , staff development , and follow-up . RESULTS Systematic analysis of 2,096 PE lessons indicated students engaged in more moderate-to-vigorous physical activity ( MVPA ) in intervention than in control schools ( P = 0.002 ) . MVPA during lessons in intervention schools increased from 37.4 % at baseline to 51.9 % , thereby meeting the established Year 2000 objective of 50 % . Intervention children reported 12 more min of daily vigorous physical activity ( P = 0.003 ) and ran 18.6 yards more than control children on a 9-min run test of fitness ( P = 0.21 ) . CONCLUSIONS The implementation of a st and ardized curriculum and staff development program increased children 's MVPA in existing school PE classes in four geographic and ethnically diverse communities . CATCH PE provides a tested model for improving physical education in American schools OBJECT Increased importance on academic achievement has result ed in many school districts focusing on improved academic performance leading to reductions in physical education time . The purpose was to examine the effects of 45 minutes of daily physical education on the cognitive ability , fitness performance and body composition of African American elementary and middle school youth . METHODS Participants completing the informed consent in grade s 2nd to 8th were included in the study . A pre/posttest design was used with repeated measures analysis of variance . Experimental and control school participants were pretested on the cognitive measures ( ie , Fluid Intelligence and Perceptual Speed ) and Fitnessgram ® physical fitness test items ( eg , aerobic capacity , muscular strength and muscular endurance , body composition ) in September 2009 and posttested in May 2010 . RESULTS Experimental elementary and middle school participants observed significantly greater improvements compared with control elementary and middle school participants on 7 of 16 fitness and body composition measures and on 8 of 26 cognitive measures . These fitness , body composition , and cognitive improvement differences were more noticeable among elementary and middle school females . CONCLUSIONS Providing 45 minutes of daily physical education can perhaps increase cognitive ability while increasing fitness and decreasing the prevalence of overweight and obese youth The aim of this study was to analyse the effects of a high-intensity aerobic training program on different components of physical fitness in adolescents aged 11 to 16 years . The subjects were divided into a high intensity ( HI ) group ( 243 girls and 260 boys ) and a control ( C ) group ( 21 girls and 27 boys ) . HI and C completed a weekly 3 hour physical education ( PE ) session . Before and after a 10-week period , the two groups performed the European physical fitness test battery ( EUROFIT ) . During these 10 weeks HI spent one hour out of three at a specific PE session . These specific sessions consisted of short intermittent exercises ( 10 seconds ) at 100 to 120 % of maximal aerobic speed . They showed a significant influence on st and ing broad jump ( 2.9 % , P<0.05 , F=4.85 ) , 20 meter shuttle run ( 3.8 % , p0.001 , F=23.21 ) and on the maximal distance covered over 7 min ( 7.6 % , P < 0.001 , F= 14.48 ) . For C there was no improvement in EUROFIT performances . It was concluded that training at high intensity improves not only children 's aerobic fitness but also performance of st and ing broad jump . Well-monitored , adequate intensive training is necessary for a more desirable functional development BACKGROUND AND PURPOSE Assessment of the quality of r and omized controlled trials ( RCTs ) is common practice in systematic review s. However , the reliability of data obtained with most quality assessment scales has not been established . This report describes 2 studies design ed to investigate the reliability of data obtained with the Physiotherapy Evidence Data base ( PEDro ) scale developed to rate the quality of RCTs evaluating physical therapist interventions . METHOD In the first study , 11 raters independently rated 25 RCTs r and omly selected from the PEDro data base . In the second study , 2 raters rated 120 RCTs r and omly selected from the PEDro data base , and disagreements were resolved by a third rater ; this generated a set of individual rater and consensus ratings . The process was repeated by independent raters to create a second set of individual and consensus ratings . Reliability of ratings of PEDro scale items was calculated using multirater kappas , and reliability of the total ( summed ) score was calculated using intraclass correlation coefficients ( ICC [ 1,1 ] ) . RESULTS The kappa value for each of the 11 items ranged from.36 to.80 for individual assessors and from.50 to.79 for consensus ratings generated by groups of 2 or 3 raters . The ICC for the total score was.56 ( 95 % confidence interval=.47-.65 ) for ratings by individuals , and the ICC for consensus ratings was.68 ( 95 % confidence interval=.57-.76 ) . DISCUSSION AND CONCLUSION The reliability of ratings of PEDro scale items varied from " fair " to " substantial , " and the reliability of the total PEDro score was " fair " to " good . PURPOSE School physical education ( PE ) is highly recommended as a means of promoting physical activity , and r and omized studies of health-related PE interventions in middle schools have not been reported . We developed , implemented , and assessed an intervention to increase physical activity during middle-school PE classes . METHODS Twenty-four middle schools ( approximately 25,000 students , 45 % nonwhite ) in Southern California participated in a r and omized trial . Schools were assigned to intervention ( N = 12 ) or control ( N = 12 ) conditions , and school was the unit of analysis . A major component of the intervention was a 2-yr PE program , which consisted of curricular material s , staff development , and on-site follow-up . Control schools continued usual programs . Student activity and lesson context were observed in 1849 PE lessons using a vali date d instrument during baseline and intervention years 1 and 2 . RESULTS The intervention significantly ( P = 0.02 ) improved student moderate to vigorous physical activity ( MVPA ) in PE , by approximately 3 min per lesson . Effects were cumulative ; by year 2 intervention schools increased MVPA by 18 % . Effect sizes were greater for boys ( d = 0.98 ; large ) than girls ( d = 0.68 ; medium ) . CONCLUSIONS A st and ardized program increased MVPA in middle schools without requiring an increase in frequency or duration of PE lessons . Program components were well received by teachers and have the potential for generalization to other schools . Additional strategies may be needed for girls BACKGROUND This study aim ed to assess whether a school-based physical education intervention was effective in improving physical abilities and influencing daily physical activity habits in primary school children . The possible effect on body mass index ( BMI ) was also considered . METHODS Twenty-six 3rd- grade classes were r and omly selected stratifying by geographic location ( city , plain , hills ) and were assigned either to an intervention ( 127 boys ; 120 girls ) or to a traditional ( 129 boys ; 121 girls ) physical education program . At baseline ( age : 8 - 9 years ) and after a 2-year follow-up ( age : 10 - 11 years ) , information was collected about sport participation and daily activity habits using a self-administered question naire . Height , weight , and BMI were measured and physical performance was assessed by means of st and ardized tests . RESULTS The enhanced program of physical education was effective in improving physical abilities of children and determining a decrease ( boys : 10 % ; girls : 12 % ) in daily sedentary activities ( preintervention versus postintervention , p < .05 ; intervention versus control group , p < .01 ) . The percentages of overweight and obese children did not vary significantly , but the experimental group showed a significantly lower rise in BMI compared to the control group ( p < .001 ) . CONCLUSION The school proved to be an ideal setting for promoting physical activity and achieving the required daily activity levels OBJECTIVES This study evaluated a health-related physical education program for fourth- and fifth- grade students design ed to increase physical activity during physical education classes and outside of school . METHODS Seven schools were assigned to three conditions in a quasi-experimental design . Health-related physical education was taught by physical education specialists or trained classroom teachers . Students from these classes were compared with those in control classes . Analyses were conducted on 955 students with complete data . RESULTS Students spent more minutes per week being physically active in specialist-led ( 40 min ) and teacher-led ( 33 min ) physical education classes than in control classes ( 18 min ; P < .001 ) . After 2 years , girls in the specialist-led condition were superior to girls in the control condition on abdominal strength and endurance ( P < .001 ) and cardiorespiratory endurance ( P < .001 ) . There were no effects on physical activity outside of school . CONCLUSIONS A health-related physical education curriculum can provide students with substantially more physical activity during physical education classes . Improved physical education classes can potentially benefit 97 % of elementary school students BACKGROUND Physical education ( PE ) lessons are an ideal setting to improve child fundamental movement skills ( FMSs ) and increase physical activity ( PA ) for optimal health . Despite this , few studies have assessed the potential to do both simultaneously . The " Move It Groove It " primary school intervention in New South Wales , Australia , had this opportunity . METHODS A whole school approach to implementation included establishment of school project teams , a teacher " buddy " system , project Web site , teacher training workshops , and small grants for equipment . The quasi-experimental evaluation involved 1,045 year 3 and 4 children ( aged 7 to 10 years ) in nine intervention and nine control rural primary schools ( 53 % boys/47 % girls ) . It utilised pre- and postobservational surveys of ( 1 ) mastery or near mastery levels for each of eight FMSs , ( 2 ) proportion of PE lesson time spent in moderate to vigorous PA ( MVPA ) and vigorous PA ( VPA ) , and ( 3 ) teacher- and lesson-related context ual covariates . Data were analysed by hierarchical logistic multiple regression . RESULTS For FMSs , overall mastery or near mastery level at baseline was 47 % ranging from 22.7 % for the overarm throw among girls to 75.4 % for the static balance among boys . The intervention delivered substantial improvements in every FMS for both genders ranging from 7.2 % to 25.7 % ( 13 of 16 comparisons were significant ) . For PA level , mean MVPA at baseline was 34.7 % . Baseline MVPA for boys was 38.7 % and for girls was 33.2 % . The intervention was associated with a nonsignificant 4.5 % increase in MVPA and a significant 3.0 % increase in VPA . This translates to a gain of < 1 minute of MVPA per average 21-minute lesson . CONCLUSIONS This is the first study to show that by modifying existing PE lessons , significant improvements in FMS mastery can be gained without adversely affecting children 's MVPA and VPA . To increase PA levels , we recommend increasing the number of PE lessons per week BACKGROUND Of the few exercise intervention studies focusing on pediatric population s , none have confined the intervention to the scheduled physical education curriculum . OBJECTIVE To examine the effect of an 8-month school-based jumping program on the change in areal bone mineral density ( aBMD ) , in grams per square centimeter , of healthy third- and fourth- grade children . STUDY DESIGN Ten elementary schools were r and omized to exercise ( n = 63 ) and control groups ( n = 81 ) . Exercise groups did 10 tuck jumps 3 times weekly and incorporated jumping , hopping , and skipping into twice weekly physical education classes . Control groups did regular physical education classes . At baseline and after 8 months of intervention , we measured aBMD and lean and fat mass by dual-energy x-ray absorptiometry ( Hologic QDR-4500 ) . Calcium intake , physical activity , and maturity were estimated by question naire . RESULTS The exercise group showed significantly greater change in femoral trochanteric aBMD ( 4.4 % vs 3.2 % ; P < .05 ) . There were no group differences at other sites . Results were similar after controlling for covariates ( baseline aBMD change in height , change in lean , calcium , physical activity , sex , and ethnicity ) in hierarchical regression . CONCLUSIONS An easily implemented school-based jumping intervention augments aBMD at the trochanteric region in the prepubertal and early pubertal skeleton BACKGROUND This study tests the feasibility of an innovative school-based program for obesity prevention among adolescent girls . New Moves was implemented as a multicomponent , girls-only , high-school physical education class . METHODS Six schools were equally r and omized into intervention and control conditions . Data were collected at baseline , postintervention , and 8-month follow-up to assess program impact on physical activity , eating patterns , self-perceptions , and body mass index ( BMI ) among 89 girls in the intervention and 112 girls in the control conditions . Program evaluation also included interviews with school staff , parent surveys , and participant interviews and process evaluation surveys . RESULTS The feasibility of implementing New Moves was high , as indicated by strong satisfaction among participants , parents , and school staff , and by program sustainability . Participants perceived a positive program impact on their physical activity , eating patterns , and self-image . Girls in the intervention significantly progressed in their stage of behavioral change for physical activity from baseline to follow-up . However , for the majority of outcome variables , differences between intervention and control schools at postintervention and follow-up were not statistically significant . CONCLUSIONS New Moves was well received and fills a needed niche within school physical education programs . An exp and ed intervention and evaluation is needed to enhance and assess long-term program effectiveness PURPOSE Physical activity ( PA ) declines dramatically during adolescence , and activity levels are consistently lower among children living in low-income communities . Competency in a range of fundamental movement skills ( FMS ) may serve as a protective factor against the decline in PA typically observed during adolescence . The purpose of this study was to evaluate the effect of a 12-month multicomponent PA and FMS intervention on children attending primary schools in low-income communities . METHODS The Supporting Children 's Outcomes using Rewards , Exercise , and Skills intervention was evaluated using a cluster r and omized controlled trial . The sample included 25 classes from eight primary schools located in low-income communities . Participants were 460 children ( 54.1 % girls ) age 8.5 ± 0.6 yr . Primary outcomes were objective ly measured PA ( ActiGraph GT3X and GT3X+ accelerometers ) , FMS competency ( Test of Gross Motor Development 2 , six locomotor and six object control skills ) , and cardiorespiratory fitness ( 20-m multistage fitness test ) assessed at baseline , midprogram ( 6-months ) , and at posttest ( 12 months ) . Linear mixed models , adjusted for sex , age , body mass index z-score , socioeconomic status , ethnicity , and school class as a r and om factor , were used to assess the effect of the intervention . RESULTS At midprogram , there were no significant intervention effects for any of the outcomes . At posttest ( study 's primary time point ) , there were intervention effects for daily moderate-to-vigorous PA ( MVPA ) ( adjusted mean difference , 12.7 min·d of MVPA ; 95 % confidence interval ( CI ) , 5.0 - 20.5 ) , overall FMS competency ( 4.9 units ; 95 % CI , -0.04 to 9.8 ) , and cardiorespiratory fitness ( 5.4 laps ; 95 % CI , 2.3 - 8.6 ) . CONCLUSIONS A school-based multicomponent PA and FMS intervention maintained daily MVPA , improved overall FMS competency , and increased cardiorespiratory fitness among children attending primary schools in low-income communities OBJECTIVES Many adolescent girls fail to meet national guidelines for physical activity , and the prevalence of obesity is increasing among this group . Our study examined the effects of a comprehensive school-based intervention on physical activity among high-school girls . METHODS A group-r and omized controlled field trial was conducted at 24 high schools . A school-based sample of 2744 girls ( 48.7 % African American , 46.7 % White ) participated in a measurement protocol when they were in eighth and then ninth grade . A comprehensive physical activity intervention was design ed to change the instructional program and the school environment to increase support for physical activity among girls . RESULTS At follow-up , 45 % of girls in the intervention schools and 36 % of girls in the control schools reported vigorous physical activity during an average of 1 or more 30-minute time blocks per day over a 3-day period . CONCLUSIONS A comprehensive school-based intervention can increase regular participation in vigorous physical activity among high-school girls PURPOSE Children and adolescents are encouraged to maintain a habitually active lifestyle because of the known health benefits associated with regular physical activity , but there are some reports that a high level of activity may be associated with increased fracture risk . This prospect i ve controlled exercise intervention study in prepubertal children evaluated if a school-based exercise intervention could enhance growth-related gains in muscle strength and muscular function without affecting fracture risk . METHODS Fractures were registered in 417 girls and 500 boys age 7 - 9 yr in the intervention and in 836 age-matched girls and 872 boys . The intervention included 40 min·d of school physical education for 2 yr , whereas the controls achieved 60 min·wk . In a sub sample consisting of 49 girls and 80 boys in the intervention and 50 girls and 53 boys in the control group , body composition was measured by dual-energy x-ray absorptiometry , muscle strength by isokinetic peak torque ( PT ) of the knee extensors , and flexors at 60 and 180 ° ·s by a computerized dynamometer and neuromuscular performance by vertical jump height . RESULTS The rate ratio ( 95 % confidence interval ) for children in the intervention group to sustain a fracture was 1.07 ( 0.66 - 1.68 ) . The annual gain in knee extensor PT at 180 ° ·s was significantly higher for both girls ( P < 0.001 ) and boys ( P < 0.01 ) in the intervention compared with the control group . Boys in the intervention group also had a greater annual gain in knee flexion PT at 180 ° ·s ( P < 0.001 ) , and girls had a greater gain in vertical jump height ( P < 0.05 ) . CONCLUSION An increase in school-based physical education from 60 to 200 min·wk enhanced muscle strength in prepubertal children without affecting fracture risk Background Although cardiorespiratory fitness ( CRF ) in childhood and adolescence may be linked to future cardiovascular health , there is currently limited evidence for a longitudinal association . Objectives To provide a systematic review on the prospect i ve association between CRF in childhood and adolescence and cardiovascular disease ( CVD ) risk factors at least 2 years later . Methods Using a systematic search of Medline , Embase , and SPORTD iscus , relevant articles were identified by the following criteria : generally healthy children and adolescents between 3 and 18 years of age with CRF assessed at baseline , and a follow-up period of ≥ 2 years . The outcome measures were CVD risk factors . We appraised quality of the included articles with STROBE and QUIPS checklists . Results After screening 7524 titles and abstract s , we included 38 articles , assessing 44,169 children and adolescents followed up for a median of 6 years . Eleven articles were of high quality . There was considerable heterogeneity in methodology , measurement of CRF , and outcomes , which hampered meta- analysis . In approximately half of the included articles higher CRF in childhood and adolescence was associated with lower body mass index ( BMI ) , waist circumference , body fatness and lower prevalence of metabolic syndrome in later life . No associations between CRF in childhood and adolescence and future waist-to-hip ratio , blood pressure , lipid profile , and glucose homeostasis were observed . Conclusion Although about half of the included articles reported inverse associations between CRF in childhood and adolescence and future BMI , body fatness , and metabolic syndrome , evidence for other CVD risk factors was unconvincing . Many articles did not account for important confounding factors such as adiposity . Recommendations for future research include st and ardizing the measurement of CRF , i.e. by reporting VO2max , using st and ardized outcome assessment s , and performing individual patient data meta-analyses Background Metabolic health in people with obesity is determined by body composition . In this study , we examined the influence of a combined strength exercise and motivational programme –embedded in the school curriculum– on adolescents body composition and daily physical activity . Methods A total of 695 adolescents ( 11 - 15y ) from nine Dutch secondary schools participated in a one year cluster r and omised controlled trial ( RCT ) . In the intervention schools , physical education teachers were instructed to spend 15–30 min of all physical education lessons ( 2 × per week ) on strength exercises . Monthly motivational lessons were given to stimulate students to be more physically active . Control schools followed their usual curriculum . The primary outcome measure was body composition assessed by the deuterium dilution technique . Daily physical activity and sedentary behaviour measured by accelerometry served as a secondary outcome . Results After 1 year , a 1.6 % fat mass difference was found in favour of the intervention group ( p = .007 ) . This reflected a 0.9 kg difference in fat free mass ( intervention > control ; p = .041 ) and 0.7 kg difference in fat mass ( intervention < control ; p = .054 ) . Daily physical activity decreased from baseline to posttest in both groups , but less so in the intervention group ( p = .049 ) . After 1 year , a difference of 0.4 % was found for moderate to vigorous physical activities in favour of the intervention group ( p = .046 ) . No differences in sedentary behaviour , or light physical activity were found between groups . Conclusion In 11–15 year olds , the combination of strength exercises plus motivational lessons contributed to an improvement in body composition and a smaller decrease in physical activity level . Trial registration ID(NTR5676 – retrospectively registered 8 February 2016 ; enrolment of first participant : 2 March 2015 ) |
14,085 | 32,310,261 | Conclusions and Relevance The findings suggest that sexual health interventions are associated with improvements in sexual well-being among black adolescents . | Importance Black adolescents are at increased risk of contracting HIV and other sexually transmitted infections ( STIs ) and experiencing unplanned pregnancy .
Although sexual health interventions aim ed at decreasing these risks exist , evidence of the association between sexual health interventions and the sexual behavior of black adolescents has not been synthesized to our knowledge .
Objective To examine the associations between sexual health interventions and behavioral , biological , and psychological outcomes . | Although there are now several adolescent HIV and STD preventive interventions of demonstrated efficacy in the literature , little is understood about the portability of these interventions . This study replicated Stanton 's Focus on Kids intervention , developed for inner city African American adolescents , in a different population , transferring it to a multicultural city . Despite careful replication of the original study 's procedures , youth in the preventive intervention condition of the replication study did not improve in attitudes , perceived norms , self-efficacy , or intentions toward sexual initiation , condom use , or abstinence compared with a carefully matched control condition . We discuss several possible reasons for this failure to replicate , concluding that the most likely reason is the lower rates of sexual activity among youth in the replication city The purpose of this study was to document the effectiveness of small group condom motivation education in reducing new and reinfection rates of sexually transmitted diseases ( STD ) among female teenagers . Two hundred and five ( 205 ) female adolescents ( age 13 - 20 ) with a current STD were studied at two sites of a Teen Health Clinic . There were 86 teens in the Study Group and 119 in the Comparison Group . Patients were sample d from December 1992 to July 1993 . The patients in the Study Group received a condom motivation class given by the clinic STD educator in small groups of four or more adolescents . The Comparison Group , comparable in age and ethnicity , received treatment for their STD but did not participate in condom motivation classes . All teens were given treatment and condoms . The sample was followed for 6 months . The total number of patients returning with new infections was 21 ( 14.7 % ) . The total number of patients with reinfections was 14 ( 9.8 % ) . There were no significant differences between the Study and Comparison Group on return rates , new and reinfection rates or on any socio-demographic variables . The comparison of these groups suggests that a specific condom motivation class has minimal effectiveness in urban teens . However , almost 70 % of the teens returned to the clinic for their scheduled visits . It is suggested that adolescent clinics which combine family planning and STD treatment services maintain high client enrollment and therefore may be ideal locations to initiate new and continuous interventions for condom use especially for high risk teens Young Black men ( YBM ) , aged 13 to 24 years , face a disproportionate burden of sexually transmitted infections ( STIs ) . STI acquisition among YBM is due to incorrect and inconsistent condom use and is exacerbated by multiple sexual partners . Sexual and reproductive health is influenced by a complex interaction of biological , psychological , and social determinants that contribute to increased risk for STI acquisition . However , there are key social determinants of sexual health that play a major role in adolescent sexual risk – taking behaviors : gender norms , environment , peers , and families as well as a desire to impregnate a woman . Associations between context ual factors ( risky environmental context , desire to impregnate a woman , and peer norms supportive of unsafe sex ) and sexual risk behaviors were examined among a sample of YBM attending adolescent health clinics . This study used baseline data from a r and omized controlled trial ( N = 702 ) . Parental monitoring was also examined as an effect modifier of those associations . Sexual risk behaviors were the frequency of condomless vaginal sex , number of sexual partners within the previous 2 months , and lifetime number of sexual partners . Mean age was 19.7 . In the adjusted model , peer norms was the only significant predictor for all sexual risk outcomes ( p < .05 ) . Parental monitoring was an effect modifier for the perceived peer norms and lifetime sexual partners association ( p = .053 ) where the effect of peer norms on lifetime sexual partners was lower for participants with higher levels of perceived parental monitoring OBJECTIVE : To compare the efficacy of a r and omized controlled trial of the Sexual Awareness For Everyone ( SAFE ) behavioral intervention on teenagers ( aged 14 to 18 years ) compared with adult rates of reinfection with Neiserria gonorrhea or Chlamydia trachomatis cervicitis , and to identify behaviors associated with recurrent infection . METHODS : Mexican-American and African-American females with a nonviral sexually transmitted disease ( STD ) were enrolled in SAFE or assigned to the control group . All participants were interviewed and examined at baseline , 6 , and 12 months . The primary outcome variable was reinfection with N. gonorrhea or C. trachomatis . Secondary outcomes were changes in risky sexual behavior . RESULTS : Teens r and omized to participation in SAFE had a statistically lower incidence of recurrent N. gonorrhea and C. trachomatis at 0 to 6 months ( 52 % , P=.04 ) and cumulatively ( 39 % , P=.04 ) compared with teens in the control group . Cumulatively , teens as a group had higher rates of reinfection ( 33.1 % ) than adults ( 14.4 % ) ( P<.001 ) . Adolescent reinfection was explained by unprotected sex with untreated partners ( adjusted odds ratio [ OR ] 5.58 ) , nonmonogamy ( adjusted OR 5.14 ) , and rapid partner turnover ( adjusted OR 2.02 ) . In adults , reinfection was predicted by unprotected sex with untreated partners ( adjusted OR 4.90 ) , unsafe sex ( adjusted OR 2.18 ) , rapid partner turnover ( adjusted OR 3.13 ) , and douching after sex ( adjusted OR 2.14 ) . CONCLUSION : Sexual Awareness for Everyone significantly reduced recurrent STDs in teenagers . Adults and teens r and omized to the SAFE intervention had significant decreases in high-risk sexual behaviors as compared with those in the control group . Although not specifically design ed for teens , the SAFE intervention worked very well in this high-risk population . CLINICAL TRIAL REGISTRATION : www . clinical trials.gov , Clinical Trials.gov , HSC2004415H LEVEL OF EVIDENCE : OBJECTIVE To evaluate the efficacy of an abstinence-only intervention in preventing sexual involvement in young adolescents . DESIGN R and omized controlled trial . SETTING Urban public schools . PARTICIPANTS A total of 662 African American students in grade s 6 and 7 . INTERVENTIONS An 8-hour abstinence-only intervention targeted reduced sexual intercourse ; an 8-hour safer sex-only intervention targeted increased condom use ; 8-hour and 12-hour comprehensive interventions targeted sexual intercourse and condom use ; and an 8-hour health-promotion control intervention targeted health issues unrelated to sexual behavior . Participants also were r and omized to receive or not receive an intervention maintenance program to extend intervention efficacy . OUTCOME MEASURES The primary outcome was self-report of ever having sexual intercourse by the 24-month follow-up . Secondary outcomes were other sexual behaviors . RESULTS The participants ' mean age was 12.2 years ; 53.5 % were girls ; and 84.4 % were still enrolled at 24 months . Abstinence-only intervention reduced sexual initiation ( risk ratio [ RR ] , 0.67 ; 95 % confidence interval [ CI ] , 0.48 - 0.96 ) . The model-estimated probability of ever having sexual intercourse by the 24-month follow-up was 33.5 % in the abstinence-only intervention and 48.5 % in the control group . Fewer abstinence-only intervention participants ( 20.6 % ) than control participants ( 29.0 % ) reported having coitus in the previous 3 months during the follow-up period ( RR , 0.94 ; 95 % CI , 0.90 - 0.99 ) . Abstinence-only intervention did not affect condom use . The 8-hour ( RR , 0.96 ; 95 % CI , 0.92 - 1.00 ) and 12-hour comprehensive ( RR , 0.95 ; 95 % CI , 0.91 - 0.99 ) interventions reduced reports of having multiple partners compared with the control group . No other differences between interventions and controls were significant . CONCLUSION Theory-based abstinence-only interventions may have an important role in preventing adolescent sexual involvement . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00640653 BACKGROUND Although numerous interventions have been demonstrated to reduce targeted adolescent risk behaviors for brief periods , sustained behavior changes covering multiple risk behaviors have been elusive . OBJECTIVE To determine whether a parental monitoring intervention ( Informed Parents and Children Together [ ImPACT ] ) with and without boosters can further reduce adolescent truancy , substance abuse , and sexual risk behaviors and can alter related perceptions 24 months after intervention among youth who have all received an adolescent risk-reduction intervention , Focus on Kids ( FOK ) . DESIGN R and omized , controlled , 3-celled longitudinal trial . SETTING Thirty-five low-income , urban community sites . PARTICIPANTS Eight hundred seventeen African American youth aged 13 to 16 at baseline . Intervention All youth participated in FOK , an 8-session , theory-based , small group , face-to-face risk-reduction intervention , 496 youth and parents received the 1-session ImPACT intervention ( a videotape and discussion ) , 238 of the ImPACT youth also received four 90-minute FOK boosters delivered in small groups . MAIN OUTCOME MEASURES Responses at baseline and 24 months after intervention to a question naire assessing risk and protective behaviors and perceptions . Analyses used General Linear Modeling , intraclass correlation coefficient , analysis of covariance , and multiple comparisons with least significant difference test adjustment . RESULTS After adjusting for the intraclass correlation coefficient , 6 of 16 risk behaviors were significantly reduced ( P < or = .05 ) among youth receiving ImPACT compared with youth who only received FOK ( respectively , mean number of days suspended , 0.65 vs 1.17 ; carry a bat as a weapon , 4.1 % vs 9.6 % ; smoked cigarettes , 12.5 % vs 22.7 % ; used marijuana , 18.3 % vs 26.8 % ; used other illicit drugs , 1.4 % vs 5.6 % ; and , asked sexual partner if condom always used , 77.9 % vs 64.9 % ) . Four of the 7 theory-based subscales reflected significant protective changes among youth who received ImPACT . ImPACT did not produce any significant adverse effects on behaviors or perceptions . CONCLUSION A parent monitoring intervention can significantly broaden and sustain protection beyond that conferred through an adolescent risk-reduction intervention CONTEXT African American adolescents are at high risk of contracting sexually transmitted infection with human immunodeficiency virus ( HIV ) , but which behavioral interventions to reduce risk are most effective and who should conduct them is not known . OBJECTIVE To evaluate the effects of abstinence and safer-sex HIV risk-reduction interventions on young inner-city African American adolescents ' HIV sexual risk behaviors when implemented by adult facilitators as compared with peer cofacilitators . DESIGN R and omized controlled trial with 3- , 6- , and 12-month follow-up . SETTING Three middle schools serving low-income African American communities in Philadelphia , Pa. PARTICIPANTS A total of 659 African American adolescents recruited for a Saturday program . INTERVENTIONS Based on cognitive-behavioral theories and elicitation research , interventions involved 8 1-hour modules implemented by adult facilitators or peer cofacilitators . Abstinence intervention stressed delaying sexual intercourse or reducing its frequency ; safer-sex intervention stressed condom use ; control intervention concerned health issues unrelated to sexual behavior . MAIN OUTCOME MEASURES Self-reported sexual intercourse , condom use , and unprotected sexual intercourse . RESULTS Mean age of the enrollees was 11.8 years ; 53 % were female and 92.6 % were still enrolled at 12 months . Abstinence intervention participants were less likely to report having sexual intercourse in the 3 months after intervention than were control group participants ( 12.5 % vs 21.5 % , P=.02 ) , but not at 6- or 12-month follow-up ( 17.2 % vs 22.7 % , P=.14 ; 20.0 % vs 23.1 % , P=.42 , respectively ) . Safer-sex intervention participants reported significantly more consistent condom use than did control group participants at 3 months ( odds ratio [OR]=3.38 ; 95 % confidence interval [ CI ] , 1.25 - 9.16 ) and higher frequency of condom use at all follow-ups . Among adolescents who reported sexual experience at baseline , the safer-sex intervention group reported less sexual intercourse in the previous 3 months at 6- and 12-month follow-up than did control and abstinence intervention ( adjusted mean days over prior 3 months , 1.34 vs 3.77 and 3.03 , respectively ; P < or = .01 at 12- month follow-up ) and less unprotected intercourse at all follow-ups than did control group ( adjusted mean days , 0.04 vs 1.85 , respectively , P<.001 , at 12-month follow-up ) . There were no differences in intervention effects with adult facilitators as compared with peer cofacilitators . CONCLUSION Both abstinence and safer-sex interventions can reduce HIV sexual risk behaviors , but safer-sex interventions may be especially effective with sexually experienced adolescents and may have longer-lasting effects Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more This study translated SiHLE ( Sisters Informing , Healing , Living , and Empowering ) , a 12-hour Centers for Disease Control and Prevention evidence -based group-level intervention for African American females 14 - 18 years of age , into a 2-hour computer-delivered individual-level intervention . A r and omized controlled trial ( n = 178 ) was conducted to examine the efficacy of the new Multimedia SiHLE intervention . Average condom-protected sex acts ( proportion of vaginal sex acts with condoms , last 90 days ) for sexually active participants receiving Multimedia SiHLE rose from M = 51 % at baseline to M = 71 % at 3-month follow-up ( t = 2.06 , p = .05 ) ; no statistically significant difference was found in the control group . Non-sexually active intervention group participants reported a significant increase in condom self-efficacy ( t = 2.36 , p = .02 ) ; no statistically significant difference was found in the control group . The study provides preliminary support for the efficacy of a computer-delivered adaptation of a proven HIV prevention program for African American teenage women . This is consistent with meta-analyses that have shown that computer-delivered interventions , which can often be disseminated at lower per-capita cost than human-delivered interventions , can influence HIV risk behaviors in positive fashion OBJECTIVES To evaluate the efficacy of an intervention to reduce incident sexually transmitted disease ( STD ) and enhance STD/human immunodeficiency virus (HIV)-preventive behaviors and psychosocial mediators . DESIGN A r and omized controlled trial of an HIV prevention program . SETTING Clinic-based sample in Atlanta , Georgia . PARTICIPANTS African American adolescent females ( N = 715 ) , aged 15 to 21 years , seeking sexual health services . Participants completed an audio computer-assisted self-interview and provided self-collected vaginal specimens for STD testing . Intervention Intervention participants received two 4-hour group sessions and 4 telephone contacts over a 12-month period , targeting personal , relational , sociocultural , and structural factors associated with adolescents ' STD/HIV risk , and were given vouchers facilitating male partners ' STD testing/treatment . Main Outcome Measure Incident chlamydial infections . RESULTS Over the 12-month follow-up , fewer adolescents in the intervention had a chlamydial infection ( 42 vs 67 ; risk ratio [ RR ] , 0.65 ; 95 % confidence interval [ CI ] , 0.42 to 0.98 ; P = .04 ) or recurrent chlamydial infection ( 4 vs 14 ; RR , 0.25 ; 95 % CI , 0.08 to 0.83 ; P = .02 ) . Adolescents in the intervention also reported a higher proportion of condom-protected sex acts in the 60 days preceding follow-up assessment s ( mean difference , 10.84 ; 95 % CI , 5.27 to 16.42 ; P < .001 ) and less frequent douching ( mean difference , -0.76 ; 95 % CI , -1.15 to -0.37 ; P = .001 ) . Adolescents in the intervention were also more likely to report consistent condom use in the 60 days preceding follow-up assessment s ( RR , 1 . 41 ; 95 % CI , 1.09 to 1.80 ; P = .01 ) and condom use at last intercourse ( RR , 1.30 ; 95 % CI , 1.09 to 1.54 ; P = .005 ) . Intervention effects were observed for psychosocial mediators of STD/HIV-preventive behaviors . CONCLUSION Interventions for African American adolescent females can reduce chlamydial infections and enhance STD/HIV-preventive behaviors and psychosocial mediators of STD/HIV-preventive behaviors . Trial Registration clinical trials.gov Identifier : NCT00633906 Two hundred forty-six African American adolescents were r and omly assigned to an educational program or an 8-week intervention that combined education with behavior skills training including correct condom use , sexual assertion , refusal , information provision , self-management , problem solving , and risk recognition . Skill-trained participants ( a ) reduced unprotected intercourse , ( b ) increased condom-protected intercourse , and ( c ) displayed increased behavioral skills to a greater extent than participants who received information alone . The patterns of change differed by gender . Risk reduction was maintained 1 year later for skill-trained youths . It was found that 31.1 % of youths in the education program who were abstinent at baseline had initiated sexual activity 1 year later , whereas only 11.5 % of skills training participants were sexually active . The results indicate that youths who were equipped with information and specific skills lowered their risk to a greater degree , maintained risk reduction changes better , and deferred the onset of sexual activity to a greater extent than youths who received information alone We examined the long-term effects of two interventions design ed to reduce sexual risk behavior among African American adolescents . African American adolescents ( N = 1383 , ages 14–17 ) were recruited from community-based organizations over a period of 16 months in two northeastern and two southeastern mid-sized U.S. cities with high rates of sexually transmitted infection ( STI ) . Participants were screened for three STIs ( gonorrhea , chlamydia , and trichomoniasis ) and completed an audio computer-assisted attitude , intention , and behavior self-interview . Youth who tested positive for an STI ( 8.3 % ) received treatment and risk reduction counseling . In addition , television and radio HIV-prevention messages were delivered during the recruitment period and 18 months of follow-up in one r and omly selected city in each region . Analyses determined effects of the media program for those receiving a positive versus negative STI test result on number of sexual partners and occurrence of unprotected sex . Adolescents who tested STI-positive reduced their number of vaginal sex partners and the probability of unprotected sex over the first 6 months . However , in the absence of the mass media program , adolescents returned to their previously high levels of sexual risk behavior after 6 months . Adolescents who tested STI-positive and received the mass media program showed more stable reductions in unprotected sex . Community-based STI treatment and counseling can achieve significant , but short-lived reductions in sexual risk behavior among STI-positive youth . A culturally sensitive mass media program has the potential to achieve more stable reductions in sexual risk behavior and can help to optimize the effects of community-based STI screening Few HIV/STI interventions exist for African American adolescent girls in juvenile detention . The objective was to evaluate the efficacy of an intervention to reduce incident STIs , improve HIV-preventive behaviors , and enhance psychosocial outcomes . We conducted a r and omized controlled trial among African American adolescent girls ( 13–17 years , N = 188 ) in juvenile detention from March 2011 to May 2012 . Assessment s occurred at baseline and 3- and 6-months post-r and omization and included : audio computer-assisted self-interview , condom skills assessment , and self-collected vaginal swab to detect Chlamydia and gonorrhea . The Imara intervention included three individual-level sessions and four phone sessions ; expedited partner therapy was offered to STI-positive adolescents . The comparison group received the usual care provided by the detention center : STI testing , treatment , and counseling . At the 6-month assessment ( 3-months post-intervention ) , Imara participants reported higher condom use self-efficacy ( p < 0.001 ) , HIV/STI knowledge ( p < 0.001 ) , and condom use skills ( p < 0.001 ) compared to control participants . No significant differences were observed between trial conditions in incident Chlamydia or gonorrhea infections , condom use , or number of vaginal sex partners . Imara for detained African American adolescent girls can improve condom use skills and psychosocial outcomes ; however , a critical need for interventions to reduce sexual risk remains PURPOSE This study was undertaken to determine whether the Adult Identity Mentoring ( AIM ) project successfully promotes abstinence , delays initiation of sex , and decreases intention to engage in sex . METHODS Twenty middle school classes of African-American seventh grade rs were r and omly assigned to receive either the AIM intervention or a st and ard health education control curriculum . The AIM is a 10-session curriculum based on the theory of possible selves . Class exercises encourage students to articulate a possible future self-identity and to develop self-promotion skills . Surveys about sexual activity were conducted before the intervention , 19 weeks after baseline , and again at 1 year after the intervention . RESULTS Hierarchical logistic regression analyses showed significant effects for the intervention on sexual intentions , abstinence , and a trend toward fewer virgins initiating intercourse for the first time , 19 weeks after baseline . Specifically , students who received the intervention showed decreased intention to engage in sex and increased abstinence compared with students not receiving the intervention . Effects for 1-year follow-up , with smaller sample size , showed only that AIM male participants maintained the significant abstinence effect . CONCLUSIONS A new intervention , AIM was evaluated among African-American seventh grade rs . This program , by focusing students on positive future selves , effectively modified sexual risk without directly providing instruction on sexually explicit topics CONTEXT African American adolescent girls are at high risk for human immunodeficiency virus ( HIV ) infection , but interventions specifically design ed for this population have not reduced HIV risk behaviors . OBJECTIVE To evaluate the efficacy of an intervention to reduce sexual risk behaviors , sexually transmitted diseases ( STDs ) , and pregnancy and enhance mediators of HIV-preventive behaviors . DESIGN , SETTING , AND PARTICIPANTS R and omized controlled trial of 522 sexually experienced African American girls aged 14 to 18 years screened from December 1996 through April 1999 at 4 community health agencies . Participants completed a self-administered question naire and an interview , demonstrated condom application skills , and provided specimens for STD testing . Outcome assessment s were made at 6- and 12-month follow-up . INTERVENTION All participants received four 4-hour group sessions . The intervention emphasized ethnic and gender pride , HIV knowledge , communication , condom use skills , and healthy relationships . The comparison condition emphasized exercise and nutrition . MAIN OUTCOME MEASURES The primary outcome measure was consistent condom use , defined as condom use during every episode of vaginal intercourse ; other outcome measures were sexual behaviors , observed condom application skills , incident STD infection , self-reported pregnancy , and mediators of HIV-preventive behaviors . RESULTS Relative to the comparison condition , participants in the intervention reported using condoms more consistently in the 30 days preceding the 6-month assessment ( unadjusted analysis , intervention , 75.3 % vs comparison , 58.2 % ) and the 12-month assessment ( unadjusted analysis , intervention , 73.3 % vs comparison , 56.5 % ) and over the entire 12-month period ( adjusted odds ratio , 2.01 ; 95 % confidence interval [ CI ] , 1.28 - 3.17 ; P = .003 ) . Participants in the intervention reported using condoms more consistently in the 6 months preceding the 6-month assessment ( unadjusted analysis , intervention , 61.3 % vs comparison , 42.6 % ) , at the 12-month assessment ( unadjusted analysis , intervention , 58.1 % vs comparison , 45.3 % ) , and over the entire 12-month period ( adjusted odds ratio , 2.30 ; 95 % CI , 1.51 - 3.50 ; P<.001 ) . Using generalized estimating equation analyses over the 12-month follow-up , adolescents in the intervention were more likely to use a condom at last intercourse , less likely to have a new vaginal sex partner in the past 30 days , and more likely to apply condoms to sex partners and had better condom application skills , a higher percentage of condom-protected sex acts , fewer unprotected vaginal sex acts , and higher scores on measures of mediators . Promising effects were also observed for chlamydia infections and self-reported pregnancy . CONCLUSION Interventions for African American adolescent girls that are gender-tailored and culturally congruent can enhance HIV-preventive behaviors , skills , and mediators and may reduce pregnancy and chlamydia infection HIV/AIDS disproportionately affects young women of color . Young women who use hormonal contraception are less likely to use condoms . Brief , inexpensive HIV-prevention interventions are needed for high-volume clinics . This study was a r and omized clinical trial of two interventions : ( a ) a video made for this study and ( b ) an adaptation of Project RESPECT counseling . Four hundred Black and Latina teenage women completed a question naire about their sexual behaviors and were r and omly assigned to ( a ) see the video , ( b ) get counseling , ( c ) see the video and get counseling , or ( d ) receive usual care . At 3-month follow-up , those who saw the video and received counseling were 2.5 times more likely to have used a condom at last intercourse with their main partner than teens in the usual care group . These differences did not persist at 12-month follow-up . This suggests that a brief intervention can positively affect condom use in the short term BACKGROUND Some interventions to reduce the risk of the acquired immunodeficiency syndrome ( AIDS ) that target youths have result ed in short-term increases in self-reported condom use . However , long-term intervention effects have not been assessed . STUDY QUESTION Can a theoretically and culturally based , AIDS-risk reduction intervention delivered to naturally formed peer groups increase self-reported condom use among African-American early adolescents at 6 and 12 months of follow-up ? METHOD A r and omized , controlled trial of a community-based intervention delivered in eight weekly sessions involved 76 naturally formed peer groups consisting of 383 ( 206 intervention and 177 control ) African-American youths 9 to 15 years of age . A theory-based , culturally and developmentally tailored instrument that assessed perceptions , intentions , and self-reported sexual behaviors was administered to all subjects at baseline ( preintervention ) and 6 and 12 months later . RESULTS At baseline , 36 % of youths were sexually experienced , and by 12 months of follow-up , 49 % were sexually experienced . Self-reported condom use rates were significantly higher among intervention than control youths ( 85 % vs 61 % ; P<.05 ) at the 6-month follow-up . However , by 12 months , rates were no longer significantly higher among intervention youths . The intervention impact at 6 months was especially strong among boys ( 85 % vs 57 % ; P<.05 ) and among early teens ( 13 to 15 years old ) ( 95 % vs 60 % ; P<.01 ) . Self-reported condom use intention was also increased among intervention youths at 6 months but not at 12 months . Some perceptions were positively affected at 6 months , but the change did not persist at 12 months . CONCLUSIONS High rates of sexual intercourse underscore the urgent need for effective AIDS-risk reduction interventions that target low-income urban , African-American preteens and early teens . A developmentally and culturally tailored intervention based on social-cognitive theory and delivered to naturally formed peer groups recruited from community setting s can increase self-reported condom use . The strong short-term improvements in behaviors and intentions followed by some relapse over longer periods argue for a strengthened program and research focus on sustainability OBJECTIVES We evaluated the effectiveness of an HIV/STD risk-reduction intervention when implemented by community-based organizations ( CBOs ) . METHODS In a cluster-r and omized controlled trial , 86 CBOs that served African American adolescents aged 13 to 18 years were r and omized to implement either an HIV/STD risk-reduction intervention whose efficacy has been demonstrated or a health-promotion control intervention . CBOs agreed to implement 6 intervention groups , a r and om half of which completed 3- , 6- , and 12-month follow-up assessment s. The primary outcome was consistent condom use in the 3 months prior to each follow-up assessment , averaged over the follow-up assessment s. RESULTS Participants were 1707 adolescents , 863 in HIV/STD-intervention CBOs and 844 in control-intervention CBOs . HIV/STD-intervention participants were more likely to report consistent condom use ( odds ratio [ OR ] = 1.39 ; 95 % confidence interval [ CI ] = 1.06 , 1.84 ) than were control-intervention participants . HIV/STD-intervention participants also reported a greater proportion of condom-protected intercourse ( beta = 0.06 ; 95 % CI = 0.00 , 0.12 ) than did the control group . CONCLUSIONS This is the first large , r and omized intervention trial to demonstrate that CBOs can successfully implement an HIV/STD risk-reduction intervention whose efficacy has been established This study was design ed to test the efficacy of Parents Who Care © ( PWC ) , a seven-session universal prevention program which includes parenting , youth , and family components design ed to prevent substance use and other problem behaviors . Using an intent-to-treat experimental design , this study tests the program efficacy across race within a balanced sample of European American ( EA ) and African American ( AA ) youth and their parents ( n = 331 nAA = 163 ; nEA = 168 ) . Families were recruited , r and omly assigned to three conditions ( group-administered [ PA ] , self-administered with telephone support [ SA ] , and no-treatment control ) and the intervention was administered when the adolescents were in the eighth grade . Analyses on key teen outcomes of the Parent ’s Who Care program at 24-month follow-up are reported here and include perceptions of drug use harm ; favorable attitudes about drug use ; delinquent and violent behavior ; and initiation into cigarette , alcohol , other drug use , or sexual activity . Repeated measures mixed model regressions found no effect of the intervention on rate of change in attitudes about drug use or frequency of delinquent or violent behavior . Regression analyses with multiple imputations for missing data detected group differences in means at 24-month follow-up . Both program formats reduced favorable attitudes toward drug use among youth ( SA d = 0.39 , PA d = 0.22 ) ; and AA youth in the self-administered intervention reported significantly less violent behavior than their control counterparts ( d = 0.45 ) . No effects were found for drug use harm or delinquency . Finally , logistic regression predicting a combined outcome measure of initiation of alcohol , tobacco , drug use , and /or sexual activity found AA youth in both the group- and self-administered intervention conditions significantly less likely to initiate substance use and /or sexual activity than those in the control condition . Odds ratios indicated the chances of initiating sex or substance use were reduced by almost 70 % ( OR = 0.31 ) for AA teens in the SA condition compared to controls , and 75 % ( OR = 0.25 ) for the AA teens in the PA compared to controls BACKGROUND The number of reported cases of acquired immune deficiency syndrome ( AIDS ) is increasing disproportionately among Blacks in the United States . The relatively high incidence of sexually transmitted diseases among Black adolescents suggest the need for AIDS prevention programs to reduce their risk of sexually transmitted human immunodeficiency virus ( HIV ) infection . METHODS Black male adolescents ( n = 157 ) were r and omly assigned to receive an AIDS risk reduction intervention aim ed at increasing AIDS-related knowledge and weakening problematic attitudes toward risky sexual behavior , or to receive a control intervention on career opportunities . RESULTS The adolescents who received the AIDS intervention subsequently had greater AIDS knowledge , less favorable attitudes toward risky sexual behavior , and lower intentions to engage in such behavior than did those in the control condition . Follow-up data collected 3 months later revealed that the adolescents who had received the AIDS intervention reported fewer occasions of coitus , fewer coital partners , greater use of condoms , and a lower incidence of heterosexual anal intercourse than did the other adolescents . CONCLUSIONS These results suggest that interventions that increase knowledge about AIDS and change attitudes toward risky sexual behavior may have salutary effects on Black adolescents ' risk of HIV infection Low-income African American inner city adolescent females continue to be at disproportionately high risk for contracting HIV . Though it has been speculated that mothers ' involvement in HIV risk reduction may be helpful in the fight against HIV , very few interventions involve mothers . The Mother/Daughter HIV Risk Reduction intervention ( MDRR ) , an innovative community-based intervention , trains mothers to be their daughters ' primary HIV educators . A split-plot repeated measures design was used to test the effectiveness of the MDRR in decreasing daughters ' sexual activity over a 2-month period . The mediating variables were daughters ' HIV transmission knowledge , self-efficacy and intention to refuse sex . The sample consisted of 262 daughters with a mean age of 12.4 years . The results revealed that mothers were effective in increasing the mediating variables and in reducing their daughters ' level of sexual activity . Active involvement of mothers is cost-effective and should be integrated into HIV intervention programs OBJECTIVES We tested the efficacy of an intervention among 11- to 14-year-old adolescent boys to promote delay of sexual intercourse , condom use among those who were sexually active , and communication on sexuality between fathers ( or father figures ) and sons . METHODS Sites were r and omly assigned to the intervention and control groups . Assessment s were conducted prior to the intervention and at 3- , 6- , and 12-month follow-up interviews . RESULTS A total of 277 fathers and their sons completed baseline assessment s. Most participants were African American , and most fathers lived with their sons . Significantly higher rates of sexual abstinence and condom use and of intent to delay initiation of sexual intercourse were observed among adolescent boys whose fathers participated in the intervention . Fathers in the intervention group reported significantly more discussion s about sexuality and greater intentions to discuss sexuality than did control-group fathers . CONCLUSIONS The study demonstrates that fathers can serve as an important educator on HIV prevention and sexuality for their sons ABSTRACT HIV/sexually transmitted infection ( STI ) risk-reduction interventions are needed to address the complex risk behaviors among African-American female adolescents in disadvantaged communities in North Carolina . In a two-group r and omized trial , we reached 237 sexually active , substance-using African-American female adolescents , to test a risk-reduction intervention , the Young Women 's CoOp ( YWC ) , relative to a nutrition control . In efficacy analyses adjusting for baseline condom use , at three-month follow-up participants in the YWC were significantly less likely to report sex without a condom at last sex relative to control . There were mixed findings for within-group differences over follow-up , underscoring the challenges for intervening with substance-using female youths PURPOSE To compare the effectiveness of a theory-based HIV educational video tool with in-person HIV counseling in promoting safer sex behaviors among adolescent patients of an urban Emergency Department ( ED ) . METHODS This was a r and omized controlled trial taking place in the Emergency Department of Jacobi Medical Center in the Bronx , New York . A total of 203 stable , sexually active patients aged 15 - 21 years completed pre-intervention and postintervention measures . Participants were r and omized to the intervention video series ( 102 participants ) , a theory-based , youth-friendly human immunodeficiency virus ( HIV ) educational video , or an in-person HIV counseling session with a trained HIV counselor ( 101 participants ) . Participants completed pre-intervention and postintervention measures on the primary outcomes : condom intention , outcome expectancy , and self-efficacy . RESULTS Participants in the video group improved condom use intention ( adjusted differential mean improvement [ ADMI ] = .98 units ; confidence interval [ CI ] , .20 - 1.77 ; Holm adjusted p = .028 ) , condom self-efficacy outcome ( ADMI = .26 units ; CI , .04-.48 ; Holm adjusted p = .019 ) , and condom outcome expectancy scores ( ADMI = .15 units ; CI , .07-.23 ; Holm adjusted p < .001 ) significantly more than those in the counselor group , adjusting for stage of change . The intervention helped participants progress to the next level of readiness or maintain their positive behavior , and did not differ by age , gender , or race . CONCLUSIONS A theory-based , youth-friendly video can be a valid means to provide posttest HIV education and prevention messages within an urban emergency department . The theory-based prevention messages can improve teenagers ' condom intentions , condom self-efficacy , and condom outcome expectancies immediately after the intervention PURPOSE To test the long-term effects of a mass media intervention that used culturally and developmentally appropriate messages to enhance human immunodeficiency virus (HIV)-preventive beliefs and behavior of high-risk African American adolescents . METHODS Television and radio messages were delivered for more than 3 years in two cities ( Syracuse , NY ; and Macon , GA ) that were r and omly selected within each of the two regionally matched city pairs , with the other cities ( Providence , RI ; and Columbia , SC ) serving as controls . African American adolescents , aged 14 - 17 years ( N = 1,710 ) , recruited in the four cities over a 16-month period , completed audio computer-assisted self-interviews at recruitment and again at 3 , 6 , 12 , and 18-months postrecruitment to assess the long-term effects of the media program . To identify the unique effects of the media intervention , youth who completed at least one follow-up and who did not test positive for any of the three sexually transmitted infections at recruitment or at 6- and 12-month follow-up were retained for analysis ( N = 1,346 ) . RESULTS The media intervention reached virtually all the adolescents in the trial and produced a range of effects including improved normative condom-use negotiation expectancies and increased sex refusal self-efficacy . Most importantly , older adolescents ( aged 16 - 17 years ) exposed to the media program showed a less risky age trajectory of unprotected sex than those in the nonmedia cities . CONCLUSION Culturally tailored mass media messages that are delivered consistently over time have the potential to reach a large audience of high-risk adolescents , to support changes in HIV-preventive beliefs , and to reduce HIV-associated risk behaviors among older youth PURPOSE Few computer-based HIV , sexually transmitted infection ( STI ) , and pregnancy prevention programs are available , and even fewer target early adolescents . In this study , we tested the efficacy of It 's Your Game (IYG)-Tech , a completely computer-based , middle school sexual health education program . The primary hypothesis was that students who received IYG-Tech would significantly delay sexual initiation by ninth grade . METHODS We evaluated IYG-Tech using a r and omized , two-arm nested design among 19 schools in a large , urban school district in southeast Texas ( 20 schools were originally r and omized ) . The target population was English-speaking eighth- grade students who were followed into the ninth grade . The final analytic sample included 1,374 students . Multilevel logistic regression models were used to test for differences in sexual initiation between intervention and control students , while adjusting for age , gender , ethnicity , time between measures , and family structure . RESULTS There was no significant difference in the delay of sexual activity or in any other sexual behavior between intervention and control students . However , there were significant positive between-group differences for psychosocial variables related to STI and condom knowledge , attitudes about abstinence , condom use self-efficacy , and perceived norms about sex . Post hoc analyses conducted among intervention students revealed some significant associations : " full exposure " ( completion of all 13 lessons ) and " mid-exposure " ( 5 - 8 lessons ) students were less likely than " low exposure " ( 1 - 4 lessons ) students to initiate sex . CONCLUSIONS Collectively , our findings indicate that IYG-Tech impacts some determinants of sexual behavior , and that additional efficacy evaluation with full intervention exposure may be warranted PURPOSE To evaluate the efficacy of two , theory-based , multimedia , middle school sexual education programs in delaying sexual initiation . METHODS Three-armed , r and omized controlled trial comprising 15 urban middle schools ; 1,258 predominantly African American and Hispanic seventh grade students followed into ninth grade . Both programs included group and individualized , computer-based activities addressing psychosocial variables . The risk avoidance ( RA ) program met federal abstinence education guidelines ; the risk reduction ( RR ) program emphasized abstinence and included computer-based condom skills-training . The primary outcome assessed program impact on delayed sexual initiation ; secondary outcomes assessed other sexual behaviors and psychosocial outcomes . RESULTS Participants were 59.8 % females ( mean age : 12.6 years ) . Relative to controls , the RR program delayed any type of sexual initiation ( oral , vaginal , or anal sex ) in the overall sample ( adjusted odds ratio [ AOR ] : .65 , 95 % CI : .54-.77 ) , among females ( AOR : .43 , 95 % CI : .31-.60 ) , and among African Americans ( AOR : .38 , 95 % CI : .18-.79 ) . RR students also reduced unprotected sex at last intercourse ( AOR : .67 , 95 % CI : .47-.96 ) , frequency of anal sex in the past 3 months ( AOR : .53 , 95 % CI : .33-.84 ) , and unprotected vaginal sex ( AOR : .59 , 95 % CI : .36-.95 ) . The RA program delayed any sexual initiation among Hispanics ( AOR : .40 , 95 % CI : .19-.86 ) , reduced unprotected sex at last intercourse ( AOR : .70 , 95 % CI : .52-.93 ) , but increased the number of recent vaginal sex partners ( AOR : 1.69 , 95 % CI : 1.01 - 2.82 ) . Both programs positively affected psychosocial outcomes . CONCLUSIONS The RR program positively affected sexually inexperienced and experienced youth , whereas the RA program delayed initiation among Hispanics and had mixed effects among sexually experienced youth PURPOSE The Strong African American Families-Teen ( SAAF-T ) program , a family-centered preventive intervention that included an optional condom skills unit , was evaluated to determine whether it prevented unprotected intercourse and increased condom efficacy among rural African American adolescents . Ancillary analyses were conducted to identify factors that predicted youth attendance of the condom skills unit . METHODS Sixteen-year-old African American youths ( N = 502 ) and their primary caregivers were r and omly assigned to SAAF-T ( n = 252 ) or an attention control ( n = 250 ) intervention . SAAF-T families participated in a 5-week family skills training program that included an optional condom skills unit . All families completed in-home pretest , posttest , and long-term follow-up interviews during which adolescents reported on their sexual behavior , condom use , and condom efficacy . Because condom use was addressed only in an optional unit that required caregiver consent , we analyzed efficacy using complier average causal effect analyses . RESULTS Attendance in both SAAF-T and the attention control intervention averaged 4 of 5 sessions ; 70 % of SAAF-T youth attended the condom skills unit . Complier average causal effect models indicated that SAAF-T was efficacious in reducing unprotected intercourse and increasing condom efficacy among rural African American high school students . Exploratory analyses indicated that religious caregivers were more likely than nonreligious caregivers to have their youth attend the condom skills unit . CONCLUSIONS Results suggest that brief condom skills educational modules in the context of a family-centered program are feasible and reduce risk for sexually transmitted infections and unplanned pregnancies |
14,086 | 32,411,816 | Microgravity-induced bone changes depend on the skeletal-site position relative to the gravitational vector .
Post-flight recovery depends on spaceflight duration and is limited to a short post-flight period during which bone formation exceeds resorption | Bone loss in space travelers is a major challenge for long- duration space exploration . | Exercise has shown little success in mitigating bone loss from long- duration spaceflight . The first crews of the International Space Station ( ISS ) used the " interim resistive exercise device " ( iRED ) , which allowed loads of up to 297 lb(f ) ( or 1337 N ) but provided little protection of bone or no greater protection than aerobic exercise . In 2008 , the Advanced Resistive Exercise Device ( ARED ) , which allowed absolute loads of up to 600 lb(f ) ( 1675 N ) , was launched to the ISS . We report dietary intake , bone densitometry , and biochemical markers in 13 crewmembers on ISS missions from 2006 to 2009 . Of these 13 , 8 had access to the iRED and 5 had access to the ARED . In both groups , bone-specific alkaline phosphatase tended to increase during flight toward the end of the mission ( p = 0.06 ) and increased 30 days after l and ing ( p < 0.001 ) . Most markers of bone resorption were also increased in both groups during flight and 30 days after l and ing ( p < 0.05 ) . Bone densitometry revealed significant interactions ( time and exercise device ) for pelvis bone mineral density ( BMD ) and bone mineral content ( p < 0.01 ) , hip femoral neck BMD ( p < 0.05 ) , trochanter BMD ( p < 0.05 ) , and total hip BMD ( p < 0.05 ) . These variables were unchanged from preflight only for ARED crewmembers , who also returned from flight with higher percent lean mass and lower percent fat mass . Body mass was unchanged after flight in both groups . All crewmembers had nominal vitamin D status ( 75 ± 17 nmol/L ) before and during flight . These data document that resistance exercise , coupled with adequate energy intake ( shown by maintenance of body mass determined by dual-energy X-ray absorptiometry [ DXA ] ) and vitamin D , can maintain bone in most regions during 4- to 6-month missions in microgravity . This is the first evidence that improving nutrition and resistance exercise during spaceflight can attenuate the expected BMD deficits previously observed after prolonged missions Summary We report the results of alendronate ingestion plus exercise in preventing the declines in bone mass and strength and elevated levels of urinary calcium and bone resorption in astronauts during 5.5 months of spaceflight . Introduction This investigation was an international collaboration between NASA and the JAXA space agencies to investigate the potential value of antiresorptive agents to mitigate the well-established bone changes associated with long- duration spaceflight . Methods We report the results from seven International Space Station ( ISS ) astronauts who spent a mean of 5.5 months on the ISS and who took an oral dose of 70 mg of alendronate weekly starting 3 weeks before flight and continuing throughout the mission . All crewmembers had available for exercise a treadmill , cycle ergometer , and a resistance exercise device . Our assessment included densitometry of multiple bone regions using X-ray absorptiometry ( DXA ) and quantitative computed tomography ( QCT ) and assays of biomarkers of bone metabolism . Results In addition to pre- and post-flight measurements , we compared our results to 18 astronauts who flew ISS missions and who exercised using an early model resistance exercise device , called the interim resistance exercise device , and to 11 ISS astronauts who exercised using the newer advanced resistance exercise device ( ARED ) . Our findings indicate that the ARED provided significant attenuation of bone loss compared with the older device although post-flight decreases in the femur neck and hip remained . The combination of the ARED and bisphosphonate attenuated the expected decline in essentially all indices of altered bone physiology during spaceflight including : DXA-determined losses in bone mineral density of the spine , hip , and pelvis , QCT-determined compartmental losses in trabecular and cortical bone mass in the hip , calculated measures of fall and stance computed bone strength of the hip , elevated levels of bone resorption markers , and urinary excretion of calcium . Conclusions The combination of exercise plus an antiresoptive drug may be useful for protecting bone health during long- duration spaceflight |
14,087 | 19,017,592 | These studies reported no substantial differences in efficacy or harms among agents .
Such studies have greater generalizability of results than efficacy trials because they enroll less selected study population s , use treatment modalities that mimic clinical practice , and assess health outcomes along with adverse events .
Evidence suggests that indirect comparisons agree with head-to-head trials if component studies are similar and treatment effects are expected to be consistent in patients included in different trials ( 13 ) , although these assumptions are usually not verifiable . | Major depressive disorder ( MDD ) is the most prevalent axis I disorder , affecting more than 16 % of U.S. adults during their lifetime ( 1 ) .
In 2000 , the economic burden of depressive disorders was an estimated $ 83.1 billion ( 2 ) , more than 30 % of which was attributable to direct medical expenses .
Pharmacotherapy dominates the medical management of MDD .
Since the mid-1980s , second-generation antidepressants have gradually replaced tricyclic antidepressants and monoamine oxidase inhibitors as first-line medications , primarily because of their lower toxicity in overdose and similar general efficacy ( 3 ) .
These newer treatments include selective serotonin reuptake inhibitors , serotonin and norepinephrine reuptake inhibitors , selective serotonin and norepinephrine reuptake inhibitors , and other second-generation drugs ( Table 1 ) .
Second-Generation Antidepressants Approved for Use in the United States To date , only 2 systematic review s have assessed the comparative efficacy and harms of second-generation antidepressants ( 3 , 4 ) . | This study examined ethnic differences in response to antidepressant treatment . One hundred eighteen depressed HIV-positive patients entered an eight-week controlled trial of fluoxetine . Nineteen percent were black and 14 percent were Latino ; the remaining two-thirds were white . Attrition was greater among Latinos than either blacks or whites . Black patients were more likely than whites to be nonresponders to fluoxetine . Latinos were more likely to respond to placebo compared with blacks and whites . Ethnic groups did not differ in the presence of treatment-emergent side effects & NA ; This was a 6‐week , double‐blind , r and omized trial of the efficacy and tolerability of venlafaxine and fluoxetine in 109 patients with major depression and melancholia . Hospitalized and day care patients with DSM‐IV major depression and melancholia and a baseline Montgomery‐Asberg Depression Rating Scale ( MADRS ) score of ≥ 25 were eligible . The doses were venlafaxine 75 mg/day or fluoxetine 20 mg/day from days 1‐4 , venlafaxine 150 mg/day or fluoxetine 40 mg/day from days 5‐10 , and venlafaxine 225 mg/day or fluoxetine 60 mg/day from days 11‐42 . The intention‐to‐treat analyses included 55 patients on venlafaxine and 54 on fluoxetine . At the final evaluation , 70 % of patients with venlafaxine and 66 % with fluoxetine had ≥ 50 % reduction in the MADRS score , and 70 % with venlafaxine and 62 % with fluoxetine had a Clinical Global Impression ( CGI ) score of 1 or 2.A CGI improvement score of 1 was observed in 51 % of patients with venlafaxine and 32 % with fluoxetine ( P = 0.018 ) . A final Hamilton Depression Rating Scale ( HAM‐D ) score < 7 was attained in 41 % of venlafaxine‐treated and 36 % of fluoxetine‐treated patients . Overall , 22 % of patients in each group discontinued therapy , but only 5 % on venlafaxine and 9 % on fluoxetine discontinued for adverse events . Nausea was reported in 5.5 % of venlafaxinetreated patients and 14.8 % of fluoxetine‐treated patients . Venlafaxine was effective and well tolerated for treating in patients with major depression and melancholia . Based on remission criteria ( HAM‐D < 7 or CGI of 1 ) , venlafaxine was superior to fluoxetine BACKGROUND The highly recurrent nature of major depression in the young and the elderly warrants long-term antidepressant treatment . AIMS To compare the prophylactic efficacy of citalopram and placebo in elderly patients ; to evaluate long-term tolerability of citalopram . METHOD Out- patients , > or = 65 years , with unipolar major depression ( DSM-IV : 296.2 x or 296.3 x ) and Montgomery-Asberg Depression Rating Scale score > or = 22 were treated with citalopram 20 - 40 mg for 8 weeks . Responders continued on their final fixed dose of citalopram for 16 weeks before r and omisation to double-blind treatment with citalopram or placebo for at least 48 weeks . RESULTS Nineteen of the 60 patients using citalopram v. 41 of the 61 patients using placebo had recurrence . Time to recurrence was significantly different between citalopram- and placebo- patients , in favour of citalopram ( log-rank test , P<0.0001 ) . Long-term treatment was well tolerated . CONCLUSIONS Long-term treatment with citalopram is effective in preventing recurrence of depression in the elderly and is well tolerated & NA ; Primary care patients with a major depressive disorder and 17‐item Hamilton Rating Scale for Depression ( 17‐HAM‐D ) score > 18 were r and omized to 24 weeks of treatment with mirtazapine 30‐45 mg/day ( n= 99 ) or paroxetine 20‐30 mg/day ( n=98 ) . Both treatments were efficacious in improving depressive symptomatology , as assessed by group mean 17‐HAM‐D scores , percentages of HAM‐D responders and remitters and Clinical Global Improvement responders . The mirtazapine group showed statistically significantly larger decreases from baseline in group mean 17‐HAM‐D scores at weeks 1 , 2 and 4 , and the difference with the paroxetine group reached the level of clinical relevance at weeks 2 and 4 . Antidepressant efficacy was maintained throughout both the acute and continuation phase of treatment . Both treatments were well tolerated . The only adverse event with a statistically significantly higher incidence in the mirtazapine group was fatigue . Statistically significantly more paroxetine‐treated patients complained of increased sweating , headache and nausea . The results demonstrate that both mirtazapine and paroxetine were efficacious and well tolerated when used for 24 weeks in depressed patients treated in primary care . An observed difference in efficacy favouring mirtazapine between weeks 1 and 4 indicates that mirtazapine patients had improved earlier compared to those on paroxetine , and corroborates similar findings in other comparisons of mirtazapine versus selective serotonin reuptake inhibitors BACKGROUND Major depression is highly recurrent . Antidepressant maintenance treatment has proven efficacy against recurrent depression . AIMS Comparison of prophylactic efficacy of citalopram versus placebo in unipolar , recurrent depression . METHODS Patients 18 - 65 years of age with recurrent unipolar major depression ( DSM-IV ) , a Montgomery-Asberg Depression Rating Scale score of > or = 22 and two or more previous depressive episodes , one within the past 5 years , were treated openly with citalopram ( 20 - 60 mg ) for 6 - 9 weeks and , if responding , continued for 16 weeks before being r and omised to double-blind maintenance treatment with citalopram or placebo for 48 - 77 weeks . RESULTS A total of 427 patients entered acute treatment and 269 were r and omised to double-blind treatment . Time to recurrence was longer in patients taking citalopram than in patients taking placebo ( P:<0.001 ) . Prophylactic treatment was well tolerated . CONCLUSIONS Citalopram ( 20 , 40 and 60 mg ) is effective in the prevention of depressive recurrences . Patients at risk should continue maintenance treatment at the dose necessary to resolve symptoms in the acute treatment phase ABSTRACT Objective : This trial was conducted to compare the efficacy and tolerability of a fixed dose of escitalopram 10 mg/day with sertraline optimally dosed within its recommended dose range ( 50–200 mg/day ) for the treatment of major depressive disorder . Methods : In this multicenter trial , depressed patients ( DSM‑IV defined ; baseline Montgomery – Asberg Depression Rating Scale [ MADRS ] ≥ 22 ) aged 18–80 years were r and omly assigned to 8 weeks of double-blind treatment with escitalopram ( 10 mg/day ) or sertraline ( 50–200 mg/day ) following a 1‑week single-blind placebo lead-in period . There was no placebo comparison arm . Sertraline was initiated at 50 mg/day , and could be increased by 50 mg/day at weekly intervals based on clinical need and tolerability at the lower dose level . The blind was maintained with matching double-blind placebo capsules for the escitalopram group . Change from baseline to endpoint in MADRS total score ( last observation carried forward ) was the primary efficacy measure . Results : A total of 212 patients received double-blind medication . At week 8 , the mean sertraline dosage was 144 mg/day ( median = 150 mg/day ) . Mean changes from baseline to endpoint in MADRS scores were –19.1 and –18.4 for the escitalopram and sertraline groups , respectively . At endpoint , 75 % and 70 % of escitalopram- and sertraline-treated patients , respectively , were responders ( ≥ 50 % improvement from baseline in mean MADRS scores ) . Both treatments were generally well tolerated ; only 2 % and 4 % of patients prematurely discontinued escitalopram and sertraline treatment , respectively , due to adverse events . Conclusion : No differences in efficacy were observed for fixed-dose escitalopram 10 mg/day and sertraline flexibly dosed from 50–200 mg/day . At these doses , both escitalopram and sertraline were generally well tolerated Alcoholism and depression are common disorders that frequently cooccur in the same individual . Selective serotonin reuptake inhibitors ( SSRIs ) are effective in the treatment of depression and also had decreased drinking in some studies of heavy drinkers and alcoholics . The reported effect of serotonergic medications on alcohol intake in depressed alcoholics has not been consistent . Most previous studies have not investigated the use of an SSRI in the context of cognitive behavioral therapy ( CBT ) , a known efficacious treatment of both alcoholism and depression . The study presented here was a r and omized placebo-controlled 12-week trial of sertraline combined with individual CBT focused on both alcoholism relapse prevention and depressive symptoms . Subjects were 82 currently depressed , actively drinking alcohol-dependent individuals . Subjects had either primary ( independent ) major depression ( 70 subjects ) or substance-induced mood disorder and at least 1 first-degree relative ( parent , sibling , or child ) with an affective disorder ( 12 subjects ) . Depression and alcohol consumption outcomes were measured weekly over 12 weeks . Sertraline was well tolerated and all subjects had decreases in both depression and alcohol use during the study compared with baseline . Subjects who received sertraline had fewer drinks per drinking day than subjects who received placebo , but other drinking outcomes were not different between the 2 treatment groups . Treatment with sertraline was associated with less depression at the end of treatment in female subjects compared with female subjects who received placebo . Less drinking during the study was associated with improved depression outcome . The findings in this study suggest that sertraline , compared with placebo , may provide some modest benefit in terms of drinking outcome and also may lead to improved depression in female alcohol-dependent subjects . Additionally , alcohol relapse prevention CBT , delivered according to manual guidelines with modifications that provide specific attention to depression , appeared to be of benefit to subjects , although this interpretation is limited by the design of the study OBJECTIVE This analysis assessed the incidence , severity , onset , and duration of nausea among patients with major depressive disorder ( MDD ) treated with the new antidepressant duloxetine . METHODS Data were pooled from 8 double-blind , r and omized , placebo- and active comparator-controlled trials employing patients with MDD that were su bmi tted to the US Food and Drug Administration to support duloxetine 's new drug application for treatment of MDD . RESULTS The numbers of patients receiving each regimen were as follows : placebo , n = 777 ; duloxetine 40 mg/d , n = 177 ; duloxetine 60 mg/d , n = 251 ; duloxetine 80 mg/d , n = 363 ; duloxetine 120 mg/d , n = 348 ; paroxetine 20 mg/d , n = 359 ; and fluoxetine 20 mg/d , n = 70 . In acute placebo-controlled trials of duloxetine 40 to 120 mg/d , treatment-emergent nausea was reported by more duloxetine-treated patients than those receiving placebo ( 19.9 % [ 227/1139 ] vs 6.9 % [ 154/777 ] , respectively ; P < 0.001 ) . Among duloxetine-treated patients , the median time to onset of nausea was 1 day , and the median duration of nausea was 7 days . The incidence of nausea was similar to placebo rates after 1 week . In paroxetine-controlled studies , the incidence of treatment-emergent nausea in patients receiving duloxetine did not differ significantly from paroxetine ( 14.4 % vs 12.0 % , respectively ) . In head-to-head studies , the incidence of treatment-emergent nausea with duloxetine did not differ significantly from that with fluoxetine ( 17.1 % vs 15.7 % , respectively ) . Most duloxetine-treated patients reported nausea to be mild ( 52.9 % ) or moderate ( 41.4 % ) . Treatment discontinuation secondary to nausea occurred in more duloxetine-treated patients than those receiving placebo ( 1.4 % [ 16/1139 ] vs 0.1 % [ 1/777 ] , respectively ; P = 0.002 ) . Following abrupt discontinuation after acute treatment , 5.9 % of duloxetine-treated patients exhibited nausea compared with 0.3 % of patients receiving placebo ( P < 0.001 ) . The incidence of treatment-emergent nausea during 6-month continuation of duloxetine treatment ( 80 mg/d , 2.1 % ; 120 mg/d , 1.3 % ) was similar to placebo ( 1.6 % ) . Following abrupt discontinuation after 8 months of treatment , nausea was reported by 1.6 % of patients receiving duloxetine 120 mg/d compared with 0 % for those receiving duloxetine 80 mg/d and 0 % for placebo . CONCLUSIONS Duloxetine induced mild to moderate nausea in a subset of patients with MDD during treatment initiation . Nausea resolved rapidly with continued treatment . The incidence of duloxetine-induced nausea resembled that produced by paroxetine and fluoxetine Pramipexole , a dopamine D2 receptor agonist , was tested in 174 patients with major depression , with or without melancholia and without psychotic features . Three daily dose levels ( 0.375 mg , 1.0 mg , and 5.0 mg ) were compared to fluoxetine ( Prozac ) at 20 mg and placebo in a r and omized , double-blind , parallel-group study . After a 1 week placebo run-in period , patients were treated for 8 weeks , had a post- study follow-up ( week 9 ) , and were evaluated primarily with the Hamilton Psychiatric Rating Scale for Depression ( HAM-D ) , the Montgomery-Asberg Depression Rating Scale ( MADRS ) , and the Clinician 's Global Impressions-Severity of Illness scale ( CGI-SI ) . All patients who received one dose of study medication were included in the observed-case analysis ( no missing data were replaced ) . Results indicated that by endpoint ( week 8) , patients receiving pramipexole at the 1.0 mg per day dose had significant improvement over baseline compared to the placebo group by measure of the HAM-D , MADRS , and CGI-SI . Significant improvement in this dose group was seen at other timepoints as well . The most obvious improvement was seen in the pramipexole 5.0 mg group , although a substantial dropout rate for this group precluded statistical tests vs. placebo late in the study . Patients taking fluoxetine also showed significant improvements at endpoint on the MADRS and earlier in the study on the HAM-D. No new or unusual safety concerns were generated during this study . Pramipexole helped safely alleviate the symptoms of depression at 1.0 mg per day and especially in those patients who could tolerate the escalation to 5 mg per day A placebo-controlled , double-blind study of 63 in patients with major affective disorder was performed to compare the safety and efficacy of fluvoxamine and imipramine . Results indicate that fluvoxamine and imipramine are superior to placebo and demonstrate a trend toward superiority of fluvoxamine over imipramine . Fluvoxamine was generally well tolerated in most patients Using data from a larger 12-week clinical trial , the authors evaluated the comparative efficacy and safety of sertraline ( n=42 ) and fluoxetine ( n=33 ) in patients over age 70 with a diagnosis of major depressive disorder . Similar improvement on measures of depression , including remission of depressive symptoms , was evident , although significantly more sertraline-treated patients achieved a criterion clinical response . Significantly greater improvement for the sertraline group was apparent on the Digit Symbol Substitution Test , but not on two other measures of cognitive functioning . Although there was no difference in the rate of adverse events experienced , fluoxetine-treated patients lost significantly more body weight over the 12-week trial than did sertraline-treated patients , whereas the latter group exhibited significantly more " shaking . BACKGROUND Previous comparative studies of the selective serotonin reuptake inhibitors ( SSRIs ) have rarely included a placebo control group and have rarely demonstrated significant between-group differences . The study reported on here was a placebo-controlled comparison of the antidepressant effects of two SSRIs , citalopram and sertraline . METHODS Three hundred twenty-three patients with DSM-IV-defined major depressive disorder were r and omized to 24 weeks of double-blind treatment with citalopram ( 20 - 60 mg/day ) , sertraline ( 50 - 150 mg/day ) , or a placebo . The primary efficacy measure was the Hamilton Depression Rating Scale ( HAMD ) and the primary statistical analysis was an analysis of variance comparing the change from baseline to the last observation carried forward in each treatment group . RESULTS Both citalopram and sertraline produced significantly greater improvement than placebo on the HAMD , the Montgomery-Asberg Depression Rating Scale , and the Clinical Global Impression Scale . Significant improvement was observed at earlier timepoints in the citalopram group than the sertraline group ; however , sertraline treatment was associated with increased gastrointestinal side effects and a tendency toward early discontinuation , and analyses that excluded early dropouts revealed similar acute efficacy for the two active treatments . The Hamilton Anxiety Scale demonstrated a significant anxiolytic effect of citalopram , but not sertraline , relative to placebo . CONCLUSIONS This study confirms the antidepressant efficacy of two SSRIs , citalopram and sertraline . It is hypothesized that the more consistent evidence of antidepressant activity that was observed early in treatment in the citalopram group was related to more pronounced antianxiety effects and better tolerability upon initiation of therapy OBJECTIVE Authors studied the efficacy and tolerability of mirtazapine and paroxetine in elderly patients with major depression during an acute phase ( 8 weeks ) and an extension phase ( 16 weeks ) . METHODS Patients with major depression and without dementia , at least 65 years old , were eligible ; they were r and omized to mirtazapine or paroxetine once daily , with doses increasing over 42 days . Efficacy was assessed with the Ham-D and Clinical Global Impressions Scale , and tolerability was assessed from adverse events . RESULTS Of 255 patients r and omized , 126 on mirtazapine and 120 on paroxetine were included in the efficacy analysis . Differences favoring mirtazapine were observed for the mean change from baseline in Ham-D-17 score . Other significant differences were in the proportion of patients classified as responders ( 50 % decrease from baseline Ham-D-17 scores ) at Day 14 and in remission ( Ham-D-17 score of 7 or less ) at Day 42 . The median time to response was 26 days in the mirtazapine group and 40 days in the paroxetine group . The mirtazapine group also showed more reduction in Ham-D Factor I ( Anxiety/Somatization ) and Factor VI ( Sleep Disturbance ) scores . Efficacy of both drugs was maintained during the extension phase . Patients on paroxetine were more likely to discontinue therapy in the acute phase because of adverse events . CONCLUSION During the first weeks of treatment , antidepressant effects were more pronounced in the mirtazapine group , suggesting that mirtazapine has an earlier onset of action . Mirtazapine also demonstrated a better tolerability profile and represents a valuable option for the treatment of depression in elderly patients BACKGROUND This prospect i ve 105-site study was conducted to determine the rate of seizures and other serious adverse experiences associated with the therapeutic use of the sustained-release formulation of bupropion ( bupropion SR ) . METHOD 3100 patients with a DSM-III-R diagnosis of depression without a current or past diagnosis of an eating disorder and with no personal or family history of seizure disorders were treated for up to 8 weeks with bupropion SR in an open-label study . Dosing was initiated at 50 mg b.i.d . and increased to a maximum of 150 mg b.i.d . unless not tolerated . Patients had the option to continue treatment with bupropion SR ( 50 mg b.i.d . to 150 mg b.i.d . ) in a continuation phase lasting up to 1 year . During the acute and continuation phases , patients were evaluated for the occurrence of seizures and other serious adverse experiences . Clinical response to and tolerability of bupropion SR were also evaluated . RESULTS Three patients each experienced a seizure associated with the therapeutic use of bupropion SR during the acute and continuation phases combined . The observed seizure rate during the 8-week acute phase was 2 seizures in 3094 evaluable patients , or 0.06 % . The observed seizure rate for the acute and continuation phases combined was 3 seizures in 3094 patients , or 0.10 % . Survival analysis yielded a cumulative seizure rate of 0.08 % for the acute phase and 0.15 % for both phases combined . Two patients who intentionally overdosed with bupropion SR also experienced seizures ; however , these events were not included in calculations of the overall seizure rate . Therapeutic doses of bupropion SR were well tolerated and clinical ly efficacious . CONCLUSION The therapeutic use of bupropion SR at total daily doses up to 300 mg/day in depressed patients without predisposition to seizures is associated with a seizure rate that is well within the range observed with other marketed antidepressants BACKGROUND Short-term studies have demonstrated a modest weight-reducing to weight-neutral effect among patients receiving bupropion sustained-release ( SR ) for the treatment of depression . OBJECTIVE This study was conducted to evaluate the long-term effects of bupropion SR on body weight in patients with depression . METHODS This analysis was conducted within a long-term relapse-prevention study in patients with major depression . Those whose depression had responded to open-label treatment with bupropion SR were r and omized to 44 weeks of double-blind treatment with bupropion SR 300 mg/d or placebo . Patients were categorized by body mass index ( BMI ) as follows : BMI < 22 , BMI 22 to 26 , BMI > or = 27 , and BMI > or = 30 . RESULTS Four hundred twenty-three patients were enrolled in the double-blind phase of the study , 210 receiving bupropion SR and 213 receiving placebo . At the end of the open-label phase , the following mean weight losses were seen in the 4 BMI groups : BMI < 22 , 0.5 kg ; BMI 22 to 26 , 1.1 kg ; and BMI > or = 27 and BMI > or = 30 , 1.8 kg each . At the end of double-blind treatment , mean change-from-baseline weights were as follows : BMI < 22 , -0.1 kg ; BMI 22 to 26 , -0.6 kg ; BMI > or = 27 , -1.4 kg ; and BMI > or = 30 , -2.4 kg . The rate of change in body weight during the double-blind phase was statistically significant compared with baseline BMI ( P < 0.001 , analysis of covariance ) . CONCLUSIONS Modest mean weight losses that increased with increasing baseline body weight were observed with long-term bupropion SR treatment . The findings of this analysis suggest that bupropion SR may be an appropriate therapeutic option in normal-weight or overweight patients with depression who are concerned about weight gain These data provide evidence for the antidepressant efficacy of paroxetine . Paroxetine- and imipramine-treated patients were significantly different from placebo-treated patients , but little different to each other , on all depressive outcome measures . However , paroxetine appeared to have a possibly greater and earlier beneficial effect on anxiety symptoms associated with depression , when compared with imipramine . Both active therapies were effective in treating patients with severe depression . Side effects for paroxetine were typical of other serotonin ( 5-HT ) uptake inhibitors but different from those of imipramine . In particular , anticholinergic and cardiovascular symptoms were reduced , and premature withdrawal less likely BACKGROUND We compared the efficacy and tolerability of venlafaxine XR with that of fluoxetine in a multicenter , r and omized , double-blind , placebo-controlled study in depressed out patients . METHODS Out patients , 18 years and older , who met DSM-IV criteria for major depressive disorder were included ( n = 301 r and omized ; 232 completed ) . Patients were r and omly assigned to eight weeks of treatment with either venlafaxine XR 75 - 225 mg/day ( n = 100 ) , fluoxetine 20 - 60 mg/day ( n = 103 ) , or placebo ( n = 98 ) . The primary efficacy outcome measures were the final ratings on the Hamilton Rating Scale for Depression ( HAM-D21 ) total score , HAM-D21 depressed mood item , Montgomery-Asberg Depression Rating Scale total score , and Clinical Global Impressions Scale . RESULTS Withdrawal from the study due to adverse events occurred in 6 % of the patients in the venlafaxine XR group and 9 % of the patients in the fluoxetine group . Patients treated with venlafaxine XR , but only rarely those treated with fluoxetine , had statistically significant improvements in their depression ratings compared with placebo at the end of the study . The percentages of patients who achieved full remission of their depression ( HAM-D21 total score < or = 7 ) at the end of treatment were 37 % , 22 % and 18 % for the venlafaxine XR , fluoxetine and placebo groups , respectively . The differences in remission rates between venlafaxine XR and the other groups were statistically significant ( p < 0.05 ) . LIMITATIONS The superior remission outcome observed with venlafaxine XR treatment needs to be replicated in additional studies . CONCLUSION Venlafaxine XR is a well-tolerated and efficacious treatment for depression . The results of this study suggest that venlafaxine XR is as well-tolerated as fluoxetine but may have some efficacy advantages over fluoxetine BACKGROUND Recent studies have suggested clinical differences among selective serotonin reuptake inhibitors . In a 12-week r and omized , multicenter , double-blind trial , the antidepressant and anxiolytic efficacy of the selective serotonin reuptake inhibitors paroxetine and fluoxetine was compared in patients with moderate to severe depression . METHODS A total of 203 patients were r and omized to fixed doses ( 20 mg/day ) of paroxetine or fluoxetine for the first six weeks of therapy . From week 7 - 12 , dosing could be adjusted biweekly , as required ( paroxetine 20 - 50 mg/day , and fluoxetine 20 - 80 mg/day ) . The mean prescribed doses were paroxetine 25.5 mg/day ( range 20.0 - 40.2 mg/day ) , and fluoxetine 27.5 mg/day ( range 20.0 - 59.5 mg/day ) . Emergence of motor nervousness or restlessness was assessed using the ESRS scale for akathisia . RESULTS Both active treatments demonstrated comparable antidepressant efficacy ( HAM-D , CGI ) . Anxiolytic activity of the two drugs ( COVI , STAI , HAM-D ) was also comparable . However , paroxetine was found to be superior to fluoxetine on two subscore measures at week 1 of therapy ( HAM-D Agitation item , p < 0.05 ; Psychic Anxiety item , p < 0.05 ) , with no differences detected after week 2 . The overall incidence of adverse effects was comparable in the two treatment groups . Constipation , dyspepsia , tremor , sweating and abnormal ejaculation were more common in paroxetine-treated subjects , whereas nausea and nervousness were more frequent in fluoxetine-treated patients . Weight loss was more common in the fluoxetine versus paroxetine group ( 11.88 % versus 2.94 % , respectively ) . ESRS scores for akathisia were low throughout the study and showed little change . LIMITATIONS Differences observed between the two drugs in antianxiety effects were limited to two measures of anxiety among several others . DISCUSSION The data indicate that paroxetine and fluoxetine have comparable antidepressant and anxiolytic efficacy . Paroxetine appears to produce an earlier improvement in agitation and psychic anxiety symptoms compared with fluoxetine CONTEXT In patients with diabetes mellitus , depression is a prevalent and recurrent problem that adversely affects the medical prognosis . OBJECTIVE To determine whether maintenance therapy with sertraline hydrochloride prevents recurrence of major depression in patients with diabetes . DESIGN A r and omized , double-blind , placebo-controlled , maintenance treatment trial . Patients who recovered from depression during open-label sertraline treatment continued to receive sertraline ( n = 79 ) or placebo ( n = 73 ) and were followed up for up to 52 weeks or until depression recurred . SETTING Outpatient clinics at Washington University , St Louis , MO , the University of Washington , Seattle , and the University of Arizona , Tucson . PATIENTS One hundred fifty-two patients with diabetes ( mean age , 52.8 years ; 59.9 % female ; 82.9 % with type 2 diabetes ) who recovered from major depression ( 43.3 % of those initially assigned ) during 16 weeks of open-label treatment with sertraline ( mean dose , 117.9 mg/d ) . INTERVENTION Sertraline continued at recovery dose or identical-appearing placebo . MAIN OUTCOME MEASURES The primary outcome was length of time ( measured as the number of days after r and omization ) to recurrence of major depression as defined in DSM-IV . The secondary outcome was glycemic control , which was assessed via serial determinations of glycosylated hemoglobin levels . RESULTS Sertraline conferred significantly greater prophylaxis against depression recurrence than did placebo ( hazard ratio = 0.51 ; 95 % confidence interval , 0.31 - 0.85 ; P = .02 ) . Elapsed time before major depression recurred in one third of the patients increased from 57 days in patients who received placebo to 226 days in patients treated with sertraline . Glycosylated hemoglobin levels decreased during the open treatment phase ( mean + /- SD glycosylated hemoglobin level reduction , -0.4 % + /- 1.4 % ; P = .002 ) . Glycosylated hemoglobin levels remained significantly lower than baseline during depression-free maintenance ( P = .002 ) and did not differ between treatment groups ( P = .90 ) . CONCLUSIONS In patients with diabetes , maintenance therapy with sertraline prolongs the depression-free interval following recovery from major depression . Depression recovery with sertraline as well as sustained remission with or without treatment are associated with improvements in glycosylated hemoglobin levels for at least 1 year To compare the safety and antidepressant efficacy of paroxetine , imipramine , and placebo , data from six centres using the same protocol were pooled . A double-blind parallel-group design was used , with therapy lasting six weeks . From week 2 onwards , both the 240 paroxetine-treated and the 237 imipramine-treated patients were significantly different from the 240 placebo-treated patients , but no different from each other . Side-effects with paroxetine were less likely to lead to drop-out than with imipramine . Paroxetine had a possible earlier antidepressant effect than imipramine , and a possible earlier beneficial effect on anxiety symptoms associated with depression BACKGROUND Major depressive disorder is a recurrent illness that often requires maintenance antidepressant treatment . Escitalopram is a selective serotonin reuptake inhibitor ( SSRI ) that has shown efficacy in both acute and continuation treatment of major depressive disorder . The current trial examined the efficacy of maintenance escitalopram treatment in preventing depression recurrence in patients who responded to acute SSRI therapy . METHOD Patients with recurrent DSM-IV-defined major depressive disorder ( > or= 2 previous episodes ; baseline Montgomery-Asberg Depression Rating Scale [ MADRS ] score > or= 22 ) who had responded ( MADRS score < or= 12 ) to acute open-label treatment ( 8 weeks ) with 1 of 4 SSRIs ( fluoxetine , sertraline , paroxetine , or citalopram ) received open-label , flexible-dose continuation treatment ( 16 weeks ) with escitalopram ( 10 - 20 mg/day ) . At the end of continuation treatment , patients maintaining response criteria were r and omly assigned to 52 weeks of double-blind , fixed-dose maintenance treatment with escitalopram ( 10 or 20 mg/day ) or placebo . Recurrence was defined as a MADRS score > or= 22 or insufficient therapeutic response during the double-blind phase . The study was conducted between October 16 , 2000 , and February 4 , 2003 . RESULTS A total of 234 patients who responded to acute open-label treatment with 1 of 4 SSRIs received at least 1 dose of open-label escitalopram continuation treatment . Of 164 patients who completed escitalopram continuation treatment , 139 were r and omly assigned to double-blind maintenance treatment with escitalopram ( N = 73 ) or placebo ( N = 66 ) . Mean baseline MADRS scores at the start of the maintenance phase were < 5 for both the placebo- and escitalopram-treatment groups . Time to recurrence was significantly longer in patients who received maintenance treatment with escitalopram compared with patients switched to placebo ( hazard ratio = 0.26 , 95 % CI = 0.13 to 0.52 , p < .001 ) . Long-term escitalopram treatment was well tolerated . CONCLUSION Maintenance treatment with escitalopram was well tolerated and significantly reduced the risk for recurrence of depression . Patients with few residual symptoms following continuation treatment with escitalopram experienced a high rate of depression recurrence when switched to placebo , demonstrating the need for maintenance therapy of recurrent major depressive disorder beyond 4 to 6 months of initial symptom resolution even if few residual symptoms are present OBJECTIVE To examine the efficacy of fluoxetine in the treatment of depression in patients with probable Alzheimer 's disease ( AD ) . METHODS This double-blind , parallel- design study included a consecutive series of 41 AD subjects meeting DSM-IV criteria for major or minor depression who were r and omized to receive fluoxetine ( up to 40 mg/day ) or identical-appearing placebo . All patients received biweekly evaluations consisting of the Hamilton Depression Scale ( HAM-D ) and the Clinical Global Impression as primary efficacy measures , and the Mini-Mental State Exam , Hamilton Rating Scale for Anxiety , and the Functional Independence Measure as secondary efficacy measures . RESULTS Complete remission of depression was found in 47 % of subjects treated with fluoxetine and in 33 % of subjects treated with placebo . Both the fluoxetine and the placebo groups showed a significant decline in HAM-D scores over time , but the magnitude of mood improvement was similar for both groups . Fluoxetine was well tolerated , and most side effects were mild . CONCLUSION Fluoxetine treatment for depression in AD did not differ significantly from treatment with placebo . Our study also confirms the presence of a placebo effect in the treatment of depression in AD BACKGROUND About one-third of patients fail to respond to initial antidepressant therapy , which suggests a need for more effective drugs . AIMS To compare the efficacy and safety of venlafaxine and paroxetine in 122 patients with non-chronic treatment-resistant depression . METHOD In- patients or out- patients satisfying DSM-III-R criteria for major depression in evolution for less than eight months , having a baseline HAM-D score > or = 18 and a HAM-D Item 3 score < 3 were eligible . Patients were required to have a history of resistance to two previous antidepressant treatments and a CGI improvement score of 3 at the beginning of treatment . Doses were adjusted to 200 - 300 mg/day for venlafaxine and 30 - 40 mg/day for paroxetine . RESULTS For the observed-case analysis , the response rate was 51.9 % for venlafaxine and 32.7 % for paroxetine ( P = 0.044 ) , and a remission was achieved in 42.3 % of venlafaxine-treated and 20.0 % of paroxetine-treated patients ( P = 0.01 ) . The incidence of adverse effects was comparable between treatment groups . CONCLUSIONS Venlafaxine showed some evidence of superiority to paroxetine in this difficult-to-treat patient population The aim of this double-blind study was to compare the efficacy and safety of venlafaxine vs. fluoxetine in the treatment of patients with depression and anxiety . A total of 146 moderately depressed patients with associated anxiety were r and omized to receive 75 mg/d venlafaxine or 20 mg/d fluoxetine for 12 wk . Dose increases were permitted after 2 wk of treatment , to 150 mg/d venlafaxine and 40 mg/d fluoxetine , to optimize response . At the final visit , a statistically significantly greater efficacy of venlafaxine over fluoxetine was observed on depressive symptoms and concomitant anxiety , and 75.0 and 50.7 % of patients administered venlafaxine and fluoxetine , respectively , showed an overall response . A sustained response ( for at least 2 wk ) , present at the end of the study was achieved in 57.8 and 43.3 % of patients in the venlafaxine and fluoxetine groups , respectively , and at the final visit , 59.4 and 40.3 % of patients , respectively , were in remission ( virtually asymptomatic ) . Dose increases were required by a greater percentage of patients in the fluoxetine group ( 52.9 % ) , than in the venlafaxine group ( 37.1 % ) , and in those patients whose dose was increased , a higher efficacy was again observed with venlafaxine . Venlafaxine and fluoxetine were well tolerated , with the most frequently experienced adverse events being nausea and headache . Fewer patients in the venlafaxine group than in the fluoxetine group reported at least one adverse event ( 55.7 and 67.1 % patients , respectively ) . Venlafaxine therefore proved to be significantly more effective than fluoxetine in improving depressive symptoms and concomitant anxiety A double-blind , placebo-controlled , r and omized trial was carried out to compare the efficacy and tolerability of paroxetine in out patients with moderate to moderately severe depression without mania . Paroxetine was found to be an effective antidepressant drug when compared to placebo . For most of the measures of efficacy the benefit appeared after two weeks of therapy , but sleep was improved after one week . Patients taking paroxetine complained of more adverse effects than those on placebo ; they were mainly gastrointestinal with nausea the most commonly reported The authors compared the nontricyclic antidepressant trazodone with amitriptyline and placebo in a double-blind study of 202 unipolar depressed out patients . Trazodone 's clinical efficacy was similar to that of amitriptyline , with both active drugs producing significantly more clinical improvement than placebo . The incidence of anticholinergic side effects was lower for the patients taking trazodone than for those taking amitriptyline BACKGROUND While emotional symptoms such as depressed mood and loss of interest have traditionally been considered to constitute the core symptoms of major depressive disorder ( MDD ) , the prevalence and importance of painful physical symptoms such as back pain , abdominal pain , and musculoskeletal pain is becoming increasingly appreciated . Antidepressants possessing dual serotonin/norepinephrine ( 5-HT/NE ) reuptake inhibition may demonstrate greater efficacy in the alleviation of pain . The efficacy of duloxetine , a balanced and potent dual reuptake inhibitor of 5-HT and NE , was evaluated within a cohort of depressed patients with associated painful physical symptoms . METHODS In this multicenter , double-blind , placebo-controlled study , patients meeting DSM-IV criteria for MDD were r and omized to receive placebo ( N=141 ) or duloxetine 60 mg QD ( N=141 ) . Patients were required to have a 17-item Hamilton Rating Scale for Depression ( HAMD17 ) total score 15 , a Clinical Global Impression of Severity ( CGI-S ) score 4 , and a Brief Pain Inventory ( BPI ) Average Pain score 2 at baseline . The primary efficacy measure was the BPI Average Pain score , while secondary measures included other BPI items , the HAMD17 total score , CGI-S , the Patient Global Impression of Improvement ( PGI-I ) scale , Visual Analog Scales ( VAS ) for pain , and the Symptom Question naire , Somatic Subscale ( SQSS ) . Safety was evaluated by recording treatment-emergent adverse events ( spontaneously reported ) , vital signs , and laboratory analytes . RESULTS Mean changes in BPI Average Pain for duloxetine- and placebo-treated patients differed significantly at most visits , but only approached significance at endpoint p=0.066 . For the main effect of treatment ( pooling all visits ) , significant advantages for duloxetine-treated patients were found in 10 of 11 assessed BPI pain severity and pain interference items , in addition to VAS overall pain and back pain . Mean changes in pain measures for duloxetine-treated patients corresponded to improvements of 25 - 50 % , compared with 19 - 39 % for placebo . Mean changes at endpoint in depression rating scales ( HAMD17 , CGI-S , PGI-I ) did not differ significantly between duloxetine and placebo treatment groups due to unusually high placebo response . The magnitude of placebo treatment effects ( as measured by HAMD17 total score and Maier subscale ) was significantly smaller in patients with 1 previous depressive episode , compared to those patients with no previous episodes . In patients with 1 previous depressive episode the advantage of duloxetine over placebo was similar to previous studies . Rates of discontinuation due to adverse events were 14.2 % vs. 2.1 % for duloxetine and placebo , respectively p<0.001 . Treatment-emergent adverse events reported at a significantly higher rate by duloxetine-treated patients included nausea , dry mouth , fatigue , and decreased appetite . CONCLUSIONS In this study , duloxetine ( 60 mg QD ) was shown to be an effective treatment for the painful physical symptoms which are frequently associated with depression . Improvements in pain severity occurred independently of changes in depressive symptom severity BACKGROUND A simple , once-weekly dosing regimen could be a convenient alternative for many patients during long-term treatment of depression . Such a strategy might also be effective for improving medication compliance and the outcome of continuation treatment . The safety and effectiveness of a new formulation of enteric-coated fluoxetine ( 90 mg ) given once weekly was tested during the continuation treatment of major depressive disorder . METHOD Patients meeting DSM-IV criteria for major depressive disorder with modified 17-item Hamilton Rating Scale for Depression ( HAM-D-17 ) scores > or = 18 and Clinical Global Impressions-Severity of Illness scale ( CGI-S ) scores > or = 4 were treated 13 weeks with open-label 20 mg/day of fluoxetine in a multicenter U.S. study . Responders ( N = 501 ) were r and omly assigned to receive 20 mg of fluoxetine daily , placebo , or 90 mg of enteric-coated fluoxetine weekly for 25 weeks of double-blind continuation treatment . The primary efficacy measure was the percentage of patients who relapsed . Time to relapse was tested over the 25-week continuation period using log-rank analyses of the Kaplan-Meier estimates of relapse rates . Additional analyses of efficacy included comparison of change from baseline to endpoint for the HAM-D-17 , CGI-S , and HAM-D-28 subscales by last observation carried forward ( LOCF ) . Safety measures included comparison of treatment-emergent adverse events , both spontaneous and solicited ( using the Association for Methodology of Documentation in Psychiatry-Module 5 ) , vital signs , and laboratory measures . RESULTS Relapse rates for patients assigned to fluoxetine , either 20 mg daily or 90 mg weekly , were significantly lower than for placebo by log-rank analysis and LOCF analyses of secondary efficacy measures . Efficacy did not significantly differ between the 2 active drug groups by these measures . Enteric-coated fluoxetine at a once-weekly dose of 90 mg was well tolerated , and its safety profile was similar to that of daily 20 mg of fluoxetine . CONCLUSION The formulation of enteric-coated fluoxetine taken once weekly is effective , safe , and well tolerated for continuation treatment of depression in patients who responded to acute treatment with 20 mg/day of fluoxetine . Monitoring during long-term treatment for evidence of sustained remission is important regardless of dosing regimen BACKGROUND Despite the high prevalence of dysthymia and its associated morbidity , few controlled trials have evaluated the efficacy of antidepressant medication for this disorder . A 12-week , double-blind , placebo-controlled , r and omized , multicenter trial was performed to evaluate the safety and efficacy of sertraline hydrochloride and imipramine hydrochloride in treating dysthymia . METHODS A total of 416 out patients ( 271 women and 145 men ) aged 25 to 65 years with DSM-III-R-defined , early-onset , primary dysthymia without concurrent major depression were r and omized to 12 weeks of treatment with sertraline , imipramine , or placebo . RESULTS Both active treatments result ed in significantly reduced scores on the 17-item Hamilton Rating Scale for Depression ( P = .04 and P = .01 for sertraline and imipramine vs placebo , respectively ) , the Montgomery-Asberg Depression Rating Scale ( P = .01 and P = .003 vs placebo , respectively ) , Hopkins Symptom Checklist ( P < .05 ) , and the self-rated version of the Inventory of Depressive Symptoms ( P < .05 ) . With the use of a Clinical Global impressions improvement score of 1 or 2 ( very much or much improved ) to define response , response rates were 59 % for sertraline , 64 % for imipramine , and 44 % for placebo ( P = .02 for sertraline vs placebo and P < .001 for imipramine vs placebo ) . A significantly greater proportion of patients receiving imipramine than those receiving sertraline or placebo discontinued treatment because of adverse events ( P = .001 and P < .001 , respectively ) . CONCLUSIONS Pharmacotherapy provides considerable relief from the symptoms of dysthymia in patients suffering from this chronic affective disorder , with both sertraline and imipramine being more effective than placebo . The greater tolerability of sertraline is an important consideration because of the chronicity of dysthymia , which may require prolonged treatment with antidepressant medication BACKGROUND The necessity of antidepressant continuation-phase therapy following acute-phase response has result ed in the need to characterize the longer-term efficacy and safety of all new medications . Previous studies using " extension " protocol s suggest that mirtazapine has sustained antidepressant effects . The current study was performed to evaluate the efficacy and safety of up to 1 year of mirtazapine therapy , using a more rigorous , r and omized , placebo-controlled discontinuation design . METHOD An intent-to-treat sample of 410 patients meeting DSM-IV criteria for moderate-to-severe recurrent or chronic major depressive episodes began 8 to 12 weeks of open-label therapy with mirtazapine ( flexibly titrated , 15 - 45 mg/day ) . Thereafter , 156 fully remitted patients ( according to Hamilton Rating Scale for Depression and Clinical Global Impressions-Improvement scores ) were r and omly assigned to receive 40 weeks of double-blind continuation-phase therapy with either mirtazapine or placebo . RESULTS Mirtazapine therapy reduced the rate of depressive relapse by more than half , with 43.8 % of patients relapsing on treatment with placebo as compared with 19.7 % of the mirtazapine-treated patients . The discontinuation rate due to adverse events was 11.8 % for active mirtazapine therapy versus 2.5 % for placebo . Although weight gain was significantly greater in the group receiving active medication during the double-blind phase ( p = .001 ) , patients taking mirtazapine gained only 1.4 kg ( 3.1 lb ) across the 40 weeks of continuation therapy , and there was no difference in the rates of weight gain as a newonset adverse event . CONCLUSION Continuation-phase therapy with mirtazapine is effective and well tolerated The objective of this report is to compare antidepressant response rates and tolerability in younger and older women . One hundred fifteen female out patients who met DSM-IV criteria for major depressive disorder were evaluated before and after 8 weeks of treatment with a selective serotonin reuptake inhibitor , nefazodone , or venlafaxine . The sample was divided into younger and older groups based on age to approximate premenopausal and postmenopausal status . Eighty-six age-matched male out patients formed the comparison group . Younger women compared with older women had significantly lower Hamilton Rating Scale for Depression scores after 8 weeks of antidepressant treatment and achieved significant higher rates of remission . There were no differences in overall drug tolerability . This pattern was not replicated in the male patients . Younger women with depression are more responsive to serotonergic antidepressants . This may relate to changes in menstrual status . Limitations of the study and implication s for the role of female sex hormones are discussed . Future investigations should include measurement of reproductive hormone levels This 8-week , r and omised , double-blind study compared the efficacy and tolerability of escitalopram to that of venlafaxine XR in primary care patients with major depressive disorder . The efficacy of escitalopram ( 10– 20 mg ; n = 148 ) was similar to venlafaxine XR ( 75– 150 mg ; n = 145 ) , based on mean change from baseline to week 8 in Montgomery and Åsberg Depression Rating Scale total score . In ad hoc analyses , escitalopram-treated patients achieved sustained remission significantly faster than did venlafaxine-treated patients . More venlafaxine-treated patients had nausea , constipation , and increased sweating ( p < 0.05 ) . When treatment was completed after 8 weeks , significantly more venlafaxine-treated patients had discontinuation symptoms ( p < 0.01 ) . Thus escitalopram treatment was similar to venlafaxine treatment with respect to efficacy and was better tolerated by patients in primary care BACKGROUND This was the first controlled continuation phase study ( up to 1-year total treatment ) to evaluate the safety and efficacy of bupropion SR for decreasing the risk for relapse of depression in patients who responded to bupropion SR . METHODS Patients with recurrent major depression were treated with bupropion SR 300 mg/day during an 8-week open-label phase . Responders ( based on Clinical Global Impressions Scale for Improvement of Illness scores ) entered a r and omized , double-blind phase where they received bupropion SR 300 mg/day or placebo for up to 44 weeks . After r and omization , relapse was defined as the point at which the investigator intervened by withdrawing the patient from the study to treat depression . RESULTS Four hundred twenty-three patients were r and omized . A statistically significant difference in favor of bupropion SR over placebo was seen in the time to treatment intervention for depression when survival curves were compared ( log-rank test , p = .003 ) . Statistically significant separation between bupropion SR and placebo began at double-blind week 12 ( p < .05 ) . Adverse events in bupropion SR-treated patients accounted for 9 % and 4 % of discontinuations from the open-label and double-blind phases , respectively . CONCLUSIONS Bupropion SR was shown to be effective and well tolerated in decreasing the risk for relapse of depression for up to 44 weeks BACKGROUND We examined the efficacy and safety of three different dosages of venlafaxine hydrochloride ( 75 , 225 , and 375 mg/day ) in a multicenter , r and omized , double-blind , placebo-controlled , four-group study . METHOD Out patients , 18 to 65 years old , who met DSM-III criteria for major depression were included ( N = 358 r and omized ; 194 completed ) . Of the total patients completing the trial , 59 % , 56 % , 51 % , and 51 % were in the placebo , 75-mg , 225-mg , and 375-mg groups , respectively . The primary outcome measures were the Hamilton Rating Scale for Depression ( HAM-D21 ) total , HAM-D21 depression item , Montgomery-Asberg Depression Rating Scale total , and Clinical Global Impressions scale . RESULTS Each dosage of venlafaxine was associated with statistically significant improvement as compared with placebo , based on the intent-to-treat sample . The two higher dosages were associated with a modestly greater antidepressant response than was the 75-mg dosage . Nausea , dizziness , somnolence , and anorexia were the most common adverse events attributable to venlafaxine . Since headache occurred at a similar frequency in both the drug and placebo groups , we did not consider it to be attributable to venlafaxine use . Withdrawal from the study due to adverse events occurred in 5 % , 17 % , 24 % , and 30 % of the patients in the placebo , 75-mg , 225-mg , and 375-mg groups , respectively . CONCLUSION Venlafaxine , at dosages of 75 - 375 mg/day , is an effective and well-tolerated antidepressant . With increasing dosage , greater efficacy and possibly more adverse effects will occur BACKGROUND There have been very few controlled studies of antidepressants in dysthymia , particularly in sample s diagnosed reliably and with an adequate length of follow-up . In this investigation , we measured the long-term outcome in a large group of patients meeting DSM-III-R criteria for dysthymia . This study was design ed to investigate whether fluoxetine is effective in the treatment of dysthymia . METHOD This r and omised study including 140 patients , compared fluoxetine ( 91 patients ) and placebo ( 49 patients ) on a double-blind basis in two distinct phases : a short-term end-point ( 3 months with 20 mg/day fluoxetine ) and a medium-term end-point ( 6 months ) where the initial responders continued double-blind treatment unchanged and non-responders received an additional treatment of 20 mg/day fluoxetine . RESULTS After three months of treatment , response was seen more frequently in the fluoxetine group ( 42/72 ) than in the placebo group ( 14/39 , P < 0.0001 ) . Improved patients at 3 months were still improved at 6 months . Furthermore , 50 % of the nonresponders at 3 months improved and rated as responders at 6 months , after fluoxetine was increased to 40 mg daily . CONCLUSIONS This study showed the significant and persistent action of fluoxetine on dysthymia . The finding that 50 % of the non-responders at 3 months were improved at 6 months , after fluoxetine dosage was increased to 40 mg daily , argues in favour of treating dysthymic patients for at least 6 months , and with a higher dosage if the initial doses are ineffective Sixty-eight male and female individuals with both DSM-IV diagnoses of cocaine dependence and major depressive disorder were r and omly assigned to one of two medication conditions ( placebo vs. 40 mg per day ) as part of a double-blind , placebo-controlled clinical efficacy trial of fluoxetine for the treatment of this dual diagnosis . During the 12-week outpatient treatment phase all participants also received individual cognitive-behavioral psychotherapy targeting both cocaine use and depression . Depressive symptoms remitted as a function of time in treatment , with no significant medication effects found . Fewer cocaine positive urines were found during the first 6 weeks of treatment in the placebo group compared with the 40-mg group . Cocaine use and depressive symptoms during treatment were significantly correlated . The findings fail to support the role of fluoxetine for treatment of cocaine use and depression in dually-diagnosed patients Two hundred twenty-four out patients with major depression entered a 6-week , five-center , double-blind trial of bupropion 300 mg/day and placebo . A total of 216 patients were included in the efficacy analysis . In the combined center analysis , greater efficacy for bupropion was found on one or more measures ( Hamilton Rating Scale for Depression , Montgomery-Asberg Depression Rating Scale , and Clinical Global Impressions ) at treatment Days 21 , 28 , 35 , and 42 . Bupropion was well tolerated ; only four adverse events were reported at least 5 % more often in the bupropion group than in the placebo group . Six bupropion patients versus 5 placebo patients discontinued treatment because of adverse events . This study extends earlier findings of efficacy for higher-dose treatment in an inpatient population to lower-dose treatment in an outpatient population Previous studies have shown a positive association between pain and depression , though evidence supporting a direct link between these two variables is less robust . Using a placebo-controlled trial , the authors examined the analgesic and antidepressant efficacy of paroxetine ( 20 mg ) in chronic low back pain sufferers . The authors examined the associations among pain , depression , disability , and illness attitudes . Paroxetine showed no effects on pain or depression compared with placebo ; however , subjects r and omized to paroxetine were more likely to reduce concomitant analgesic medication . The cross-sectional association of depression and pain at baseline ( r = 0.2 , P = 0.02 ) was weaker than the association between depression and disability ( r = 0.3 , P = 0.004 ) . Similarly , the association of change in depression scores with change in pain ( r = 0.25 , P = 0.016 ) was weaker than change between depression and disability ( r = 0.49 , P<0.0005 ) . Whereas the relationship between pain and depression became nonsignificant when disability and illness attitudes were controlled , the relationship between depression and disability remained highly significant when pain and illness attitudes were controlled . These data are consistent with the association between pain and depression being wholly modulated by disability and illness attitudes , with no direct relationship between pain and depression OBJECTIVE The aim of this study was to compare over 1 year the effect of sertraline and citalopram on depressive symptoms and cognitive functions of nondemented elderly patients with minor depressive disorder and subsyndromal depressive symptomatology . METHOD We recruited 138 consecutive non-demented out patients of either sex , aged > or = 65 years , who were classified as meeting research criteria for minor depressive disorder or sub-syndromal depressive symptomatology using the Structured Clinical Interview for DSM-IV . Subjects were assigned to receive citalopram 20 mg/day ( 66 patients ) or sertraline 50 mg/day ( 72 patients ) orally for 1 year . Patients were assessed at baseline and after 1 , 2 , 3 , and 6 months and at 1 year by raters masked with regard to patients ' treatment assignments . The Hamilton Rating Scale for Depression , the Geriatric Depression Scale , and the Global Assessment of Functioning were administered to assess the course of depressive symptoms and social functioning during the study . Cognitive measures included Trail Making Test-Parts A and B , Wechsler Memory Scale , Mini-Mental State Examination , and a verbal fluency test . Data were collected from March 2000 to March 2003 . RESULTS The overall completion rate was 72 % . Both treatments induced a significant , sustained , and comparable improvement in depressive symptoms and in social functioning . Nearly half of the subjects in the 2 groups achieved remitter status at study endpoint . Significant within-group improvements also were observed in all cognitive measures . Both drugs were well tolerated during the whole study period . CONCLUSION Our results suggest that sertraline and citalopram can improve depressive symptoms and cognitive functions of minor depressive disorder and subsyndromal depressive symptomatology in elderly nondemented patients BACKGROUND This study aims to investigate the efficacy of fluoxetine and paroxetine on the levels of depression-anxiety , quality of life , disability , and metabolic control in type II diabetes mellitus ( DM ) patients . METHODS The patients were first applied the Hospital Anxiety-Depression Scale ( HADS ) . After a psychiatric interview with patients who had scores above the cut-off point , those who were diagnosed as having a major depressive disorder according to DSM-IV criteria were applied the Hamilton Depression Rating Scale ( HDRS ) and the Hamilton Anxiety Rating Scale ( HARS ) . Twenty three patients who scored 16 or above on the HDRS were included in the study and given the Short Form-36 ( SF-36 ) , and the Brief Disability Question naire ( BDQ ) and HbA1c levels were measured . Patients were r and omized on 20 mg/day fluoxetine or 20 mg/day paroxetine treatment . The patients were evaluated with the same scales at the 2(nd ) , 4(th ) , 6(th ) , and the 12(th ) weeks . RESULTS Both groups showed a statistically significant decrease in HDRS , HARS , and BDQ scores with comparison to the index assessment . At the end of treatment , though not statistically significant , a decrease was observed in HbA1c values of the fluoxetine-administered group . CONCLUSIONS Fluoxetine and paroxetine effectively reduce the severity of major depressive disorder in type II DM patients . There is need for further and longer-lasting monitoring studies with more patients in order to determine whether there is any difference in terms of their effects on glycemic control To compare the safety and efficacy of paroxetine ( n= 167 ) and placebo ( n= 169 ) , data from 4 centres using the same protocol were pooled . A double‐blind parallel group design was used , with therapy lasting 6 weeks . Significant differences between paroxetine‐ and placebo‐treated patients were found on the major efficacy outcome variables by week 2 and on all efficacy variables by week 4 of the study . Improvement on the sleep factor of the Hamilton Rating Scale for Depression was found after 7 d. Observer and patient global efficacy ratings were in agreement by week 4 . No serious adverse events occurred , and paroxetine had no clinical ly significant effects on vital signs or laboratory safety data . Side effects were more common on paroxetine and were similar to other serotonin reuptake inhibitors . In general , these were well tolerated and did not lead to dropout . Symptoms of increased arousal were not seen during early therapy Nefazodone is a phenylpiperazine antidepressant with 5-HT2 antagonism and 5-HT reuptake inhibition . Two hundred and eighty-three out- patients with a diagnosis of DSM-III-R major depression of at least one-month duration ( 65 % ill for over 6 months ) , and a mean score of 24 on the 17-item Hamilton Rating Scale for Depression ( HRSD ) , were r and omised to treatment with nefazodone , imipramine , or placebo . The double-blind treatment period was 8 weeks in duration . Nefazodone 's antidepressant efficacy was comparable with imipramine 's , with both drug treatments significantly better than placebo in a variety of outcome measures . For example , after 8 weeks of therapy , 78 % of nefazodone and 83 % of imipramine but only 55 % of placebo patients ( P < 0.01 ) were globally much or very much improved . Nefazodone was better tolerated than imipramine , with fewer drop-outs and a lower incidence of side-effects during treatment Escitalopram , a selective serotonin reuptake inhibitor ( SSRI ) , was compared to placebo in a study of patients with major depressive disorder ( DSM-IV ) who had baseline Montgomery – Åsberg Depression Rating Scale ( MADRS ) total scores ≥22 and ≤40 . After a 1-week , single-blind placebo period , patients were r and omized to receive escitalopram 10 mg/day ( n = 191 ) or placebo ( n = 189 ) in an 8-week , double-blind period . The primary efficacy analysis of adjusted mean change in MADRS total score from baseline showed a statistically significantly larger effect for escitalopram than for placebo with a treatment difference at week 8 ( last observation carried forward , LOCF ) of 2.7 points ( SE 0.85;P = 0.002 ) . In further by-week efficacy analyses , the effect of escitalopram was consistently larger than that of placebo ( P < 0.05 ) beginning at week 1 ( Clinical Global Impression – Improvement score ) , week 2 ( MADRS score ) or week 3 ( Clinical Global Impression – Severity score ) . Escitalopram was very well tolerated with a low overall withdrawal rate similar to that for placebo . Nausea was the only adverse event reported significantly more in escitalopram-treated patients than in placebo-treated patients , although it was infrequent and transient . Escitalopram 10 mg/day had a statistically significantly better antidepressant effect than placebo as early as week 1 , and was safe and very well tolerated Background : Major depressive disorder occurs commonly in association with alcohol dependence , both in clinical sample s and in the community . Efforts to treat major depressive disorder in alcoholics with antidepressants have yielded mixed results . This multicenter , double-blind , placebo-controlled trial of sertraline was design ed to address many of the potential method ological shortcomings of studies of co-occurring disorders . Method : Following a 1-week , single-blind , placebo lead-in period , 328 patients with co-occurring major depressive disorder and alcohol dependence were r and omly assigned to receive 10 weeks of treatment with sertraline ( at a maximum dose of 200 mg/d ) or matching placebo . R and omization was stratified , based on whether initially elevated scores on the 17-item Hamilton Depression Rating Scale declined with cessation of heavy drinking , result ing in a sample of 189 patients with Hamilton Depression Rating Scale scores ≥17 ( group A ) and 139 patients with Hamilton Depression Rating Scale scores ≤16 ( group B ) . Results : Both depressive symptoms and alcohol consumption decreased substantially over time in both groups . There were no reliable medication group differences on depressive symptoms or drinking behavior in either group A or B patients . Conclusion : Despite careful attention to method ological considerations , this study does not provide consistent support for the use of sertraline to treat co-occurring major depressive disorder and alcohol dependence . The high rate of response among placebo-treated patients may help to explain these findings . Further research is needed to identify efficacious treatments for patients with these commonly co-occurring disorders Existing therapies for major depressive disorder ( MDD ) have either limited efficacy and /or poor tolerability . The present study examined the effects of duloxetine , a potent and balanced dual reuptake inhibitor of serotonin ( 5-HT ) and norepinephrine ( NE ) , in patients with MDD . Adult patients ( N = 267 ) with MDD were r and omly assigned to receive duloxetine ( 60 mg/day ) or placebo in this 9-week , multi-center , double-blind , parallel-group clinical trial . Efficacy was evaluated using the 17-item Hamilton Depression Rating Scale ( HAMD(17 ) ) , Visual Analog Scales ( VAS ) for pain , Clinical Global Impression of Severity ( CGI-S ) , Patient 's Global Impression of Improvement ( PGI-I ) , and Quality of Life in Depression Scale ( QLDS ) . Safety was evaluated by assessing discontinuation rates , adverse event rates , vital signs , and laboratory tests . Duloxetine ( 60 mg QD ) significantly reduced the HAMD(17 ) total score compared with placebo at the end of 9-week therapy . Estimated probabilities of response and remission were 65 and 43 % , respectively , for duloxetine compared with 42 and 28 % for placebo . Duloxetine also reduced overall pain , back pain , shoulder pain and time in pain while awake significantly more than placebo . Global measures of improvement , including PGI-I and QLDS , were significantly improved by duloxetine compared with placebo . Discontinuations due to adverse events were more frequent for duloxetine-treated patients ( 12.5 % ) than for placebo-treated patients ( 4.3 % ) . Nausea , dry mouth , dizziness , and constipation were more frequent for duloxetine than placebo . There was no significant incidence of hypertension , nor any other safety issues . Duloxetine 60 mg administered once daily appears to be a safe and effective treatment for MDD The purpose of this study was to prospect ively examine the occurrence and severity of sexual dysfunction symptoms in depressed patients before and after 6 months of treatment with selective serotonin reuptake inhibitors . The study was part of a r and omized , double-blind , controlled trial of sertraline or citalopram in patients with a DSM-III-R major depressive disorder treated by general practitioners . Three hundred eight patients ( 221 women and 87 men ) were assessed at baseline and after 6 months of treatment by means of the Montgomery-Åsberg Depression Rating Scale and five items from the Utvalg for Kliniske Undersogelser ( UKU ) Side Effect Scale covering different aspects of sexual functioning . As measured by the UKU Side Effect Scale , sexual desire and mean total score significantly improved in women , and sexual desire improved in men . Men reported no change in orgasmic dysfunction , erectile dysfunction , or mean total score , but there was a trend toward worsening of ejaculatory dysfunction . However , in the subgroup of women who reported no sexual problems at baseline , 11.8 % reported decreased sexual desire , and 14.3 % reported orgasmic dysfunction at week 24 . The corresponding figures in the same subgroup of men were 16.7 % and 18.9 % , respectively , and as many as 25 % experienced ejaculatory dysfunction after 24 weeks . There were no statistically significant differences between sertraline and citalopram in the magnitude or frequency of adverse sexual side effects A double‐blind , multinational study was conducted to compare the efficacy and safety of fluvoxamine and fluoxetine in out patients with major depressive episode ; 184 patients were r and omised to fluvoxamine ( 100 mg/day ) or fluoxetine ( 20 mg/day ) for 6 weeks . Both drugs were effective and there were no statistically significant differences between them in the area under the curve of change from baseline in the Hamilton depression rating scale ( HAMD ) total score . However , the percentage of HAMD responders ( ≥ 50 % decrease in HAMD total score ) at week 2 , the clinical global improvement severity of illness score at week 2 and the depression subscale of the irritability , depression and anxiety scale at weeks 1 , 2 and 4 , all showed significant advantages for fluvoxamine . During the last 2 weeks , fluvoxamine was significantly more effective in improving the HAMD sleep disturbance scale . Both drugs were well tolerated and there were no marked differences in their side effect profiles which were typical of SSRIs . Fluvoxamine and fluoxetine have similar efficacy and safety profiles in the treatment of major depressive episode ; the findings of this study indicate that fluvoxamine may have a faster onset of action with respect to resolution of depressive symptoms and result in a better improvement in sleep quality . Copyright © 2003 John Wiley & Sons , Depression is the most common comorbid psychiatric illness in patients with alcohol dependence . This double-blind study tested the efficacy of nefazodone versus placebo for the treatment of depression in actively drinking alcohol-dependent patients who were also participating in weekly group treatment for alcoholism . Sixty-four subjects with major depression disorder and alcohol dependence with a history of at least one prior episode of depression when not drinking were r and omly assigned to receive 12 weeks of either nefazodone or placebo and participated in a weekly psychoeducational group on alcoholism . Subjects were assessed every 2 weeks for depression , anxiety , side effects , and drinking frequency . Subjects taking nefazodone were significantly more likely to complete the study ( 62 % ) than those taking placebo ( 34 % ) . Analyses of covariance using drinks per week as a time-dependent covariate showed lower Hamilton Rating Scale for Depression scores at week 8 for end-point analysis and at weeks 8 and 12 for completers . The endpoint analysis demonstrated a significantly greater response in the nefazodone group ( 48 % ) than in the placebo group ( 16 % ) . Both groups showed a similarly significant decrease in the average number of alcoholic drinks consumed per day over the course of the study . Although the number of adverse effects was significantly greater for the nefazodone group , there were no severe adverse events , and nefazodone was well tolerated . Nefazodone is a safe and effective antidepressant to use in a population of alcohol-dependent patients with depression who have a high degree of comorbidity . Nefazodone treatment was superior to placebo in alleviating depression in these patients but did not add any advantage over the psychoeducational group in terms of drinking outcomes BACKGROUND The efficacy , tolerability , and effects on sexual function and satisfaction of nefazodone and sertraline were compared in a multicenter , r and omized , double-blind , parallel-group study in out patients with major depression . METHOD One hundred sixty patients , 18 years of age or older , who met DSM-III-R criteria for single or recurrent nonpsychotic major depressive episodes were r and omly assigned to 6 weeks of treatment with either nefazodone ( 100 - 600 mg/day ) or sertraline ( 50 - 200 mg/day ) . Symptoms were assessed before and during treatment using the 17-item Hamilton Rating Scale for Depression ( HAM-D-17 ) , Clinical Global Impressions ( CGI ) Improvement scale , the CGI Severity of Illness scale , and a sexual function question naire . RESULTS Of 143 patients evaluable for efficacy , 72 received sertraline and 71 received nefazodone . The mean modal daily dose at endpoint was 148 mg for sertraline and 456 mg for nefazodone . Analysis of efficacy measures ( HAM-D-17 and CGI ) showed consistent and comparable improvement in symptoms of depression for both treatment groups . Sertraline had negative effects on sexual function and satisfaction in both men and women , and nefazodone had no adverse effect on sexual well-being . Safety assessment s based on adverse events , vital sign measurements , electrocardiographs , physical examinations , and clinical laboratory tests revealed no serious adverse events or organ toxicity associated with nefazodone or sertraline administration . CONCLUSION Nefazodone and sertraline are well tolerated , and there was no statistically significant difference in their antidepressant activity . Sertraline treatment has negative effects on sexual function and performance in both sexes , while nefazodone has none . These findings may have clinical implication s when choosing antidepressant therapy The effectiveness of fluoxetine as an antidepressant was contrasted with trazodone in a 6-week double-blind trial in 40 patients . The total score on the Hamilton Rating Scale for Depression and the global improvement score on the Clinical Global Impressions scale favored trazodone at the end of 3 weeks of treatment . However , that difference was no longer apparent during the remainder of the study . The authors hypothesize that fluoxetine 20 mg/day may be an ineffective dosage of the drug or that fluoxetine has a slower onset of antidepressant action than does trazodone The chronic and recurrent nature of major depression is well recognized , and recent data suggest that maintenance therapy with full-dose phar-macotherapy ( i.e. , the dose used to treat the index episode ) is effective in preventing relapse and recurrence . We present results from a 1-year , double-blind trial of paroxetine and imipramine in patients who successfully completed a 6-week acute course of therapy . A total of 717 out patients were included in the 6-week , r and omized , double-blind , placebo-controlled comparative study of paroxetine and imipramine conducted at six centers . At the end of the acute treatment phase , patients showing a therapeutic response were eligible to enter a long-term extension of the study in which they would continue to receive the same drug ( or placebo ) in double-blind fashion for up to 1 year . Of the 219 patients who entered the long-term phase , 94 received paroxetine , 79 received imipramine , and 46 received placebo . During the 1-year maintenance study , both paroxetine and imipramine were more effective than placebo in maintaining euthymia among patients who had responded to short-term treatment . However , approximately twice as many imipramine-treated patients dropped out of the study prematurely because of adverse experiences compared to paroxetine-treated patients , suggesting that paroxetine is more readily tolerated than imipramine during long-term treatment BACKGROUND The efficacy , safety , and tolerance of nefazodone and paroxetine in the treatment of depressed out patients were compared in a r and omized , double-blind parallel group study at 20 centers in the United Kingdom and Republic of Irel and . METHOD The study population comprised 206 out patients meeting DSM-III-R criteria for a moderate-to-severe nonpsychotic major depressive episode . Patients considered to be at serious risk of suicide were excluded from participation in the study . After a drug-free baseline phase of 1 to 4 weeks , patients were r and omly assigned to treatment with either nefazodone or paroxetine . Outcome measures for efficacy included the Clinical Global Impressions scales , Hamilton Rating Scale for Depression , Hamilton Rating Scale for Anxiety , Montgomery-Asberg Depression Rating Scale , and Patient Global Assessment scale . Tolerance and safety were assessed using spontaneously reported adverse events , vital signs , and laboratory investigations . RESULTS There were no significant differences between the groups in clinical outcome . Analysis of the efficacy measures revealed a consistent and continuous improvement in both groups . A similar proportion of patients in each group discontinued treatment owing to adverse events : 15 ( 14 % ) in the nefazodone group and 13 ( 13 % ) in the paroxetine group . CONCLUSION Nefazodone and paroxetine have similar efficacy and tolerability in the treatment of out patients with major depression Objective : This study looks to compare the antidepressant efficacy and safety of a st and ardized extract of St John 's wort with both placebo and fluoxetine . Method : After a 1-week single-blind washout , patients with major depressive disorder diagnosed by Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders , Fourth Edition were r and omized to 12 weeks of double-blind treatment with LI-160 St John 's wort extract ( 900 mg/d ) , fluoxetine ( 20 mg/d ) , or placebo . The 17-item Hamilton Rating Scale for Depression ( HAMD-17 ) was the primary efficacy measure , and analysis of covariance was used to compare differences in end point HAMD-17 scores across the 3 treatment groups , treating the baseline HAMD-17 as the covariate . Results : One hundred thirty-five patients ( 57 % women ; mean age , 37.3 ± 11.0 ; mean HAMD-17 , 19.7 ± 3.2 ) were r and omized to double-blind treatment and were included in the intent-to-treat analyses . Analysis of covariance analyses showed lower mean HAMD-17 scores at end point in the St John 's wort group ( n = 45 ; mean ± SD , 10.2 ± 6.6 ) compared with the fluoxetine group ( n = 47 ; 13.3 ± 7.3 ; P < 0.03 ) and a trend toward a similar finding relative to the placebo group ( n = 43 ; 12.6 ± 6.4 ; P = 0.096 ) . There was also a trend toward higher rates of remission ( HAMD-17 < 8) in the St John 's wort group ( 38 % ) compared with the fluoxetine group ( 30 % ) and the placebo group ( 21 % ) . Overall , St John 's wort appeared to be safe and well tolerated . Conclusion : St John 's wort was significantly more effective than fluoxetine and showed a trend toward superiority over placebo . A ( 25 % ) smaller than planned sample size is likely to account for the lack of statistical significance for the advantage ( indicating a moderate effect size , d = 0.45 ) of St John 's wort over placebo OBJECTIVE Sertraline may produce dual neurotransmitter effects similar to the serotonin-norepinephrine reuptake inhibitors ( SNRIs ) ; however , it has been tested against an SNRI in only 1 previous study , and never at an optimal dose . The objective of the current multisite study was to compare relatively higher doses of sertraline ( i.e. , 150 mg/day ) and venlafaxine extended release ( XR ) ( 225 mg/day ) in out patients with major depressive disorder . METHOD Subjects with DSM-IV major depressive disorder were r and omly assigned to 8 weeks of double-blind treatment with sertraline ( N = 82 ) or venlafaxine XR ( N = 78 ) . The study ran from January 2002 through January 2003 . The primary outcome measure was the Quality of Life Enjoyment and Satisfaction Question naire ; secondary outcome variables included the 17-item Hamilton Rating Scale for Depression . RESULTS Both treatments led to significant improvement in depressive symptoms and quality -of-life measures . No significant differences were noted between treatment groups for final scores on the primary or secondary measures . The treatment groups did not differ significantly in the percentage of responders ( sertraline = 55 % , venlafaxine XR = 65 % ; intent-to-treat [ ITT ] sample ) or remitters ( sertra-line = 38 % , venlafaxine XR = 49 % ; ITT sample ) , although the proportions are similar to those found in earlier selective serotonin reuptake inhibitor ( SSRI ) vs. venlafaxine meta-analyses . In patients who achieved the maximum dose of drug and maintained it for 3 weeks , response rates were similar to those found at lower doses ( sertraline = 59 % , venlafaxine XR = 70 % ) ; however , remission rates for this sample were comparable for both drug groups ( sertraline = 48 % , venlafaxine XR = 50 % ) . CONCLUSIONS The efficacies of sertraline and venlafaxine XR were comparable . Although response and remission rates did not differ statistically , the rates were analogous to those reported in previous meta-analyses . However , at clinical ly relevant higher doses , the remission rates were very similar . CLINICAL TRIALS REGISTRATION Clinical Trials.gov identifier NCT00179283 CONTEXT Paroxetine controlled release ( CR ) is approved for the treatment of major depressive disorder ( MDD ) in the dosage range of 25 to 62.5 mg daily . However , lower daily doses ( 12.5 mg and 25 mg ) of this formulation have not been investigated in the treatment of MDD . If the 12.5-mg and 25-mg doses are found to be efficacious , these lower doses may well convey a superior tolerability profile for paroxetine CR in the treatment of MDD . OBJECTIVE To evaluate the antidepressant efficacy and tolerability profile of daily doses of paroxetine CR 12.5 mg and 25 mg versus placebo in the treatment of MDD . DESIGN AND SETTING R and omized , double-blind , placebo-controlled clinical trial conducted in 40 clinical investigation centers in the United States . PARTICIPANTS 447 adult ( > or = 18 years of age ) out patients who met DSM-IV criteria for MDD and with a baseline 17-item Hamilton Rating Scale for Depression ( HAM-D ) score of at least 20 comprised the intent-to-treat study population ( mean age = 38.8 years ; 58.4 % female ; 75.6 % white ) . INTERVENTION Eligible patients completing a 1-week single-blind placebo run-in period were r and omly assigned to receive once-a-day study medication ( paroxetine CR 12.5 mg [ N = 156 ] , paroxetine CR 25 mg [ N = 154 ] , or placebo [ N = 149 ] ) in an 8-week , double-blind , parallel cell comparison . MAIN OUTCOME MEASURES The primary efficacy measure was the change from baseline to study endpoint ( week 8) as measured by the HAM-D. Secondary efficacy measures included change from baseline to study endpoint as assessed by both the depressed mood item on the HAM-D and the Clinical Global Impressions ( CGI ) Severity of Illness scale ( CGI-S ) . The proportion of patients considered at study endpoint to be in response ( CGI-Improvement score of 1 or 2 ) or in remission ( HAM-D < or = 7 ) in the 3 treatment groups was also compared . Quality of life was assessed by the change from baseline in total score of the short form of the Quality of Life Enjoyment and Satisfaction Question naire ( Q-LES-Q ) . Safety observations were made by assessing the proportion of patients who had adverse experiences , including laboratory and electrocardiographic abnormalities , during the treatment period . RESULTS The primary efficacy analysis revealed that both the 12.5-mg and the 25-mg paroxetine CR treatment groups were associated with significant therapeutic effects ( change in HAM-D score ) from baseline to study endpoint ( LOCF : p = .038 , 95 % CI = -3.38 to -0.09 and p = .005 , 95 % CI = -4.06 to -0.74 , respectively ) . Results from the Wilcoxon rank sum test of the depressed mood item of the HAM-D ( p = .011 , 95 % CI = -0.57 to -0.07 ) demonstrated significant efficacy in the 25-mg treatment group but not in the 12.5-mg group . However , LOCF analysis of the CGI-S revealed significant therapeutic effects for both the 12.5-mg ( p = .018 , 95 % CI = -0.61 to -0.06 ) and 25-mg ( p < .001 , 95 % CI = -0.78 to -0.22 ) treatment groups . Significantly more patients in the 25-mg paroxetine CR-treated group than in the placebo-treated group met criteria for response ( CGI-Improvement score of 1 or 2 , p = .035 , OR = 1.68 , 95 % CI = 1.04 to 2.73 ) as well as for remission ( HAM-D score < /= 7 , p = .013 , OR = 1.96 , 95 % CI = 1.15 to 3.33 ) . Neither HAM-D remission analysis nor CGI responder analysis showed statistical separation from placebo for paroxetine CR 12.5-mg treatment . Quality of life improvements were statistically significant for the 25-mg treatment ( p = .041 , 95 % CI = 0.17 to 8.03 ) on the Q-LES-Q total score . Post hoc LOCF analyses of HAM-D sleep disturbance , psychic anxiety , and anxiety/somatization factors revealed significant improvements from baseline in the paroxetine CR 25-mg and 12.5-mg treatment groups . The types of adverse events reported in the 12.5-mg and 25-mg groups were similar to those reported with paroxetine CR at the customary 25-mg to 62.5-mg range ; however , the lower doses of paroxetine CR were associated with a relatively reduced incident rate of these adverse events and an overall improved tolerability compared with the incident rate and tolerability profile associated with the customary dose range of paroxetine CR ( 25 to 62.5 mg ) . CONCLUSION Paroxetine CR , at 12.5 mg/day and 25 mg/day , demonstrated significant antidepressant effects Background and Purpose The aim of the study was to investigate the efficacy and safety of the selective serotonin reuptake inhibitor citalopram in treating poststroke depression , since available treatments are usually poorly tolerated . Methods A 6-week double-blind , placebo-controlled trial was undertaken . Diagnosis and outcome were determined using the Hamilton Depression Scale , and unwanted effects were measured using the UKU side effect rating scale . Sixtysix consecutive depressed patients from an unselected population of 285 stroke patients aged 25 to 80 years entered the trial 2 to 52 weeks after stroke . They were assigned to equally sized treatment and placebo groups . The initial level of depression was comparable in the two groups ( mean baseline Hamilton Depression scores , 19.4 and 18.9 , respectively ) . Demographic parameters were also comparable in the two groups . Results Significantly greater improvement was seen in patients treated with citalopram ( 10 to 40 mg/d ) for 3 and 6 weeks , both when including all patients ( intention-to-treat analysis , p<.05 ) and excluding patients who dropped out during the first 3 weeks ( efficacy analysis , P<.005 ) . Half of the 28 patients who entered the trial 2 to 6 weeks after stroke recovered within 1 month , independent of the treatment given . This indicates a high degree of spontaneous recovery in the early phase after stroke . In contrast , recovery was infrequent in placebo group patients who became depressed 7 weeks or more after stroke . No serious side effects related to the treatment were detected ; those present were mild and usually transient . Conclusions This trial demonstrates that the selective serotonin reuptake inhibitor citalopram offers an advantageous new treatment of poststroke depression that is both safe and effective & NA ; Approximately 20 million patients suffer from major depressive disorder each year , indicating a need for antidepressant agents that are synonymous with effectiveness , tolerability and patient compliance . The authors examined the effects of fluvoxamine , a selective serotonin reuptake inhibitor , in the treatment of out patients meeting DSM‐III‐R criteria for major depressive disorder . A r and omized , double‐blind , parallel group , placebo‐ and imipramine‐controlled single center study was conducted in 150 out patients . Patients were r and omized to receive up to 150 mg/day of fluvoxamine as a single bedtime dose , 240 mg/day of imipramine on a twice‐daily ( BID ) schedule , or placebo for six weeks . Efficacy measurements included HAM‐D , MADRS , CGI , Raskin‐Covi and SCL‐56 scales . The HAM‐D total score indicated that both active treatment groups showed significantly ( p ≤ 0.05 ) greater therapeutic benefit than did placebo . Severely depressed patients ( HAM‐D ≥ 30 ) responded better to fluvoxamine in five of six measures . Side‐effects from fluvoxamine were similar to those reported for other selective serotonin reuptake inhibitors ( nausea , somnolence ) and were well tolerated . Imipramine was associated with anticholinergic effects such as dry mouth and dizziness . The pharmacokinetic properties of fluvoxamine which allow the drug to be administered as a single daily dose should aid in the maintenance of patient compliance , while offering significant clinical benefit in the improvement of depressive symptoms BACKGROUND Duloxetine is a balanced and potent dual reuptake inhibitor of serotonin ( 5-HT ) and norepinephrine ( NE ) that has previously been shown to be effective in the acute treatment of major depressive disorder ( MDD ) . This placebo-controlled study assesses the safety and efficacy of duloxetine ( 80 or 120 mg/day ) and paroxetine ( 20 mg QD ) during an initial 8-week acute phase and subsequent 6-month continuation phase treatment of MDD . METHOD In this r and omized , double-blind , placebo-controlled trial , adult out patients ( age > or= 18 years ) meeting DSM-IV criteria for MDD received placebo ( n = 93 ) , duloxetine 80 mg/day ( 40 mg BID ; n = 95 ) , duloxetine 120 mg/day ( 60 mg BID ; n = 93 ) , or paroxetine ( 20 mg QD ; n = 86 ) for 8 weeks . Patients who had a > or= 30 % reduction from baseline in HAMD(17 ) total score during the acute phase were allowed to continue on the same ( blinded ) treatment for a 6-month continuation phase . Efficacy measures included the 17-item Hamilton Rating Scale for Depression ( HAMD(17 ) ) total score , HAMD(17 ) subscales , the Montgomery-Asberg Depression Rating Scale ( MADRS ) , the Hamilton Anxiety Rating Scale ( HAMA ) , Visual Analog Scales ( VAS ) for pain , the Clinical Global Impression of Severity ( CGI-S ) and Patient Global Impression of Improvement ( PGI-I ) scales , the 28-item Somatic Symptom Inventory ( SSI ) , and the Sheehan Disability Scale ( SDS ) . Safety and tolerability were assessed using treatment-emergent adverse events , discontinuations due to adverse events , vital signs , ECGs , laboratory tests , and the Arizona Sexual Experiences Scale ( ASEX ) . RESULTS During the acute phase , patients receiving duloxetine 80 mg/day , duloxetine 120 mg/day , or paroxetine 20 mg QD had significantly greater reductions in HAMD(17 ) total score compared with placebo . Both duloxetine ( 80 and 120 mg/day ) and paroxetine treatment groups had significantly greater improvement , compared with placebo , in MADRS , HAMA , CGI-S , and PGI-I scales . Estimated probabilities of remission at week 8 for patients receiving duloxetine 80 mg/day ( 51 % ) , duloxetine 120 mg/day ( 58 % ) , and paroxetine ( 47 % ) were significantly greater compared with those receiving placebo ( 30 % ) . The rate of discontinuation due to adverse events among duloxetine-treated patients ( 80 and 120 mg/day ) did not differ significantly from the rate in the placebo group . Treatment-emergent adverse events reported significantly more frequently by duloxetine-treated patients than by patients receiving placebo were constipation ( 80 and 120 mg/day ) , increased sweating ( 120 mg/day ) , and somnolence ( 120 mg/day ) . The incidence of acute treatment-emergent sexual dysfunction in duloxetine- and paroxetine-treated patients was 46.5 % and 62.8 % , respectively . During the 6-month continuation phase , duloxetine ( 80 and 120 mg/day ) and paroxetine treatment groups demonstrated significant improvement in HAMD(17 ) total score . Treatment-emergent adverse events occurring most frequently in each active treatment group during the continuation phase were viral infection ( duloxetine 80 mg/day ) , diarrhea ( duloxetine 120 mg/day ) , and headache ( paroxetine 20 mg QD ) . CONCLUSION These data support previous findings that duloxetine is safe , efficacious , and well tolerated in the acute treatment of MDD . Furthermore , these data provide the first demonstration under double-blind , placebo-controlled conditions that the efficacy and tolerability of duloxetine are maintained during chronic treatment BACKGROUND Paroxetine is a potent and selective serotonin reuptake inhibitor ( SSRI ) . The present study assessed the efficacy and tolerability of paroxetine against placebo in depressed out patients . METHOD A double-blind , parallel-group study was undertaken in four st and -alone centers . Patients aged 18 - 65 years , meeting DSM-III criteria for major depression , and having a Hamilton Rating Scale for Depression ( HAM-D ) score > or = 18 on the first 17 items of the HAM-D-21 were r and omized to paroxetine or placebo for 6 weeks of treatment . Efficacy outcome variables included the HAM-D , the Montgomery-Asberg Depression Rating Scale , the Clinical Global Impressions Scale ( CGI ) , and the Covi Anxiety Scale . Tolerability was assessed by asking a non-leading question . Routine laboratory safety and vital sign data from all four centers were pooled . The primary analysis used the intention-to-treat sample and for efficacy variables the last-observation-carried-forward data set was employed . Statistical methods included one-way analysis of variance for parametric and Fisher exact test for nonparametric variables . RESULTS Significant differences ( p < or = .05 ) were found between paroxetine and placebo on the HAM-D and CGI by Week 2 and on all efficacy outcome variables by Week 4 . Improvement on the HAM-D sleep factor occurred 2 weeks prior to that seen on the retardation factor . Similar results were obtained when an adequate treatment group ( therapy for > or = 28 days ) was considered . A full clinical response ( CGI-severity of illness score 1 or 2 ) was seen in over 40 % of subjects . Adverse events were more common for paroxetine compared with placebo ( p < or = .01 ) . Somnolence was twice more common than nervousness . Dropout due to adverse events was similar between therapies . Paroxetine had no clinical ly significant effect on laboratory safety data or vital signs . CONCLUSION Paroxetine was an effective , well tolerated , and safe antidepressant . Side effects were typical of the SSRI class of drugs . Symptoms indicative of a nonalerting profile were more common than those associated with alerting effects Considerable research shows that serotonin dysfunction is implicated in major depression . Paroxetine is an investigational antidepressant that appears to act by selectively blocking neuronal serotonin uptake . Seventy-two out patients with moderate-to-severe major depression entered this 6-week , double-blind comparison of paroxetine and placebo . The results showed clear and significant superiority of paroxetine on all of the major outcome variables . These included physician-rated measures such as the Hamilton Rating Scale for Depression and its four factor scores , the Clinical Global Impressions scale , the Montgomery and Asberg Depression Rating Scale , and the Raskin Depression Scale . Results on these agreed well with patient-rated measures like the Hopkins Symptom Checklist and Patient Global Evaluation Scale . Paroxetine was also very well tolerated . Nausea and constipation occurred significantly more often with paroxetine , but only 9 % of paroxetine patients dropped out of the study due either in whole or in part to an adverse effect . This compares to 8 % of the placebo patients who were discontinued for the same reason . This study suggests that paroxetine is a safe and effective medication for the treatment of major depression Since depression impacts all body systems , antidepressant treatments should relieve both the emotional and physical symptoms of depression . Duloxetine demonstrated antidepressant efficacy at a dose of 60 mg qd in two placebo-controlled , r and omized , double-blind studies and significantly improved remission rates compared with placebo . Duloxetine-treated patients had significant reduction in severity of the symptoms of depression as assessed by the HAM-D17 , anxious symptoms as measured by the HAM-A and quality of life measures compared to placebo . Duloxetine also improved somatic symptoms , particularly painful symptoms which may have contributed to significantly improved remission rates compared to placebo . Approximately 10 % of the 1139 patients with major depressive disorder in placebo-controlled trials discontinued treatment due to an adverse event , compared to 4 % of the 777 patients receiving placebo . In addition to nausea ( 1.4 % incidence ) , which was the most common reason for discontinuation , dizziness , somnolence , and fatigue were the most common AEs reported as reasons for discontinuation and all were considered drug-related . Duloxetine treatment lacks effects on ECG , increases heart rate , and has little effect on blood pressure or weight The effectiveness of selective serotonin reuptake inhibitors for depression in remitted schizophrenia has not been clearly demonstrated . A r and omized , double-blind , prospect i ve placebo-controlled study was performed of 48 subjects meeting DSM-IV criteria for both schizophrenia in remission and for a major depressive episode . Twenty-seven patients were r and omized to placebo and 21 to sertraline . All subjects had a 1-week anticholinergic phase before r and omization . The treatment duration was 6 weeks . Sertraline was started at 50 mg/day ; this could be increased to 100 mg after 4 weeks for an inadequate response . There were no statistically significant differences in symptoms between the two groups at r and omization . There were no differences in outcome between treatment groups . In both groups , between 40 % and 50 % of subjects showed a 50 % reduction in depression score . This study does not provide support for the efficacy of sertraline in the treatment of depression in remitted schizophrenia . The small sample size limits the strength of the conclusions that can be drawn from this study . The study design called for a sample size of 96 on the basis of an expected placebo response rate of 30 % . Recruitment for the study was difficult because of the placebo design . The placebo response was 50 % . Clinicians and patients underestimate the strength of the placebo response and may overestimate the risk of participating in such a study . Testing the efficacy of widely accepted but poorly evaluated treatments should be a research priority . Future studies require a larger sample size and longer duration of treatment In a double-blind , placebo-controlled study the authors found that fluoxetine , a potent and selective inhibitor of serotonin reuptake , was an effective antidepressant in moderately depressed , ambulatory out patients . Typical adverse effects reported by patients treated with fluoxetine included agitation , nausea , fatigue , and insomnia . Compared to imipramine , fluoxetine was associated with fewer complaints of dry mouth , constipation , and dizziness ABSTRACT Objectives : To evaluate the efficacy and safety of trazodone prolonged release compared with paroxetine in the treatment of patients with major depression . Research design and methods : A total of 108 patients aged 20–68 years were enrolled in this multicentre , double-blind , double-dummy , r and omised , paroxetine-controlled study . Each patient received 3 days single-blind placebo treatment followed by 6 weeks double-blind treatment with either trazodone prolonged release 150–450 mg/day ( n = 55 ) or paroxetine 20–40 mg/day ( n = 53 ) . Outcome measures : Efficacy was evaluated by the rate of patients responding to each treatment and considered to be in remission , and by mean changes from baseline in the Hamilton Depression Rating scale scores ( HAM-D ) , Montgomery Asberg Depression Rating Scale scores ( MADRS ) , and Clinical Global Impression ( CGI ) – Severity and Global Improvement scores . Time to onset of efficacy and safety were assessed . Results : Trazodone and paroxetine were equally effective at reducing symptoms of depression and promoting remission . Onset of efficacy was slightly faster for patients treated with paroxetine . Overall , there were no significant differences between the groups at endpoint in efficacy measures , and in percentage of responders ( > 85 % ) or patients in remission ( > 65 % ) . Sleep disorders ( HAM-D subset ) were significantly less evident for patients in the trazodone group at the end of the study ( p < 0.05 ) . Adverse drug reactions were reported by 35 % of trazodone-treated patients ( mainly of the nervous system ) and 26 % of paroxetine-treated patients ( mainly gastrointestinal ) , although none was considered to be serious . Conclusions : This study showed that after a 6-week period trazodone and paroxetine are not different in reducing the symptoms of depression and , in many patients , in producing the remission of the illness . The known divergence in tolerability profile of the two medications , related to their differing pharmacological properties , was also confirmed . Trazodone may be of advantage in depressed patients with sleep difficulties BACKGROUND The comparative efficacy of selective serotonin reuptake inhibitors ( SSRIs ) and serotonin-norepinephrine reuptake inhibitors ( SNRIs ) was recently debated . Meta-analyses , based mainly on fluoxetine comparator data , suggest that the SNRI venlafaxine has superior efficacy to SSRIs in treatment of major depression . OBJECTIVE To compare quality of life ( QOL ) , efficacy , safety , and tolerability associated with sertraline and venlafaxine extended release ( XR ) for treatment of DSM-IV major depression . METHOD This was an 8-week , double-blind , r and omized study of sertraline ( 50 - 150 mg/day ) versus venlafaxine XR ( 75 - 225 mg/day ) , followed by a 2-week taper period . Subjects were recruited from 7 sites in Turkey and 6 sites in Australia between October 2002 and July 2003 . The primary outcome measure was the Quality of Life Enjoyment and Satisfaction Question naire . Secondary outcome measures included measures of depression ( including response and remission ) , anxiety , pain , safety ( e.g. , blood pressure ) , and tolerability ( e.g. , discontinuation symptoms ) . RESULTS A total of 163 subjects received study treatment ( women , 69 % ; mean age , 37.0 [ SD = 12.9 ] years ) . No significant differences in QOL or efficacy were noted between treatments on the primary or secondary endpoints for the total study population or the anxious depression and severe depression subgroups . A priori analyses of symptoms associated with treatment discontinuation demonstrated no difference between treatment groups . However , in post hoc analyses , sertraline was associated with less burden of moderate to severe discontinuation symptoms . Venlafaxine XR was associated with a relative increase in mean blood pressure ( supine diastolic blood pressure , -4.4 mm Hg difference at week 8/last observation carried forward ) . CONCLUSION Sertraline and venlafaxine XR demonstrated comparable effects on QOL and efficacy in treatment of major depression , although sertraline may be associated with a lower symptom burden during treatment discontinuation and a reduced risk of blood pressure increase BACKGROUND Chronic forms of depression are associated with significant functional and psychosocial impairments . To date , no study has measured psychosocial functioning in this population during long-term maintenance antidepressant treatment or following the double-blind discontinuation of treatment . METHODS Patients with chronic major or double depression completed 12 weeks of short-term treatment followed by 16 weeks of continuation treatment with sertraline hydrochloride . Responders at the end of the continuation phase were r and omized , double-blind , to 18 months of maintenance therapy with either sertraline ( n = 77 ) or placebo ( n = 84 ) . Multiple domains of psychosocial functioning were assessed during double-blind therapy . RESULTS Substantial worsening in psychosocial function measures occurred in patients taking placebo compared with sertraline during maintenance . Patients with reemergence of depression lost psychosocial gains regardless of treatment . In the sub sample of patients who remained in remission throughout maintenance , most of the observed improvement in psychosocial functioning occurred during short-term treatment . By maintenance end point , normalization of functioning was achieved by 58 % to 84 % of remitters , depending on the outcome measure used . CONCLUSIONS These results indicate that long-term treatment of chronic forms of depression can result in sustained psychosocial benefits . Discontinuation of treatment results in frequent reemergence of symptoms and loss of psychosocial gains . Long-term treatment result ed in only modest further improvement of psychosocial measures over that achieved in the short-term phase AIMS We performed a double-blind , placebo-controlled r and omized trial of sertraline in recently detoxified alcohol-dependent patients with current depressive symptoms . The objectives of the study were to evaluate the efficacy of sertraline at achieving stable abstinence , at ameliorating depressive symptoms and at improving quality of life in these patients . METHODS The study included 83 patients , who received either sertraline ( 50 - 150 mg/day ) or placebo for 24 weeks . The primary outcome criteria were the rate of relapse into alcohol consumption and the rate of response on the Montgomery and Asberg Depression Rating Scale ( MADRS ) . RESULTS At the end of the treatment period , relapse rates were 23.1 % in the placebo group and 31.8 % in the sertraline group . Responder rates for depression were 38.5 % for the placebo group and 44.2 % for the sertraline group . There was no significant difference between treatment groups with either variable . However , when patients were stratified into severe ( MADRS score > or=26 ) and moderate ( MADRS score < 26 ) depression at inclusion , a significant treatment benefit with sertraline was observed in the former group . Quality of life , determined by the SF-36 , improved in both groups , with more benefit observed for the sertraline group on mental health items . Sertraline was well tolerated , and the incidence of adverse events was similar in the two treatment groups . CONCLUSIONS The explanation for the overall good outcome in both treatment groups and for the inability to demonstrate a clear treatment effect may reside in the clinical features of the patients included Objective Depression and hostility are significant risk factors for mortality and morbidity after myocardial infa rct ion ( MI ) . Much research is still needed to identify effective ways to reduce emotional distress in patients with cardiovascular disease . This double-blind , placebo-controlled study investigated the efficacy and safety of the antidepressant fluoxetine in patients with depression after their first MI . Methods Fifty-four patients with major depression after MI were r and omly assigned to receive a flexible-dose regimen of fluoxetine or placebo for the first 9 weeks of a double-blind , placebo-controlled trial . Patients without serious adverse effects who wished to continue participating in the study were given fluoxetine or placebo for an additional 16 weeks . To evaluate the efficacy of fluoxetine , the 17-item Hamilton Depression Rating Scale ( HAMD-17 ) and the Hostility Scale of the 90-item Symptom Check List ( SCL-90 ) were used as primary measures of outcome . To evaluate the safety of fluoxetine , cardiac function was measured before and after treatment with echocardiography and electrocardiography . Results The a priori difference in antidepressive efficacy ( 4-point difference in HAMD-17 scores between the fluoxetine and placebo groups ) was not met . However , the response rate among patients receiving fluoxetine was significantly greater than that among patients receiving placebo at week 25 ( 48 vs. 26 % , p = .05 ) . Among patients with mild depression ( HAMD-17 score ≤21 ) , HAMD-17 scores were significantly different ( p < .05 ) between the fluoxetine and placebo groups at weeks 9 ( by 5.4 points ) and 25 ( by 5.8 points ) . Also , hostility scores at week 25 were significantly reduced among patients receiving fluoxetine ( p = .02 ) . Analysis of electrocardiographic and echocardiographic parameters revealed no decrease in cardiac function as a result of treatment with fluoxetine . Conclusions : Although the overall difference between the fluoxetine and placebo groups was not significant , there was a trend favoring fluoxetine in this relatively small sample . The response rate in the group receiving fluoxetine was comparable with that observed in other studies of patients with cardiovascular disease . In addition , fluoxetine seemed to be particularly effective in patients with mild depression and was associated with a statistically significant reduction in hostility . The results of this study suggest that fluoxetine can be safely used to treat patients with post-MI depression beginning 3 months after the event CONTEXT Insufficient evidence exists for recommendation of specific effective treatments for older primary care patients with minor depression or dysthymia . OBJECTIVE To compare the effectiveness of pharmacotherapy and psychotherapy in primary care setting s among older persons with minor depression or dysthymia . DESIGN R and omized , placebo-controlled trial ( November 1995-August 1998 ) . SETTING Four geographically and clinical ly diverse primary care practice s. PARTICIPANTS A total of 415 primary care patients ( mean age , 71 years ) with minor depression ( n = 204 ) or dysthymia ( n = 211 ) and a Hamilton Depression Rating Scale ( HDRS ) score of at least 10 were r and omized ; 311 ( 74.9 % ) completed all study visits . INTERVENTIONS Patients were r and omly assigned to receive paroxetine ( n = 137 ) or placebo ( n = 140 ) , starting at 10 mg/d and titrated to a maximum of 40 mg/d , or problem-solving treatment- primary care ( PST-PC ; n = 138 ) . For the paroxetine and placebo groups , the 6 visits over 11 weeks included general support and symptom and adverse effects monitoring ; for the PST-PC group , visits were for psychotherapy . MAIN OUTCOME MEASURES Depressive symptoms , by the 20-item Hopkins Symptom Checklist Depression Scale ( HSCL-D-20 ) and the HDRS ; and functional status , by the Medical Outcomes Study Short-Form 36 ( SF-36 ) physical and mental components . RESULTS Paroxetine patients showed greater ( difference in mean [ SE ] 11-week change in HSCL-D-20 scores , 0.21 [ 0 . 07 ] ; P = .004 ) symptom resolution than placebo patients . Patients treated with PST-PC did not show more improvement than placebo ( difference in mean [ SE ] change in HSCL-D-20 scores , 0.11 [ 0.13 ] ; P = .13 ) , but their symptoms improved more rapidly than those of placebo patients during the latter treatment weeks ( P = .01 ) . For dysthymia , paroxetine improved mental health functioning vs placebo among patients whose baseline functioning was high ( difference in mean [ SE ] change in SF-36 mental component scores , 5.8 [ 2.02 ] ; P = . 01 ) or intermediate ( difference in mean [ SE ] change in SF-36 mental component scores , 4.4 [ 1.74 ] ; P = .03 ) . Mental health functioning in dysthymia patients was not significantly improved by PST-PC compared with placebo ( P>/=.12 for low- , intermediate- , and high-functioning groups ) . For minor depression , both paroxetine and PST-PC improved mental health functioning in patients in the lowest tertile of baseline functioning ( difference vs placebo in mean [ SE ] change in SF-36 mental component scores , 4.7 [ 2.03 ] for those taking paroxetine ; 4.7 [ 1.96 ] for the PST-PC treatment ; P = .02 vs placebo ) . CONCLUSIONS Paroxetine showed moderate benefit for depressive symptoms and mental health function in elderly patients with dysthymia and more severely impaired elderly patients with minor depression . The benefits of PST-PC were smaller , had slower onset , and were more subject to site differences than those of paroxetine Many studies have demonstrated that venlafaxine is an efficacious and safe treatment for major depressive disorder ( MDD ) . This double-blind , placebo-controlled study was performed to evaluate the efficacy of venlafaxine extended-release ( XR ) ( 75 - 225 mg/day ) in the prevention of relapse of depression . Patients with MDD who responded to an 8-week course of venlafaxine XR treatment , i.e. , had a score < or = 3 on the Clinical Global Impressions scale-Severity of Illness item ( CGI-S ) and a 21-item Hamilton Rating Scale for Depression ( HAM-D(21 ) ) score < or = 10 , were r and omly assigned to receive continuation treatment ( up to 6 months ) with venlafaxine XR ( n=161 ) or placebo ( n=157 ) . The main efficacy outcome measure was the number of patients who experienced a relapse of depression . Relapse was defined by either a combination of a patient meeting Diagnostic and Statistical Manual of Mental Disorders , Fourth Edition criteria for MDD and a CGI-S score > or = 4 , two consecutive CGI-S scores > or = 4 , or a final CGI-S score > or = 4 for a patient who withdrew from the study . The cumulative probability of relapse was calculated using the Kaplan-Meier method of survival analysis . During the 6-month evaluation period , significantly more patients in the placebo group had a relapse of MDD than did patients who continued treatment with venlafaxine XR . Cumulative relapse rates at 3 and 6 months were 19 and 28 % , respectively , for venlafaxine XR , and 44 and 52 % , respectively , for placebo . This study demonstrates that venlafaxine XR is an effective and safe continuation therapy BACKGROUND This trial was conducted to determine the incidence of seizures associated with the use of bupropion . METHOD A total of 3341 depressed patients from 102 sites were enrolled in this 8-week , prospect i ve , open trial . Following the 8-week treatment phase , patients could elect to enroll in a humanitarian continuation phase of unlimited duration . Dosing was initiated at 225 mg/day and increased to 450 mg/day as tolerated . Investigators carefully monitored seizure occurrences and rated their patients ' response to and tolerance of bupropion . RESULTS A total of 1986 patients ( 61 % ) completed the 8-week treatment phase , and 1616 ( 81 % ) of these elected to be maintained on bupropion treatment in the humanitarian continuation phase . The observed seizure rate was 0.24 % for the treatment phase and 0.40 % for the entire study . An 8-week survival analysis performed on patients with a dosing regimen of 300 to 450 mg/day yielded a cumulative rate of 0.36 % . Patients , including those previously resistant to antidepressant treatment , responded to and tolerated bupropion well . CONCLUSION These rates confirm earlier seizure estimates and fall within accepted parameters for antidepressant drugs . This trial enhances bupropion 's position as a valuable alternative for the management of depression OBJECTIVES To determine the response of physically ill elderly depressed patients to treatment . DESIGN Acute geriatric medical in patients with depression , r and omly assigned to an 8-week double-blind placebo-controlled trial of fluoxetine . MAIN OUTCOME MEASURE Response rate as defined by the 17-item Hamilton Depression Rating Scale . RESULTS Eighty-two patients entered the trial ; 62 patients ( all those who had completed at least 3 weeks of treatment ) were included in the efficacy analysis . Forty-two completed the full 8 weeks ( 21 in each group ) with response rates of 67 % in the fluoxetine group and 38 % in the placebo group . No significant difference was found between the responses of the two groups ( p = 0.12 ) . There was a trend for results in the fluoxetine group to continue to improve with time . On secondary analysis those patients with serious physical illness who completed 5 or more weeks ( N = 37 ) showed a significant improvement in mood if treated with fluoxetine ( p = 0.02 ) . CONCLUSIONS The main benefit of antidepressants is to approximately double the chances of recovery . This trial showed the response rate of the fluoxetine treated group was increased by a factor of 1.8 over the placebo group in an 8-week period . The presence of physical illness , often severe and /or multiple , did not reduce the effectiveness of the medication , which was well tolerated overall . Those with serious physical disease responded significantly better to drug treatment ; this will require further work . Psychological support was also considered to be important BACKGROUND After unsuccessful treatment for depression with a selective serotonin-reuptake inhibitor ( SSRI ) , it is not known whether switching to one antidepressant is more effective than switching to another . METHODS We r and omly assigned 727 adult out patients with a nonpsychotic major depressive disorder who had no remission of symptoms or could not tolerate the SSRI citalopram to receive one of the following drugs for up to 14 weeks : sustained-release bupropion ( 239 patients ) at a maximal daily dose of 400 mg , sertraline ( 238 patients ) at a maximal daily dose of 200 mg , or extended-release venlafaxine ( 250 patients ) at a maximal daily dose of 375 mg . The study was conducted in 18 primary and 23 psychiatric care setting s. The primary outcome was symptom remission , defined by a total score of 7 or less on the 17-item Hamilton Rating Scale for Depression ( HRSD-17 ) at the end of the study . Scores on the Quick Inventory of Depressive Symptomatology - Self Report ( QIDS-SR-16 ) , obtained at treatment visits , determined secondary outcomes , including remission ( a score of 5 or less at exit ) and response ( a reduction of 50 percent or more on baseline scores ) . RESULTS Remission rates as assessed by the HRSD-17 and the QIDS-SR-16 , respectively , were 21.3 percent and 25.5 percent for sustained-release bupropion , 17.6 percent and 26.6 percent for sertraline , and 24.8 percent and 25.0 percent for extended-release venlafaxine . QIDS-SR-16 response rates were 26.1 percent for sustained-release bupropion , 26.7 percent for sertraline , and 28.2 percent for extended-release venlafaxine . These treatments did not differ significantly with respect to outcomes , tolerability , or adverse events . CONCLUSIONS After unsuccessful treatment with an SSRI , approximately one in four patients had a remission of symptoms after switching to another antidepressant . Any one of the medications in the study provided a reasonable second-step choice for patients with depression . ( Clinical Trials.gov number , NCT00021528 . ) BACKGROUND This was an 8-week , multicenter , r and omized , double-blind , parallel-group study of the efficacy and tolerability of venlafaxine and fluoxetine . METHOD Out patients with DSM-III-R major depression , a minimum score of 20 on the 21-item Hamilton Rating Scale for Depression ( HAM-D ) , and depressive symptoms for at least 1 month were eligible . Patients were r and omly assigned to treatment with venlafaxine , 37.5 mg twice daily , or fluoxetine , 20 mg once daily . The dose could be increased to venlafaxine , 75 mg twice daily , or fluoxetine , 20 mg twice daily , after 3 weeks for a poor response . The primary efficacy variables were the final on-therapy scores on the HAM-D , Montgomery-Asberg Depression Rating Scale ( MADRS ) , and Clinical Global Impressions Severity of Illness ( CGI-S ) and Improvement ( CGI-I ) scales . RESULTS Three hundred eighty-two patients were r and omly assigned to therapy and included in the intent-to-treat analysis . Both venlafaxine and fluoxetine produced significant reductions from baseline to day 56 in mean HAM-D , MADRS , and CGI-S scores , but no significant differences were noted between groups . Among patients who increased their dose at 3 weeks , significantly ( p < .05 ) more patients taking venlafaxine than taking fluoxetine had a CGI-I score of 1 ( very much improved ) at the final evaluation . The most frequent adverse events were nausea , headache , and dizziness with venlafaxine and nausea , headache , and insomnia with fluoxetine . CONCLUSION These results support the efficacy and tolerability of venlafaxine in comparison with fluoxetine for treating out patients with major depression ABSTRACT Objective : This r and omised , double-blind , fixed-dose study evaluated the efficacy of escitalopram and paroxetine in the long-term treatment of severely depressed patients with major depressive disorder ( MDD ) . Research design and methods : Patients with a primary diagnosis of MDD and baseline Montgomery-Åsberg Depression Rating Scale ( MADRS ) ≥ 30 were r and omised to 24 weeks of double-blind treatment with fixed doses of either escitalopram ( 20 mg ) ( n = 232 ) or paroxetine ( 40 mg ) ( n = 227 ) . The primary analysis of efficacy was an analysis of covariance ( ANCOVA ) of change from baseline to endpoint ( Week 24 ) in MADRS total score ( last observation carried forward , LOCF ) . Main outcome measures ; results : At endpoint ( 24 weeks ) , the mean change from baseline in MADRS total score was –25.2 for patients treated with escitalopram ( n = 228 ) and –23.1 for patients with paroxetine ( n = 223 ) , result ing in a difference of 2.1 points ( p < 0.05 ) . The difference in the change in the MADRS total score ( LOCF ) was significantly in favour of escitalopram from Week 8 onwards . The proportion of remitters ( MADRS ≤ 12 ) after 24 weeks was 75 % for escitalopram and 67 % for paroxetine ( p < 0.05 ) . The results on the primary efficacy scale were supported by significantly greater differences in favour of escitalopram on the Hamilton Anxiety , Hamilton Depression and Clinical Global Impression-Improvement and -Severity scales . For very severely depressed patients ( baseline MADRS ≥ 35 ) , there was a difference of 3.4 points at endpoint in the MADRS total score in favour of escitalopram ( p < 0.05 ) . The overall withdrawal rate for patients treated with escitalopram ( 19 % ) was significantly lower than with paroxetine ( 32 % ) ( p < 0.01 ) . The withdrawal rate due to adverse events was significantly lower for escitalopram ( 8 % ) compared to paroxetine ( 16 % ) ( p < 0.05 ) . There were no significant differences in the incidence of individual adverse events during treatment . Conclusion : Escitalopram is significantly more effective than paroxetine in the long-term treatment of severely depressed patients A new formulation of fluoxetine has been developed that is intended to allow for weekly dosing during the long-term treatment of depression . This 90-mg enteric-coated formulation of fluoxetine was compared with 20-mg daily fluoxetine and placebo during a 25-week continuation treatment period in a study of 501 depressed patients who had responded to acute treatment with 20-mg daily fluoxetine . Both active drug formulations were statistically superior to placebo in maintaining the acute treatment response and prolonging the time to relapse . Patients with high baseline anxiety responded similarly to the 90-mg weekly and 20-mg daily fluoxetine treatments . In addition , the 90-mg weekly fluoxetine dose had a safety profile similar to that of both daily fluoxetine dosing and placebo . The once-weekly fluoxetine formulation provides an effective and tolerable treatment option for patients requiring extended depression therapy Bupropion and trazodone were compared in a two-center , double-blind clinical trial of out patients with moderate to severe major depression . After a 1-week placebo lead-in , 124 patients were r and omly assigned to receive either bupropion ( N = 63 ) or trazodone ( N = 61 ) for 6 weeks ; data from 111 patients were used in the efficacy analysis . Dosing ranged from 225 to 450 mg/day for bupropion and 150 to 400 mg/day for trazodone . The overall efficacy for each of the two drugs was similar ; although improvement in the trazodone treatment group was significantly greater on day 7 because of the effects on sleep . At the end of treatment , 58 % of the bupropion-treated patients and 46 % of the trazodone-treated patients were considered much or very much improved . Weight measurements at the time of discontinuation indicated a 2.5-lb mean weight loss for the bupropion treatment group and a 1.2-lb mean weight gain for the trazodone treatment group . The adverse experience profiles for bupropion and trazodone were consistent with their known pharmacologic profiles ( i.e. , activating versus sedating ) . Anorexia and anxiety were reported significantly more often for the bupropion treatment group , whereas somnolence , appetite increase , and edema were reported significantly more often for the trazodone treatment group BACKGROUND A large proportion of the elderly population complains of depressive symptoms . The ideal antidepressant for these patients , who often suffer from numerous concomitant diseases , should not worsen their cognitive functions and should be free of contraindications . METHOD To assess the effects of 2 selective serotonin reuptake inhibitors on cognitive functions in elderly depressed patients ( ICD-10 criteria ) , we conducted a double-blind , r and omized , parallel-group , multicenter study comparing paroxetine ( 20 - 40 mg daily ) and fluoxetine ( 20 - 60 mg daily ) treatment for 1 year . Cognitive performance was evaluated by means of the Buschke Selective Reminding Test , the Blessed Information and Memory Test , the Clifton Assessment Schedule , the Cancellation Task Test , and the Wechsler Paired Word Test ; the Hamilton Rating Scale for Depression ( HAM-D ) and the Clinical Anxiety Scale were administered to assess the course of depressive and anxiety symptoms , respectively . RESULTS 242 patients were enrolled ( mean + /- SD age = 75.4 + /- 6.6 years ) . During the study , no deterioration of cognition was observed ; on the contrary , most of the tested cognitive functions improved . Good antidepressant efficacy was maintained for over 1 year with both drugs , based on the percentage of responders to treatment ( patients achieving a HAM-D total score < 10 ; 60 % ) . Both drugs showed a good tolerability and safety profile . CONCLUSION The 2 antidepressants proved to be suitable for the long-term treatment of depression in the elderly and to be devoid of detrimental effects on the tested cognitive functions A placebo‐controlled , r and omized , double‐blind study was carried out in out patients suffering from major unipolar depressive disorder to assess the efficacy and tolerability of paroxetine in the treatment of depression . The study lasted for six weeks . After a placebo washout period of 4 to 14 days patients took 20 mg of paroxetine or matched placebo as a morning dose for one week ; thereafter the dose of paroxetine could be titrated between 10 and SOmg/day . Patients were evaluated at baseline , weekly during the first four weeks of the study , and at the end of sixweeks ; patients who entered a six‐week extensionphasewere evaluated at 9 and 12 weeks . Evaluations were carried out using HAMD ( including ECDEU factors ) , MADRS , HSCL , Covi anxiety and Raskin depression scales , CGI , and a seven‐point rating of global improvement . Adverse events and laboratory values were also recorded at each assessment . One hundred and eleven patients entered the study , and efficacy data were available for 102 of these ( 49 on paroxetine and 53 on placebo ) . Efficacy measurements demonstrated significantly greater clinical improvement with paroxetine than placebo after two weeks of treatment , and this became even more marked after six weeks . Patients who continued treatment for a further six weeks maintained their clinical improvement . When adverse events were examined , statistically significant differences between paroxetine and placebo were seen only for sweating , diarrhoea , nausea , and somnolence . No significant changes were seen in any of the laboratory parameters measured . If these results are confirmed in future studies , paroxetine will represent an important addition to the treatments available for depression This study assessed whether fluoxetine , sertraline , and paroxetine differ in efficacy and tolerability in depressed patients and the impact of baseline insomnia on outcomes . Patients ( N = 284 ) with DSM-IV major depressive disorder were r and omly assigned in a double-blind fashion to fluoxetine , paroxetine , or sertraline for 10 to 16 weeks of treatment . Using the Hamilton Rating Scale for Depression ( HAM-D ) sleep disturbance factor score , patients were categorized into low ( < 4 ) or high ( ≥4 ) baseline insomnia subgroups . Changes in depression and insomnia were assessed . Safety assessment s included treatment-emergent adverse events ( AEs ) , reasons for discontinuation , and AEs leading to discontinuation . In addition , AEs were evaluated within insomnia subgroups to determine emergence of activation or sedation . Depression improvement , assessed with the HAM-D-17 total score , was similar among treatments in all patients ( p = 0.365 ) and the high ( p = 0.853 ) and low insomnia ( p = 0.415 ) subgroups . Insomnia improvement , assessed with the HAM-D sleep disturbance factor score , was similar among treatments in all patients ( p = 0.868 ) and in the high ( p = 0.852 ) and low insomnia ( p = 0.982 ) subgroups . Analyses revealed no significant differences between treatments in the percentages of patients with substantial worsening , any worsening , worsening at endpoint , or improvement at endpoint in the HAM-D sleep disturbance factor in either insomnia subgroup . Treatments were well tolerated in most patients . No significant differences between treatments in the incidence of AEs suggestive of activation or sedation were seen in the insomnia subgroups . These data show no significant differences in acute treatment efficacy and tolerability across fluoxetine , sertraline , and paroxetine in major depressive disorder patients . Improvement in overall depression and in associated insomnia was achieved by most patients regardless of baseline insomnia BACKGROUND Recent reports describe discontinuation-emergent adverse events upon cessation of selective serotonin reuptake inhibitors including dizziness , insomnia , nervousness , nausea , and agitation . We hypothesized that interruption of fluoxetine treatment would be associated with fewer discontinuation-emergent adverse events than interruption of sertraline or paroxetine treatment , based on fluoxetine 's longer half-life . METHODS In this 4-week study , 242 patients with remitted depression receiving maintenance therapy with open-label fluoxetine , sertraline , or paroxetine for 4 - 24 months had their maintenance therapy interrupted with double-blind placebo substitution for 5 - 8 days . The Symptom Question naire ( SQ ) , the Discontinuation-Emergent Signs and Symptoms checklist , the 28-item Hamilton Depression Rating Scale , and the Montgomery-Asberg Depression Rating Scale were used to assess somatic distress and stability of antidepressant response . RESULTS Two hundred twenty patients ( 91 % ) completed the study . Following interruption of therapy , fluoxetine-treated patients experienced fewer discontinuation-emergent events than either sertraline-treated or paroxetine-treated patients ( p < .001 ) . The mean SQ somatic symptom scale score in fluoxetine-treated patients was significantly lower than that in sertraline-treated and paroxetine-treated patients ( p < .001 ) . Fluoxetine-treated patients also experienced less reemergence of depressive symptoms than sertraline-treated or paroxetine-treated patients ( p < .001 ) . CONCLUSIONS Abrupt interruption of antidepressant therapy for 5 - 8 days was associated with the emergence of new somatic and psychological symptoms in patients treated with paroxetine and to a lesser degree sertraline , with few symptoms seen with fluoxetine Selective serotonin reuptake inhibitors may be associated with new adverse events after abrupt discontinuation . Hypothesizing that the long half-life of fluoxetine would be protective , this study analyzed the effects of abrupt fluoxetine discontinuation during a r and omized , double-blind , placebo-controlled study of depression maintenance treatment . After 12 weeks of fluoxetine treatment ( 20 mg/day ) , 395 responders were abruptly r and omized to placebo ( N = 96 ) or to continued fluoxetine ( N = 299 ) . Patients were seen at weeks 1 , 2 , 4 , and 6 after r and omization . Reports of new or worsened adverse events were similar for both groups at each visit after r and omization . Patient discontinuations related to adverse events were also similar in both groups . Mild , self-limited lightheadedness or dizziness occurred in a small percentage of patients who discontinued fluoxetine treatment but was of little clinical significance . No cluster of symptoms suggestive of a discontinuation syndrome was observed . Abrupt discontinuation of fluoxetine treatment was well tolerated and did not seem to be associated with significant clinical risk . Fluoxetine may offer a potential safety advantage over shorter-acting agents with respect to treatment interruption and /or discontinuation and may be a better choice for those patients who are likely to miss doses because of travel or forgetfulness BACKGROUND Depression is an international public health problem . The aim of this study was to compare the efficacy and tolerability of mirtazapine and fluoxetine treatment in a sample population consisting of Iranian patients suffering major depressive disorder . METHODS Thirty-six in patients and out patients with a diagnosis of major depressive disorder ( Diagnostic and Statistical Manual of Mental Disorders-IV ) and a score > or = 18 on the 17-item Hamilton Rating Scale for Depression ( HAM-D-17 ) were r and omly assigned to 6 weeks of treatment with mirtazapine ( 30 mg/day ) or fluoxetine ( 20 mg/day ) . Efficacy was assessed by HAM-D-17 . Information about adverse events was obtained by question ing of participants and /or their examination . Assessment s were performed at weeks 0 , 1 , 2 , 3 , 4 and 6 . RESULTS Sixteen of mirtazapine-treated patients and fifteen of fluoxetine-treated patients completed the 6-week study period . Both treatment groups were well matched at baseline with respect to demographic and disease characteristics . Both drugs showed a significant improvement over the 6 weeks of treatment ( P < 0.001 ) . There was no statistically significant difference between the mean + /- SEM HAM-D scores of two groups at weeks 1 , 2 , 3 , 4 , and at the end point . There were no significant differences between two groups in terms of response to treatment ( > or = 50 % decrease from baseline in HAM-D-17 total score ) and remission ( HAM-D-17 score of < or = 7 ) . None of the differences in reported adverse events was statistically significant . CONCLUSION In this study , mirtazapine and fluoxetine were equally effective and well tolerated after 6 weeks of treatment in patients with major depressive disorder The purpose of the present 6-week multicenter dose finding study was to compare the efficacy and tolerability of mirtazapine ( preferentially presynaptic alpha 2-adrenergic receptor blocker ) to placebo in hospitalized patients with major depression . The clinical efficacy was evaluated with the Hamilton Depression Scale ( HAM-D ) , Montgomery-Asberg Depression Rating Scale ( MADRS ) , Beck Self-Rating Depression Scale , Global Assessment Scale ( GAS ) , and Brief Psychiatric Rating Scale ( BPRS ) . The side effects were recorded on a checklist of emergent symptoms ( ROSE ) and physical examinations , ECG , clinical chemistry , and hematology tests were carried out . The dosages of mirtazapine were gradually raised from 15 mg to 50 mg . One hundred and fourteen patients were included . Twenty-two patients ( 37 % ) in mirtazapine group and 24 ( 44 % ) in the placebo group were prematurely withdrawn from the study mainly due to inadequate efficacy . The decrease in HAM-D and MADRS was generally more pronounced in the mirtazapine group than in the placebo group . Minor side effects were reported in less than 15 % of the patients in both groups . Only fatigue and faintness were slightly more pronounced in the mirtazapine group than in the placebo group . No significant changes were found in laboratory parameters . Because of method ological flaws like combining a dose finding study with a placebo controlled study , further conclusions should not be made on the efficacy of mirtazapine when treating depressive patients Pre- clinical studies , active-control clinical trials and meta-analyses indicate that escitalopram ( S-citalopram ) might be more effective than citalopram , the racemic mixture of S- and R-citalopram . The present study aim ed to confirm the superior efficacy of escitalopram over citalopram . A double-blind , r and omized clinical trial was performed in which general practitioners and psychiatrists compared fixed doses of escitalopram ( 20 mg/day ) with citalopram ( 40 mg/day ) over 8 weeks in out patients with major depressive disorder ( MDD ) [ baseline Montgomery – Asberg Depression Rating Scale ( MADRS ) score ≥30 ] . Primary efficacy parameter was change from baseline to last assessment in the MADRS total score . Out of 138 ( aged 44.1±10.9 years ; initial MADRS score 36.3±4.8 ) and 142 ( aged 46.2±11.1 years ; initial MADRS score 35.7±4.4 ) evaluable patients who were r and omized to escitalopram and citalopram , respectively , six and 15 withdrew prematurely ( P=0.05 ) . The MADRS score decreased more in the escitalopram than in the citalopram arm ( –22.4±12.9 versus –20.3±12.7 ; P<0.05 ) . There were more treatment responders with escitalopram ( 76.1 % ) than with citalopram ( 61.3 % , P<0.01 ) . Adjusted remitter rates were 56.1 % and 43.6 % , respectively ( P<0.05 ) . Tolerability was similar in both groups . This r and omized double-blind trial confirms that escitalopram has a superior effect to citalopram in MDD OBJECTIVE Minor depressive disorder is both common and associated with significant psychosocial impairment . This study examined antidepressant treatment efficacy in a large group of patients with minor depressive disorder . METHOD One hundred sixty-two patients with minor depressive disorder were r and omly assigned to receive fluoxetine or placebo in a 12-week , double-blind study ; 73 % ( 59 of 81 ) of the patients in each treatment group completed the study . Patients were evaluated weekly with st and ard depression rating instruments and measures of psychosocial impairment . Hypotheses were tested by last-observation-carried-forward analysis of variance ( ANOVA ) and confirmed by mixed ( r and om-effects ) regression analysis . RESULTS At baseline , minor depressive disorder patients were mildly to moderately depressed , with a corresponding degree of functional impairment . Over 12 weeks of treatment , both ANOVA and mixed regression showed fluoxetine to be superior to placebo as indicated by significantly greater improvement of fluoxetine-treated patients in scores on the 30-item clinician-rated Inventory of Depressive Symptomatology , the 17-item and 21-item Hamilton Depression Rating Scale , the Beck Depression Inventory , and the Clinical Global Impression severity scale . Improvement in Global Assessment of Functioning Scale score was significantly greater for the fluoxetine group in mixed regression analysis only . Patients in both treatment groups reported a similar number and severity of adverse events during the 12-week treatment period . CONCLUSIONS Clinicians frequently encounter minor depressive disorder either as a prodromal or residual phase of illness in major depressive disorder or as de novo minor depressive disorder episodes . Fluoxetine is significantly superior to placebo in reducing minor depressive disorder symptoms within a 12-week period . Improvement in psychosocial function with fluoxetine may take longer than 12 weeks OBJECTIVE Previous reports suggesting that selective serotonin reuptake inhibitor ( SSRI ) use is associated with increased suicidal risk have not assessed completed suicides . The authors analyzed reports from r and omized controlled trials to compare suicide rates among depressed patients assigned to an SSRI , other antidepressants , or placebo . METHOD Food and Drug Administration ( FDA ) summary reports of the controlled clinical trials for nine modern FDA -approved antidepressants provided data for comparing rates of suicide . RESULTS Of 48,277 depressed patients participating in the trials , 77 committed suicide . Based on patient exposure years , similar suicide rates were seen among those r and omly assigned to an SSRI ( 0.59 % , 95 % confidence interval [CI]=0.31%-0.87 % ) , a st and ard comparison antidepressant ( 0.76 % , 95 % CI=0.49%-1.03 % ) , or placebo ( 0.45 % , 95 % CI=0.01%-0.89 % ) . CONCLUSIONS These findings fail to support either an overall difference in suicide risk between antidepressant- and placebo-treated depressed subjects in controlled trials or a difference between SSRIs and either other types of antidepressants or placebo Antidepressant medications are typically taken on a daily basis owing to both tradition and the pharmacokinetics of these agents . Because fluoxetine and its primary metabolite norfluoxetine have long half-lives and flat dose-response curves , we examined the tolerability of a weekly dose and its equivalence to daily dosing during the continuation phase of treatment for major depressive disorder ( MDD ) . Open-label treatment with 20 mg of fluoxetine daily for 7 weeks began with 114 subjects . Subsequently , 70 subjects who met criteria for response were r and omly assigned in a double-blind design to 1 of 3 treatment groups ( 20 mg of fluoxetine daily [ N = 21 ] , 60 mg of fluoxetine weekly [ N = 28 ] , or placebo [ N = 21 ] ) and followed for 7 weeks . No statistically significant differences were observed in several clinical measures . Tolerability in the 3 groups was similar ; there was no difference in dropout rates or adverse events . Hence , weekly dosing of fluoxetine appears to be well tolerated and possibly as effective as daily dosing in the treatment of MDD . It is proposed that less frequent dosing could potentially benefit patients by enhancing adherence and minimizing the risk of side effects and drug-drug interactions Somatic symptoms often complicate the diagnosis and psychopharmacological treatment of depression in HIV illness . We treated 33 depressed HIV-positive men and women with medically symptomatic HIV or AIDS ( CDC stages 2B , 2C , 3B , or 3C ) in a 6 week open-label trial with sertraline , paroxetine , or fluoxetine , to assess their effectiveness and tolerability . We further assessed whether treatment of depression result ed in a reduction in both affective and somatic symptoms in this medically ill population . Twenty-four subjects ( 73 % ) completed the trial ( 7 on sertraline , 7 on paroxetine , 10 on fluoxetine ) , 20 ( 83 % ) of whom were clinical responders . Nine dropped out within 1 - 3 weeks of treatment because of adverse effects , mostly agitation , anxiety , and insomnia . Subjects who completed 6 weeks of SSRI treatment experienced significant reductions in both affective and somatic symptoms , many of the latter having been attributed to HIV rather than depression . These results suggest that , even in later stages of HIV illness , the contribution of depression to perceived somatic symptoms may be significant , and that these symptoms may improve with antidepressant treatment BACKGROUND Several different classes of antidepressants have been associated with sexual adverse effects . This double-blind , r and omized trial compared the effects of nefazodone and sertraline on reemergence of sexual dysfunction in depressed patients who had experienced sexual dysfunction as a result of sertraline treatment . Depressive symptoms were also monitored . METHOD One hundred five patients with DSM-III-R major depressive episode who were experiencing sexual dysfunction attributable to sertraline ( 100 mg/day ) were screened for entry . Eligible patients entered a 1-week washout period that was followed by a 7- to 10-day single-blind placebo phase . Patients without symptoms of sexual dysfunction at the end of the single-blind placebo phase were r and omly assigned to receive double-blind treatment with either nefazodone ( 400 mg/day ) or sertraline ( 100 mg/day ) for 8 weeks . RESULTS Nearly 3 times more sertraline-treated patients ( 76 % ; 25/33 ) experienced reemergence of sexual dysfunction ( ejaculatory and /or orgasmic difficulty ) than did nefazodone-treated patients ( 26 % ; 10/39 ) ( p < .001 ) . In addition , patients treated with nefazodone were more satisfied with their sexual functioning than were patients treated with sertraline . Both treatment groups demonstrated a similar and sustained improvement in depressive symptoms . Both drugs were well tolerated , and the overall incidence of adverse reactions was similar for both treatment groups ; however , 9 sertraline-treated patients ( 26 % ) discontinued because of adverse events compared with 5 nefazodone-treated patients ( 12 % ) . Of the patients discontinuing therapy for adverse events , 5 of the sertraline-treated patients did so because of sexual dysfunction reported as an adverse event , whereas only 1 of the nefazodone-treated patients discontinued therapy secondary to sexual dysfunction . CONCLUSION In this sample of patients with major depression who had recovered from sexual dysfunction induced by treatment with sertraline , nefazodone treatment result ed in significantly less reemergence of sexual dysfunction than did renewed treatment with sertraline and provided continued antidepressant activity OBJECTIVE To investigate whether differences in antidepressant efficacy are moderated by an interaction of age and gender . METHODS A pooled data set from eight r and omized , controlled trials of patients with major depressive disorder ( MDD ) was reanalyzed to compare remission rates following therapy with venlafaxine ( n = 851 ) , one of several selective serotonin reuptake inhibitors ( SSRIs ) ( n = 748 ) , or placebo ( n = 446 ) . Remission was defined as a final Hamilton Rating Scale for Depression ( HAM-D ) score < or = 7 . Pairwise comparisons were conducted using stepwise multiple logistic regression models with main effect and interaction terms for treatment , sex , and age ( younger : < 50 ; older : > or = 50 ) . Among older women , the impact of hormone replacement therapy ( HRT ) on remission rates also was examined . RESULTS Remission rates on venlafaxine therapy were not affected by age , sex , or HRT use . Among women , but not men , there was a significant interaction reflecting poorer SSRI response in the older age group ( Wald chi-square = 4.21 , df = 1 , p = 0.04 ) ; HRT appeared to eliminate this difference . Whereas the advantage in remission rates favoring venlafaxine was modest for men and younger women ( 6%-9 % ) , the difference among older women not taking HRT was 23 % . CONCLUSIONS These findings provide further evidence that age , gender , and HRT moderate response to antidepressant medications Major depression during later life represents a clinical challenge . Conventional antidepressant pharmacotherapy is relatively less well tolerated in geriatric patients compared with younger patients . Despite the striking impairments associated with this disorder , clinical investigations into the relative risk-benefit ratio of various depression treatment strategies have been limited . In this multicentre , placebo-controlled , double-blind trial with fluoxetine , 671 major depressed ( DSM-III-R-compatible ) out patients aged 60 years or older were evaluated . The 21-item Hamilton Depression Rating le ( HAMD21 ) response ( p = 0.014 ) and remission ( p = 0.008 ) criteria favoured fluoxetine over placebo . Analysis of the treatment effect on change in the HAMD21 factors ( anxiety/somatization , cognitive disturbance , psychomotor retardation , and sleep disturbance ) revealed advantages for fluoxetine within the cognitive disturbance and psychomotor retardation factors . Overall , the rate of discontinuation for an adverse event between fluoxetine ( 11.6 % ) and placebo ( 8.6 % ) was not statistically significant . Baseline HAMD21 factor scores were not predictive of adverse events leading to premature treatment discontinuation . Fluoxetine , 20 mg/day , is a well-tolerated and effective treatment option in the management of geriatric major depression BACKGROUND Nefazodone hydrochloride , a 5-HT2 receptor antagonist that selectively inhibits serotonin reuptake , was evaluated in a double-blind , dose-finding study of novel design , involving 240 patients with major depression . METHOD Patients were r and omly assigned to three treatment groups and received either placebo ( 2 - 6 capsules per day ) , a lower-dose range of nefazodone ( 50 - 300 mg/day ) , or a higher-dose range of nefazodone ( 100 - 600 mg/day ) for 6 weeks . RESULTS At the end of treatment , the Hamilton Rating Scale for Depression and the clinician- and patient-rated Inventory for Depressive Symptomatology scores showed significant improvement ( p < or = .05 ) for patients receiving higher-dose range nefazodone ( mean = 392 mg/day ) compared with placebo treatment . The percentage of responders ( at least " much improved " on the Clinical Global Impressions-Improvement scale ) in the higher-dose range nefazodone group ( 58 % ) was significantly greater ( p < or = .05 ) than in the placebo group ( 39 % ) . The treatment group receiving nefazodone in the lower-dose range was not differentiated in clinical response from placebo controls . The rate of discontinuation for adverse experience ( 14 % ) was similar for patients treated with higher-dose range nefazodone and placebo . CONCLUSION The findings of this study indicate that nefazodone is an effective and well-tolerated antidepressant drug , with a recommended therapeutic dose range of 100 to 600 mg/day and a starting dose of 100 mg b.i.d BACKGROUND We conducted a r and omized , double-blind , placebo-controlled study of the efficacy and safety of once-daily venlafaxine extended release ( XR ) and fluoxetine in out patients with major depression and concomitant anxiety . METHOD Patients who met DSM-IV criteria for major depressive disorder and satisfied eligibility criteria were r and omly assigned to once-daily venlafaxine XR , fluoxetine , or placebo for 12 weeks . Efficacy was assessed with the Hamilton Rating Scale for Depression ( HAM-D ) , Hamilton Rating Scale for Anxiety ( HAM-A ) , and Clinical Global Impressions scale . RESULTS Among 359 out patients , venlafaxine XR and fluoxetine were significantly superior ( p < .05 ) to placebo on the HAM-D total score beginning at week 2 and continuing to the end of the study . Venlafaxine XR but not fluoxetine was significantly better than placebo at week 2 on the HAM-D depressed mood item . At week 12 , the HAM-D response rate was 43 % on placebo , 67 % on venlafaxine XR , and 62 % on fluoxetine ( p < .05 ) . The HAM-D remission rate was significantly higher ( p < .05 ) at weeks 3 , 4 , 6 , 8 , 12 , and final evaluation with venlafaxine XR and at weeks 8 , 12 , and final evaluation with fluoxetine than with placebo . The HAM-A response rate was significantly higher ( p < .05 ) with venlafaxine XR than with fluoxetine at week 12 . The incidence of discontinuation for adverse events was 5 % with placebo , 10 % with venlafaxine XR , and 7 % with fluoxetine . CONCLUSION Once-daily venlafaxine XR is effective and well tolerated for the treatment of major depression and concomitant anxiety and provides evidence for superiority over fluoxetine This study tested the effectiveness of fluoxetine as a treatment for depression in a population of methadone-maintained opioid addicts . Methadone-maintained opioid addicts ( 44 ) with depression received fluoxetine or placebo in addition to their methadone , in a double-blind r and omized trial , for 12 weeks . Depressive symptoms decreased significantly overall with no significant differences between the groups treated with fluoxetine versus placebo . In addition , drug use outcomes , including cocaine and heroin self-reported use and urine toxicology were measured . There was a significant decrease in heroin use in treatment , but no medication effect . Cocaine use , was unchanged from pre-treatment to endpoint . In separately analyzing data for the sub sample of subjects with the most severe depression , there was a significant decrease in depression during treatment and a significant decrease in self-reported cocaine use , but no medication effect on either depressive symptoms or on cocaine use . This study suggests that fluoxetine is not an effective agent in treating depression or cocaine use in this population BACKGROUND There has been a paucity of well- design ed studies comparing selective serotonin reuptake inhibitor ( SSRI ) medications in the treatment of depression in the elderly . This multicenter study was design ed to examine the efficacy and safety of sertraline and fluoxetine in depressed elderly out patients . A secondary objective was to examine the effects of SSRI treatment on quality of life and cognitive function . METHOD Two hundred thirty-six out patients 60 years of age and older who met DSM-III-R criteria for major depressive disorder received 1 week of single-blind placebo before being r and omly assigned to 12 weeks of double-blind , parallel-group treatment with flexible daily doses of either sertraline ( range , 50 - 100 mg ) or fluoxetine ( range , 20 - 40 mg ) . Primary efficacy measures consisted of the 24-item Hamilton Rating Scale for Depression and Clinical Global Impressions scale ratings . Secondary outcome assessment s included clinician- and patient-rated measures of depression symptoms and factors , cognitive functioning , and quality of life , as well as plasma drug concentrations , which were correlated with clinical response . RESULTS Both drugs produced a similarly positive response on the primary efficacy measures , with 12-week responder rates of 73 % for sertraline and 71 % for fluoxetine . Sertraline-treated patients showed statistically greater cognitive improvement on several measures . Both drugs were safe and well tolerated . CONCLUSION Data indicate that both drugs are effective antidepressants for the treatment of depressed elderly out patients . Differences in cognitive performance effects deserve further investigation OBJECTIVE The research ers evaluated the effectiveness of paroxetine and Problem-Solving Treatment for Primary Care ( PST-PC ) for patients with minor depression or dysthymia . STUDY DESIGN This was an 11-week r and omized placebo-controlled trial conducted in primary care practice s in 2 communities ( Lebanon , NH , and Seattle , Wash ) . Paroxetine ( n=80 ) or placebo ( n=81 ) therapy was started at 10 mg per day and increased to a maximum 40 mg per day , or PST-PC was provided ( n=80 ) . There were 6 scheduled visits for all treatment conditions . POPULATION A total of 241 primary care patients with minor depression ( n=114 ) or dysthymia ( n=127 ) were included . Of these , 191 patients ( 79.3 % ) completed all treatment visits . OUTCOMES Depressive symptoms were measured using the 20-item Hopkins Depression Scale ( HSCL-D-20 ) . Remission was scored on the Hamilton Depression Rating Scale ( HDRS ) as less than or equal to 6 at 11 weeks . Functional status was measured with the physical health component ( PHC ) and mental health component ( MHC ) of the 36-item Medical Outcomes Study Short Form . RESULTS All treatment conditions showed a significant decline in depressive symptoms over the 11-week period . There were no significant differences between the interventions or by diagnosis . For dysthymia the remission rate for paroxetine ( 80 % ) and PST-PC ( 57 % ) was significantly higher than for placebo ( 44 % , P=.008 ) . The remission rate was high for minor depression ( 64 % ) and similar for each treatment group . For the MHC there were significant outcome differences related to baseline level for paroxetine compared with placebo . For the PHC there were no significant differences between the treatment groups . CONCLUSIONS For dysthymia , paroxetine and PST-PC improved remission compared with placebo plus nonspecific clinical management . Results varied for the other outcomes measured . For minor depression , the 3 interventions were equally effective ; general clinical management ( watchful waiting ) is an appropriate treatment option BACKGROUND Antidepressants , especially selective serotonin reuptake inhibitors ( SSRIs ) , venlafaxine , and clomipramine , are frequently associated with sexual dysfunction . Other antidepressants ( nefazodone , mirtazapine , bupropion , amineptine , and moclobemide ) with different mechanisms of action seem to have fewer sexual side effects . The incidence of sexual dysfunction is underestimated , and the use of a specific question naire is needed . METHOD The authors analyzed the incidence of antidepressant-related sexual dysfunction in a multicenter , prospect i ve , open-label study carried out by the Spanish Working Group for the Study of Psychotropic-Related Sexual Dysfunction . The group collected data from April 1995 to February 2000 on patients with previously normal sexual function who were being treated with antidepressants alone or antidepressants plus benzodiazepines . One thous and twenty-two out patients ( 610 women , 412 men ; mean age = 39.8 + /- 11.3 years ) were interviewed using the Psychotropic-Related Sexual Dysfunction Question naire , which includes questions about libido , orgasm , ejaculation , erectile function , and general sexual satisfaction . RESULTS The overall incidence of sexual dysfunction was 59.1 % ( 604/1022 ) when all antidepressants were considered as a whole . There were relevant differences when the incidence of any type of sexual dysfunction was compared among different drugs : fluoxetine , 57.7 % ( 161/279 ) ; sertraline , 62.9 % ( 100/159 ) ; fluvoxamine , 62.3 % ( 48/77 ) ; paroxetine , 70.7 % ( 147/208 ) ; citalopram , 72.7 % ( 48/66 ) ; venlafaxine , 67.3 % ( 37/55 ) ; mirtazapine , 24.4 % ( 12/49 ) ; nefazodone , 8 % ( 4/50 ) ; amineptine , 6.9 % ( 2/29 ) ; and moclobemide , 3.9 % ( 1/26 ) . Men had a higher frequency of sexual dysfunction ( 62.4 % ) than women ( 56.9 % ) , although women had higher severity . About 40 % of patients showed low tolerance of their sexual dysfunction . CONCLUSION The incidence of sexual dysfunction with SSRIs and venlafaxine is high , ranging from 58 % to 73 % , as compared with serotonin-2 ( 5-HT2 ) blockers ( nefazodone and mirtazapine ) , moclobemide , and amineptine The efficacy and safety of fluvoxamine maleate , a selective serotonin reuptake inhibitor , was compared with placebo and imipramine in patients with major depressive disorder . Previous literature has cited a dose range of 100 to 300 mg/day of fluvoxamine maleate for the treatment of major depression ; however , this study demonstrates that a dose range of 50 to 150 mg/day is as effective as imipramine ( 80 - 240 mg/day ) . After a 1- to 2-week , single-blind , placebo washout phase , 150 depressed out patients were r and omized to double-blind treatment with fluvoxamine maleate ( 50 - 150 mg/day ) , imipramine ( 80 - 240 mg/day ) , or placebo for 6 weeks . Fluvoxamine produced a significant therapeutic benefit over placebo ( p < or = 0.05 ) as assessed by the total score on the Hamilton Rating Scale for Depression ; imipramine ( 80 - 240 mg/day ) produced similar results . The secondary outcome variables ( i.e. , Clinical Global Impression severity of illness item and 56-Item Hopkins Symptom Checklist depression factor ) also showed significant differences between fluvoxamine maleate and placebo during three of the four final weeks of the study . Both fluvoxamine maleate and imipramine appeared to be safe and well tolerated by the majority of patients . As expected from the pharmacology of these agents , the imipramine groups reported more anticholinergic effects ( dry mouth , dizziness , and urinary retention ) and electrocardiographic effects , whereas the fluvoxamine group reported more nausea , somnolence , and abnormal ejaculation . The majority of these adverse events were mild to moderate and , with the exception of dry mouth ( imipramine ) and abnormal ejaculation ( fluvoxamine ) , were transient . The data clearly demonstrate the antidepressant activity and tolerability of fluvoxamine maleate ( 50 - 150 mg/day ) as compared with placebo ; it is also as effective as the tricyclic antidepressant imipramine ( 80 - 240 mg/day ) in patients with major depressive disorder This multinational , r and omized , double-blind , flexible-dose study evaluated the short- and long-term antidepressant tolerability and efficacy of escitalopram and paroxetine . Tolerability was assessed by monitoring adverse events throughout the study , and discontinuation events during brief treatment interruption and tapered withdrawal . Discontinuation-emergent effects were evaluated in two separate double-blind periods . First , to mimic the consequences of non-compliance , patients were r and omized to one of two treatment interruption periods ( placebo-substitution for 3–5 days ) . Second , patients were r and omized to a 1–2-week tapered withdrawal period r and omly scheduled between weeks 28 and 31 . The pre-specified primary efficacy endpoint was the mean change from baseline in total Montgomery – Åsberg Depression Rating Scale ( MADRS ) score at week 8 , using the principle of last observation carried forward . A total of 323 patients entered 8 weeks of double-blind treatment and received at least one flexible dose of escitalopram ( 10–20 mg/day ) or paroxetine ( 20–40 mg/day ) . Patients who demonstrated evidence of a significant clinical improvement ( Clinical Global Impression – Improvement of 1 or 2 ) at week 8 entered a 19-week , double-blind maintenance period during which they were treated with the same dose they received at week 8 , followed by a 1–2-week tapered withdrawal period . A total of 89 patients ( 28 % ) withdrew during the study ; significantly ( P<0.01 ) more patients withdrew from the paroxetine group ( 34 % ) than from the escitalopram group ( 21 % ) , and significantly ( P<0.05 ) more paroxetine patients withdrew due to lack of efficacy . The mean MADRS total score improved for both treatment groups from baseline to week 8 , with no statistical difference between groups . In severely depressed patients ( baseline MADRS total score ≥30 ) , escitalopram was superior ( P<0.05 ) to paroxetine at week 27 ( end of maintenance treatment ) . There was a high prevalence of sexual dysfunction at baseline : the mean Arizona Sexual Experience Scale ( ASEX ) score was approximately 20 points in both treatment groups . Mean total ASEX scores increased slightly above baseline values during the acute period and declined slightly below baseline values towards the end of the maintenance period . During taper and cessation of treatment , patients in the paroxetine group demonstrated significantly more discontinuation symptoms relative to escitalopram based on the Discontinuation Emergent Signs and Symptoms scores The efficacy of paroxetine and fluoxetine and their effects on cognitive and behavioural function were compared in a 6 week , double-blind , r and omized study of 106 elderly depressed patients ( aged 61 to 85 years ) . Antidepressant efficacy was assessed using the Hamilton depression rating scale ( HAMD ) , Montgomery-Asberg Depression Rating Scale ( MADRS ) and Clinical Global Impression ( CGI ) scale . The S and oz Clinical Assessment Geriatric scale ( SCAG ) , the Mini-Mental State Examination ( MMSE ) , and HAMD cognitive factor scores were used to assess cognitive and behavioural function . Paroxetine demonstrated comparable efficacy to fluoxetine in the treatment of elderly depressed patients , but at the end of treatment , there was a significantly higher proportion of responders to paroxetine than to fluoxetine . Both treatments produced improvements in all measures of cognitive and behavioural function , but paroxetine was significantly superior to fluoxetine from Week 3 , indicating a possible early effect . There was no difference between the two agents in either the tolerability or safety of treatment ABSTRACT Objectives : To evaluate the efficacy and safety of trazodone prolonged-release compared with sertraline in the treatment of patients with major depression . Research design and methods : A total of 122 patients aged 19–64 years were enrolled in this multicenter , double-blind , double-dummy , r and omized , comparator-controlled study . Patients received 7 days of single-blind placebo treatment followed by 6 weeks of double-blind treatment with trazodone prolonged-release 150–450 mg/day ( n = 62 ) or sertraline 50–100 mg/day ( n = 60 ) . Outcome measures : Efficacy was evaluated by mean changes from baseline in the Hamilton Depression Rating scale ( HAM‐D ) , Montgomery Asberg Depression Rating Scale , Hamilton Anxiety Rating scale , and the Clinical Global Impression-Global Improvement/Severity scores ; and by the rates of patients responding to treatment and considered to be in remission . Time to onset of efficacy and safety were assessed . Results : Trazodone and sertraline were equally effective in reducing depressive symptoms and promoting remission , and had similar onset times . In the Intent-to-Treat population , there were no significant differences in favor of trazodone at study endpoint in all efficacy measures , while a statistically significant difference was detected in the Per- Protocol population on HAM‐D and in the percentage of responders . Analysis of HAM‐D factors ( anxiety/somatization , cognitive disturbance , retardation , and sleep disturbance ) indicated that sleep disturbances were significantly less evident for patients taking trazodone at study endpoint . Adverse drug reactions , mostly of mild intensity , were reported in 42 % of trazodone-treated patients ( mainly of the nervous system ) and 43 % of sertraline-treated patients ( mainly gastrointestinal ) . One event was considered to be serious : a patient treated with trazodone 450 mg/day showed moderate anxiety/tremor/insomnia and was hospitalized . Treatment was discontinued ; the patient made a full recovery . Conclusions : This study showed that after 6 weeks , trazodone and sertraline were not different in reducing symptoms of depression and in producing disease remission . Tolerability profiles reflected the differing pharmacological properties of these antidepressants . Trazodone may be a therapeutic option in the treatment of patients with major depression showing prevalent sleep disturbances We report results from a multicenter , placebo-controlled , r and omized , double-blind comparison of the efficacy and tolerability of paroxetine and fluoxetine in out patients with major depression . Across five U.S. sites , 128 out patients ( mean age : 41.3 + /- 12.6 ; 63 men and 65 women ) with moderate to moderately severe major depression without a history of mania or hypomania were recruited between 1993 and 1994 . All 128 patients completed a 1-week placebo washout period , and were then r and omized to 12 weeks of double-blind treatment with paroxetine up to 50 mg/day ( n = 55 ) , fluoxetine up to 80 mg/day ( n = 54 ) , or placebo ( n = 19 ) . Subjects were evaluated weekly for the first 4 weeks , then at weeks 6 , 9 , and 12 with the 21-item HAMD and the Covi Anxiety Scale . There were no significant differences among the three treatment groups in baseline and endpoint depression and anxiety severity , as well as in the degree of depression and anxiety improvement . There were no statistically significant differences in rates or mean numbers of adverse events between paroxetine-treated patients and fluoxetine-treated patients . In summary , our results , although limited by the lack of a significant difference from placebo in treatment outcome , suggest that the SSRIs paroxetine and fluoxetine have comparable antidepressant and antianxiety efficacies among depressed out patients , as well as similar safety and tolerability profiles OBJECTIVE Fluoxetine has been associated with weight loss during acute treatment , but no controlled studies of weight change during long-term treatment with fluoxetine or other selective serotonin reuptake inhibitors have been reported . Weights were assessed for patients whose depressive symptoms had disappeared with acute fluoxetine treatment . Patients were then r and omly assigned to continuation treatment with fluoxetine or placebo . METHOD Patients whose illness had remitted after 12 weeks of treatment with fluoxetine , 20 mg/day , were r and omly assigned to receive up to 38 weeks of treatment with fluoxetine or placebo . Weight was assessed at each visit . Change in weight was analyzed during the initial 12 weeks of acute treatment and after 14 , 26 , and 38 weeks . Relationships between weight change and body mass index and between weight change and appetite change were assessed . RESULTS During the initial 4 weeks of therapy , a mean absolute weight decrease of 0.4 kg was observed for all patients . Among patients who completed 50 weeks of therapy , the mean absolute weight increase during continuation treatment was similar for both the placebo- and fluoxetine-treated groups . Weight increase was not related to initial body mass index but was related to both poor appetite at study entry and to improvement in appetite after recovery . No patients discontinued therapy because of weight gain . CONCLUSIONS Acute therapy with fluoxetine is associated with modest weight loss . After remission of depressive symptoms , weight gain for patients taking fluoxetine for longer periods is not different from that for patients taking placebo and is most likely related to recovery from depression BACKGROUND Citalopram , the most selective serotonin reuptake inhibitor ( SSRI ) , is a bicyclic phthalane derivative with a chemical structure that is unrelated to that of other SSRIs and available antidepressants . The drug is approved for use in 69 countries . This 6-week , fixed-dose , placebo-controlled , parallel-arm , multicenter trial was performed to confirm its efficacy and safety in treatment of out patients with major depression in the United States . METHOD Six hundred and fifty adult out patients with moderate-to-severe major depression ( DSM-III-R ) were r and omly assigned to receive citalopram at doses of 10 mg ( N = 131 ) , 20 mg ( N = 130 ) , 40 mg ( N = 131 ) , or 60 mg ( N = 129 ) or placebo ( N = 129 ) once daily . Outcome assessment s were the 21-item Hamilton Rating Scale for Depression ( HAM-D ) , the Montgomery-Asberg Depression Rating Scale ( MADRS ) , and the Clinical Global Impressions scale . RESULTS Between-group comparisons of the change from baseline to endpoint revealed significantly greater improvement in the citalopram patients relative to the placebo patients on all 3 efficacy measures . Patients r and omly assigned to 40 mg/day and 60 mg/day of citalopram showed significantly greater improvement than placebo on all efficacy measures , as well as on the HAM-D symptom clusters measuring depressed mood , melancholia , cognitive disturbance , and psychomotor retardation . Patients who received 10 mg/day and 20 mg/day of citalopram also showed consistent improvement relative to placebo on all efficacy ratings , with statistical significance demonstrated in the MADRS response rate , the HAM-D depressed mood item , and the HAM-D melancholia subscale . Citalopram was well tolerated , with only 15 % of patients discontinuing for adverse events . The side effects most commonly associated with citalopram treatment were nausea , dry mouth , somnolence , insomnia , and increased sweating . CONCLUSION Citalopram was significantly more effective than placebo in the treatment of moderate-to-severe major depression , especially symptoms of depressed mood and melancholia , with particularly robust effects shown at doses of 40 and 60 mg/day . Citalopram was well tolerated in spite of forced upward titration to fixed-dose levels , with a low incidence of anxiety , agitation , and nervousness BACKGROUND Poststroke depression is a frequent condition and important to treat . The aim of this trial was to study the efficacy and tolerability of sertraline . METHOD In 4 Swedish stroke centers , 123 patients ( aged 70.7 + /- 9.9 years ) were enrolled during the period September 1998 to January 2001 in a r and omized , double-blind , placebo-controlled 26-week trial , at a mean of 128 + /- 97 days ( range , 3 - 375 days ) after stroke , if they fulfilled DSM-IV criteria of major depressive episode ( N = 76 ) or minor depressive disorder ( N = 47 ) . The primary efficacy variable was a change in depression assessed by the Montgomery-Asberg Depression Rating Scale . The Emotional Distress Scale ( EDS ) was administered and the occurrence of emotionalism and quality of life ( QoL ) were assessed , as well as neurologic recovery . Efficacy analyses were intention-to-treat , short-term ( week 6 ) and long-term ( week 26 ) . RESULTS Of the 123 patients , 62 were treated with sertraline ( 50 - 100 mg/day ) and 61 with placebo . Both groups improved substantially , with no differences between the treatments , either for major depressive episode or minor depressive disorder , or for short- or long-term antidepressant effect and neurologic outcome . EDS revealed a better outcome with sertraline at week 6 ( p < .05 ) . At week 26 , the improvement in QoL was better in sertraline patients ( p < .05 ) and there was a trend for emotionalism ( p = .07 ) . No serious side effects were seen . CONCLUSION Poststroke depression as measured by a conventional depression rating scale improved over time irrespective of treatment . Positive effects specific to sertraline were identified in emotional distress , emotionalism , and QoL. The study indicates that poststroke emotional reactions comprise depression and other domains susceptible to pharmacologic therapy The aim of this multicenter , r and omized , double-blind , 8-week study was to compare the antidepressant efficacy and tolerability of mirtazapine and venlafaxine in the treatment of hospitalized patients with DSM-IV diagnosis of severe depressive episode with melancholic features . Patients with a baseline score of ≥ 25 on the 17-item Hamilton Rating Scale for Depression ( HAM-D-17 ) were r and omly assigned to receive treatment with either mirtazapine ( N = 78 , 15–60 mg/day ) or venlafaxine ( N = 79 , 75–375 mg/day , twice a day ) in a rapid up-titration schedule . Efficacy was assessed with the Montgomery-Åsberg Depression Rating Scale ( MADRS ) , HAM-D-17 , and Clinical Global Impression scale , and quality of life was assessed with the Quality of Life , Enjoyment , and Satisfaction Question naire and Quality of Life in Depression Scale . Tolerability was assessed with the Utvalg for Kliniske Undersogelser ( UKU ) side effect scale and by reporting adverse events . Both drugs were effective in reducing overall symptoms of depression , showing substantial reductions in group mean MADRS scores ( −20.1 for mirtazapine and −17.5 for venlafaxine ) and HAM-D-17 scores ( −17.1 for mirtazapine and −14.6 for venlafaxine ) at the end of the treatment . Although not statistically significant , at all assessment times higher percentages of patients treated with mirtazapine were classified as responders ( ≥50 % reduction ) on the HAM-D ( at endpoint , 62 % vs. 52 % ) and MADRS ( at endpoint : 64 % vs. 58 % ) . Likewise were the percentages of remitters ( HAM-D score ≤7 ; MADRS score ≤12 ) also higher in the mirtazapine group . A statistically significant difference favoring mirtazapine was found on the HAM-D Sleep Disturbance factor at all assessment points ( p ≤ 0.03 ) . Both treatments were well tolerated . Although slightly more subjects treated with mirtazapine reported at least one adverse event , a statistically significantly higher percentage of patients treated with venlafaxine ( 15.3 % ) than mirtazapine ( 5.1 % ) dropped out because of adverse events ( p = 0.037 ) . Quality of life improved in both treatment groups . In this study , treatment with mirtazapine result ed in a trend toward more responders and remitters than treatment with venlafaxine and in significantly fewer dropouts as a result of adverse events 90 patients between 18 and 65 years , with a DSM-III diagnosis of moderate or severe major depressive episode , were r and omized to 6 weeks of treatment with Org 3770 or placebo in a double-blind trial . On main efficacy parameters , the 17-item HAMD , MADRS and CGI , Org 3770 was significantly superior to placebo ( P < or = 0.05 ) in weeks 1 - 4 and at endpoint and recommended as continuation treatment to significantly more patients . The tolerability of Org 3770 was good : the only significant differences as compared with placebo were in the incidences of somnolence and increased appetite . The results show that Org 3770 is an effective and well-tolerated drug for the treatment of major depressive disorder In a double-blind study in a primary -care setting in France , out patients fulfilling DSM IV criteria for a major depressive episode were r and omised to receive sertraline ( 50 to 150 mg/day ; n = 122 ) or fluoxetine ( 20 to 60 mg/day ; n = 120 ) . Assessment s , including clinical evaluation [ Montgomery-Asberg Depression Rating Scale ( MADRS ) , Clinical Global Impressions ( CGI ) ] and quality of life [ Functional Status Question naire ( FSQ ) ] , were made at study entry and after 4 and 6 months of treatment . Use of medical services , absences from work and productivity losses were recorded for calculation of direct and indirect costs from both the overall societal perspective and in terms of sickness insurance . In total , 231 patients ( 116 receiving sertraline , 115 receiving fluoxetine ) were included in an intention-to-treat analysis assessed up to the last visit . Statistically significant clinical and quality -of-life improvements from baseline were observed in both treatment groups , with no between-group differences . Utilisation of medical re sources was higher in fluoxetine-treated patients , with significantly more consultations with specialists . The 2 treatment groups were similar in terms of number of hospitalisations and duration of stay , whether related to depression or not . There were no significant differences between groups for work or productivity losses . Cost comparisons favoured sertraline treatment from both the societal ( FF7780 vs FF8706 ) and sickness insurance ( FF2936 vs FF3224 ) viewpoints , with cost differentials of FF926 and FF288 , respectively . From the societal perspective , the total cost per patient over the 6-month course of the trial , irrespective of the study treatment given , was FF8241 , and the corresponding sickness insurance cost was FF3079 . At the time of the study , FF1 = $ US0.1993 BACKGROUND Elderly patients with major depression , including those having a first episode , are at high risk for recurrence of depression , disability , and death . METHODS We tested the efficacy of maintenance paroxetine and monthly interpersonal psychotherapy in patients 70 years of age or older who had depression ( 55 percent of whom were having a first episode ) in a 2-by-2 , r and omized , double-blind , placebo-controlled trial . Among patients with a response to treatment with paroxetine and psychotherapy , 116 were r and omly assigned to one of four maintenance-treatment programs ( either paroxetine or placebo combined with either monthly psychotherapy or clinical -management sessions ) for two years or until the recurrence of major depression . Clinical -management sessions , conducted by the same nurses , social workers , and psychologists who provided psychotherapy , involved discussion of symptoms . RESULTS Major depression recurred within two years in 35 percent of the patients receiving paroxetine and psychotherapy , 37 percent of those receiving paroxetine and clinical -management sessions , 68 percent of those receiving placebo and psychotherapy , and 58 percent of those receiving placebo and clinical -management sessions ( P=0.02 ) . After adjustment for the effect of psychotherapy , the relative risk of recurrence among those receiving placebo was 2.4 times ( 95 percent confidence interval , 1.4 to 4.2 ) that among those receiving paroxetine . The number of patients needed to be treated with paroxetine to prevent one recurrence was 4 ( 95 percent confidence interval , 2.3 to 10.9 ) . Patients with fewer and less severe coexisting medical conditions ( such as hypertension or cardiac disease ) received greater benefit from paroxetine ( P=0.03 for the interaction between treatment with paroxetine and baseline severity of medical illness ) . CONCLUSIONS Patients 70 years of age or older with major depression who had a response to initial treatment with paroxetine and psychotherapy were less likely to have recurrent depression if they received two years of maintenance therapy with paroxetine . Monthly maintenance psychotherapy did not prevent recurrent depression . ( Clinical Trials.gov number , NCT00178100 . ) & NA ; A 24‐week , double‐blind , r and omized trial was performed to compare the efficacy and tolerability of venlafaxine and paroxetine in patients with major depression or dysthymia . Out patients aged 18‐70 years with a baseline score of 17 on the 21‐item Hamilton Depression Rating Scale ( HAM‐D ) were eligible . Patients were r and omly assigned to venlafaxine , 37.5 mg , in the morning and evening or paroxetine , 20 mg , in the morning and placebo in the evening , which could be increased to venlafaxine , 75 mg twice daily , or paroxetine , 20 mg twice daily , after 4 weeks . Efficacy was assessed with the 21‐item HAM‐D , the Montgomery‐Asberg Rating Scale , the Hamilton Anxiety Rating Scale , and the Clinical Global Impressions Scale . Forty‐one patients were r and omized to venlafaxine and 43 to paroxetine . At week 6 , a response was observed in 55 % of patients on venlafaxine and 29 % on paroxetine ( P = 0.03 ) . At week 12 , significantly ( P = 0.011 ) more patients in the venlafaxine group had a HAM‐D remission score of 8 or less ( 59 % versus 31 % ) . Discontinuation for any reason occurred in 16 ( 39 % ) patients on venlafaxine and 11 ( 26 % ) on paroxetine . The most common adverse events were nausea ( 28 % ) , headache ( 18 % ) and dry mouth ( 15 % ) with venlafaxine and headache ( 40 % ) and constipation ( 16 % ) with paroxetine . Venlafaxine was effective and well tolerated for the treatment of patients with mild to moderate depression or dysthymia . A consistently higher proportion of patients had a response or remission on venlafaxine than on paroxetine Depression in the geriatric population is a frequent , serious , and potentially reversible disorder , yet relatively few blinded , controlled , antidepressant trials have been reported . A number of age related issues complicate safe and effective pharmacotherapy . In a 6-week , double-blind trial in moderately to severely depressed ( nonpsychotic ) out patients over age 60 , fluoxetine ( N = 335 ) was statistically significantly more efficacious than placebo ( N = 336 ) in overall response ( 43.9 % vs. 31.6 % , p = .002 ) and remission ( 31.6 % vs. 18.6 % , p < .001 ) rates . Analyses of early discontinuations because of an adverse drug event revealed no statistically significantly greater rate with fluoxetine ( n = 39 ; 11.6 ) than was seen with placebo ( n = 29 ; 8.6 % ) . These results corroborate that major depression in an older population is responsive to antidepressant pharmacotherapy . Specifically , fluoxetine , at a conventional 20-mg dose , was both safe and effective relative to placebo in this special population BACKGROUND Nefazodone hydrochloride , an antidepressant that acts as a 5-HT2 antagonist and serotonin ( 5-HT ) and norepinephrine uptake inhibitor , was evaluated in a double-blind , imipramine- and placebo-controlled study involving 128 patients with major depression . METHOD Eligible patients were r and omly assigned to receive placebo ( 2 to 6 capsules/day ) , imipramine ( 100 to 300 mg/day ) , or nefazodone ( 200 to 600 mg/day ) for 8 weeks . The principal efficacy outcome measure assessed was the number of patients who experienced an adequate response during treatment . RESULTS Based on global improvement ( Clinical Global Impressions-Improvement ) , 67 % of nefazodone-treated patients ( p < or = .01 ) and 63 % of imipramine-treated patients ( p < or = .05 ) responded during 8 weeks of treatment , compared with 36 % of placebo controls . Sixty-two percent of nefazodone-treated , 53 % of imipramine-treated , and 26 % of placebo-treated patients had 17-item Hamilton Rating Scale for Depression ( HAM-D-17 ) scores < or = 10 on completion of acute treatment . Nefazodone-treated patients had a lower incidence of premature treatment discontinuation and fewer dropouts for adverse events than the imipramine group . CONCLUSION In a three arm comparison with imipramine and placebo , nefazodone had the greatest number of patients with major depression who responded to therapy . Nefazodone , a new antidepressant with novel pharmacology , is a well-tolerated , efficacious antidepressant This 12-week , double-blind , placebo-controlled study evaluated the efficacy and safety of venlafaxine as first-line therapy for the treatment of major depression and major depression associated with anxiety in 384 adult out patients . Fixed total daily dosages of 75 , 150 , and 200 mg of venlafaxine were administered in a twice-a-day regimen . Primary efficacy parameters were the Hamilton Rating Scale for Depression ( HAM-D ) total score , the HAM-D Depressed Mood Item , the Montgomery-Asberg Depression Rating Scale total score , and the Clinical Global Impressions Scale . Overall , a higher percentage of patients responded to venlafaxine than to placebo . Efficacy data indicated a dose-related response , most evident in the onset of clinical improvement ; statistically significant improvements in some primary parameters were seen as early as 1 to 2 weeks after initiation of treatment , especially in the 150- and 200-mg/day groups . These dose-related clinical improvements continued through week 12 . Venlafaxine-treated patients who had depression associated with anxiety showed significant dose-related improvements compared with placebo-treated patients ; improvement was noted by scores on the HAM-D Anxiety-Psychic Item and Anxiety-Somatization Factor . Few clinical ly significant changes were observed in laboratory values , vital signs , or electrocardiogram tracings . Venlafaxine was generally well tolerated at all dosages . The most common study events included nausea , dizziness , somnolence , insomnia , dry mouth , and asthenia , which are consistent with findings of previous studies . The current study demonstrated that 75 to 200 mg/day of venlafaxine twice daily produced a dose-related improvement in the primary efficacy parameters and in the onset of significant antidepressant effects , which was noted at weeks 1 to 2 with the highest dosage tested ( 200 mg/day ) . The study also demonstrated that these dosages of venlafaxine were safe and effective as first-line therapy for major depression and depression associated with anxiety BACKGROUND The objectives of the study were to compare efficacy and tolerability of venlafaxine ER 75 - 150 mg/day with that of citalopram 10 - 20 mg/day in elderly patients with major depression according to DSM-IV criteria . METHODS A r and omised , double-blind , parallel group 6-month study . Efficacy was assessed by MADRS , CGI Global Improvement , CGI Severity of Illness and GDS-20 scores and safety by physical examinations , vital signs , adverse events and UKU side effect rating . Plasma levels of venlafaxine , its major metabolite O-desmethylvenlafaxine and citalopram were followed . RESULTS One hundred and fifty-one male and female patients ( 64 - 89 years ) were enrolled and 118 patients completed the study . Comparable improvements in MADRS , CGI Severity of Illness , CGI Global Improvement and GDS-20 were observed during venlafaxine and citalopram treatment . The MADRS remission rate was 19 % for venlafaxine and 23 % for citalopram . Side effects were common during both treatments but differed in tremor being more common during citalopram and nausea/vomiting during venlafaxine treatment . There were no clinical ly significant changes in blood pressure or body weight . CONCLUSION The observed benefits of venlafaxine treatment in elderly patients with major depression were similar to those observed in younger adults as were reported adverse events and side effects . Treatment with venlafaxine ER was well tolerated and induced beneficial effects of similar magnitude as those of citalopram BACKGROUND Maintenance treatment to prevent recurrences is recommended for chronic forms of major depressive disorder ( MDD ) , but few studies have examined maintenance efficacy of antidepressants with chronic MDD . This r and omized , placebo-controlled study of the efficacy and safety of nefazodone in preventing recurrence was conducted for patients with chronic MDD . METHODS A total of 165 out patients with chronic , nonpsychotic MDD , MDD plus dysthymic disorder ( " double-depression " ) , or recurrent MDD with incomplete inter-episode recovery , who achieved and maintained a clinical response during acute and continuation treatment with either nefazodone alone or nefazodone combined with psychotherapy , were r and omized to 52 weeks of double-blind nefazodone ( maximum dose 600 mg/day ) or placebo . The occurrence of major depressive episodes during maintenance treatment was assessed with the 24-item Hamilton Rating Scale for Depression , a DSM-IV MDD checklist , and a blinded review of symptom exacerbations by a consensus committee of research clinicians . RESULTS Application of a competing-risk model that estimated the conditional probability of recurrence among those patients remaining on active therapy revealed a significant ( p = .043 ) difference between nefazodone ( n = 76 ) and placebo ( n = 74 ) when the latter part of the 1-year maintenance period was emphasized . At the end of 1 year , the conditional probability of recurrence was 30.3 % for nefazodone-treated patients , compared with 47.5 % for placebo-treated patients . Prior concomitant psychotherapy during acute/continuation treatment , although enhancing the initial response , was not associated with lower recurrence rates . Discontinuations due to adverse events were relatively low for both nefazodone ( 5.3 % ) and placebo ( 4.8 % ) . Somnolence was significantly greater among the patients taking active medication ( 15.4 % ) , compared with placebo ( 4.6 % ) . CONCLUSIONS Nefazodone is well-tolerated and is an effective maintenance therapy for chronic forms of MDD BACKGROUND The efficacy and safety of fluoxetine ( N = 65 ; median sustained dose , 20 mg/day ) and of trazodone ( N = 61 ; median sustained dose , 250 mg/day ) were compared in a trial in out patients with major depressive episode . The incidence and temporal patterns of activation and sedation were also assessed . METHOD Men and women who met DSM-III criteria for nonpsychotic major depressive episode ( but with a current episode greater than or equal to 4 weeks ) and had a 21-item Hamilton Rating Scale for Depression ( HAM-D21 ) score greater than 20 were selected . After single-blind placebo was administered for 1 week , eligible patients were r and omized to double-blind fluoxetine or trazodone treatment for up to 6 weeks . Efficacy ( HAM-D21 , Clinical Global Impressions Scales for Severity and Improvement , Patient Global Impressions Scale for Improvement , Guild Memory Test ) and adverse events were evaluated weekly . RESULTS The HAM-D21 score improved within both treatment groups ( p less than .001 ) . The groups were similar with respect to endpoint mean HAM-D21 improvement . For individual adverse events that developed or worsened during therapy , more fluoxetine-treated patients reported rhinitis and tremor ( p less than or equal to .05 ) , while more trazodone-treated patients reported somnolence and dizziness ( p less than or equal to .05 ) . More combined events suggesting activation ( agitation , anxiety , nervousness , insomnia ) were reported with fluoxetine than with trazodone ( 15.4 % vs. 3.3 % , p less than or equal to .05 ) , while more combined events suggesting sedation ( somnolence , asthenia ) were reported with trazodone than with fluoxetine ( 42.6 % vs. 21.5 % , p less than or equal to .05 ) . Discontinuation rates for activation and sedation did not differ between treatments . Numerically , more sedation ( 21.5 % ) than activation ( 15.4 % ) was reported with fluoxetine . CONCLUSIONS There was little clinical difference between treatments with regard to efficacy and safety . The occurrence and temporal patterns of activation and sedation differed within and between treatments BACKGROUND Escitalopram is the single isomer responsible for the serotonin reuptake inhibition produced by the racemic antidepressant citalopram . The present r and omized , double-blind , placebo-controlled , fixed-dose multicenter trial was design ed to evaluate the efficacy and tolerability of escitalopram in the treatment of major depressive disorder . METHOD Out patients with an ongoing DSM-IV major depressive episode ( N = 491 ) were r and omly assigned to placebo , escitalopram , 10 mg/day , escitalopram , 20 mg/day , or citalopram , 40 mg/day , and entered an 8-week double-blind treatment period following a 1-week single-blind placebo lead-in . Clinical response was evaluated by the Montgomery-Asberg Depression Rating Scale ( MADRS ) , the 24-item Hamilton Rating Scale for Depression ( HAM-D ) , the Clinical Global Impressions ( CGI ) scales , the Hamilton Rating Scale for Anxiety ( HAM-A ) , and patient-rated quality -of-life scales . RESULTS Escitalopram , at both doses , produced significant improvement at study endpoint relative to placebo on all measures of depression ; significant separation of escitalopram from placebo was observed within I week of double-blind treatment . Citalopram treatment also significantly improved depressive symptomatology compared with placebo ; however , escitalopram , 10 mg/day , was at least as effective as citalopram , 40 mg/day , at endpoint . Anxiety symptoms and quality of life were also significantly improved by escitalopram compared with placebo . The incidence of discontinuations due to adverse events for the escitalopram 10 mg/day group was not different from the placebo group ( 4.2 % vs. 2.5 % ; p = .50 ) , and not different for the escitalopram 20 mg/day group and the citalopram 40 mg/day group ( 10.4 % vs. 8.8 % ; p = .83 ) . CONCLUSION Escitalopram , a single isomer SSRI , is well-tolerated and has demonstrated antidepressant efficacy at a dose of 10 mg/day BACKGROUND The selective serotonin reuptake inhibitor sertraline has been shown to be efficacious and well tolerated for the treatment of major depressive disorder . Relatively few trials , however , have examined the role of pharmacotherapy in dysthymia without concurrent major depression . The current investigation focuses on the use of sertraline for the treatment of dysthymia . METHOD In this 12-week , multicenter , double-blind study , 310 patients with a DSM-III-R diagnosis of dysthymic disorder without concurrent major depression were r and omly assigned to receive either sertraline ( N = 158 ) or placebo ( N = 152 ) . Sertraline was initiated at a dose of 50 mg daily , with titration permitted to a maximum of 200 mg daily . The primary evaluation criteria were the Structured Interview Guide for the Hamilton Depression Rating Scale , Seasonal Affective Disorder Version ( SIGH-SAD ) , the Montgomery-Asberg Depression Rating Scale ( MADRS ) , and the Clinical Global Impressions-Severity of Illness ( CGI-S ) and -Improvement ( CGI-I ) scales . RESULTS Mean percentage reductions for the intent-to-treat population in SIGH-SAD scores were 44.6 % for the sertraline-treated group and 33.2 % for the placebo-treated group ( p = .03 ) ; MADRS scores , 43.6 % and 33.0 % ( p = .02 ) ; and CGI-S scores , 32.8 % and 22.8 % ( p = .02 ) . A significantly greater proportion of the sertraline-treated group was classified as responders ( defined for HAM-D and MADRS scores as a 50 % score reduction and for CGI-I as a score of 1 or 2 by the final visit ) and remitters ( SIGH-SAD score < or = 8) relative to the placebo-treated group by the final visit . In addition , sertraline-treated patients experienced greater improvements in all 9 domains of the Battelle Quality of Life Question naire than placebo-treated patients did , with a significant difference observed in favor of sertraline in 8 of the 9 domains . The life satisfaction and social interaction quality of life domains showed significantly greater response in sertraline responders compared with placebo SIGH-SAD responders . Sertraline was well tolerated . Thirteen percent of the sertraline-treated group versus 8 % of the placebo-treated group withdrew from therapy owing to adverse events ( p = .14 ) . CONCLUSION Sertraline is efficacious and well tolerated in the short-term treatment of dysthymia without concurrent major depression An eight-week double-blind , multicentre study was performed to evaluate the efficacy and safety of sertraline vs. fluoxetine in the treatment of major depression ( DSM-III-R ) . There were 108 out- patients , from nine Italian centres , entered into the study , of whom 88 were evaluable ( 48 sertraline , 40 fluoxetine ) . The final mean daily dose of sertraline was 72 mg and for fluoxetine it was 28 mg . Both treatment groups showed a statistically significant improvement from baseline at one week , and this was maintained until the end of treatment for all of the following measures : Hamilton Rating Scales for Depression and Anxiety , the Montgomery Asberg Depression Rating Scale , Clinical Global Impressions Scale , Zung Self-Rating Scale for Anxiety and the Leeds Sleep Evaluation Question naire . Although there was a numerical advantage for sertraline on several efficacy measures , there was no statistically significant difference found between the treatment groups . The incidence of adverse events was similar for both treatments ; 40.4 % for sertraline and 39.3 % for fluoxetine . However , adverse events were generally rated by patients as of lower severity in the sertraline group . In addition , for the fluoxetine group , there was a higher incidence of agitation , anxiety and insomnia than for sertraline . Sertraline was considered to be better tolerated than fluoxetine overall , since only 9.6 % of sertraline-treated patients discontinued treatment due to therapy failure whereas in the fluoxetine-treated group this figure was 19.6 % . By contrast , 13.5 % of sertraline-treated patients discontinued prematurely because of clinical improvement , compared with 10.7 % of fluoxetine-treated patients A 6-week , double-blind , parallel group study compared the efficacy and tolerability of paroxetine and fluoxetine in 106 depressed geriatric out patients ( age , ≥65 years ) . Patients with an acute major depressive episode were r and omized to receive either paroxetine ( 20 to 40 mg ; N = 54 ) or fluoxetine ( 20 to 60 mg ; N = 52 ) after a 3− to 7-day washout . Efficacy evaluations at weeks 1 , 3 , and 6 used the 21-item Hamilton Rating Scale for Depression ( HAM-D ) . Cognitive function was assessed by use of the Mini-Mental State Examination ( MMSE ) and the S and oz Clinical Assessment Geriatric Scale ( SCAG ) . Tolerability was assessed by response to a nonleading question concerning adverse events . There were no significant differences between treatments at week 6 on the HAMD total , change from baseline . However , there was a statistically significant difference ( p < 0.05 ) at week 3 in favor of paroxetine . Results from the MMSE and SCAG showed that , during treatment , patients in the paroxetine group were characterized by greater improvement in cognitive function than were those in the fluoxetine group . This result was statistically significant at week 3 for both scales ( p < 0.05 ) . Adverse events occurred most frequently within the gastrointestinal and nervous systems for both drugs , with no significant differences between treatments BACKGROUND This study was undertaken to compare the efficacy and safety of bupropion and fluoxetine . METHOD Moderately to severely depressed out patients who fulfilled the DSM-III-R criteria for nonpsychotic major depressive disorder and had a score of 20 or more on the Hamilton Rating Scale for Depression ( 21 item ) participated in this two-center study . Following a 1-week placebo phase , patients were r and omly assigned to receive either bupropion or fluoxetine for 6 weeks of double-blind treatment . Weekly efficacy assessment s included Hamilton Rating Scale for Depression , Hamilton Rating Scale for Anxiety , Clinical Global Impressions-Severity , and Clinical Global Impressions-Improvement . Vital signs and adverse experiences were also assessed weekly . RESULTS A total of 61 patients were r and omly assigned to receive bupropion ( 225 - 450 mg/day ) and 62 were r and omly assigned to receive fluoxetine ( 20 - 80 mg/day ) . The mean daily dose at the end of the study was 382 mg/day for the bupropion treatment group and 38 mg/day for the fluoxetine treatment group . There were no statistically significant differences between treatments on any of the efficacy variables . On the basis of a 50 % or greater reduction in the HAM-D scores , 63 % ( N = 37 ) of the bupropion-treated and 58 % ( N = 35 ) of the fluoxetine-treated patients were categorized as responders , and on the basis of CGI scores , 68 % ( N = 40 ) of the bupropion-treated and 58 % ( N = 35 ) of the fluoxetine-treated patients were rated as much or very much improved . HAM-A scores decreased by 59 % for both treatment groups . The incidence of treatment-emergent adverse events was low with no statistically significant differences between treatments . Twenty-six percent ( N = 16 ) of the bupropion-treated and 29 % ( N = 18 ) of the fluoxetine-treated patients prematurely discontinued treatment . CONCLUSION Both bupropion and fluoxetine demonstrated similar efficacy in relieving depression and accompanying symptoms of anxiety , and both exhibited a similar , favorable safety profile BACKGROUND Despite the high prevalence of depression in elderly patients , few well- design ed , placebo-controlled studies of antidepressants have been conducted in this population . This masked , placebo-controlled trial assessed the efficacy and safety of venlafaxine and fluoxetine in depressed patients older than 65 years . METHOD Three hundred patients were r and omly assigned to treatment with venlafaxine immediate release ( [ IR ] ; N = 104 ) , fluoxetine ( N = 100 ) , or placebo ( N = 96 ) in an eight-week trial . Venlafaxine doses were titrated from 37.5 to 225 mg per day and fluoxetine doses were titrated from 20 to 60 mg per day , as necessary , over 29 days . Efficacy variables included the 21-item Hamilton Depression Rating Scale ( HAM-D21 ) total score , HAM-D21 depressed mood item score , scores on the Montgomery Asberg Depression Rating Scale ( MADRS ) , Clinical Global Impression-Severity of Illness ( CGI-S ) and Improvement ( CGI-I ) scales , and rates of response ( based on change from baseline HAM-D or MADRS score or CGI-I score ) and remission ( HAM-D17 < or = 7 ) . For the purpose s of this report , efficacy analyses are focused on the HAM-D21 total score . Safety assessment s included monitoring of adverse events ( AEs ) , physical examinations , vital signs assessment s , laboratory determinations , and electrocardiograms . RESULTS In all three of the treatment groups , there was a significant reduction at week 8 compared with the baseline HAM-D21 total score . However , there were no significant differences among the three treatment groups on the change in HAM-D21 , MADRS , or CGI scores from baseline to week 8 . There was no statistically significant difference in the proportion of remitters at the last on-therapy visit . The incidence of individual AEs was higher in the venlafaxine group ( 27 % ) compared with patients taking fluoxetine ( 19 % ) or placebo ( 9 % ) . CONCLUSION In this study , there was no significant difference in efficacy among placebo , venlafaxine , and fluoxetine for the treatment of depression 1 . This was a r and omized , double-blind comparison of the efficacy and safety of venlafaxine and fluoxetine in out patients with major depression . 2 . Three hundred fourteen patients were r and omly assigned to either venlafaxine 37.5 mg twice daily or fluoxetine 20 mg once daily for a maximum of 8 weeks . 3 . If the response was inadequate after two weeks of treatment , the dosage of venlafaxine could be increased to 75 mg twice daily . 4 . A clinical response , defined as at least a 50 % decrease from baseline in the total HAM-D score , was attained at week 6 in 72 % of patients on venlafaxine and 60 % of patients on fluoxetine ( p = 0.023 ) . 5 . Among patients who increased their dose at 2 weeks , venlafaxine was significantly ( p < 0.05 ) superior from week 3 onward on the HAM-D. 6 . Venlafaxine 75 mg daily is comparable to fluoxetine , but at 150 mg daily , it may be superior to fluoxetine in out patients with major depression who do not respond early to treatment OBJECTIVE To compare the emergent sexual effects of moclobemide and selective serotonin reuptake inhibitors ( SSRIs ) during acute and maintenance therapy in routine practice . METHOD 268 patients were evaluated for sexual function at baseline , 6 weeks , 3 and 6 months of treatment using physician ratings and self-rating question naires . Patients received moclobemide , an reversible monoamine oxidase A inhibitor ( RIMA ) , or a SSRI ( fluoxetine , fluvoxamine , paroxetine , sertraline ) . RESULTS Baseline values were similar in all groups . Incidences of impairments of sexual functioning with treatment , whether clinical ly relevant or not , were 24.3 % with moclobemide and 61.5 % with SSRIs ( physician ratings ) , with no significant tolerance to these effects . There was a suggestion of differences between the SSRIs in their specific dysfunctions they cause . SSRIs ( 21.6 % of patients ) had about ten times the moclobemide rate ( 1.9 % ) of sexual dysfunction reported as adverse events . Antidepressant efficacy was comparable between treatments . CONCLUSION In patients for whom sexual function is important or sexual dysfunction is present , moclobemide should be considered a first line antidepressant BACKGROUND Depression is the second most common neuropsychiatric disorder in older Americans , with significant clinical and public health costs . Despite advances in treatment , late-life depression remains a clinical challenge . Although the selective serotonin reuptake inhibitors ( SSRIs ) are the most common pharmacologic intervention for late-life depression , few placebo-controlled trials have assessed the efficacy of SSRIs for this condition . METHOD In this 12-week , multicenter , placebo-controlled , flexible-dose , double-blind , r and omized trial , 319 elderly patients ( mean age = 70 years ) were treated with controlled-release paroxetine ( paroxetine CR ) up to 50 mg/day ( N = 104 ) , immediate-release paroxetine ( paroxetine IR ) up to 40 mg/day ( N = 106 ) , or placebo ( N = 109 ) . Patients met DSM-IV criteria for major depressive disorder and had a total score of 18 or more on the 17-item Hamilton Rating Scale for Depression ( HAM-D ) . The primary efficacy measure was change from baseline to endpoint in HAM-D total score . RESULTS The primary efficacy analysis showed an adjusted difference between change from baseline in HAM-D score for paroxetine CR and placebo of -2.6 ( 95 % confidence interval [ CI ] = -4.47 to -0.73 , p = .007 ) at the week 12 last-observation-carried-forward ( LOCF ) endpoint . The adjusted difference between paroxetine IR and placebo was -2.8 ( 95 % CI = -4.65 to -0.99 , p = .003 ) at week 12 . Paroxetine CR and IR were more effective than placebo , with mean + /- SD endpoint HAM-D total scores of 10.0 + /- 7.41 and 10.0 + /- 7.10 , respectively , for the active treatments compared with 12.6 + /- 7.34 for placebo . Response , defined as a score of 1 or 2 on the Clinical Global Impressions-global improvement scale , was achieved by 72 % of paroxetine CR patients ( LOCF ; p < .002 vs. placebo ) , 65 % of paroxetine IR patients ( p = .06 vs. placebo ) , and 52 % of placebo patients . Remission , defined as a HAM-D total score < or = 7 , was achieved by 43 % of paroxetine CR patients ( LOCF ; p = .009 vs. placebo ) , 44 % of paroxetine IR patients ( p = .01 vs. placebo ) , and 26 % of placebo patients . In a post hoc analysis , mean HAM-D improvement for paroxetine CR and paroxetine IR was greater than for placebo in both chronically depressed patients ( duration > 2 years ) and those with short-term ( < or = 2 years ) depression . Dropout rates due to adverse events were 12.5 % for paroxetine CR , 16.0 % for paroxetine IR , and 8.3 % for placebo . CONCLUSION Paroxetine CR and paroxetine IR are effective and well tolerated treatments for major depressive disorder in elderly patients , including those with chronic depression We prolonged from 24 to 48 months a follow-up study of unipolar subjects with high recurrence rate treated with fluvoxamine ( N=25 ) and sertraline ( N=22 ) . During the two-year additional period a significant risk of recurrences was observed during the third year of follow-up , without differences in the two long-term therapy groups . During the fourth year no patients showed new episodes of illness BACKGROUND Escitalopram is the most selective serotonin reuptake inhibitor ( SRI ) antidepressant available . Venlafaxine is a non-selective SRI that also inhibits noradrenergic re-uptake . This study compared escitalopram and venlafaxine extended release ( XR ) in depressed out patients at the highest doses recommended in the United States . METHOD In this r and omized trial , patients ( diagnosis of DSM-IV-defined major depressive disorder ; baseline Hamilton Rating Scale for Depression score of > /= 20 ) received 1 week of single-blind placebo treatment , followed by 8 weeks of double-blind , fixed-dose treatment with either escitalopram or venlafaxine XR ( rapidly titrated to 20 mg/day and 225 mg/day , respectively , in accordance with prescribing information ) . The primary efficacy variable was change from baseline to week 8 in Montgomery-Asberg Depression Rating Scale ( MADRS ) total score . Data were collected from May to December 2002 . RESULTS Mean baseline MADRS scores for the escitalopram ( N = 97 ) and venlafaxine XR ( N = 98 ) groups were 30.7 and 30.0 , respectively . There were no significant differences in measures of efficacy between the 2 antidepressants . Mean changes from baseline to endpoint in MADRS total score for escitalopram and venlafaxine XR were -15.9 and -13.6 , respectively . Remission ( MADRS score of < /= 10 ) rates at endpoint were 41.2 % for escitalopram and 36.7 % for venlafaxine XR . Response ( > /= 50 % reduction from baseline MADRS score ) rates for the escitalopram and venlafaxine XR groups were 58.8 % and 48.0 % , respectively . Tolerability measures favored escitalopram over venlafaxine XR treatment . The venlafaxine XR group had a higher incidence than the escitalopram group of treatment-emergent adverse events ( 85.0 % vs. 68.4 % ) and discontinuation due to adverse events ( 16.0 % vs. 4.1 % ; p < .01 ) . CONCLUSION Results of this study indicate that , when titrated rapidly to their maximum recommended doses , escitalopram is at least as effective as venlafaxine XR and significantly better tolerated . These results do not support the hypothesis that nonselective SRIs have greater efficacy than selective SRIs A r and omized , double‐blind , parallel‐group , 6‐week study was undertaken to compare the efficacy and tolerability of once or twice daily administration of the selective serotonin reuptake inhibitors paroxetine and fluoxetine . After a 1‐week placebo wash‐out , patients suffering from DSM‐III major depression and with a score of 18 or more on the 21‐item Hamilton Rating Scale for Depression ( HRSD ) received either paroxetine or fluoxetine . The patients were assessed for efficacy using the HRSD , Montgomery‐Åsberg Depression Rating Scale and Clinical Global Impression ; for tolerability , adverse events were elicited by the use of a non‐leading question and a side effects checklist . The groups of patients were comparable on entry to the study . One hundred patients were recruited into the study , of whom 78 were evaluable for the efficacy analysis . Paroxetine and fluoxetine showed comparable efficacy at the end of the 6‐week treatment period , but a statistically significant difference in the number of responders at week 3 in favour of paroxetine was observed . This could suggest an earlier onset of action with paroxetine . Also , associated anxiety symptoms were significantly reduced on paroxetine compared with fluoxetine at week 3 . Patients on paroxetine reported fewer adverse events than those on fluoxetine . The most commonly reported adverse events were nausea and vomiting in both groups PURPOSE To evaluate the safety profile of sertraline versus other Selective Serotonin Reuptake Inhibitors ( SSRIs ) directly following the introduction of sertraline to the Dutch market . METHODS In a prospect i ve follow-up study , 109 psychiatrists included patients with a new episode of treatment with sertraline and an equal number of patients starting treatment with other SSRIs . All Adverse Events ( AEs ) during follow-up were recorded by the psychiatrists for the duration of SSRI treatment until discontinuation or until at least 12 months . RESULTS A total of 1251 patients were included in the study of which 659 used sertraline and 592 used other SSRIs ( paroxetine , fluoxetine or fluvoxamine ) . The most frequently reported events in sertraline users and users of other SSRIs were nausea ( 160 ( 24.3 % ) sertraline patients versus 160 ( 27.0 % ) patients using other SSRIs ) , headache ( 127 ( 19.3 % ) sertraline patients versus 101 ( 17.1 % ) patients using other SSRIs ) , diarrhoea ( 94 ( 14.0 % ) sertraline patients versus 40 patients using other SSRIs ( 6.8 % , p < 0.05 ) ) , sweating ( 88 ( 13.4 % ) sertraline patients versus 69 ( 11.7 % ) patients using other SSRIs ) and dizziness ( 75 ( 11.4 % ) sertraline patients versus 70 ( 11.8 % ) patients using other SSRIs ) . A total of 121 patients reported 134 different unlabelled AEs of which 10 were reported by more than 1 % of the population . CONCLUSIONS In this study we found that almost three out of four patients reported an adverse event . When comparing with other SSRIs and the literature , we found a similar distribution of the most frequently reported adverse events in patients using sertraline . However , in this observational study we found over 100 different unlabelled adverse events The efficacy of duloxetine in the treatment of major depressive disorder in women of approximately perimenopausal age ( 40 - 55 years ; 62 placebo subjects and 55 subjects taking duloxetine , 60 mg/day ) was compared with that observed in cohorts of younger ( < 40 years , 94 placebo subjects and 85 duloxetine subjects ) and older ( > 55 years , 26 placebo subjects and 25 duloxetine subjects ) women . Women ( ages 40 - 55 years ) receiving duloxetine demonstrated significantly greater improvement in total scores on the 17-item Hamilton Rating Scale for Depression compared with placebo at the study endpoint ( week 9 ) . Significant advantages for duloxetine over placebo were observed on 17-item Hamilton depression scale subscales ( core , Maier , anxiety , retardation , and sleep ) , in addition to the Clinical Global Impression severity and Patient Global Impression of Improvement Scale , the Quality of Life in Depression Scale , and Visual Analog Scales assessing pain severity . The magnitude of duloxetine 's treatment effect in women ages 40 - 55 years was similar to that observed in younger ( age < 40 years ) and older ( age > 55 years ) female patients . In the placebo treatment groups , however , mean changes differed substantially by age group with the smallest placebo responses observed in the 40 - 55 age group . Duloxetine ( 60 mg/day ) was demonstrated to be an effective treatment for major depressive disorder in this cohort of women ages 40 - 55 years reuptake inhibitors ( SSRIs ) during continuation therapy . This investigation reports the differential effect of 6 months of treatment with sertraline versus paroxetine for symptoms of depression , quality of life , and personality outcomes . Out patients with unipolar major depression ( DSM-III-R ) were r and omly assigned to receive 24 weeks of double-blind treatment with flexible doses of paroxetine ( 20 - 40 mg ) or sertraline ( 50 - 150 mg ) . Assessment s included the Montgomery-Asberg Depression Rating Scale ( MADRS ) , the Clinical Global Impression Scale , the Battelle Quality of Life Question naire , and the Structured Clinical Interview for DSM-III-R Personality Disorders screen question naire . One hundred seventy-six patients ( mean age , 43 years ; 64 % female ; baseline MADRS , 30.3 ) were treated with sertraline and 177 patients ( mean age , 42 years ; 71 % female ; MADRS , 30.7 ) with paroxetine . Antidepressant efficacy during continuation therapy was sustained , with only 2 % of patients receiving sertraline and 9 % of patients receiving paroxetine suffering a relapse . Continuation therapy result ed in a substantial conversion of responders during short-term treatment to full remission : remitter rates increased from 52 % to 80 % for sertraline and from 57 % to 74 % for paroxetine . The improvements in quality of life were related to a reduced depression score . SSRI treatment had significant beneficial effects on both categorical and dimensional measures of personality . A logistic regression analysis identified early response ( 25 % reduction in MADRS scores at week 2 ) as the most important predictor of treatment response , whereas high severity , chronicity , and poor baseline quality of life had no effect . Both treatments were well-tolerated , with sertraline having a somewhat lower side effect profile . Sertraline and paroxetine demonstrated comparable efficacy during short-term and continuation therapy . Treatment was associated with significant improvement in quality of life and with reductions in axis II personality psychopathology Abrupt interruption or cessation of selective serotonin reuptake inhibitor ( SSRI ) treatment may result in discontinuation or treatment interruption symptoms . Recent reports suggested these symptoms occur more frequently with shorter half-life SSRIs . Previous studies indicated a 5–8-day treatment interruption result ed in fewer discontinuation-emergent adverse events in fluoxetine-treated patients than in paroxetine-treated patients . This study examines the effects of shorter treatment interruption ( 3–5 days ) , as would occur if patients miss just a few doses of medication . Patients successfully treated for depression with fluoxetine or paroxetine underwent treatment interruption in a double-blind fashion . Treatment interruption-emergent symptoms were assessed using the Discontinuation-Emergent Signs and Symptoms checklist . Other assessment s included the Montgomery – Åsberg Depression Rating Scale , Clinical Global Impressions-Severity scale and a social functioning question naire . Of 150 patients enrolled , 141 completed the study . Following treatment interruption , fluoxetine-treated patients experienced fewer treatment interruption-emergent events than did paroxetine-treated patients . The paroxetine treatment group also experienced significant increases in depressive symptoms , clinical global severity scores and difficulty in social functioning ; the fluoxetine treatment group did not . These results are consistent with reports suggesting abrupt interruption of treatment with paroxetine is more often associated with somatic and psychological symptoms than is abrupt interruption of fluoxetine . Patients treated with fluoxetine appeared to be protected by its longer half-life OBJECTIVE The purpose of this study was to determine the effects of antidepressant pharmacotherapy on mood symptoms and psychosocial outcomes in dysthymia . METHOD In a multicenter , double-blind , parallel-group trial , 416 patients with a diagnosis of early-onset primary dysthymia ( DSM-III-R ) of at least 5 years ' duration without concurrent major depression were r and omly assigned to 12 weeks of acute-phase therapy with sertraline , imipramine , or placebo . The psychosocial outcome measures used in the study were the Global Assessment of Functioning Scale , the Social Adjustment Scale , the Longitudinal Interval Follow-up Evaluation psychosocial ratings , and the Quality of Life Enjoyment and Satisfaction Question naire . RESULTS Sertraline and imipramine were significantly better than placebo in improving psychosocial outcomes as measured by the first three instruments . The Quality of Life Enjoyment and Satisfaction Question naire scores demonstrated significant improvements from baseline , and both active treatments produced significantly greater improvements than placebo . Significantly fewer patients discontinued sertraline ( 6.0 % ) than discontinued imipramine ( 18.4 % ) because of adverse events . CONCLUSIONS Pharmacotherapy is an effective treatment for dysthymia in terms of psychosocial functioning as well as depressive symptoms , even when the dysthymia is long-st and ing Sertraline and fluoxetine have different pharmacologic and pharmacokinetic profiles which may be of clinical relevance in the determination of response in different subtypes of depression . A r and omized , double-blind , 6-week study comparing sertraline ( 50 - 100 mg/day ) with fluoxetine ( 20 - 40 mg/day ) in 286 out patients with major depression , who had demonstrated comparable efficacy and tolerability for the two drugs , was analysed by subgroups of patients at baseline with melancholia , severe depression , single depressive episode , multiple depressive episodes , high anxiety , low anxiety , psychomotor retardation and psychomotor agitation . Multiple logistic regression with regressors including treatment-by-subgroup variables revealed that , within certain subgroups , the efficacy might differ substantially from that of the whole treatment group . However , the only treatment-by-subgroup interaction term that was significant was anxiety ( P < 0.05 ) . There was no evidence of interaction in single or recurrent episode subgroups , and these were not included in subsequent analyses . Subsequent two- sample statistical comparison tests of response ( i.e. Hamilton Depression Scale reduction > or = 50 % ) rates at study endpoint between treatment groups demonstrated that patients with melancholic depression and those with symptoms of psychomotor agitation yielded a significantly greater proportion of responders with sertraline compared to fluoxetine ( P < 0.05 ) . Response rates in sertraline- and fluoxetine-treated patients , respectively , were : overall study 59 % , 51 % ; melancholia 59 % , 44 % ; severe depression 59 % , 41 % ; low anxiety 71 % , 55 % ; high anxiety 47 % , 48 % ; psychomotor retardation , 48 % , 46 % ; and psychomotor agitation 62 % , 39 % . Multiple logistic regression adjusting for possible confounding factors , that included a treatment by anxiety interaction term , also led to similar findings . In particular , the analysis showed that significant differences existed in favour of sertraline in patients with low anxiety in the melancholia and severe depression subgroups ( P < 0.05 ) , indicating that these characteristics predicted a superior response to 6 weeks of treatment with sertraline relative to fluoxetine . Sertraline also demonstrated advantages over fluoxetine on parameters such as sleep and weight disturbance in severely depressed patients , and sleep disturbance , weight , cognitive disturbance and retardation in melancholic patients BACKGROUND There are few published placebo-controlled clinical trials demonstrating the efficacy of the newer antidepressants in markedly or severely depressed hospitalized patients . This study demonstrates the efficacy of nefazodone compared with placebo in the treatment of patients hospitalized for major depression . METHOD Nefazodone and placebo treatment were compared in a 6-week trial of 120 patients hospitalized for DSM-III-R diagnosed major depression ( without psychosis ) at 2 study centers . Efficacy was evaluated using st and ard psychiatric rating scales , and patients were monitored for safety . RESULTS Nefazodone treatment result ed in a significant reduction ( p < .01 ) of the 17-item Hamilton Rating Scale for Depression ( HAM-D-17 ) total score compared with placebo from the end of the first treatment week through the end of the study ( -12.2 nefazodone vs. -7.7 placebo ) . At the end of the trial , significantly more nefazodone-treated patients ( 50 % ) than placebo-treated patients ( 29 % ) had responded , as indicated by their Clinical Global Impressions-Improvement score ( p = .021 ) or by a > or = 50 % reduction in their HAM-D-17 scores ( p = .017 ) . Significantly more patients treated with nefazodone ( 36 % ) than placebo-treated patients ( 14 % ) had a HAM-D-17 score < or = 10 at the end of treatment ( p = .004 ) . Significant treatment differences ( p < .01 ) in favor of nefazodone were also seen in the Montgomery-Asberg Depression Rating Scale ; the HAM-D retardation , anxiety , and sleep disturbance factors ; and HAM-D item 1 ( depressed mood ) . Patients with dysthymia in addition to major depression also showed significant improvement ( p < .05 ) when treated with nefazodone , with significant differences in response rates seen as early as week 2 and through the end of the trial . The mean nefazodone dose was 491 mg/day at the end of week 2 and 503 mg/day at the end of treatment . Nefazodone was well tolerated , and the number of patients discontinuing owing to adverse events was small , with no significant safety issues noted in either treatment group . Fewer nefazodone-treated than placebo-treated patients discontinued owing to lack of efficacy . CONCLUSION Nefazodone was superior to placebo in the treatment of marked to severe major depression in patients requiring hospitalization . The clinical benefit of nefazodone was evident as early as the first week of treatment as judged by several measures of efficacy , with significant differences from placebo sustained throughout the trial BACKGROUND A sustained-release formulation of bupropion ( bupropion SR ) , developed with an improved pharmacokinetic profile to permit less frequent dosing than the immediate-release form , has not been evaluated in active comparator trials . This r and omized , double-blind , parallel-group trial was conducted to compare the efficacy and safety of bupropion SR and sertraline . METHOD Out patients with moderate to severe major depressive disorder ( DSM-IV ) received bupropion SR ( 100 - 300 mg/day ) or sertraline ( 50 - 200 mg/day ) for 16 weeks . Psychiatric evaluations , including the Hamilton Rating Scale for Depression ( HAM-D ) , the Hamilton Rating Scale for Anxiety ( HAM-A ) , the Clinical Global Impressions scale for Severity of Illness ( CGI-S ) , and for Improvement ( CGI-I ) were completed , and adverse events were assessed in the clinic periodically throughout treatment . Patients ' orgasm function was also assessed . RESULTS Mean HAM-D , HAM-A , CGI-I , and CGI-S scores improved over the course of treatment in both the bupropion SR group and the sertraline group ; no between-group differences were observed on any of the scales . Orgasm dysfunction was significantly ( p < .001 ) more common in sertraline-treated patients compared with bupropion SR-treated patients . The adverse events of nausea , diarrhea , somnolence , and sweating were also experienced more frequently ( p < .05 ) in sertraline-treated patients . No differences were noted between the two treatments for vital signs and weight . CONCLUSION This double-blind comparison of bupropion SR and sertraline demonstrates that bupropion and sertraline are similarly effective for the treatment of depression . Both compounds were relatively well tolerated , and orgasm dysfunction , nausea , diarrhea , somnolence , and sweating were reported more frequently in sertraline-treated patients BACKGROUND We evaluated and compared the efficacy and safety of sertraline and fluvoxamine in a r and omized , double-blind , parallel-group study during a follow-up of 24 months . METHOD Sixty-four patients with recurrent , unipolar depression ( DSM-IV criteria ) who had at least one depressive episode during the 18 months preceding the index episode were accepted into the trial . Patients were r and omly assigned to one of the two long-term treatment groups and evaluated monthly by trained psychiatrists , blinded to treatment option , on the basis of the Hamilton Rating Scale for Depression . RESULTS All patients completed the 24-month follow-up period . Sertraline and fluvoxamine showed an equal efficacy in preventing new recurrences . In fact , there was no significant difference in survival rates between the two medication groups : 7 sertraline-treated patients ( 21.9 % ) and 6 fluvoxamine-treated patients ( 18.7 % ) had a single new recurrence ( z = 0.14 ; p = .88 ) . Moreover , recurrence observed during maintenance therapies was less severe and /or of shorter duration than index episodes . CONCLUSION Long-term treatment with sertraline or fluvoxamine has been shown to be effective for prevention of highly recurrent unipolar depression . The high tolerability of these compounds , together with their prophylactic effectiveness , has an important role in improving the quality of life of these patients BACKGROUND Despite treatment advances , major depressive disorder ( MDD ) is still a significant cause of morbidity and mortality . Current therapies frequently fall short of providing full remission . In addition , physical symptoms are commonly seen in MDD patients , increasing overall morbidity and health care utilization . Duloxetine hydrochloride , a dual reuptake inhibitor of serotonin and norepinephrine , was evaluated for efficacy and tolerability/safety in the treatment of MDD and associated physical symptoms . METHOD In this multicenter , double-blind , parallel-group study , adult patients with DSM-IV MDD were r and omly assigned to receive placebo ( N = 122 ) or duloxetine ( 60 mg/day , N = 123 ) for 9 weeks . The primary efficacy measure was the 17-item Hamilton Rating Scale for Depression ( HAM-D-17 ) total score . Painful physical symptoms were assessed using visual analog scales , and global illness and quality of life were evaluated using the Clinical Global Impressions-Severity scale , the Patient Global Impressions-Improvement scale , and the Quality of Life in Depression Scale . Safety and tolerability were determined by monitoring discontinuation rates , adverse events , vital signs , and laboratory results . RESULTS Duloxetine was significantly superior to placebo ( p < .001 ) in reducing HAM-D-17 total scores , starting at week 2 . The estimated probability of remission for duloxetine-treated patients ( 44 % ) was almost 3 times that of placebo patients ( 16 % ) . Duloxetine significantly reduced painful physical symptoms in comparison with placebo . Discontinuation due to adverse events for duloxetine-treated patients ( 13.8 % ) compared favorably with the rates reported for SSRIs in other studies . Nausea , dry mouth , and somnolence were the most common adverse events ; no significant incidence of hypertension was seen . CONCLUSION Duloxetine , 60 mg/day , is a well-tolerated and effective treatment for MDD that reduces painful physical symptoms . These findings suggest that duloxetine may be a first-line treatment for patients with MDD and associated painful physical symptoms & NA ; Two selective serotonin reuptake inhibitors ( SSRIs ) , citalopram and fluoxetine , both at a daily dose of 20 mg , were compared in patients with unipolar major depression treated in general practice . This was a multicentre , double‐blind , r and omized trial carried out in France . The duration of treatment was 8 weeks . Patients were assessed by means of the Montgomery‐Åsberg Depression Rating Scale ( MADRS ) , the 17 items Hamilton Depression Rating Scale ( HAMD ) and the investigator 's Clinical Global Impressions ( CGI ) . Observed and spontaneously reported adverse events were also recorded . A total of 357 patients of both sexes , aged between 21 and 73 years , entered the double‐blind phase of the trial . A clear reduction of both the MADRS and the HAMD mean total scores was observed in both treatment groups with no statistically significant differences between treatments . Apart from back pain recorded more frequently in the citalopram group , no significant difference was found between the two treatment groups with regard to adverse events , and both citalopram and fluoxetine were considered to be well tolerated . It was concluded that citalopram was as effective as fluoxetine in the treatment of unipolar major depression . Citalopram showed an earlier onset of recovery than fluoxetine OBJECTIVE This study determined the efficacy of antidepressant medication for the treatment of depression in the " old-old . " METHOD This r and omized 8-week medication trial compared citalopram , 10 - 40 mg/day , to placebo in the treatment of patients 75 and older with unipolar depression . RESULTS A total of 174 patients who were 58 % women with a mean age of 79.6 years ( SD=4.4 ) and a mean baseline Hamilton Depression Rating Scale score of 24.3 ( SD=4.1 ) were r and omly assigned to treatment at 15 sites . There was a main effect for site but not for treatment condition . The remission rate , defined as a final Hamilton depression scale score < 10 , was 35 % for the citalopram and 33 % for the placebo groups . However , patients with severe depression ( baseline Hamilton depression scale score > 24 ) tended to have a higher remission rate with medication than with placebo ( 35 % versus 19 % ) . CONCLUSIONS In the oldest group of community-dwelling patients to be studied to date , medication was not more effective than placebo for the treatment of depression . However , given the considerable psychosocial support received by all patients , the placebo condition represents more than the ingestion of an inactive pill . Across sites , there was considerable range in response to medication , 18 % to 82 % , and to placebo , 16 % to 80 % CONTEXT The chronic form of major depression is associated with a high rate of prevalence and disability , but no controlled research has examined the impact of long-term treatment on the course and burden of illness . OBJECTIVE To determine if maintenance therapy with sertraline hydrochloride can effectively prevent recurrence of depression in the high-risk group of patients experiencing chronic major depression or major depression with antecedent dysthymic disorder ( " double depression " ) . DESIGN A 76-week r and omized , double-blind , parallel-group study , conducted from September 1993 to November 1996 . SETTING Outpatient psychiatric clinics at 10 academic medical centers and 2 clinical research centers . INTERVENTION Maintenance treatment with either sertraline hydrochloride ( n = 77 ) in flexible doses up to 200 mg or placebo ( n = 84 ) . PATIENTS A total of 161 out patients with chronic major or double depression who responded to sertraline in a 12-week , double-blind , acute-phase treatment trial and continued to have a satisfactory therapeutic response during a subsequent 4-month continuation phase . MAIN OUTCOME MEASURE Time to recurrence of major depression . RESULTS Sertraline afforded significantly greater prophylaxis against recurrence than did placebo ( 5 [ 6 % ] of 77 in the sertraline group vs 19 [ 23 % ] of 84 in the placebo group ; P = .002 for the log-rank test of time-to-recurrence distributions ) . Clinical ly significant depressive symptoms reemerged in 20 ( 26 % ) of 77 patients treated with sertraline vs 42 ( 50 % ) of 84 patients who received placebo ( P = .001 ) . With use of a Cox proportional hazards model , patients receiving placebo were 4.07 times more likely ( 95 % CI , 1.51 - 10.95 ; P = .005 ) to experience a depression recurrence , after adjustment for study site , type of depression , and r and omization strata . CONCLUSIONS Maintenance therapy with sertraline is well tolerated and has significant efficacy in preventing recurrence or reemergence of depression in chronically depressed patients BACKGROUND The aim was to compare the efficacy and tolerability of mirtazapine with those of paroxetine . METHOD 275 out patients with a diagnosis of major depressive episode ( DSM-IV ) and a score > or = 18 on the 17-item Hamilton Rating Scale for Depression ( HAM-D-17 ) were r and omly assigned to 6 weeks of treatment with mirtazapine ( 15 - 45 mg/day ) or paroxetine ( 20 - 40 mg/day ) . Efficacy was assessed by the HAM-D-17 , Hamilton Rating Scale for Anxiety ( HAM-A ) , and Clinical Global Impressions scales ( Severity and Improvement ) , and analyses were performed on the intent-to-treat sample ( 127 mirtazapine-treated patients and 123 paroxetine-treated patients ) . RESULTS Mean daily doses were 32.7 mg of mirtazapine and 22.9 mg of paroxetine . Thirty patients in the mirtazapine group and 33 in the paroxetine group dropped out . Both drugs were equally effective in reducing symptoms of depression . At week 1 , the mean HAM-D-17 total score was significantly lower in mirtazapine- than paroxetine-treated patients ( 16.5 vs. 18.8 , p = .0032 ) . Similarly , significantly more mirtazapine-treated patients were HAM-D-17 responders ( > or = 50 % decrease from baseline ) at weeks 1 ( 23.2 % vs. 8.9 % , p = .002 ) and 4 ( 58.3 % vs. 44.5 % , p = .04 ) . Both treatments were equally effective in reducing anxiety . However , the reduction in mean HAM-A total score was significantly greater with mirtazapine than with paroxetine at week 1 ( -5.1 vs. -3.5 , p = .0435 ) . Tolerability of both treatments was good , with more nausea , vomiting , tremor , and sweating in the paroxetine group and more weight increase and influenza-like symptoms in the mirtazapine group . CONCLUSION Mirtazapine and paroxetine were equally effective after 6 weeks of therapy and were both well tolerated . A potentially faster onset of overall therapeutic efficacy of mirtazapine was suggested by significant differences between treatments after 1 week of therapy that were due to slightly larger improvements of several core symptoms of depression as well as distinct prevention of treatment-emergent worsening of anxiety and physical components of depression Abstract Introduction : Depression is a major global problem associated with large medical , sociological and economic burdens . Mirtazapine ( Remeron ® , Organon NV , The Netherl and s ) is an antidepressant with a unique mechanism of action that has similar or superior efficacy to TCAs and SSRIs in moderate-to-severe depression . However , this agent has not yet been tested in patients with severe depression alone . Objective : To compare the antidepressant efficacy and tolerability of mirtazapine and fluoxetine and their effects on anxiety and quality of life in patients with severe depression ( ≥25 points on the first 17 items of the Hamilton Depression Rating Scale [ HDRS-17 ] ) . Methods : In this double-blind study , 297 severely depressed patients were r and omised to receive mirtazapine 15–60 mg/day ( n = 147 ) or fluoxetine 20–40 mg/day ( n = 152 ) for 8 weeks . 294 subjects were actually treated and 292 included in the intent-to-treat population . Symptom severity was measured by the HDRS-17 , Montgomery-Asberg Depression Rating Scale ( MADRS ) and Clinical Global Impression ( CGI ) rating scale . Quality of life was self-assessed by patients using the Leeds Sleep Evaluation Question naire and the Quality of Life , Enjoyment and Satisfaction Question naire . Adverse events were recorded throughout the study . Results : No statistically significant differences were noted between the two groups in change from baseline HDRS-17 score at any time point ; both treatments were associated with large ( ∼15 points ) decreases by study end . However , more mirtazapine-treated patients tended to exhibit a ≥50 % decrease in HDRS score ( significant at day 7 ; 9.0 % vs 0.7 % , p = 0.002 ) . Significant differences in favour of mirtazapine were also observed at day 14 for changes in MADRS scores ( −10.9 vs −8.5 , p = 0.006 ) and the proportion of patients with ≥50 % decrease in MADRS score ( 21.4 % vs 10.9 % , p = 0.031 ) . On the CGI , the proportion of ‘ much/very much improved ’ patients tended to be greater with mirtazapine ( significant at day 7 ; 9.7 % vs 3.4 % , p = 0.032 ) . No significant between-group differences were observed for the majority of quality -of-life measures . However , mirtazapine produced significantly better improvements on ‘ sleeping assessment 1 ’ ( 14.9 ± 5.2 vs 13.7 ± 5.4 , p = 0.028 ) and ‘ sleeping assessment 2 ’ ( p = 0.013 ) than fluoxetine . Both agents were generally well tolerated but mirtazapine-treated patients experienced a mean weight gain of 0.8 ± 2.7 kg compared with a mean decrease in weight of 0.4 ± 2.1 kg for fluoxetine-treated patients ( p < 0.001 ) . Conclusions : Mirtazapine is as effective and well tolerated as fluoxetine in the treatment of patients with severe depression BACKGROUND Previous small trials have suggested that nefazodone does not suppress rapid-eye-movement ( REM ) sleep or increase REM latency in depressed patients , in contrast to fluoxetine . The effects of nefazodone and fluoxetine on sleep architecture and on clinician- and patient-rated sleep measures were directly compared in this 8-week , multicenter , double-blind , r and omized , parallel-group study . METHOD Forty-four out patients with moderate to severe , nonpsychotic major depressive disorder ( DSM-III-R ) and insomnia were r and omly assigned to receive nefazodone ( Days 1 - 7 , 200 mg/day ; Days 8 - 56 , 400 mg/day ) or fluoxetine ( Days 1 - 56 , 20 mg/day ) . Sleep measures were obtained at baseline , while patients were unmedicated , and at Weeks 2 , 4 , and 8 of treatment . RESULTS In 43 evaluable patients ( 23 nefazodone , 20 fluoxetine ) , nefazodone and fluoxetine demonstrated similar antidepressant efficacy . All significant values were p < .05 . Fluoxetine significantly decreased sleep efficiency and REM sleep and increased number of awakenings , Stage 1 sleep , and REM latency compared with baseline . In contrast , nefazodone significantly decreased percentage of awake and movement time and did not alter sleep efficiency or number of awakenings , Stage 1 or REM sleep , or REM latency compared with baseline . Nefazodone was associated with significantly less change from baseline for sleep efficiency , number of awakenings , percentage of awake and movement time , percentage of REM and Stage 1 sleep , and REM latency compared with fluoxetine . Both fluoxetine- and nefazodone-treated patients also showed significant improvement in some clinician- and patient-rated sleep disturbance scores , but nefazodone-treated patients improved to a significantly greater extent than fluoxetine-treated patients in most measures . CONCLUSION While nefazodone and fluoxetine showed equivalent antidepressant efficacy , more objective , subjective , and clinician-rated measures of sleep disturbance were improved during treatment with nefazodone than with fluoxetine . These results suggest that antidepressant effects of medications can occur independently of drug-induced changes in objective , subjective , and clinician-rated measures of sleep . Further studies , including parallel placebo-controlled comparisons with nefazodone , are needed to further test this hypothesis OBJECTIVE There have been few placebo-controlled trials of selective serotonin reuptake inhibitors for depressed elderly patients . This placebo-controlled study of sertraline was design ed to confirm the results of non-placebo-controlled trials . METHOD The subjects were out patients age 60 years or older who had a DSM-IV diagnosis of major depressive disorder and a total score on the 17-item Hamilton Depression Rating Scale of 18 or higher . The patients were r and omly assigned to 8 weeks of double-blind treatment with placebo or a flexible daily dose of 50 or 100 mg of sertraline . The primary outcome variables were the Hamilton scale and Clinical Global Impression ( CGI ) scales for severity and improvement . RESULTS A total of 371 patients assigned to sertraline and 376 assigned to placebo took at least one dose . At endpoint , the patients receiving sertraline evidence d significantly greater improvements than those receiving placebo on the Hamilton depression scale and CGI severity and improvement scales . The mean changes from baseline to endpoint in Hamilton score were -7.4 points ( SD=6.3 ) for sertraline and -6.6 points ( SD=6.4 ) for placebo . The rate of CGI-defined response at endpoint was significantly higher for sertraline ( 45 % ) than for placebo ( 35 % ) , and the time to sustained response was significantly shorter for sertraline ( median , 57 versus 61 days ) . There were few discontinuations due to treatment-related adverse events , 8 % for sertraline and 2 % for placebo . CONCLUSIONS Sertraline was effective and well tolerated by older adults with major depression , although the drug-placebo difference was not large in this 8-week trial ABSTRACT Objective : A r and omized , double-blind , 24‐week fixed-dose study comparing the efficacy and safety of escitalopram to that of citalopram was conducted in primary care patients with moderate to severe major depressive disorder ( MDD ) . Research design and methods : This was a r and omized , double-blind , 24‐week fixed-dose study . Patients were r and omly assigned to treatment with escitalopram 10 mg/day ( n = 175 ) or citalopram 20 mg/day ( n = 182 ) . Clinical response was evaluated using the Montgomery – Åsberg Depression Rating Scale ( MADRS ) and Clinical Global Impression-Severity ( CGI‐S ) scale . The prospect ively defined primary parameter of antidepressant efficacy was the change from baseline in the mean MADRS total score during the 24 weeks of double-blind treatment , using a repeated measures analysis of variance to compare the treatment groups over all assessment points simultaneously . Results : Based on the primary parameter , escitalopram was at least as efficacious as citalopram . Based on the prospect ively defined secondary parameter , mean change from baseline in the CGI‐S score , escitalopram was statistically significantly superior to citalopram at Week 24 . The importance of long-term treatment could be demonstrated , in that more than half ( 55 % and 51 % ) of the patients who had not responded by Week 8 achieved remission by Week 24 . Both escitalopram and citalopram were safe and well tolerated in acute and long-term treatment , and the overall adverse event profiles for the two drugs were similar . For the intent-to-treat population , there were statistically significantly fewer withdrawals in the escitalopram group than in the citalopram group , particularly after Week 8 . Conclusion : Patients with MDD responded well to long-term treatment with either escitalopram or citalopram . This study demonstrated the importance of extending treatment of depression beyond 8 weeks BACKGROUND This study was design ed to compare the efficacy , safety , tolerability profiles , and effects on quality of life of the serotonin selective reuptake inhibitor antidepressant sertraline versus the nonselective tricyclic antidepressant amitriptyline and placebo in patients with major depression . METHOD Out patients with DSM-III-R major depression were r and omly assigned to double-blind treatment for 8 weeks with sertraline ( 50 - 200 mg daily ) , amitriptyline ( 50 - 150 mg daily ) , or matching placebo . Assessment s included the Hamilton Rating Scale for Depression , Montgomery-Asberg Depression Rating Scale , Clinical Global Impressions-Severity of Illness scale , Clinical Global Impressions-Improvement scale , Global Assessment Scale , Profile of Mood States , Beck Depression Inventory , Quality of Life Enjoyment and Satisfaction Question naire , and Health-Related Quality of Life battery . RESULTS All treatment groups demonstrated statistically significant improvement from baseline in depression ratings by Week 1 and thereafter . The antidepressant effects of amitriptyline and sertraline were significantly ( p < .05 ) greater than placebo and did not differ significantly from each other . Sertraline was associated with significantly ( p < .05 ) greater subjective ( i.e. , patient-rated ) improvement in mood than amitriptyline or placebo . Both active drugs were associated with greater improvements than placebo on most quality of life measurements . On several items , sertraline , but not amitriptyline , was superior to placebo . There was a discernible effect of sertraline earlier than amitriptyline on most quality of life scales . Amitriptyline therapy was associated with significantly more treatment-related adverse events , and discontinuations due to treatment-related adverse events , in comparison to both sertraline and placebo therapy . CONCLUSION Sertraline and amitriptyline each were effective treatments for major depression as assessed by both physician- and patient-rated scales . These results show that sertraline therapy is better tolerated than amitriptyline therapy . Quality of life was also improved by effective antidepressant treatment , with sertraline showing a tendency to produce greater improvements on quality of life measures BACKGROUND This was a r and omized , double-blind , placebo-controlled evaluation of the efficacy and safety of once-daily venlafaxine extended release ( XR ) in out- patients with DSM-IV major depression . METHOD Patients were r and omly assigned to venlafaxine XR ( 75 - 225 mg ) once daily or placebo for up to 8 weeks . The primary efficacy variables were the 21-item Hamilton Rating Scale for Depression ( HAM-D ) total score and HAM-D depressed mood item , the Montgomery-Asberg Depression Rating Scale ( MADRS ) total scores , and the Clinical Global Impressions ( CGI ) Severity scale . Data were analyzed on a modified intent-to-treat basis using the last-observation-carried-forward method . RESULTS Venlafaxine XR ( N = 91 ) was significantly more effective than placebo ( N = 100 ) beginning at Week 2 on the CGI Severity scale , at Week 3 on the HAM-D depressed mood item , and at Week 4 on the HAM-D and MADRS ; this superiority was maintained through Week 8 . The most common treatment-emergent adverse events associated with venlafaxine XR were nausea , insomnia , and somnolence . The incidence of nausea was highest during the first week , decreased by 50 % during the second week , and was comparable to that of placebo from Week 3 onward . CONCLUSION These results demonstrate that venlafaxine XR is an effective and well-tolerated treatment of major depression BACKGROUND Sexual dysfunction commonly occurs during antidepressant treatment . However , the reported rates of sexual dysfunction vary across antidepressants and are typically underreported in product literature . The objectives of this study were ( 1 ) to estimate the prevalence of sexual dysfunction among patients taking newer antidepressants ( bupropion immediate release [ IR ] , bupropion sustained release [ SR ] , citalopram , fluoxetine , mirtazapine , nefazodone , paroxetine , sertraline , venlafaxine , and venlafaxine extended release [ XR ] ) and ( 2 ) to compare physician-perceived with patient-reported prevalence rates of antidepressant-associated sexual dysfunction . METHOD This cross-sectional , observational study was conducted in 1101 U.S. primary care clinics . Adult out patients ( 4534 women and 1763 men ) receiving antidepressant monotherapy were enrolled . The prevalence of sexual dysfunction was measured using the Changes in Sexual Functioning Question naire . RESULTS In the overall population , bupropion IR ( 22 % ) and SR ( 25 % ) and nefazodone ( 28 % ) were associated with the lowest risk for sexual dysfunction , whereas selective serotonin reuptake inhibitor ( SSRI ) antidepressants , mirtazapine , and venlafaxine XR were associated with higher rates ( 36%-43 % ) . In a prospect ively defined sub population unlikely to have predisposing factors for sexual dysfunction , the prevalence of sexual dysfunction ranged from 7 % to 30 % , with the odds of having sexual dysfunction 4 to 6 times greater with SSRIs or venlafaxine XR than with bupropion SR . Physicians consistently underestimated the prevalence of antidepressant-associated sexual dysfunction . CONCLUSION Ours is the first study to assess sexual dysfunction across the newer antidepressants using consistent methodology and a vali date d rating scale . Overall , SSRIs and venlafaxine XR were associated with higher rates of sexual dysfunction than bupropion or nefazodone . Because antidepressant-associated sexual dysfunction is considerably underestimated by physicians , greater recognition and education are imperative when prescribing antidepressant treatment OBJECTIVE The atypical subtype of depression appears to be both well vali date d and common . Although monoamine oxidase inhibitors are effective in treating atypical depression , their side effects and prescription-associated dietary restrictions reduce their suitability as a first-line treatment . The objective of this study was to estimate the efficacy of the selective serotonin reuptake inhibitor ( SSRI ) fluoxetine in the treatment of major depression with atypical features . METHOD One hundred fifty-four subjects with DSM-IV major depression who met the Columbia criteria for atypical depression were r and omly assigned to receive fluoxetine , imipramine , or placebo for a 10-week clinical trial . Imipramine was included because its known efficacy for treatment of atypical depression helped to calibrate the appropriateness of the study group . RESULTS In both intention-to-treat and completer groups , the effectiveness of both fluoxetine and imipramine was significantly better than that of placebo . The two medications did not differ from each other in effectiveness . Significantly more patients dropped out of treatment with imipramine than with fluoxetine . Before treatment , patients on average rated themselves as very impaired on psychological dimensions of general health and moderately impaired on physical dimensions , compared with population norms . The self-ratings of patients who responded to treatment essentially normalized on these measures . CONCLUSIONS Despite earlier data that SSRIs might be the treatment of choice , fluoxetine appeared to be no better than imipramine in the treatment of atypical depression , although fluoxetine was better tolerated than imipramine BACKGROUND Many antidepressants are associated with sexual dysfunction , a side effect that may lead to patients ' dissatisfaction and noncompliance with treatment . OBJECTIVE This study compared the efficacy , tolerability , and effects on sexual functioning of bupropion sustained release ( bupropion SR ) and the selective serotonin reuptake inhibitor fluoxetine . METHODS In this multicenter , r and omized , double-blind , double-dummy , parallel-group study , patients with recurrent major depression were treated with bupropion SR 150 to 400 mg/d , fluoxetine 20 to 60 mg/d , or placebo for up to 8 weeks . Depression and sexual-functioning status were assessed by site-specific trained investigators at weekly clinic visits ; tolerability was assessed primarily by monitoring adverse events . RESULTS Four hundred fifty-six patients participated in the study , 150 receiving bupropion SR , 154 fluoxetine , and 152 placebo . The majority of patients in each group completed the study ( 63 % each , bupropion SR [ n = 94 ] and fluoxetine [ n = 97 ] ; 67 % , placebo [ n = 102 ] ) . Bupropion SR and fluoxetine were similarly effective in the treatment of depressive symptoms . Beginning at week 2 and continuing throughout the study , significantly more fluoxetine-treated patients experienced orgasm dysfunction than did patients receiving bupropion SR or placebo ( P < 0.001 ) ; similar results were seen in patients defined as clinical responders ( > or = 50 % decrease from baseline in 21-item Hamilton Rating Scale for Depression [ HAM-D ] total score ) ( P < 0.001 ) and in those experiencing remission of depression ( HAM-D total score < 8) ( P < 0.05 ) . At various time points , worsened sexual functioning , sexual desire disorder , sexual arousal disorder , and dissatisfaction with sexual functioning in those satistied at baseline were more frequently associated with fluoxetine treatment than with bupropion SR or placebo . Both active treatments were well tolerated . CONCLUSIONS Bupropion SR and fluoxetine were similarly effective and well tolerated in the treatment of depression . Fluoxetine , however , was more frequently associated with sexual dysfunction compared with bupropion SR . Bupropion SR may be an appropriate initial choice for the treatment of depression in patients concerned about sexual functioning In a 6-week , r and omized , double-blind , multicenter trial , sertraline 50 mg , 100 mg , or 200 mg , or placebo , was administered once daily to 369 patients with DSM-III-defined major depression . Efficacy variables included changes from baseline scores for total Hamilton Rating Scale for Depression ( HAMD ) , HAMD Bech Depression Cluster , Clinical Global Impressions ( CGI ) Severity , CGI Improvement , and Profile of Mood States Depression/Dejection Factor . For the evaluable- patients analysis , all sertraline groups showed significantly ( p < 0.05 or better ) greater improvements in all efficacy variables except one when compared with the placebo group . For the all- patients analysis , all efficacy variables in the 50 mg group were statistically significantly ( p < 0.05 ) better than placebo . Side effects increased with increasing dosage but were usually mild and well tolerated . The results of this study show that sertraline 50 mg once daily is as effective as higher dosages for the treatment of major depression with fewer side effects and therapy discontinuations BACKGROUND Major depression with high levels of anxiety ( anxious depression ) is a common subtype of depression associated with greater psychosocial impairment and poorer response to antidepressant treatment . It is unclear whether in this population there are differences in efficacy or tolerability across selective serotonin reuptake inhibitors . For this reason , using head-to-head acute treatment comparison , we compared efficacy and tolerability of fluoxetine , sertraline , and paroxetine among depressed patients with high levels of anxiety . METHODS Patients ( N = 108 ) with DSM-IV major depression and high levels of anxiety ( a HAM-D-Anxiety/Somatization Factor score > or = 7 ) were r and omized to fluoxetine , sertraline , or paroxetine treatment in a double-blind fashion . Changes in overall depression and anxiety were assessed . RESULTS Patients demonstrated similar baseline-to-endpoint improvement in HAM-D-17 and HAM-D-Anxiety/Somatization Factor scores . Patients also demonstrated similar change-over-time improvement in HAM-D-17 and HAM-D-Anxiety/Somatization Factor scores , except at week one where fluoxetine- and sertraline-treated patients had statistically significantly greater improvement than paroxetine-treated patients in the HAM-D-Anxiety/Somatization Factor score . There were no significant differences across treatments in percentages of patients with substantial emergence , any worsening , or improvement at endpoint in individual HAM-D Items 9 ( agitation ) , 10 ( psychic anxiety ) , and 11 ( somatic anxiety ) . Overall , all treatments were well tolerated . CONCLUSION These data showed no significant differences in efficacy and tolerability of fluoxetine , sertraline , and paroxetine in patients with high levels of baseline anxiety symptoms during the acute treatment of major depression . Each treatment was similarly effective in improving depression in this subtype of patients with anxious depression BACKGROUND Sertraline and fluoxetine have pharmacokinetic and pharmacologic differences , which may be of clinical relevance . METHOD A r and omized , double-blind , parallel-group study of 6 weeks ' duration comparing the efficacy and safety of sertraline ( 50 - 100 mg/day ) with those of fluoxetine ( 20 - 40 mg/day ) was conducted in 286 psychiatric out patients with DSM-III-R major depression or bipolar disorder ( depressed ) . Primary efficacy measurements consisted of the 17-item Hamilton Rating Scale for Depression ( HAM-D ) and the Clinical Global Impressions ( CGI ) scale . Secondary measurements included the Hamilton Rating Scale for Anxiety ( HAM-A ) , the Raskin Depression Scale , the Covi Anxiety Scale , and the Leeds Sleep Question naire . Additionally , scores for two items and five factors from the HAM-D were analyzed . RESULTS Efficacy was based on 124 evaluable patients in each treatment group . As measured by HAM-D and CGI-Severity scores , there was a significant ( p < .001 ) improvement from baseline to each follow-up visit in both treatment groups with no statistically significant difference between groups . There was also no significant difference in the proportion of responders in each group . CGI-Improvement responder rates were 69 % for sertraline and 67 % for fluoxetine . Results of secondary efficacy measurements followed the same trend , although from the second week of treatment there was a numerical advantage ( not statistically significant ) for sertraline over fluoxetine in improving anxiety symptoms as measured by the total HAM-A score . Headache and nausea were the most frequently reported events for both drugs . The incidence of early patient withdrawals due to treatment-emergent adverse events was 14 % for sertraline and 13 % for fluoxetine . The starting dosage ( sertraline 50 mg/day , fluoxetine 20 mg/day ) was the final dosage in 76 % of patients in both treatment groups . CONCLUSION Sertraline and fluoxetine were equally effective and well tolerated in patients with major depression and associated anxiety OBJECTIVE Because physical illness may influence quality of life , we assessed its impact on functional status and treatment outcome in older depressed patients who participated in a clinical trial , which showed a significantly higher remission rate for fluoxetine over placebo ( 31.6 % vs 18.6 % , P < .001 ) . DESIGN Six-week , r and omized , double-blind , placebo-controlled trial of fluoxetine , 20 mg daily . SETTING Multiple clinical sites , both university and private . PARTICIPANTS Out patients ( N = 671 ) were > or = 60 years ( mean + /- SD = 67.7 + /- 5.7 ) , met DSM-III-R criteria for unipolar major depression and had baseline scores > or = 16 on the Hamilton Depression Rating Scale . MEASUREMENTS The 36-item short-form health survey ( SF-36 ) was used to measure baseline and posttreatment functional health and well-being . Physical illness was rated by number of current chronic or historical illnesses . Change from baseline to endpoint in the Hamilton Depression Rating Scale total score was used to measure depression outcome . MAIN RESULTS Most patients reported physical illness : 83 % had one or more chronic illness , and 89 % had one or more historical illness . Greater numbers of baseline chronic illness indicated worse physical functioning , general health perceptions , and vitality and greater bodily pain and role limitation from physical problems . Historical physical illness was associated with worse physical functioning , vitality , general health perceptions , social functioning , and mental health . Although the number of chronic illnesses did not influence treatment response , historical physical illness was associated with greater fluoxetine response and lower placebo response . CONCLUSIONS These findings suggest that both current and previous physical illness are associated with lower quality of life in geriatric depression and that depressed older patients with chronic physical illness respond to antidepressants as well as those without such illness . Recovery from previous physical illness should be explored as a potential predictor of antidepressant treatment outcome Objective : The primary objective was to evaluate sexual function ( SF ) separately in men and women with major depressive disorder ( MDD ) before and during treatment with bupropion sustained release ( SR ) or paroxetine . The secondary objectives involved a comparative evaluation of the Sex Effects Scale ( Sex FX ) and the Investigator-Rated Sexual Desire and Functioning Scale ( IRSD-F ) , as well as a comparison of antidepressant outcomes and an examination of the relation between level of depression and SF over time . Method : There were 141 patients ( 68 women and 73 men ) who met DSM-IV criteria for a current major depressive episode . They were r and omly assigned to receive bupropion SR ( 150 to 300 mg daily ) or paroxetine ( 20 to 40 mg daily ) under double-blind trial conditions . Patients were assessed at baseline and at 2 , 4 , 6 , and 8 weeks with the 17-item Hamilton Depression Rating Scale ( HDRS17 ) , Sex FX , and IRSD-F. Results : Prior to treatment , women reported significantly lower SF on both the Sex FX and IRSD-F scales , compared with men . During treatment , there were no significant drug differences on measures of SF over time for women ; however , men who were treated with paroxetine reported a worsening of SF , whereas bupropion SR did not significantly alter SF . Both bupropion SR and paroxetine produced clinical ly and statistically significant reductions in HDRS17 scores as well as comparable rates of response and remission . There was a statistically significant correlation between the 2 measures of SF at all visits . There was also a significant inverse relation between depression and SF in women , but not in men , irrespective of drug . Conclusion : According to the Sex FX scale , a significant difference in antidepressant-related sexual dysfunction was detected in men , but not women , during treatment with bupropion SR or paroxetine The antidepressant efficacy and short-term safety of venlafaxine and fluoxetine were compared in 68 patients hospitalized with major depression and melancholia . Venlafaxine was superior in efficacy to fluoxetine ; total scores for both the MADRS and the HAM-D were significantly ( p < or = 0.05 ) lower in the venlafaxine group than in the fluoxetine group at Weeks 4 and 6 . Overall tolerance was similar for the two treatments OBJECTIVE The goals of this study were to determine whether fluoxetine is superior to placebo in treating HIV-seropositive patients with major depression or dysthymia or both , whether severity of immunosuppression is associated with treatment response , and whether fluoxetine treatment is associated with change in immune status as measured by CD4 cell count . METHOD A double-blind , r and omized , placebo-controlled 8-week trial of fluoxetine was conducted in a university-affiliated research outpatient clinic . The fluoxetine-placebo r and omization was 2:1 . All patients were offered 4 months of additional open treatment . Main outcome measures included the Clinical Global Impression , Hamilton Depression Rating Scale , and CD4 cell count . RESULTS Of 120 patients r and omly assigned to fluoxetine or placebo , 87 completed 8 weeks of treatment . In the total group , 51 % had AIDS . All but three were men , 35 % were nonwhite , and 6 % had intravenous drug use as a risk factor . In an intention-to-treat analysis , 57 % of fluoxetine patients and 41 % of placebo patients were responders . Among patients who completed the study , 74 % responded to fluoxetine and 47 % to placebo ; this difference was statistically significant . Severity of immunosuppression was not related to antidepressant response , attrition , or side effects , and fluoxetine treatment was not associated with change in CD4 cell count . CONCLUSIONS Fluoxetine is an effective antidepressant in the context of HIV illness . However , both placebo response and attrition were substantial , suggesting both that nonspecific factors may be more salient and that yet another medication ( i.e. , an antidepressant ) may be less acceptable among patients with serious medical illness already requiring multiple concomitant medications Paroxetine is a novel phenylpiperidine antide-pressant agent that acts as a potent and selective inhibitor of serotonin reuptake . We report results of a 6-week , r and omized , double-blind , multicenter study comparing paroxetine and fluoxetine in the treatment of major depression . One hundred seventy-eight in patients , who met DSM-III-R criteria for a major depressive episode and had a Montgomery Asberg Depression Rating Scale ( MADRS ) score of 24 or more , were included in the study . Their ages ranged from 18 to 65 years . Subjects were r and omized to receive either paroxetine or fluoxetine for 6 weeks . A 20-mg fixed dose , given once daily in the morning , was used for both drugs . After baseline , regular assessment s were made at the end of weeks 1,2,3,4 , and 6 . Efficacy measures included the MADRS , the Clinical Global Impression severity of illness scale , the Hamilton Rating Scale for Anxiety , the Hospital Anxiety and Depression scale , and the Visual Analogue Scale for anxiety . Safety and tolerability were assessed by adverse event reports , clinical examinations , vital signs , and laboratory data . A marked antidepressant response and good tolerability were seen with both drugs . These results further support the usefulness of paroxetine in the treatment of depressive illness OBJECTIVE Current clinical knowledge holds that antidepressants have a delayed onset of efficacy . However , the delayed onset hypothesis has been question ed recently by survival analytical approaches . We aim ed to test whether early improvement under antidepressant treatment is a clinical ly useful predictor of later stable response and remission . METHOD We analyzed data from a r and omized double-blind controlled trial with mirtazapine and paroxetine in patients with major depression ( DSM-IV ) . Improvement was defined as a 17-item Hamilton Rating Scale for Depression ( HAM-D-17 ) score reduction of > or = 20 % . Stable response was defined as > or = 50 % HAM-D-17 score reduction at week 4 and week 6 , and stable remission as a HAM-D-17 score of < or = 7 at week 4 and week 6 . Sensitivity , specificity , positive predictive value ( PPV ) , and negative predictive value ( NPV ) were calculated . RESULTS Improvement occurred in a majority of the analyzed patients within 2 weeks ( mirtazapine : 72.7 % of 109 patients ; paroxetine : 64.9 % of 103 patients ) . Early improvement was a highly sensitive predictor of later stable response or stable remission for both drugs . NPV approached maximum values as early as week 2 for mirtazapine and week 3 for paroxetine . After 2 weeks of treatment with mirtazapine and 3 weeks with paroxetine , almost none of the patients who had not yet improved became a stable responder or stable remitter in the later course . CONCLUSION Our results strongly suggest that early improvement predicts later stable response with high sensitivity . These empirically derived data question the delayed onset hypothesis for both antidepressants tested and provide important clinical clues for an individually tailored antidepressant treatment AIM To compare the efficacy and tolerability of mirtazapine and fluoxetine treatment in a sample population consisting of Chinese patients suffering moderate-to-severe depression . METHOD 133 patients with a diagnosis of major depressive episode ( DSM-IV ) and scoring 15 or more on the 17-item Hamilton Rating Scale for Depression ( HAM-D ) were r and omly assigned to receive 6 weeks of treatment with either mirtazapine ( 15 - 45 mg/day ) or fluoxetine ( 20 - 40 mg/day ) . Efficacy was assessed using the HAM-D and Clinical Global Impressions scale , with analyses performed on the intent-to-treat sample using the last-observation-carried-forward method . Safety analysis was based on the all-subjects-treated group . RESULTS Mean daily doses were 34.1 mg for mirtazapine ( N = 66 ) and 30.7 mg for fluoxetine ( N = 66 ) . Thirty patients in the mirtazapine group and 22 in the fluoxetine group dropped out . Both drugs proved equally effective for reduction of the overall symptoms of depression throughout the treatment period . At day 42 , the mean reductions in HAM-D total score ( compared with baseline ) were 11.8 and 10.6 for the mirtazapine and fluoxetine groups , respectively ; however , the changes were not statistically significant . Both treatments were well tolerated , with more nausea and influenza-like symptoms observed for the fluoxetine group , and greater weight increase and somnolence for the mirtazapine analog . CONCLUSION Both mirtazapine and fluoxetine were indistinguishable in effectiveness for treatment of depressive symptoms , and both were well tolerated by our population of depressed Chinese patients . In line with analogous Western reports , the safety of mirtazapine and fluoxetine was comparable for our depressed Chinese patients ; however , slightly different side effect profiles were noted for the 2 drugs in our study BACKGROUND Current guidelines for antidepressant use recommend 4 to 6 months of continuation treatment to prevent relapse of depression following symptom resolution . This study evaluates the efficacy and safety of continuation escitalopram treatment . METHOD Out patients diagnosed with DSM-IV major depressive disorder ( male or female , aged 18 to 81 years ) who had completed 8 weeks of r and omized double-blind treatment with escitalopram , citalopram , or placebo entered an 8-week flexible-dose , open-label phase in which all patients received escitalopram ( 10 - 20 mg/day ) . This study was initiated November 3 , 1999 , and completed April 5 , 2001 . Patients who met responder criteria ( score of < or = 12 on the Montgomery-Asberg Depression Rating Scale [ MADRS ] ) were r and omly assigned in a 2:1 ratio to escitalopram ( at the dose each patient was receiving at the end of the open-label phase ) or placebo for 36 weeks of double-blind treatment . The primary efficacy variable was time to depression relapse ( defined as MADRS score > or = 22 or discontinuation due to an insufficient therapeutic response ) from the start of the double-blind treatment phase . RESULTS A total of 502 patients received open-label escitalopram treatment and had at least 1 MADRS assessment . A total of 274 evaluable subjects entered the double-blind treatment phase ; 93 received placebo and 181 received escitalopram . Time to depression relapse was significantly longer ( p = .013 ) and the cumulative rate of relapse was significantly lower in patients who received escitalopram ( 26 % escitalopram vs. 40 % placebo ; hazard ratio = 0.56 ; p = .01 ) . Escitalopram-treated subjects had significantly lower depression ratings than those of placebo-treated patients . Escitalopram continuation treatment was safe and well tolerated . Discontinuation rates due to adverse events were 7 % for the placebo group and 4 % for the escitalopram-treated group . CONCLUSION Continuation treatment with escitalopram is effective in preventing relapse into an episode of major depressive disorder This double-blind , placebo-controlled study compared venlafaxine ( immediate release ) , the first modern serotonin-norepinephrine reuptake inhibitor , with the selective serotonin reuptake inhibitor fluoxetine . Out patients were r and omly assigned to 6 weeks of treatment with venlafaxine ( 75 - 225mg/day ; n=102 ) , fluoxetine ( 20 - 60mg/day ; n=104 ) , or placebo ( n=102 ) . Efficacy was assessed using the 21-item Hamilton Depression Rating Scale ( HAM-D(21 ) ) , the Montgomery-Asberg Depression Rating Scale ( MADRS ) , the Clinical Global Impression-Severity of Illness ( CGI-S ) scale , response and remission rates , and several other measures . Intent-to-treat analyses utilized both the last observation carried forward and ETRANK methods to account for missing data . At week 6 or study endpoint , venlafaxine ( mean dose : 142mg/day ) was superior to placebo on most outcomes measures , whereas the differences between fluoxetine ( mean dose : 41mg/day ) and placebo were less consistent . Final remission ( defined as HAM-D < or = 7 ) rates were 32 % , 28 % , and 22 % for venlafaxine , fluoxetine , and placebo , respectively . Few differences between the active treatments attained statistical significance . Both active therapies were generally well tolerated ; however , attrition due to adverse events , incidence of selected side effects , and increases in pulse and blood pressure favored fluoxetine over venlafaxine . This study provides further evidence that venlafaxine is effective after 6 weeks of treatment compared with placebo . The efficacy profile of fluoxetine was somewhat less consistent . It is strongly recommended that future studies of comparative antidepressant efficacy be adequately powered to detect modest between-drug differences in efficacy The aim of the present study was to determine whether , in patients with depression who had responded favourably to the selective serotonin reuptake inhibitor citalopram , there was a therapeutic benefit in continuation treatment . Three hundred and ninety-one depressive patients were included in an open short-term citalopram treatment period . Only patients who responded to treatment at 8 weeks ( total score of 12 or less on the MADRS scale ) were r and omized to the 24 week double-blind phase . Seventy-four patients were treated with placebo and 152 with citalopram at the same constant dose to which the patient had responded in the first phase . Relapse was defined as a total score of 25 or more on the MADRS scale . Twenty-one patients ( 13.8 % ) continuing to receive citalopram relapsed compared with 18 patients ( 24.3 % ) receiving placebo . The log rank test for survival data used to test the e quality of relapse hazards between the placebo group and the citalopram group showed that patients treated with citalopram had a significantly lower relapse rate { p = 0.04 ) . The results of this study are in general agreement with those of other studies on antidepressants , and support the hypothesis that full dose continuation treatment is more effective than placebo in preventing relapse of depression BACKGROUND Fluvoxamine and paroxetine , both serotonin selective reuptake inhibitors ( SSRIs ) , were compared at two centers in a 7-week double-blind study in out patients with major depression , diagnosed by DSM-III-R criteria . METHOD Sixty patients were r and omly assigned to receive dosage titrated upward to between 50 - 150 mg/day of fluvoxamine ( N = 30 ) or 20 - 50 mg/day of paroxetine ( N = 30 ) . The mean + /- SD daily dose administered at the last assessment was 102 + /- 44 mg/day for fluvoxamine and 36 + /- 13 mg/day for paroxetine . Sixteen ( 53 % ) fluvoxamine-treated patients and 10 ( 33 % ) paroxetine-treated patients were titrated to the maximum permissible dosage of either drug . Sample size was calculated to provide at least 85 % power at 5 % level of significance to detect at least a 1.00-point difference in mean severity of adverse events , assuming a st and ard deviation of 1.0 . RESULTS Fluvoxamine and paroxetine were similarly effective in ameliorating depression as demonstrated by mean total scores of 10.9 + /- 7.3 ( p < .00 ) and 11.5 + /- 7.4 ( p < .00 ) , respectively , in the Hamilton Rating Scale for Depression ( HAM-D ) . Adverse events were mostly mild to moderate in severity . The most common events were headache ( N = 17 , 57 % ) , nausea ( N = 14 , 47 % ) , sweating ( N = 10 , 33 % ) , somnolence ( N = 9 , 30 % ) , diarrhea ( N = 9 , 30 % ) , dry mouth ( N = 8 , 27 % ) , dizziness ( N = 8 , 27 % ) , and , among males , impotence ( N = 3 , 21 % ) and ejaculatory abnormality ( N = 3 , 21 % ) in the paroxetine group , and headache ( N = 12 , 40 % ) , somnolence ( N = 12 , 40 % ) , nausea ( N = 11 , 37 % ) , dry mouth ( N = 11 , 37 % ) , insomnia ( N = 9 , 30 % ) , asthenia ( N = 7 , 23 % ) , and dyspepsia ( N = 7 , 23 % ) in the fluvoxamine group . The only statistically significant difference between treatment groups was for sweating ( 33 % paroxetine vs. 10 % fluvoxamine , p = .028 ) . CONCLUSION Observed differences in some side effects , although not statistically significant , indicate that when a patient has difficulty tolerating one SSRI , the clinician may choose to change to a different agent within the same class BACKGROUND Major depression is a common comorbid condition among individuals with alcohol dependence . This study examined the effects of nefazodone , a norepinephrine and serotonin reuptake blocker and 5-hydroxytryptamine-2 receptor antagonist , on mood and anxiety symptoms and drinking behavior in a sample of depressed alcoholics . METHODS This study was a double-blind , placebo-controlled comparison of nefazodone ( 200 - 600 mg/day ) or placebo in a sample of alcohol-dependent subjects ( n = 41 ; 52 % women ) with current major depression . After a 1-week placebo lead-in period , subjects were r and omly assigned to receive study medication and supportive psychotherapy for 10 weeks . RESULTS Depressive and anxiety symptoms declined significantly over time . Although the nefazodone group showed greater reductions in these symptoms , the effects did not reach statistical significance . Nonetheless , nefazodone-treated subjects showed a significantly greater reduction in heavy drinking days and in total drinks compared with placebo-treated subjects . CONCLUSIONS The lack of significant effects on depression and anxiety symptoms may reflect limited statistical power . Despite the small sample size , nefazodone significantly reduced some measures of alcohol consumption in this sample of depressed alcoholics 1 . The efficacy of fluvoxamine is compared to that of desipramine in a multicenter double blind placebo controlled six-week flexible dose trial of 90 out patients with major depressive disorder . 2 . Although overall drug effects were relatively weak , there were trends suggesting separation of both active drugs from placebo at week six . Both drugs were well tolerated . 3 . Studies of major depression ought to be design ed to last 8 - 10 weeks in order to demonstrate placebo active drug differences and the stability of such a difference should it occur in the first six weeks Two hundred hospitalized patients with DSM-III diagnosis of moderate to severe major depressive episode were r and omized to receive mirtazapine or trazodone for 6 weeks in a double-blind trial . The dosages were 24–72 mg/day for mirtazapine and 150–450 mg/day for trazodone . The improvement on all depression rating scales used was generally greater for mirtazapine , wish statistically significant differences over trazodone in the Hamilton Psychiatric Rating Scale for Depression total score and two subscores ( the Bech melancholia factor and retardation factor ) , the Brief Psychiatric Rating Scale total score , the General Psychiatric Impression Global Assessment Scale , the Beck score and responder rates . Mirtazapine was well tolerated , while the trazodone-treated patients experienced somnolence more frequently , particularly during the first 2 weeks of treatment . Furthermore , postural symptoms were a clinical problem in > ' 6 % of the trazodone-treated patients . In this trial , mirtazapine showed significant clinical advantages over trazodone in terms of overall efficacy and tolerability This study assessed the effect of fluoxetine 20 mg/day on weight loss in older patients treated for major depression in a multicenter , double-blind placebo-controlled , 6-week clinical trial . Thirty U.S. outpatient clinics affiliated with psychiatric programs participated in the study that involved 671 medically stable out patients at least 60 years old who had normal cognition and met DSM-III-R criteria for major depression . Weight was recorded at weekly visits . As a measure of adiposity , patients were categorized into two groups , high and low/normal body mass index ( BMI ) groups . Analyses were done for each group . The high BMI group , but not the low/normal BMI group , had a statistically greater proportion of fluoxetine-treated patients who lost at least 5 % of their baseline weight . Overall mean weight change for the fluoxetine-treated patients was about 1 % compared with essentially no change for placebo-treated patients . Only one patients , who was treated with fluoxetine and in the low/normal BMI group , discontinued from the study because of weight loss . Although 5 % weight loss occurred in more fluoxetine-treated than placebo-treated patients , most of the patients who lost weight had higher adiposity at baseline . There was not a statistically significant difference in the proportion of fluoxetine-treated and placebo-treated patients in the low/normal group who had at least 5 % weight loss . Medically relevant weight loss in older patients treated with fluoxetine was uncommon Our objective was to determine if pretreatment anxiety levels were associated with preferential response to bupropion sustained release ( n = 122 ) or sertraline ( n = 126 ) during a 16-week r and omized acute phase treatment study . Both agents had comparable antidepressant activity , and comparable anxiolytic effects using the intent-to-treat sample . Baseline anxiety levels were not related to antidepressant efficacy , and they did not differentiate responders to each agent . Time to clinical ly significant anxiolysis did not differentiate between treatment groups or between responders to each agent . These results contradict the commonly held , but unsubstantiated , belief that in clinical ly depressed anxious patients , serotonergic antidepressants are especially anxiolytic and that such patients preferentially benefit from the antidepressant or anxiolytic effects of selective serotonin reuptake inhibitors . Thus , the clinical decision to select between these two agents when treating depressed out patients can not rest on either levels of pretreatment anxiety or on anticipation of more rapid or more complete anxiolysis In a r and omized 6-week trial comparing fluoxetine with placebo , the Medical Outcomes Study 36-Item Short-Form Health Status Survey ( SF-36 ) scales were used to measure the effects of treatment on functional health and well-being among elderly ( age > or = 60 years ) out patients with major depression . In the fluoxetine and placebo groups , 261 and 271 patients , respectively , completed the SF-36 before treatment and at Weeks 3 and 6 . Compared with national norms for individuals over age 60 , study patients before treatment exhibited baseline decrements on the following SF-36 scales : mental health , role limitations due to emotional problems , social functioning , vitality , role limitations due to physical problems , and bodily pain . Analyses of SF-36 changed scores from baseline to Week 6 revealed that the fluoxetine group improved more than the placebo group across all scales . Differences in changes of scores between groups were significant ( p < .05 ) , favoring the fluoxetine group for the scales of mental health , role limitations due to emotional problems , physical functioning , and bodily pain . Improvements observed in the fluoxetine group were both clinical ly and socially significant BACKGROUND Depression is a serious and widespread emotional disorder among the elderly . This study compared the efficacy and safety of bupropion sustained release ( SR ) with the selective serotonin reuptake inhibitor paroxetine in the treatment of major depression in elderly out patients . METHOD Elderly ( > or = 60 years ) out patients with major depressive disorder ( DSM-IV criteria ) were evaluated in this 6-week multicenter , r and omized , double-blind study comparing bupropion SR , 100 - 300 mg/day , and paroxetine , 10 - 40 mg/day . Efficacy was assessed by changes in scores on the Hamilton Rating Scales for Depression ( HAM-D ) and Anxiety ( HAM-A ) and the Clinical Global Impressions-Severity of Illness and -Improvement scales . Safety was assessed by monitoring adverse events , vital signs , and body weight . RESULTS A total of 100 patients ranging in age from 60 to 88 years were r and omly assigned to treatment with bupropion SR ( N = 48 ) or paroxetine ( N = 52 ) . Measurements of efficacy were similar between the 2 treatment groups , with both groups showing improved scores on all depression rating scales . Headache , insomnia , dry mouth , agitation , dizziness , and nausea occurred in > 10 % of patients in both groups ; somnolence , diarrhea , constipation , and anorexia occurred in > 10 % of patients in the paroxetine group . No statistically significant differences between groups in vital signs or weight were found . CONCLUSION Both bupropion SR and paroxetine were safe and effective for the treatment of depression in the elderly . Because of its favorable side effect profile , bupropion SR may provide a safe and effective nonserotonergic treatment alternative that is well suited as an antidepressant for the elderly BACKGROUND Selective serotonin reuptake inhibitors ( SSRIs ) and venlafaxine have been regarded as less toxic in overdose than tricyclic antidepressants ( TCAs ) . Within the TCAs , dothiepin has greater toxicity . Venlafaxine may be more toxic than SSRIs . AIM To assess the toxicity in overdose of venlafaxine and SSRIs compared to TCAs , and of dothiepin compared to other TCAs . DESIGN Cohort study of prospect ively collected data from the Hunter area , NSW , Australia . METHODS First admissions with antidepressant deliberate self-poisoning ( DSP ) ( November 1994 to April 2000 ) were identified ; the presence of seizures , life-threatening arrhythmias , coma , serotonin toxicity or ICU admission , and QRS duration were noted . RESULTS There were 538 admissions , with no deaths . The odds ratio ( OR ) for seizures with dothiepin vs. other TCAs was 3.4 ( 95%CI 1.2 - 9.9 ) . Seizures occurred in 7/51 ( 14 % ) venlafaxine overdoses ; all patients with seizures consumed > or = 900 mg . The OR for seizures vs. TCAs was 4.4 ( 95%CI 1.4 - 13.8 ) . Coma was less likely with venlafaxine and SSRIs . SSRIs , but not venlafaxine , were less likely to prolong the QRS to > or = 100 ms . ICU admission was less likely for SSRIs . Serotonin toxicity was much more common with venlafaxine and SSRIs . DISCUSSION Venlafaxine and dothiepin are pro-convulsant in overdose . Venlafaxine is more likely to cause serotonin toxicity , but less likely to cause coma than TCAs . SSRIs are less likely to cause coma , require ICU admission , or prolong the QRS , but are more likely to cause serotonin toxicity . Antidepressants other than TCAs or venlafaxine should be considered in patients at risk of seizure or suicide The results from three 8-week escitalopram studies in major depressive disorder are presented with respect to efficacy and the effect on sleep quality , both in the full population and the sub population of patients with sleep problems at baseline . Analysis of pooled data from these r and omized , double-blind , placebo-controlled , studies in which citalopram was the active reference , showed a significant improvement for escitalopram-treated patients ( n = 52.0 ) in the Montgomery-Asberg depression rating scale ( MADRS ) item 4 ( ' reduced sleep ' ) scores at weeks 6 and 8 compared with placebo ( n=398 ; p < 0.01 ) and at weeks 4 , 6 and 8 ( n = 403 ; p < 0.05 ) compared with citalopram . Escitalopram-treated patients with sleep problems ( MADRS item 4 score > or = 4 ; n = 254 ) at baseline showed a statistically significant improvement in mean MADRS item 4 scores at weeks 4 , 6 and 8 compared with patients treated with placebo ( n = 191 ; p < 0.05 ) or citalopram ( n = 193 ; p < 0.01 ) . These patients also showed a statistically significant ( p < 0.05 ) and clinical ly relevant improvement in MADRS total score after escitalopram treatment compared with citalopram at weeks 1 , 4 , 6 and 8 ( observed cases ) and endpoint ( -2.45 ; last observation carried forward [ LOCF ] ) . Statistical significance in favour of escitalopram versus placebo treatment was found at all visits , including endpoint ( -4.2 ; LOCF).Thus , these post-hoc analyses suggest that escitalopram has a significant beneficial effect compared with placebo or citalopram in reducing sleep disturbance in patients suffering from major depressive disorder . The effect of escitalopram in improving ' reduced sleep ' scores was clearly seen in patients with more severe sleep disturbance at baseline . A further prospect i ve study is needed to establish this useful clinical effect in insomniac depressives CONTEXT Major depression affects about 25 % of the patients who have Alzheimer disease and has serious adverse consequences for patients and caregivers . Results of prior antidepressant treatment studies have produced contradictory findings and have not fully assessed the benefits of depression reduction . OBJECTIVES To assess the efficacy and safety of sertraline hydrochloride for the treatment of major depression in Alzheimer disease , and to evaluate the effect of depression reduction on activities of daily living , cognition , and nonmood behavioral disturbance . DESIGN R and omized , placebo-controlled , parallel , 12-week , flexible-dose clinical trial with a 1-week , single-blind placebo phase . The study was conducted between January 1 , 1998 , and July 19 , 2001 . SETTING University outpatient clinic . PARTICIPANTS Forty-four out patients who have probable Alzheimer disease and major depressive episodes . INTERVENTION Sertraline hydrochloride , mean dosage of 95 mg/d , or identical placebo , r and omly assigned . MAIN OUTCOME MEASURES Response rate , Cornell Scale for Depression in Dementia , Hamilton Depression Rating Scale , Mini-Mental State Examination , Psychogeriatric Depression Rating Scale-activities of daily living subscale , and Neuropsychiatric Inventory to quantify patient behavior disturbance and caregiver distress . RESULTS In the sertraline-treated group 9 patients ( 38 % ) were full responders and 11 ( 46 % ) were partial responders compared with 3 ( 20 % ) and 4 ( 15 % ) , respectively , in the placebo-treated group ( P = .007 ) . The sertraline-treated group had greater improvements in the scores for the Cornell Scale for Depression in Dementia ( P = .002 ) and Hamilton Depression Rating Scale ( P = .01 ) , and a statistical trend toward less decline in activities of daily living on the Psychogeriatric Depression Rating Scale-activities of daily living subscale ( P = .07 ) . There was no difference between the treatment groups in Mini-Mental State Examination ( P = .22 ) or Neuropsychiatric Inventory ( P = .32 ) ratings over time . When full responders , partial responders , and nonresponders were compared , full responders only , or full and partial responders had significantly better ratings on activities of daily living ( P = .04 ) , behavioral disturbance ( P = .01 ) , and caregiver distress ( P = .006 ) , but not on the Mini-Mental State Examination ( P = .76 ) . Safety monitoring indicated few differences in adverse effects between the 2 treatment groups . CONCLUSIONS Sertraline is superior to placebo for the treatment of major depression in Alzheimer disease . Depression reduction is accompanied by lessened behavior disturbance and improved activities of daily living , but not improved cognition This multicenter , r and omized , double-masked , placebo-controlled , parallel-group study compared the antidepressant efficacy and safety of bupropion sustained-release ( SR ) tablets ( 150 mg QD or 150 mg BID ) with placebo in out patients with moderate-to-severe depression . The study consisted of a 1-week placebo phase followed by 8 weeks of active treatment with bupropion SR 150 mg/d ( 150 mg QD , n = 121 ) or 300 mg/d ( 150 mg BID , n = 120 ) or placebo ( n = 121 ) . Efficacy was measured by changes in scores on the 17-item Hamilton Rating Scale for Depression ( HAM-D ) and the Clinical Global Impressions for Severity of Illness ( CGI-S ) and Clinical Global Impressions for Improvement of Illness ( CGI-I ) scales . Safety was monitored by regular assessment of vital signs and adverse events as well as by pretreatment and posttreatment physical and clinical laboratory examinations . By day 56 , both bupropion SR treatments were more effective in relieving the symptoms of depression than was placebo . Compared with those receiving placebo , patients in the bupropion SR 150- and 300-mg/d groups had significantly reduced symptoms by treatment day 56 , as measured on the 17-item HAM-D , CGI-S , and CGI-I scales ( P < 0.05 ) . Bupropion SR was well tolerated , with no serious adverse events reported by bupropion-treated patients ; 95 % of all reported adverse events were of mild or moderate intensity . No clinical ly significant changes in vital signs , laboratory test results , or physical findings were observed . A greater mean weight loss was observed at the end of treatment in both the bupropion SR 150-mg ( 0.5 kg ) and bupropion SR 300-mg ( 1.0 kg ) group compared with placebo ( 0.2 kg ) . We found that bupropion SR 150 mg administered either once or twice daily was more effective than placebo in treating depression and that once-daily dosing appears to be at least as effective as twice-daily dosing . Should this prove true , depressed patients may be able to benefit from the convenience and improved tolerability associated with once-daily dosing AIM To identify the incidence and risk of suicide and self harm , among patients prescribed antidepressant drugs . METHODS A retrospective cohort study , with nested case control , of patients identified from a nonr and om sample of general practice s in New Zeal and from 1996 to 2001 . A total of 57 361 patients who received a prescription for a single antidepressant were identified from the RNZCGP Research Unit Data base . Suicides within 120 days of a prescription were identified from the New Zeal and National Mortality Data base and self-harm events within 120 days of a prescription were identified from the New Zeal and Hospital discharge data base . RESULTS 26 suicides and 330 episodes of self-harm were identified within 120 days of an antidepressant prescription . On univariate analysis the association , expressed as OR ( 95 % CI ) , between selective serotonin reuptake inhibitors ( SSRIs ) and self harm and suicide were 2.26 ( 1.27 - 4.76 ) and 1.92 ( 0.77 - 4.83 ) , respectively . When corrected for the confounding effects of age , gender and depression/suicidal ideation there was an association between SSRIs and self harm , OR 1.66 ( 95 % CI 1.23 - 2.23 ) , but not for suicide , 1.28 ( 0.38 - 4.35 ) . Paroxetine was a significant risk factor for suicide on univariate analysis , 4.23 ( 1.19 - 14.95 ) , but not when corrected for age , gender and depression/suicidal ideation , 2.76 ( 0.30 - 24.87 ) . CONCLUSIONS Age , gender and pre-existing depression/suicidal ideation are important confounders in observational studies of the association between antidepressants and suicide or self harm This multinational , r and omized , double-blind study was specifically design ed to prospect ively compare the onset of antidepressant efficacy of mirtazapine orally disintegrating tablets and sertraline at dosages commonly used in clinical practice . A total of 345 patients with major depressive episode ( DSM-IV ) received mirtazapine ( 30–45 mg/d ) or sertraline ( 50–150 mg/d ) for 8 weeks . Mirtazapine was administered in the newly developed fast dissolving , orally disintegrating tablet formulation . Assessment s were performed at baseline and on days 4 , 7 , 10 , 14 , 28 , 42 , and 56 . The primary efficacy variable ( mean absolute change from baseline in the Hamilton Depression Rating Scale [ HAMD ] total score [ 17 items ] ) showed that mirtazapine was significantly ( P < 0.05 ) more effective than sertraline at all assessment s during the first 2 weeks of the study . After this time , HAMD total scores were similar in both groups . These findings were supported by analysis of the HAMD response rate ( ie , ≥50 % reduction in HAMD total score from baseline ) , HAMD remission rate ( HAMD total score of ≤7 ) , and the Montgomery-Åsberg Depression Rating Scale ( MADRS ) . Both treatments were well tolerated . In addition , mirtazapine had a greater effect than sertraline on sexual functioning . In conclusion , this first prospect i ve onset of action study using the orally disintegrating tablet indicates that mirtazapine has a faster onset of therapeutic effect than sertraline . The orally disintegrating tablet formulation of mirtazapine used in this study is known to enhance the convenience and compliance by the patient OBJECTIVE To compare the efficacy and tolerability of mirtazapine and fluoxetine in depressed in patients and out patients . METHOD Patients with a major depressive episode ( DSM-III-R ) , a baseline score of > or=21 on the 17-item Hamilton Rating Scale for Depression ( HAM-D ) , and > or=2 on HAM-D Item 1 ( depressed mood ) were r and omly assigned to a 6-week treatment with either mirtazapine ( N=66 , 15 - 60 mg/day ) or fluoxetine ( N=67 , 20 - 40 mg/day ) . The upper limit of the mirtazapine dose range was above the dose range approved in the United States ( 15 - 45 mg/day ) . Efficacy was evaluated by the HAM-D , Clinical Global Impressions , the Visual Analogue Mood Rating Scale ( VAMRS ) , and the Quality of Life Enjoyment and Satisfaction Question naire ( QLESQ ) . The efficacy analyses were performed on the intent-to-treat group using the last-observation-carried-forward method . RESULTS Mean total 17-item HAM-D scores at baseline were 26.0 for the mirtazapine- and 26.1 for the fluoxetine-treated group . The decrease from baseline on the HAM-D was larger in the mirtazapine than in the fluoxetine group throughout the treatment period , reaching statistical significance at days 21 and 28 . At assessment s from day 21 and onward , the absolute difference between the 2 study groups favoring mirtazapine ranged from 3.7 to 4.2 points , the magnitude of difference usually seen between an efficacious antidepressant drug and placebo . Mean dosages at weeks 1 - 4 were 36.5 mg/day for mirtazapine and 19.6 mg/day for fluoxetine ; the respective dosages at weeks 5 - 6 were 56.3 mg and 35.8 mg . Similar numbers of patients dropped out due to adverse events ; tolerability profiles were comparable except for changes in body weight from baseline which were statistically significantly more pronounced in the mirtazapine group compared to the fluoxetine group . CONCLUSION We found that mirtazapine was as well tolerated as fluoxetine and significantly more effective after 3 and 4 weeks of therapy & NA ; Escitalopram was compared to placebo in moderately to severely depressed patients in primary care with citalopram as the active reference . Patients were r and omized to receive flexible doses of 10–20 mg/day escitalopram ( n=155 ) , 20–40 mg/day citalopram ( n=160 ) , or placebo ( n=154 ) over an 8‐week double‐blind period . The primary efficacy parameter was the change from baseline to last assessment in the Montgomery – Asberg Depression Rating Scale total score . Escitalopram produced a statistically significant therapeutic difference of 2.9 points ( P=0.002 ) compared to placebo , and escitalopram was consistently and statistically significantly more efficacious than placebo from week 1 onwards . Analysis of Clinical Global Impression – Severity and Clinical Global Impression – Improvement confirmed the primary efficacy results . By week 8 , significantly more patients had responded to treatment with escitalopram than with citalopram ( P=0.021 ) or placebo ( P=0.009 ) . Escitalopram was as well tolerated as citalopram and had a similar adverse event profile . Both escitalopram‐ and citalopram‐treated patients had placebo‐level adverse event withdrawal rates ( 3 % and 4 % , respectively ) . This study demonstrates the consistent antidepressant efficacy and excellent tolerability of escitalopram 10–20 mg/day in primary care patients with major depressive disorder OBJECTIVE Management of depression in elderly patients presents a significant medical challenge , and there is a need for further clinical trials . The authors examined the efficacy and tolerability of escitalopram and fluoxetine versus placebo in the treatment of elderly patients with major depressive disorder ( MDD ) . METHODS This was an 8-week , r and omized , double-blind comparison of the efficacy and tolerability of escitalopram ( 10 mg/day ) and fluoxetine ( 20 mg/day ) , to placebo in elderly patients with MDD . The prospect ively defined primary efficacy parameter was the change from baseline in mean Montgomery-Asberg Depression Rating Scale ( MADRS ) total score at endpoint , using last observation carried forward . RESULTS The intent-to-treat set comprised 517 patients ; the escitalopram group included 173 patients ; fluoxetine , 164 patients ; and placebo , 180 patients . Mean age was 75 years , with a range of 65 to 93 . Formally , this was a " failed study " ( i.e. , neither active treatment was superior to placebo ) , and the efficacy results should , therefore , be interpreted with caution . On the basis of the primary efficacy parameter , fluoxetine showed significantly lower efficacy than both escitalopram and placebo , which were not significantly different from each other . Rates of withdrawal because of adverse events/lack of efficacy were : placebo ( 2.8%/4.4 % , respectively ) , escitalopram ( 9.8%/1.7 % , respectively ) , and fluoxetine ( 12.2%/1.8 % , respectively ) . No single adverse event occurred at an incidence > or = 10 % in escitalopram-treated patients . CONCLUSIONS Both escitalopram and fluoxetine were well tolerated by elderly patients with MDD . Neither demonstrated superior efficacy on primary endpoint versus placebo 1 . The safety and efficacy of sertraline in the treatment of moderate-to-severe major depression in elderly out patients , aged 60 years and older , with comorbid vascular disease was evaluated . 2 . An analysis of the pooled results for the sertraline treatment group drawn from two prospect i ve , r and omized , double-blind studies ( sertraline vs. fluoxetine , and sertraline vs. nortriptyline ) was done . Patients were retrospectively categorized into one of 3 clinical groups : 1 ) patients with a current diagnosis of hypertension but no other past or present cardiovascular illness ( HTN ) , 2 ) patients reporting a current or past history of cardiovascular illness , but excluding hypertension ( VASC ) , and 3 ) patients with no hypertension , and no other comorbid vascular illness ( NoVASC ) . Patients received 12 - 3 . weeks of double-blind treatment with sertraline in flexible daily doses in the range of 50 - 150 mg ( in the nortriptyline comparator trial ) or 50 - 100 mg ( in the fluoxetine comparator trial ) . 4 . Sertraline treatment yielded comparable levels of response in all 3 groups ( response criterion : CGI-much or very much improved ) at treatment endpoint on both a completer analysis ( HTN , 86 % ; VASC , 89 % ; NoVASC , 77 % ) and significantly higher response rates on a 12-week endpoint analysis ( HTN , 74 % ; VASC , 69 % ; NoVASC , 58 % ; p < 0.05 ) . Sertraline treatment was well-tolerated , with no between-group differences in rates of adverse events , or in discontinuation due to adverse events . Patients taking 5 or more concomitant medications showed no difference , when compared with patients taking none-or-one concomitant medication , either in rates of adverse events , or in discontinuation due to adverse events . 5 . Sertraline was found to be a safe , well-tolerated , and effective as an antidepressant in elderly patients suffering from hypertension and other forms of vascular comorbidity ABSTRACT Objective : The goal of a non-inferiority study is to test whether a new treatment has at least as much efficacy as an established treatment1 . The purpose of this non-inferiority study was to compare the speed of onset of antidepressant efficacy for duloxetine ( a dual serotonin and norepinephrine reuptake inhibitor ) and escitalopram ( a selective serotonin reuptake inhibitor ) . Research design and methods : This was a r and omized , double-blind , placebo- and active comparator-controlled study , in which patients ( ≥ 18 years ) meeting DSM‑IV criteria for Major Depressive Disorder ( MDD ) received duloxetine 60 mg once daily ( QD ; N = 273 ) , escitalopram 10 mg QD ( N = 274 ) , or placebo ( N = 137 ) for 8 weeks . The primary objective was to compare the onset of antidepressant efficacy , by testing the hypothesis that the percentage of duloxetine-treated patients achieving onset criteria at Week 2 was not inferior to that in the escitalopram group . Main outcome measures : Onset of efficacy was defined as a 20 % decrease from baseline on the 17‑item Hamilton Rating Scale for Depression ( HAMD17 ) Maier subscale that was maintained or exceeded at all subsequent visits . Results : Probabilities of meeting onset criteria at Week 2 for duloxetine- and escitalopram-treated patients were 42.6 % versus 35.2 % , respectively ( treatment difference = 7.4 % ; 95 % confidence interval , –1.3 % to 16.2 % ; p = 0.097 ) . Both drugs showed significant improvement compared with placebo ( p ≤ 0.05 ) on the primary efficacy measure ( Maier subscale ) at Week 1 and endpoint ( Week 8) . No differences were found between duloxetine , escitalopram , and placebo rates of remission or response at 8 weeks . Adverse events that occurred significantly more frequently among duloxetine-treated patients when compared with those receiving escitalopram were nausea , dry mouth , vomiting , yawning , and irritability . The rate of discontinuation due to adverse events did not differ significantly between treatment groups . Limitations : Given the difficulties in constructing appropriate dose comparisons , the results of this study should be interpreted specific to the doses tested and not extrapolated to the drug as a whole . This study employed a fixed-dose design ; flexible-dose design s are more likely to find a difference between antidepressants and placebo . Conclusion : In this study , both duloxetine and escitalopram showed significantly greater improvement on the primary efficacy measure than placebo over the 8‑week acute treatment period , while no differences were observed between drugs or between drugs and placebo on response and remission rates at 8 weeks . Escitalopram at a starting dose of 10 mg QD was better tolerated than duloxetine at a starting dose of 60 mg QD . This study met its pre-defined primary objective of assessing if duloxetine was non-inferior to escitalopram in antidepressant onset efficacy , and the results show that duloxetine is at least as fast as ( non-inferior to ) escitalopram . Trial registration : Clinical Trials.gov identifier : NCT00073411 The objective of this study was to compare the safety and efficacy of paroxetine with imipramine and placebo in depressed out patients . Following a 4- to 14-day placebo washout , patients were r and omized into treatment groups and received study compound for up to 42 days . At Day 42 , paroxetine was significantly more effective than placebo ( p less than .05 ) in several observer- and patient-rated scales : the Retardation and Anxiety/Somatization factors of the Hamilton Rating Scale for Depression ( HAM-D ) , the Montgomery-Asberg Depression Rating Scale ( MADRS ) , the Raskin Depression Scale , the Covi Anxiety Scale , the Clinical Global Impressions ( CGI ) Improvement Scale , the Symptom Checklist-56 ( SCL-56 ) Total , and the Patient 's Global Evaluation ( PGE ) . There were no significant differences between paroxetine and imipramine . Significantly more imipramine ( 75 % ) than paroxetine ( 35 % ) or placebo ( 23 % ) patients reported anticholinergic side effects , including blurred vision ( 5 % , 0 % , and 0 % , respectively ) , constipation ( 35 % , 8 % , and 15 % , respectively ) , and dry mouth ( 63 % , 25 % , and 15 % , respectively ) . The data from this study indicated that paroxetine is a safe , well-tolerated , effective treatment for major depressive disorder A group of 480 patients , aged 19 - 78 with an HRSD score of at least 17 and who met DSM-III criteria for major depressive disorder were studied . Patients were given placebo for a one-week single-blind run-in period , after which sertraline was administered for eight weeks . This was followed by 44 weeks in which patients received sertraline or placebo on a double-blind , r and omised basis . Patients were assessed periodically using the 17-item HRSD and the Clinical Global Impression scales . During the entire double-blind period 24 ( 13.0 % ) sertraline patients relapsed compared with 48 ( 45.7 % ) placebo patients ( P less than 0.001 ) . The protective effect of sertraline was maintained throughout the 44 weeks . The study provides evidence that sertraline prevents relapse of the index episode of depression as well as recurrence of further episodes and has few side-effects OBJECTIVE The incidence of sexual dysfunction due to antidepressant drugs reported in pre-marketing clinical efficacy trials is often several times lower than in subsequent clinical experiences and independent reports . Although it is commonly believed that the reason for this discrepancy is that the nonleading questions employed in conventional clinical trials underestimate sexual dysfunction while the direct question ing used in independent trials provides more accurate data , few studies have actually compared these 2 methods . METHOD In this study , 119 patients with a DSM-IV-defined major depressive episode ( 82 women and 37 men ) who had been treated with but not responded to a selective serotonin reuptake inhibitor ( SSRI ; either citalopram or paroxetine ) were assessed regarding sexual functioning by means of open-ended questions and direct question ing at baseline ( after SSRI treatment only ) and after 4 weeks of SSRI treatment plus buspirone or placebo . RESULTS More patients reported sexual dysfunction in response to direct question ing ( 41 % ) as compared with spontaneous report ( 6 % ) ( p < .001 ) . Sexual dysfunction correlated with the duration of the depressive episode , but not with age , dose of SSRI , plasma level of SSRI , duration of SSRI treatment , or any measurement of depression . No statistically significant differences regarding the incidence of sexual dysfunction were found between the citalopram and the paroxetine groups . CONCLUSION Open-ended questions are an insufficient tool to estimate sexual dysfunction , and premarketing clinical trials should therefore include basic explicit assessment s. The failure to find a correlation between treatment duration and sexual dysfunction adds to the notion that sexual side effects due to SSRIs do not abate over time Diagnostic criteria , r and om parallel placebo-controlled study design , and appropriate clinical assessment for both safety and efficacy are all among the essential requirements for the evaluation of a new antidepressant agent . Paroxetine and imipramine were compared for efficacy and safety in a large multicentre , r and omized , placebo-controlled , double-blind , parallel design study in the USA . The study involved 717 out patients with major depressive disorder ; after a one-week washout period they were treated for 6 weeks , being assessed at weekly intervals . The results from all six participant centres combined showed that both active drugs were statistically superior to placebo by week 2 and that the antidepressant response was significant for both . Paroxetine was better tolerated than imipramine with fewer dropouts from side effects . This combined study clearly indicated that paroxetine was an effective and well-tolerated antidepressant OBJECTIVE In this study the authors evaluated the efficacy and the tolerability of sertraline and paroxetine in the treatment of delusional depression . METHOD Under double-blind conditions , 46 hospitalized patients who met the DSM-III-R criteria for major depression with psychotic features were treated with sertraline or paroxetine for 6 weeks . RESULTS The response rates were 75 % and 46 % for sertraline and paroxetine , respectively . The dropout rate was substantial ( 41 % ) in the paroxetine group and was attributable to side effects . CONCLUSIONS Selective serotonin reuptake inhibitors administered alone are useful in the treatment of delusional depression BACKGROUND Despite a growing use of selective serotonin reuptake inhibitors in older people , only one trial has examined their prophylactic efficacy in people aged 65 years and over . AIMS To examine the efficacy of sertraline in preventing the recurrence of depression in older people living in the community . METHOD Participants were openly treated with sertraline and then r and omised into a double-blind , placebo-controlled continuation/maintenance study of about 2 years duration . Drug dosage was maintained at levels that achieved remission . RESULTS No significant difference between the sertraline and placebo groups was found in the proportion of recurrences ( -7.9 % ; 95 % CI -28.06 to 12.23 ) . Increased age and minor residual symptoms during the continuation phase were associated with recurrence . CONCLUSIONS Sertraline at therapeutic dosage does not provide significant protection against recurrence Paroxetine is a phenylpiperidine compound that selectively inhibits neuronal serotonin uptake in man . In this study , the efficacy of paroxetine was compared with that of placebo in the treatment of 66 out patients with the diagnosis of moderate-to-severe major depression . The research was a 6-week , prospect i ve , double-blind design after a 1-week placebo baseline phase . Paroxetine was associated with a consistent pattern of greater improvement on the primary efficacy scales , but the differences were not statistically significant . Paroxetine did produce significantly greater improvement than placebo for patients whose illness had lasted more than 1 year , and there was a significant reduction in suicidal ideation . Significantly fewer dropouts were due to lack of efficacy in those patients treated with paroxetine compared with those in the placebo group . Paroxetine was well tolerated . There was no difference between paroxetine and placebo in the rate of adverse effects or in the number of patients who dropped out because of adverse effects In 16 depression clinics in hospitals and outpatient facilities in the Netherl and s , a study was performed to evaluate and compare the efficacy and tolerability of citalopram and fluvoxamine and to determine the difference in the incidence of gastrointestinal side-effects . A total of 217 patients with a depressive disorder ( DSM-III-R criteria ) and a score of at least 16 on the Hamilton rating scale for depression were r and omized to treatment . The results of this study indicate that the two drugs are equally effective . The adverse events occurring during treatment show a similar pattern between the two drugs , but citalopram is better tolerated than fluvoxamine . Citalopram induces fewer gastrointestinal adverse events compared with fluvoxamine . However , this did not affect the drop-out rates A double-blind , placebo- and amitriptyline-controlled comparison study was performed to evaluate the antidepressant efficacy of sertraline , a specific serotonin uptake inhibitor . Patients with DSM-III-defined major depression r and omly received either sertraline ( N = 149 ) , amitriptyline ( N = 149 ) , or placebo ( N = 150 ) once daily for the 8-week study period . The mean final daily medication dose for the all- patients group was 145 mg and 104 mg for the sertraline- and amitriptyline-treatment groups , respectively . As measured by the Hamilton Rating Scale for Depression and the Clinical Global Impressions Scale , both the sertraline and amitriptyline treatment groups showed a significantly greater improvement from baseline ( p less than or equal to .001 ) than the placebo group . The sertraline group had a higher proportion of gastrointestinal complaints and male sexual dysfunction than either the amitriptyline or the placebo group . The amitriptyline group showed a higher proportion of anticholinergic and sedative side effects and dizziness compared with patients who received either sertraline or placebo Results are presented of the first double-blind , placebo-controlled trial of a novel antidepressant venlafaxine , which pre clinical ly has demonstrated serotonin , norepinephrine , and dopamine reuptake inhibiting effects . Sixty out patients meeting DSM-III-R criteria for major depression were r and omized to receive 6 weeks of treatment with one of three fixed doses of venlafaxine—25 mg three times a day , 75 mg three times a day , or 125 mg three times a day — or placebo . Significant improvement was observed in depression scores at all doses , with the high dose result ing in earlier improvement , by week 2 . For the combined venlafaxine treatment groups , 68 % achieved a moderate or marked improvement on the Clinical Global Impression scale , compared with only 31 % for the placebo group . Venlafaxine was well tolerated , and nervousness , sweating , and nausea were the only adverse effects observed more frequently with drug compared with placebo Paroxetine is a selective serotonin reuptake inhibitor which is being developed as an antidepressant . Previous studies suggest it is effective in the treatment of depression and has a low incidence of side effects . The authors report on a 6-week , r and omized , prospect i ve trial of paroxetine , imipramine , and placebo in 120 out patients with major depression . The results showed that paroxetine was significantly superior to placebo in relieving depression . There were no significant differences in antidepressant efficacy between paroxetine and imipramine . However , paroxetine was also significantly superior to placebo on several measures of anxiety . Imipramine either was not superior on these measures or took longer to show a significant difference . Paroxetine lacked the typical anticholinergic side effects that accompanied imipramine therapy . The results show that paroxetine is an effective antidepressant that may have value especially when depression is accompanied by significant anxiety BACKGROUND Sleep complaints are common in patients with major depressive disorder ( MDD ) . Both MDD and antidepressant drugs characteristically alter objective sleep measures . This study compares the effects of mirtazapine and fluoxetine on sleep continuity measures in DSM-IV MDD patients with insomnia . METHOD Patients ( N = 19 ) received initial baseline polysomnography evaluations over 2 consecutive nights . Subjects were r and omly assigned to either fluoxetine ( 20 - 40 mg/day ) or mirtazapine ( 15 - 45 mg/day ) treatment for an 8-week , double-blind , double-dummy treatment trial . Single-night polysomnograms were conducted at weeks 1 , 2 , and 8 , with depression ratings assessed at baseline and weeks 1 , 2 , 3 , 4 , 6 , and 8 . Statistical analysis was performed by repeated- measures analysis of variance followed by Dunnet 's post hoc analyses . RESULTS Patients receiving mirtazapine ( N = 8) had significant improvement in objective sleep physiology measures at 8 weeks . Improvements in sleep latency , sleep efficiency , and wake after sleep onset were significant after only 2 weeks of mirtazapine treatment . No significant changes in sleep continuity measures were observed in the fluoxetine group ( N = 11 ) . Both groups improved clinical ly in mood and subjective sleep measures from baseline , with no differences between groups . CONCLUSION These data demonstrate the differential effects of mirtazapine and fluoxetine , with significant improvement in favor of mirtazapine , on objective sleep parameters in MDD patients with insomnia BACKGROUND Sleep effects of antidepressants are important clinical ly and for elucidating mechanism of action : selective serotonin reuptake inhibitors disturb sleep and 5-HT(2 ) receptor-blocking compounds may enhance sleep quality . AIMS To compare the objective and subjective effects on sleep of paroxetine and nefazodone in patients with moderate to severe depression . METHOD Forty patients with depression were r and omised to take paroxetine 20 - 40 mg/day or nefazodone 400 - 600 mg/day for 8 weeks . Objective and subjective quality of sleep and depression measures were assessed throughout . RESULTS Nefazodone significantly increased objective sleep efficiency and total sleep time , and improved subjective sleep on days 3 and 10 . Paroxetine decreased sleep efficiency early in treatment and some sleep disruption remained at week 8 . Paroxetine but not nefazodone produced marked suppression of rapid eye movement ( REM ) sleep . CONCLUSIONS Nefazodone improves sleep in early treatment compared with paroxetine in patients with moderate to severe depression . These effects are seen within the first 2 weeks of treatment and diminish thereafter A sample of 31 female nursing home patients with late-stage Alzheimer 's disease participated in a double-blind clinical trial of the antidepressant medication sertraline . Measures of depression included various objective scales and two measures of facial expressions of emotion coded during a semistructured interview using a facial affect coding system . Repeated- measures ANOVAs at baseline and at the 8-week endpoint indicated that on all measures , both the treatment and placebo groups improved over time , with three of six measures showing a significant time effect . The " knit-brow " facial measure approached significance for a Treatment x Time effect . Thus , sertraline had no significant benefits over placebo . However , if , as we hypothesize , the knit-brow response is more sensitive to signs of depression in advanced dementia , our study justifies the further investigation of the use of sertraline in this population BACKGROUND A common clinical belief is that more sedating and /or serotonin-selective antidepressants are preferred for depressed patients with symptoms of anxiety compared with more activating and /or catecholamine-selective antidepressants . The purpose of this study was to determine whether higher baseline anxiety is associated with different antidepressant responses to bupropion sustained release ( SR ) or sertraline . METHODS A retrospective data analysis was conducted using pooled data from two identical 8-week , r and omized , double-blind , placebo-controlled multicenter studies of bupropion SR ( n=234 ) , sertraline ( n=225 ) , and placebo ( n=233 ) in adult out patients with recurrent , major depressive disorder . Anxiety symptoms were measured using the 14-item Hamilton Anxiety Rating Scale scores . RESULTS Baseline anxiety levels were not related to antidepressant response to treatment with either bupropion SR or sertraline , nor did they differentiate between responders to bupropion SR and responders to sertraline . CONCLUSIONS Baseline anxiety levels do not appear to be a basis for selecting between bupropion SR and sertraline in the treatment of out patients with major depressive disorder OBJECTIVE The rate of adverse events following discontinuation of treatment with extended-release venlafaxine was compared with the rate associated with discontinuation of placebo administration . METHOD The subjects were 20 out patients with major depressive disorder who had participated in a multicenter , double-blind , placebo-controlled study of the efficacy of the new extended-release formulation of venlafaxine . RESULTS During the 3 days after discontinuation of treatment with the study drug , seven ( 78 % ) of the nine venlafaxine-treated subjects and two ( 22 % ) of the nine placebo-treated patients reported the emergence of adverse events , a statistically significant difference . CONCLUSIONS These results suggest that clinicians discontinuing venlafaxine treatment should consider tapering the medication dose gradually Depression is associated with considerable morbidity and mortality . As depressive disorders carry a high risk of relapse , treatment strategies include the use of a 6-month continuation period after resolution of the acute episode . Tolerability is of major importance when determining compliance and outcome during long-term therapy . Due to the superior tolerability profile of the selective serotonin reuptake inhibitors ( SSRIs ) over the older tricyclic antidepressants ( TCAs ) , the former may be more suitable for extended therapy . Comparative studies have not shown differences between the SSRIs in terms of efficacy , but side-effect profiles may vary . A multicenter , double-blind , comparative study of sertraline and fluoxetine was carried out in out patients fulfilling DSM-III-R criteria for major depressive disorder . Patients were r and omised to receive sertraline ( 50 - 150 mg , n = 118 ) or fluoxetine ( 20 - 60 mg , n = 120 ) for 24 weeks . Assessment s for depression ( HAM-D , HAD , CGI-I , CGI-S ) , anxiety ( Covi ) , sleep ( Leeds Sleep Evaluation scale ) and quality of life ( SIP ) were made at study entry and at weeks 2 , 4 , 8 , 12 , 18 and 24 . All adverse events were recorded to allow evaluation of tolerability . In total , 88 patients in the sertraline group completed the study compared with 79 in the fluoxetine group . Side effects were responsible for the premature treatment withdrawal of seven ( 6 % ) sertraline patients and 12 ( 10 % ) fluoxetine patients . Two-hundred and thirty-four patients were included in an ITT analysis up to last visit ( 116 sertraline , 118 fluoxetine ) . At study endpoint , both treatments produced a significant improvement over baseline on all efficacy variables ( P < 0.001 ) . Although the magnitude of global changes in depression , anxiety , and quality of life was larger with sertraline than fluoxetine , none of the between-group differences reached statistical significance . However , significant differences in favour of sertraline were observed for individual HAM-D items including item 4 ( insomnia onset ) ( P = 0.04 ) , item 9 ( agitation ) ( P = 0.02 ) , and item 13 ( general somatic symptoms ) ( P = 0.008 ) . In addition , sertraline was associated with significantly superior performance on the Leeds Sleep Evaluation scale and on SIP items relating to sleep and rest , emotional behaviour and ambulation . Both sertraline and fluoxetine were well tolerated with no significant differences between treatments Sexual dysfunction , a frequently reported side effect of many antidepressants , may result in patient dissatisfaction and noncompliance with treatment regimens . This paper describes the results of the first placebo-controlled comparison of the efficacy , safety , and effects on sexual functioning of sustained-release bupropion ( bupropion SR ) and the selective serotonin reuptake inhibitor sertraline . This r and omized , double-masked , double-dummy , parallel-group , multicenter trial enrolled 360 patients with moderate-to-severe recurrent major depression . Patients were treated with bupropion SR 150 to 400 mg/d , sertraline 50 to 200 mg/d , or placebo for up to 8 weeks . Patients ' depression and sexual functioning were assessed at weekly or biweekly clinic visits ; safety was assessed by regular monitoring of adverse events , vital signs , and body weight . Treatment groups were similar at baseline in terms of age , sex , and race , and most patients had a diagnosis of moderate uncomplicated depression . Patients treated with bupropion SR or sertraline showed similar improvements on all efficacy measures ; both active treatments were superior to placebo in improving scores on all rating scales for depression at various time points . Significantly more patients treated with sertraline experienced orgasmic dysfunction throughout the study than did patients treated with bupropion SR or placebo ( P < 0.001 ) . Headache was the most frequently reported adverse event in all 3 treatment groups and occurred with similar frequency in each group ( 30 % to 40 % ) . Nausea ( 31 % ) , diarrhea ( 26 % ) , insomnia ( 18 % ) , and somnolence ( 17 % ) occurred in significantly more patients in the sertraline group than in the bupropion SR group ( 18 % , 7 % , 13 % , and 3 % , respectively ) and the placebo group ( 10 % , 11 % , 4 % , and 6 % , respectively ) . Dry mouth occurred more frequently with bupropion SR ( 19 % ) than with sertraline ( 14 % ) or placebo ( 12 % ) , although the differences were not significant . Changes in vital signs were similar in all groups . Similar ( small , but not statistically significant ) decreases in mean body weight were seen in both the bupropion SR ( -1.06 kg ) and sertraline ( -0.79 kg ) groups , whereas the placebo group experienced a minor increase ( 0.21 kg ) . Although bupropion SR and sertraline were similarly well tolerated and effective in the treatment of depression , sertraline treatment was more often associated with sexual dysfunction and certain other adverse events compared with bupropion SR and placebo . Therefore , bupropion SR may be an appropriate choice as an antidepressant for the treatment of sexually active patients The efficacy of nefazodone in prevention of relapse of depression was evaluated in a 36-week double-blind , placebo-substitution , continuation treatment trial . After 16 weeks of acute , single-blind treatment with nefazodone , 131 patients responding to treatment and in stable remission were r and omized in a 36-week double-blind trial to either nefazodone ( n = 65 ) or placebo ( n = 66 ) . Patients were defined as having relapsed if they had a total score > or = 18 on the 17-item Hamilton Depression Scale on two consecutive visits or if they discontinued treatment for lack of efficacy . Relapse rates were significantly lower for patients r and omized to continued nefazodone treatment than for patients switched to placebo . Kaplan-Meier estimates of relapse rates 9 months ( 36 weeks ) after the end of acute treatment were 1.8 % for nefazodone versus 18.3 % for placebo ( P = 0.009 ) by the Hamilton Depression Scale and 17.3 % versus 32.8 % ( P = 0.028 ) by discontinuation for lack of efficacy . The mean modal dose of nefazodone was 412 mg/day at study endpoint . These results demonstrate the clinical effectiveness of up to 1 year 's treatment ( 16 weeks acute and 36 weeks continuation ) with nefazodone in depressed patients . Long-term efficacy of nefazodone was accompanied by a good safety profile without any weight gain and with minimal symptoms of withdrawal upon abrupt discontinuation of treatment BACKGROUND Duloxetine hydrochloride , a dual reuptake inhibitor of serotonin and norepinephrine , was evaluated for therapeutic efficacy and safety/tolerability in the treatment of major depression . METHOD In an 8-week multicenter , double-blind , placebo-controlled study , 173 patients ( aged 18 - 65 years ) with DSM-IV major depressive disorder were r and omly allocated to receive placebo ( N = 70 ) , duloxetine ( N = 70 ) , or fluoxetine , 20 mg q.d . ( N = 33 ) . Duloxetine dose was titrated in the first 3 weeks in a forced-titration regimen from 40 mg ( 20 mg b.i.d . ) to 120 mg/day ( 60 mg b.i.d . ) . Patients were required to have a Clinical Global Impressions (CGI)-Severity of Illness scale score of at least moderate severity ( > or = 4 ) and a 17-item Hamilton Rating Scale for Depression ( HAM-D-17 ) total score of at least 15 . Patients could not have had any current primary DSM-IV Axis I diagnosis other than major depressive disorder , or any anxiety disorder as a primary diagnosis within the past year , excluding specific phobias . The primary efficacy measurement was the HAM-D-17 total score , and secondary measures included the Montgomery-Asberg Depression Rating Scale , CGI-Severity of Illness and CGI-Improvement , and Patient Global Impression of Improvement . Safety was evaluated by recording the occurrence of discontinuation rates and treatment-emergent adverse events and by measurement of vital signs and laboratory analytes . RESULTS Duloxetine was superior to placebo in change on the HAM-D-17 ( p = .009 ) . Estimated probabilities of response and remission were 64 % and 56 % , respectively , for duloxetine , compared with 52 % and 30 % for fluoxetine and 48 % and 32 % for placebo . Duloxetine was numerically superior to fluoxetine on the primary and most of the secondary outcome measures . In general , duloxetine was well tolerated ; 76 % of patients achieved the maximum dose , and insomnia and asthenia were the only adverse events reported statistically significantly ( p < .05 ) more frequently by duloxetine-treated patients compared with placebo-treated patients . CONCLUSION These data indicate that duloxetine is efficacious for the treatment of major depressive disorder and is well tolerated and safe Serotonin-norepinephrine reuptake inhibitors ( SNRIs ) may be used as an alternative treatment for depressed patients who do not tolerate or respond adequately to treatment with a conventional antidepressant . This r and omized , open-label , multicenter study compared the effectiveness of the SNRI venlafaxine extended release ( VXR ) with that of conventional antidepressants ( CA ) in patients who were referred to an outpatient psychiatric specialty care setting for treatment after failure to tolerate or respond to at least 4 weeks of treatment with a CA in a primary care setting . Patients with a Hamilton Depression Rating Scale ( HAM-D17 ) score > or = 17 were r and omly assigned to treatment with an alternative CA or VXR . Remission was defined as a score < or = 7 on the HAM-D17 . Efficacy analyses were carried out on 3,097 patients from the intent-to-treat ( ITT ) population ( 1,632 VXR ; 1,465 CA ) . The antidepressants prescribed most frequently in the CA group were paroxetine ( 21.3 % ) , citalopram ( 20.1 % ) , sertraline ( 19.1 % ) , fluoxetine ( 17.0 % ) , and mirtazapine ( 7.9 % ) . After 24 weeks of treatment , the VXR group demonstrated a significantly higher remission rate than did the CA group ( 59.3 % VXR ; 51.5 % CA ; P<.0001 ; odds ratio : 1.37 ; 95 % CI : 1.19 - 1.58 ; P<.01 ) . Despite the limitations of the open design , the results of this study suggest that venlafaxine extended release may be more effective than the conventional antidepressants used in this study when treating depressed patients who do not tolerate or respond adequately to treatment with a conventional antidepressant OBJECTIVE The onset or worsening of sexual dysfunction is a common treatment-emergent side effect of antidepressant medications . Post hoc analyses of pooled data from placebo-controlled studies were utilized to assess sexual functioning in patients receiving duloxetine or paroxetine . METHOD Acute-phase data were obtained from four 8-week , double-blind , placebo- and paroxetine-controlled trials of similar design in which patients meeting DSM-IV criteria for major depressive disorder were r and omly assigned to receive placebo ( N = 371 ) , duloxetine ( 40 - 120 mg/day ; N = 736 ) , or paroxetine ( 20 mg/day ; N = 359 ) . Pooling of data from these studies was anticipated during study design . This represented all available data from duloxetine studies in which the Arizona Sexual Experience Scale ( ASEX ) was administered both at baseline and endpoint . Long-term data were available from extension phases in 2 of these trials in which acute treatment responders received placebo ( N = 129 ) , duloxetine ( 80 - 120 mg/day ; N = 297 ) , or paroxetine ( 20 mg/day ; N = 140 ) for an additional 26 weeks . Data were collected between March 2000 and July 2002 . RESULTS The incidence of acute treatment-emergent sexual dysfunction was significantly lower among duloxetine-treated patients compared with those receiving paroxetine ( p = .015 ) , although both rates were significantly higher than placebo ( p = .007 and p < .001 for duloxetine and paroxetine , respectively ) . Treatment group differences in the incidence of treatment-emergent dysfunction did not vary significantly by gender . In female patients , acute treatment-emergent sexual dysfunction was significantly lower in the duloxetine treatment group compared with the paroxetine treatment group ( p = .032 ) , with both rates being significantly higher than placebo ( p = .049 and p < .001 for duloxetine and paroxetine , respectively ) . In the somewhat smaller group of male patients , acute treatment-emergent dysfunction did not differ significantly between duloxetine and placebo treatment groups , but the incidence was significantly higher in paroxetine-treated male patients compared with male placebo patients ( p = .012 ) . The long-term incidence of treatment-emergent dysfunction did not differ significantly between duloxetine- , paroxetine- , and placebo-treated patients . CONCLUSION In this analysis of pooled data , patients receiving duloxetine ( 40 - 120 mg/day ) or paroxetine ( 20 mg/day ) had a significantly higher incidence of acute treatment-emergent sexual dysfunction when compared with placebo patients . However , the incidence of acute treatment-emergent dysfunction for duloxetine was significantly lower than that observed for paroxetine We aim ed to compare the antidepressant and anxiolytic effects , tolerability and effects on quality of life of mirtazapine and citalopram in a r and omized , double-blind , multicentre , 8-week study . Patients with a Major Depressive Episode ( DSM-IV ) and a baseline score of > or = 22 on the Montgomery-Asberg Depression Rating Scale ( MADRS ) were r and omized to 8 weeks treatment with either mirtazapine ( n = 137 , 15 - 60 mg/day ) or citalopram ( n = 133 , 20 - 60 mg/day ) . Efficacy was evaluated by the MADRS , Hamilton Anxiety Scale ( HAM-A ) , Clinical Global Impression scales ( CGI ) , the Leeds Sleep Evaluation Question naire ( LSEQ ) and Quality of Life Enjoyment and Satisfaction Question naire ( QLESQ ) . The efficacy analyses were performed on the Intent-To-Treat Group using the Last Observation Carried Forward method . Vital signs and laboratory variables are measured and adverse events recorded at each weekly visit . The magnitude of reduction from baseline in group mean MADRS scores was large in both groups , reaching after 8 weeks of treatment mean scores of 9.1 in the mirtazapine group and 8.9 in the citalopram group . Both treatments also result ed in a substantial improvement in anxiety symptoms , sleep disturbances and quality of life , and high percentage of responders . However , at day 14 , statistically significantly larger magnitudes of change favouring mirtazapine were present in the group mean MADRS , HAM-A and CGI-Severity of illness and Quality of life scores . A difference of 2.3 points on MADRS favouring mirtazapine is considered indicative for a clinical ly relevant superiority between two proven antidepressants . Mirtazapine treatment was also related to faster improvement of sleep , quality of sleep and improved alertness following awakening , as shown by statistically significant differences on the self-rating LSEQ at various time points . There were no differences between two treatment groups on self-rating QLSEQ . Both drugs were well tolerated , with a low number of patients in either group prematurely terminating the study due to adverse events ( mirtazapine : 3.6 % , citalopram , 3.0 % ) . Sweating and nausea were statistically significantly more frequent in the citalopram group and increased appetite and complaints of weight increase in the mirtazapine group . There were no clinical ly relevant changes in laboratory parameters and vital sign variables with either treatment , except for clinical ly relevant increase in body weight , occurring more frequently in mirtazapine patients . In this study , mirtazapine and citalopram were equally effective in reducing symptoms of depression and anxiety , and well tolerated . However , mirtazapine was significantly more effective than citalopram after 2 weeks of treatment on the MADRS , HAM-A and CGI Severity of illness and Quality of life scales . This finding , consistently present at all major efficacy variables , suggests potentially faster onset of efficacy of mirtazapine over citalopram The authors employed a double-blind , placebo-controlled design to investigate the effectiveness of fluvoxamine versus imipramine in 54 out patients with moderate major depression . Fluvoxamine proved superior to placebo but not to imipramine on the Hamilton Rating Scale for Depression and the Montgomery and Asberg Depression Rating Scale . Nausea and hyperarousal were the most common side effects in the fluvoxamine-treated patients This r and omized , double-blind , parallel-group design study of 100 out patients with major depressive disorder is the first study in the United States to compare the efficacy and tolerability of fluvoxamine ( 100 - 150 mg/day ) and fluoxetine ( 20 - 80 mg/day ) . After a variable , single-blind , washout period , patients were r and omized to receive either fluvoxamine ( 51 patients ) of fluoxetine ( 49 patients ) for 7 weeks . Efficacy was assessed with the 21-item Hamilton Rating Scale for Depression ( HAM-D ) , and Clinical Global Impressions scale for severity and improvement . Eighty-four percent of each treatment group completed the study with each group having a mean score at end point of less than 10 . Both groups demonstrated a 60 % improvement in HAM-D scores over the 7-week trial . There were no statistically significant differences observed between the two groups on any efficacy parameter . The medications were well tolerated , with only two patients in each group who were terminated because of side effects . There were differences in the side-effect profiles , with fluvoxamine being associated with less nausea than fluoxetine . In summary , fluvoxamine and fluoxetine were equally effective in reducing depressive symptoms , but the two drugs displayed slightly different side-effect profiles Fixed daily doses of 20 mg , 40 mg , or 60 mg of fluoxetine , a highly specific serotonin reuptake inhibitor , were given to 84 depressed out patients in a double-blind , placebo-controlled , r and omized 6-week trial . The 20-mg dose produced improvement of depression in the moderate-severe depression group as expressed in significant reductions of scores on the Hamilton Rating Scale for Depression ( p greater than or equal to .007 ) and the Patient Global Impressions scale ( p greater than or equal to .011 ) , and the 20-mg dose caused fewer side effects than did the higher doses . A mildly depressed group of patients showed no improvement at any dose level of fluoxetine OBJECTIVE This study examined whether a selective serotonin reuptake inhibitor ( paroxetine ) had comparable efficacy but greater tolerability than a tricyclic antidepressant ( imipramine ) in depressed patients with HIV infection . METHOD Seventy-five HIV-positive patients ( 45 % of whom had AIDS ) were blindly and r and omly assigned to receive paroxetine ( N = 25 ) , imipramine ( N = 25 ) , or placebo ( N = 25 ) in a 12-week trial . The Hamilton Anxiety Rating Scale , the Hamilton Depression Rating Scale , the Clinical Global Impression scale , and the SAFETEE general inquiry ( for safety and tolerability ) were administered at weeks 2 , 4 , 6 , 8 , and 12 . RESULTS Fifty-six ( 75 % ) of the 75 patients completed 6 weeks and 34 ( 45 % ) completed 12 weeks of the trial . The mean daily doses of both paroxetine ( 33.9 mg ) and imipramine ( 162.5 mg ) were significantly more effective than placebo ; they were comparably effective at weeks 6 , 8 , and 12 according to the intent-to-treat analysis and at week 8 according to the analysis for the subjects who completed the trial ( for them , only imipramine was superior to placebo at week 12 ) . There were significantly more dropouts due to side effects from imipramine ( 48 % ) than from both paroxetine ( 20 % ) and placebo ( 24 % ) . CONCLUSIONS Depressed patients with HIV infection responded to imipramine or paroxetine at a higher rate than to placebo irrespective of severity of immunosuppression . Because paroxetine was much better tolerated than imipramine , its overall effectiveness may be greater . However , because of the small study group and the high attrition rate , these findings can not be generalized and may need replication in a larger study group Paroxetine is a novel antidepressant that selectively inhibits neuronal reuptake of serotonin . Results are reported from a 6-week , double-blind trial of paroxetine , imipramine , and placebo in 120 out patients with DSM-III major depression . Paroxetine was significantly superior to placebo on almost all measures . This included the main outcome variable , the Hamilton Rating Scale for Depression ( HAM-D ) , and its factor scores , anxiety-somatization , cognitive disturbance , psychomotor retardation , and sleep disturbance . There were no significant differences between paroxetine and imipramine on the same scales . Imipramine-treated patients were significantly more likely than those taking placebo to report one or more adverse effects , which were predominantly anticholinergic in nature . There was no significant difference in the number of paroxetine and placebo patients who reported one or more adverse effects . The results of this and similar studies indicate that paroxetine is an effective treatment in major depression and has a favorable side effect profile Patients ( n = 150 ) were r and omized to a 6-week , double-blind study to evaluate the relative efficacy and safety of mirtazapine , amitriptyline , and placebo in the treatment of major depressive disorder symptoms . Average daily modal doses were mirtazapine , 18 mg ; amitriptyline , 111 mg ; and placebo , 4.6 capsules . Mirtazapine- and amitriptyline-treated patients had statistically significantly greater mean Hamilton Rating Scale for Depression ( HAM-D ) score reductions ( weekly visits 1 , 2 , 4 , and endpoint ) compared to placebo . These findings were supported by the Montgomery-Asberg Depression Rating Scale ( MADRS ) ; the Zung Self-rating Depression Scale ( SDS ) ; and the Clinical Global Impressions ( CGI ) scales . Somnolence and weight gain were the only adverse clinical experiences ( ACEs ) reported substantially more often by mirtazapine-treated patients than by those in the placebo group . However , more amitriptyline-treated patients reported decreased visual accommodation , dry mouth , dyspepsia , constipation , tachycardia , hypertension , hypotension , discoordination , dizziness , and tremor than mirtazapine- or placebo-treated patients . Results of this study indicate that mirtazapine is more effective than placebo in the treatment of these patients , and superior to amitriptyline in respect to anticholinergic and cardiovascular effects CONTEXT Major depressive disorder causes significant morbidity and mortality . Current therapies fail to fully treat both emotional and physical symptoms of major depressive disorder . OBJECTIVE To evaluate duloxetine , a dual reuptake inhibitor of serotonin and norepinephrine , on improvement of emotional and painful physical symptoms . DESIGN R and omized , double-blind , evaluation of duloxetine at 40 mg/d ( 20 mg twice daily ) and 80 mg/d ( 40 mg twice daily ) versus placebo and paroxetine 20 mg/d in depressed out patients . MAIN OUTCOME MEASURES The primary efficacy measure was the 17-item Hamilton Depression Rating Scale . Visual Analog Scales for pain , Clinical Global Impression of Severity , Patient 's Global Impression of Improvement , and Quality of Life in Depression Scale were also used . Safety was evaluated by assessing discontinuation rates , adverse event rates , vital signs , and laboratory tests . RESULTS Duloxetine 80 mg/d was superior to placebo on mean 17-item Hamilton Depression Rating Scale total change by 3.62 points ( 95 % CI 1.38 , 5.86 ; P = 0.002 ) . Duloxetine at 40 mg/d was also significantly superior to placebo by 2.43 points ( 95 % CI 0.19 , 4.66 ; P = 0.034 ) , while paroxetine was not ( 1.51 points ; 95 % CI -0.55 , 3.56 ; P = 0.150 ) . Duloxetine 80 mg/d was superior to placebo for most other measures , including overall pain severity , and was superior to paroxetine on 17-item Hamilton Depression Rating Scale improvement ( by 2.39 points ; 95 % CI 0.14 , 4.65 ; P = 0.037 ) and estimated probability of remission ( 57 % for duloxetine 80 mg/d , 34 % for paroxetine ; P = 0.022 ) . The only adverse event reported significantly more frequently for duloxetine 80 mg/d than for paroxetine was insomnia ( 19.8 % for duloxetine 80 mg/d , 8.0 % for paroxetine ; P = 0.031 ) . Hypertension incidence was not affected by any treatment . CONCLUSION Duloxetine therapy was efficacious for emotional and physical symptoms of depression , with a selective serotonin reuptake inhibitor-like profile of side effects BACKGROUND Nefazodone is a 5-HT2-receptor antagonist and serotonin ( 5-HT ) selective reuptake inhibitor . This study evaluates the safety and efficacy of nefazodone in patients with major depressive disorder ( MDD ) in comparison to imipramine and placebo treatments . It also compares two dose ranges of nefazodone to investigate its optimal dose range . METHOD Nefazodone was evaluated in a 6-week , double-blind trial of novel design involving 180 patients meeting Research Diagnostic Criteria for major depressive disorder and having a minimum pretreatment score of 22 on the first 17 items of the Hamilton Rating Scale for Depression ( HAM-D ) . Patients were r and omly assigned to placebo ( 2 - 10 capsules/day ) , imipramine ( 50 - 250 mg/day ) , or nefazodone in two dose ranges ( 50 - 250 mg/day or 100 - 500 mg/day ) . RESULTS Improvement on depression measures with nefazodone in the 100 - 500-mg/day dose range ( endpoint mean = 460 mg/day ) and imipramine ( endpoint mean = 214 mg/day ) exceeded that with placebo . Some benefit was also observed in the nefazodone 50 - 250-mg/day treatment group ( endpoint mean = 242 mg/day ) , but it was suboptimal . Evidence of nefazodone 's efficacy as an antidepressant was consistently observed on physician- ( HAM-D , Clinical Global Impressions [ CGI ] ) and patient-rated ( CGI-patient rated ) scales . By patient self-report , improvement of anxiety symptoms associated with depression was evident with nefazodone as early as the first week of treatment , and benefit was seen with both nefazodone dosage groups . Analyses of the physician 's global assessment s of therapeutic effect and side effects at end of treatment showed therapeutic benefit for both nefazodone and imipramine treatments ; however , patients in the nefazodone treatment groups were significantly less troubled by adverse experiences than were imipramine-treated patients , result ing in a lower dropout rate for adverse experience . CONCLUSION Nefazodone is a well-tolerated and effective antidepressant for the treatment of major depressive disorder Results from a single-center , 6-week , double-blind , r and omized prospect i ve study of paroxetine , a selective serotonin reuptake inhibitor ; imipramine ; and placebo are reported . One hundred twenty out patients with a moderate-to-severe DSM-III diagnosis of major depression were r and omly assigned to one of the three treatments following a 4- to 10-day single-blind placebo washout period . Significant differences favoring paroxetine over placebo were present at endpoint on most major efficacy measures . Paroxetine was also well tolerated ; 5 ( 15 % ) paroxetine and 5 ( 14 % ) placebo patients dropped out of the study due to adverse effects . Imipramine , however , was comparatively poorly tolerated . Forty-five percent of imipramine-treated patients ( N = 17 ) dropped out of the study due to adverse effects . None of the efficacy measures showed a significant difference between imipramine and placebo . This finding was probably due to the high number of imipramine patients who discontinued before they could improve . These results support the efficacy of paroxetine in the treatment of major depression and underline its favorable side effect profile compared with tricyclic antidepressants BACKGROUND The effects of extended selective serotonin reuptake inhibitor ( SSRI ) treatment on weight are not well characterized . Also unknown is whether different agents have differential effects . To examine these questions , we assessed weight changes in patients r and omly assigned to long-term treatment with fluoxetine , sertraline , or paroxetine . METHOD Patients ( N = 284 ) with major depressive disorder ( DSM-IV ) were r and omly assigned to double-blind treatment with fluoxetine ( N = 92 ) , sertraline , ( N = 96 ) , or paroxetine ( N = 96 ) for a total of 26 to 32 weeks . The mean percent change in weight was compared for each group , as was the number of patients who had > or = 7 % weight increase from baseline . RESULTS Patients ( fluoxetine , N = 44 ; sertraline , N = 48 ; paroxetine , N = 47 ) who completed the trial were included in these analyses . Paroxetine-treated patients experienced a significant weight increase , fluoxetine-treated patients had a modest but nonsignificant weight decrease , and patients treated with sertraline had a modest but nonsignificant weight increase . The number of patients whose weight increased > 7 % from baseline was significantly greater for paroxetine-treated compared with either fluoxetine-treated or sertraline-treated patients . CONCLUSION Risk of weight gain during extended SSRI treatment differs depending on which SSRI is used BACKGROUND Sleep disturbances are common in major depressive disorder . In previous open-label trials , nefazodone improved sleep continuity and increased rapid eye movement ( REM ) sleep , while not affecting stage 3/4 sleep or REM latency : in contrast , fluoxetine suppressed REM sleep . This study compared the objective and subjective effects of nefazodone and fluoxetine on sleep . METHODS This paper reports combined results of three identical , multisite , r and omized , double-blind , 8-week , acute-phase trials comparing nefazodone ( n = 64 ) with fluoxetine ( n = 61 ) in out patients with nonpsychotic major depressive disorder and insomnia . Sleep electroencephalographic ( EEG ) recordings were gathered at baseline and weeks 2 , 4 , and 8 . Clinical ratings were obtained at weeks 1 - 4 , 6 , and 8 . RESULTS Nefazodone and fluoxetine were equally effective in reducing depressive symptoms ; however , nefazodone differentially and progressively increased ( while fluoxetine reduced ) sleep efficiency and reduced ( while fluoxetine increased ) the number of awakenings in a linear fashion over the 8-week trial . Fluoxetine , but not nefazodone , prolonged REM latency and suppressed REM sleep . Nefazodone significantly increased total REM sleep time . Clinical evaluations of sleep quality were significantly improved with nefazodone compared with fluoxetine . CONCLUSIONS Nefazodone and fluoxetine were equally effective antidepressants . Nefazodone was associated with normal objective , and clinician- and patient-rated assessment s of sleep when compared with fluoxetine . These differential sleep EEG effects are consistent with the notion that nefazodone and fluoxetine may have somewhat different modes and spectra of action In this study , 312 depressed out patients received either placebo or one of three venlafaxine doses twice daily ( b.i.d . ) for up to 6 weeks . The total daily doses of venlafaxine were 25 , 50 - 75 , and 150 - 200 mg/day . Hamilton Rating Scale for Depression ( HAM-D ) and Montgomery-Asberg Depression Rating Scale ( MADRS ) total scores at Week 6 were significantly lower for the high-dose group than for the placebo group . A positive dose-response trend for the primary efficacy parameters was demonstrated as early as Week 1 . Venlafaxine was well tolerated at all dose levels . The most common side effects of clinical interest were nausea and dry mouth . The frequency of nausea in the venlafaxine groups was essentially the same ( 25 - 29 % ) , whereas the frequencies of dry mouth , somnolence , and sweating were dose related . The results indicate that b.i.d . doses of venlafaxine are safe and effective in treating depression OBJECTIVE The authors compared the efficacy and side effects of fluoxetine and placebo in elderly out patients with dysthymic disorder . METHODS Patients were r and omly assigned to fluoxetine ( 20 mg-60 mg/day ) or placebo for 12 weeks in a double-blind trial . RESULTS Of 90 r and omized patients , 71 completed the trial . In the intent-to-treat sample , r and om regression analyses of the Hamilton Rating Scale for Depression ( Ham-D ; 24-item ) and Cornell Dysthymia Rating Scale ( CDRS ) scores at each visit produced significant time x treatment group interactions favoring the fluoxetine group . Analysis of percentage change in Ham-D scores yielded no effect for treatment group , but a similar analysis of percentage change in CDRS scores yielded a main effect for treatment group , favoring fluoxetine over placebo . In the intent-to-treat sample , response rates were 27.3 % for fluoxetine and 19.6 % for placebo . In the completer sample , response rates were 37.5 % for fluoxetine and 23.1 % for placebo . CONCLUSION Fluoxetine had limited efficacy in elderly dysthymic patients . The clinical features of elderly dysthymic patients are typically distinct from those of dysthymic disorder in young adults , and the findings suggest that treatments effective for young adult dysthymic patients may not be as useful in elderly dysthymic patients . Further research is needed to identify efficacious treatments for elderly patients with dysthymic disorder , and investigative tools such as electronic/computerized brain scans and neuropsychological testing may help identify the factors that moderate antidepressant treatment response and resistance OBJECTIVE The purpose of this study was to determine prospect ively the optimal length of therapy in a long-term , placebo-controlled continuation study of patients who responded to acute fluoxetine treatment for major depression ( defined by DSM-III-R ) . METHOD The study was conducted at five outpatient psychiatric clinics in the United States . Patients who met criteria for remission after 12 or 14 weeks of open-label acute fluoxetine therapy , 20 mg/day ( N=395 of 839 patients ) , were r and omly assigned to one of four arms of a double-blind treatment study ( 50 weeks of placebo , 14 weeks of fluoxetine and then 36 weeks of placebo , 38 weeks of fluoxetine and then 12 weeks of placebo , or 50 weeks of fluoxetine ) . Relapse rate was the primary outcome measure . Both Kaplan-Meier estimates and observed relapse rates were assessed in three fixed 12-week intervals after double-blind transfers from fluoxetine to placebo at the start of the double-blind period and after 14 and 38 weeks of continued fluoxetine treatment . RESULTS Relapse rates ( Kaplan-Meier estimates ) were lower among the patients who continued to take fluoxetine compared with those transferred to placebo in both the first interval , after 24 total weeks of treatment ( fluoxetine , 26.4 % ; placebo , 48.6 % ) , and the second interval , after 38 total weeks of treatment ( fluoxetine , 9.0 % ; placebo , 23.2 % ) . In the third interval , after 62 total weeks of treatment , rates were not significantly different between the groups ( fluoxetine , 10.7 % ; placebo , 16.2 % ) . CONCLUSIONS Patients treated with fluoxetine for 12 weeks whose depressive symptoms remit should continue treatment with fluoxetine for at least an additional 26 weeks to minimize the risk of relapse A total of 27 subjects began active treatment in this double-blind study comparing the efficacy and safety of trazodone and fluoxetine in geriatric depressed patients , but only 13 completed 6 weeks on study medication . Both agents were effective according to weekly and endpoint analyses , and there was no evidence of significant effects on blood pressure , pulse , or weight . Separate analysis of patients who had received an adequate trial of medication indicated a trend toward relatively more fluoxetine-treated patients meeting clinical criteria for resolved depression . ( J Geriatr Psychiatry Neurol 1989;2:208 - 214 . In an investigation of the efficacy of paroxetine in relapse prevention and prophylaxis of depression , patients who met DSMIII-R criteria for major depression with a history of two or more previous episodes in the preceding four years and who had responded to eight weeks treatment with paroxetine , were r and omized double-blind to receive either paroxetine 20–30 mg or placebo for one year . One hundred and seventy-two patients entered open treatment of whom 141 completed eight weeks treatment . One hundred and thirty-five responders entered the double-blind placebo-controlled study . There was a significant advantage for paroxetine compared with placebo in the reappearance of depression ( p < 0.01 ) and in the time to reappearance ( p < 0.001 ) over the one-year study . A significant advantage was seen for paroxetine compared with placebo in the first four months in relapse prevention ( p < 0.01 ) and in the time to relapse ( p < 0.005 ) , and in the later period of treatment in preventing recurrence in the time to recurrence ( p < 0.05 ) . Paroxetine was effective in preventing the reappearance of depression following an acute illness . These results confirm the benefit of long-term pharmacotherapy for treating depressive illness BACKGROUND In nursing home residents and other frail elderly patients , old age and potential drug-drug and drug-disease interactions may affect the relative safety and efficacy of medications . The purpose of this study was to examine the efficacy and tolerability of venlafaxine and sertraline for the treatment of depression among nursing home residents . METHOD The study was a 10-week r and omized , double-blind , controlled trial of venlafaxine ( doses up to 150 mg/day ) versus sertraline ( doses up to 100 mg/day ) among 52 elderly nursing home residents with a DSM-IV depressive disorder and , at most , moderate dementia . The primary measure of outcome was the Hamilton Rating Scale for Depression ( HAM-D ) . Adverse events were monitored and recorded systematic ally during the trial . RESULTS Twelve subjects were discontinued due to serious adverse events ( SAE ) , 5 were discontinued due to other significant side effects , and 2 withdrew consent . Tolerability estimated by the time to termination was lower for venlafaxine than sertraline for serious adverse events ( log rank statistic = 5.28 , p = .022 ) , for serious adverse events or side effects ( log rank statistic = 8.08 , p = .005 ) , or for serious adverse events , side effects , or withdrawal of consent ( log rank statistic = 10.04 , p = .002 ) . Mean ( SD ) HAM-D scores at baseline were 20.2 ( 3.4 ) for sertraline and 20.3 ( 3.7 ) for venlafaxine ; intent-to-treat endpoint HAM-D scores were 12.2 ( 5.1 ) and 15.7 ( 6.2 ) ( F = 3.45 ; p = .069 ) . There were no differences in categorical responses for the intent-to-treat sample or completers . CONCLUSION In this frail elderly population , venlafaxine was less well tolerated and , possibly , less safe than sertraline without evidence for an increase in efficacy . This unexpected finding demonstrates the need for systematic research on the safety of drugs in the frail elderly BACKGROUND The prevalence of asthma has increased in recent years and depression is common in this population . Minimal data are available on the treatment of depressed asthma patients . METHODS Ninety adults with asthma and current major depressive disorder were r and omized to receive citalopram or placebo for 12 weeks . At each visit , the Hamilton Rating Scale for Depression ( HRSD ) , Inventory of Depressive Symptomatology - Self-Report , Asthma Control Question naire , and Asthma Quality of Life Question naire were administered , and oral corticosteroid use assessed . RESULTS In the evaluable sample ( n = 82 ) , the primary outcome , a r and om regression analysis of HRSD scores , revealed no significant between-group differences . Bonferroni corrected secondary outcomes revealed HRSD scores decreased significantly in both groups with a significantly greater decrease in the citalopram group at week 6 . Changes in asthma symptoms were similar between groups . The groups had similar rates of oral corticosteroid use at baseline , but the citalopram group had less corticosteroid use during the study . Changes in asthma symptom severity correlated with changes in depressive symptom severity . CONCLUSIONS A reduction in depressive symptoms was associated with improvement in asthma . Corticosteroid use , an important measure of severe asthma exacerbations , was lower in the citalopram group . Larger clinical trials in this population are warranted OBJECTIVE Previous antidepressant maintenance trials have used the same medication from acute through maintenance phases , confounding the interpretation of prophylactic effects . The purpose of this study was to determine whether sertraline prevents the recurrence of major depressive disorder among patients with recurrent depression who had been treated to remission with medications other than sertraline . METHOD Patients who had experienced at least three documented episodes of major depressive disorder within the last 4 years and who were currently in full remission were eligible . The last episode must have been treated for at least 4 months with any antidepressant except sertraline . For the initial single-blind placebo lead-in phase , 371 patients were included ; 288 were included in the analyses for the 18-month double-blind phase in which patients were r and omly assigned to sertraline ( 50 or 100 mg ) or placebo ( two capsules per day ) . Recurrence was defined as a depressive episode that fulfilled DSM-IV criteria or the appearance of symptoms that required the administration of another antidepressant treatment . RESULTS Sixty-one patients discontinued before the double-blind phase , including 33 who experienced a relapse . Out of the 288 who entered the double-blind prophylactic phase , 123 discontinued , including 65 for recurrences . Recurrences were significantly lower in the sertraline groups compared with placebo ( sertraline , 50 mg : 16 [ 16.8 % ] of 95 ; sertraline , 100 mg : 16 [ 17.0 % ] of 94 ; placebo : 33 [ 33.3 % ] of 99 ) . Patients treated with sertraline also had a significantly longer time until recurrence compared with placebo-treated patients . CONCLUSIONS Among remitted patients with a history of multiple depressive episodes , sertraline at a dose of either 50 or 100 mg/day prevented recurrences significantly more than did placebo Background : While testosterone 's ameliorative effects on depressive disorders and fatigue in HIV-positive patients have been suggested in the literature , no placebo-controlled trial selecting for depressive disorders and including a st and ard antidepressant has been conducted . Accordingly , this double-blind trial was design ed to determine whether testosterone , as well as fluoxetine , is superior to placebo for depression , fatigue , or both . Method : One hundred twenty-three men with HIV/AIDS with a Diagnostic and Statistical Manual of Mental Disorders , Fourth Edition depressive disorder entered the 8-week trial and were r and omized to testosterone ( up to 400 mg IM testosterone cypionate biweekly ) , fluoxetine ( up to 60 mg/d ) , or double placebo . Outcome variables were the Clinical Global Impressions Scale for mood and for fatigue , the Hamilton Rating Scale for Depression , and the Chalder Fatigue Scale . Results : Ninety men completed the trial . In intention-to-treat analyses , mood response rates were 54 % , 47 % , and 44 % for fluoxetine , testosterone , and placebo , respectively . Among completers , mood response rates were 70 % , 57 % , and 53 % , respectively ; in neither analysis were differences between treatments statistically significant . In contrast , testosterone was superior to fluoxetine and placebo for completers regarding fatigue . In intention-to-treat analysis , response rates were 39 % , 56 % , and 42 % for fluoxetine , testosterone , and placebo , respectively , and for study completers , 41 % , 63 % , and 52 % , respectively , ( P < 0.05 ) , Conclusion : While over 50 % of patients treated with testosterone reported improved mood , this rate was not statistically superior to placebo . Thus , our findings do not support prescription of testosterone as a first-line treatment for depressive disorders in HIV-positive men . However , if vali date d in additional studies , testosterone may be a useful option for medically ill men experiencing significant fatigue as well as depression A double-blind , placebo-controlled trial was undertaken to compare the safety and efficacy of venlafaxine and trazodone in patients with major depression . Two hundred twenty-five patients entered an initial 6-week treatment phase , and 149 completed it . Ninety-six patients who were responders continued in a 1-year , double-blind , long-term phase during which they received the same medication and doses they had during the short-term phase . Both active treatments were significantly more effective than placebo on some measures during the short-term study , but venlafaxine produced more improvement in the cognitive disturbance and retardation factors on the Hamilton Rating Scale for Depression . Trazodone was more effective against the sleep disturbance factor . Patients on venlafaxine were most likely to enter the long-term phase and to remain in the trial longest . The side effect profiles of the three treatment groups were compared . Venlafaxine was most likely to cause nausea , whereas trazodone was associated with the most dizziness and somnolence Paroxetine is a selective serotonin reuptake inhibitor with significant antidepressant properties . This was a 6-week placebo- and imipramine-controlled study of 120 out patients with major depression . Paroxetine was statistically significantly superior to placebo on almost all outcome measures . This was apparent as early as 1 week . Paroxetine was also significantly superior to imipramine on the Hamilton Rating Scale for Depression total score . Paroxetine was generally better tolerated than imipramine . These results strongly support paroxetine 's effectiveness in the treatment of major depression and suggest that paroxetine will be a valuable addition to the options in treating depressive illness Venlafaxine is a structurally novel compound with a biochemical and pharmacological profile suggesting antidepressant properties . We report the results of a Phase II , double-blind , placebo-controlled clinical trial assessing the efficacy and safety of venlafaxine in a sample of 93 depressed out patients . Venlafaxine doses of 25 mg t.i.d . , 75 mg t.i.d . , and 125 mg t.i.d . were compared to placebo . Patients receiving venlafaxine showed a significantly greater improvement in their mood symptoms compared to those receiving placebo . Venlafaxine was well tolerated and the most common side effect was nausea . There was some evidence to suggest that venlafaxine may have antidepressant activity within the first 2 weeks of treatment Sexual dysfunction is a frequently reported side effect of many antidepressants , including serotonin reuptake inhibitors . Bupropion , an antidepressant of the aminoketone class , is relatively free of adverse sexual effects . In a r and omized , double-blind , multicenter trial , sustained-release bupropion ( bupropion SR ) and sertraline , a selective serotonin reuptake inhibitor , were found to be similarly efficacious in the treatment of out patients with moderate to severe depression . This report describes the results of a double-blind comparison of the sexual side effect profiles of bupropion SR and sertraline . Two hundred forty-eight patients who had received a diagnosis of moderate to severe major depression were r and omly assigned to receive treatment with bupropion SR ( 100 - 300 mg/day ) or sertraline ( 50 - 200 mg/day ) for 16 weeks . Eligible patients were required to be in a stable relationship and to have normal sexual functioning . Sexual functioning was assessed by the investigator at each clinic visit using investigator-rated structured interviews . A significantly greater percentage of sertraline-treated patients ( 63 % and 41 % of men and women , respectively ) developed sexual dysfunction compared with bupropion SR-treated patients ( 15 % and 7 % , respectively ) . Sexual dysfunction was noted as early as day 7 in sertraline-treated patients at a dose of 50 mg/day and persisted until the end of the 16-week treatment phase . Four patients , all of whom were treated with sertraline , discontinued from the study prematurely because of sexual dysfunction . Given the similar efficacy of the two drugs in treating depression , bupropion SR may be a more appropriate antidepressant choice than sertraline in patients for whom sexual dysfunction is a concern A total of 149 patients in 7 centers in Denmark , Norway and Sweden entered a 6‐week double‐blind trial intended to assess the antidepressant effect and safety of citalopram vs placebo in depressed elderly patients ( 65 years of age or older ) who might also suffer from somatic disorders and /or senile dementia . Results of ratings on the Hamilton Rating Scale for Depression , the Montgomery‐Åsberg Depression Rating Scale and the Clinical Global Impression Scale provided consistent evidence that the citalopram‐treated patients improved more than the placebo‐treated patients . Results of ratings on the Gottfries‐Bråne‐Steen dementia rating scale indicated that both cognitive and emotional functioning improved significantly more in the citalopram‐treated subgroup of patients with dementia than in the placebo‐treated subgroup Paroxetine , a phenylpiperidine derivative , is an antidepressant that selectively inhibits serotonin reuptake . In this study 111 out patients with major depression diagnosed by DSM-III criteria were treated with either paroxetine or placebo in a 6-week , r and omized , double-blind study . Paroxetine was significantly superior to placebo on six of the seven major efficacy variables . Significant differences in favor of paroxetine were apparent by Week 2 . Paroxetine was also well tolerated . These results support the efficacy and safety of paroxetine as a treatment for patients with major depression |
14,088 | 25,579,286 | We identified a significant reduction in MDR-GNB colonisation and infection through the use of patient-level interventions .
This effect was mostly accounted for by selective digestive decontamination . | The rising incidence of multidrug-resistant Gram-negative bacterial ( MDR-GNB ) infections acquired in intensive care units has prompted a variety of patient-level infection control efforts .
However , it is not known whether these measures are effective in reducing colonisation and infection .
The purpose of this systematic review was to assess the efficacy of patient-level interventions for the prevention of colonisation with MDR-GNB and whether these interventions are associated with a reduction in the rate of infection due to MDR-GNB in the intensive care unit . | Objective : To evaluate silver-impregnated ( Oligon ) central venous catheters and chlorhexidine – gluconate-impregnated sponges for reducing catheter-related colonization and infection , nonbacteremic or bacteremic . Design : Multicenter , prospect i ve , r and omized , controlled study . Setting : Five general intensive care units in Greece . Patients : Intensive care unit patients requiring a multilumen central venous catheter between June 2006 and May 2008 . Interventions : Patients were r and omly assigned to receive a st and ard catheter ( st and ard group ) , a st and ard catheter plus chlorhexidine – gluconate-impregnated sponge ( chlorhexidine – gluconate-impregnated sponge group ) , or an Oligon catheter ( Oligon group ) . Catheter colonization was defined as a positive quantitative tip culture ( ≥103 colony-forming units/mL ) , catheter-related infection was defined by the previous criterion plus clinical evidence of sepsis , and bacteremia catheter-related infection as catheter-related infection plus a positive peripheral blood culture with the same micro-organism as in the catheter tip . Measurements and Main Results : Data were obtained from 465 patients , 156 in the st and ard-group , 150 in the chlorhexidine – gluconate-impregnated sponge group , and 159 in the Oligon-group . Colonization occurred in 24 ( 15.4 % ) st and ard catheters , 21 ( 14 % ) in the chlorhexidine – gluconate-impregnated sponge group , and 25 ( 15.7 % ) in the Oligon catheters ( p = .35 ) ( 20.9 , 19.9 , 21.8/1000 catheter-days , respectively ) . Catheter-related infections were recorded in nine ( 5.8 % ) st and ard catheters , six ( 4 % ) in the chlorhexidine – gluconate-impregnated sponge group , and seven ( 4.4 % ) in the Oligon catheters ( p = .58 ) ( 7.8/1,000 , 5.7/1,000 , 6.1/1,000 catheter-days , respectively ) . No difference was observed between the chlorhexidine– gluconate-impregnated sponge group and the st and ard group regarding catheter colonization ( hazard ratio 1.21 ; 95 % confidence interval 0.56–2.61 ; p = .64 ) and catheter-related infections ( hazard ratio 0.65 ; 95 % confidence interval 0.23–1.85 ; p = .42 ) . The Oligon catheter did not reduce colonization or catheter-related infections when compared with the st and ard catheter ( colonization : hazard ratio 1.0 ; 95 % confidence interval 0.46–2.21 ; p = .98 ; catheter-related infection : hazard ratio 0.72 ; 95 % confidence interval 0.27–1.95 ; p = .52 ) . Seven patients ( 1.5 % , 2.09/1,000 catheter-days ) presented bacteremic catheter-related infections . Central venous catheters inserted either in the internal jugular or the femoral vein had greater risk to be colonized than catheters inserted in the subclavian vein ( internal jugular vs. subclavian : hazard ratio 3.29 ; 95 % confidence interval 1.26–8.61 ; p = .01 ; femoral vs. subclavian : hazard ratio 3.36 ; 95 % confidence interval 1.17–9.65 ; p = .02 ) . Acinetobacter baumannii was the predominant pathogen ( 37.1 % episodes of colonization , 36.4 % catheter-related infections , 57.1 % bacteremic catheter-related infections ) . Conclusion : For short-term ( median duration 7 days ) central venous catheters in intensive care units with high prevalence of multiresistant Gram-negative bacteria , chlorhexidine-impregnated sponges and Oligon catheters as single preventive measures did not reduce catheter colonization or catheter-related infections . As a result of the limited amount of events , no conclusion could be reached regarding bacteremic catheter-related infections . The femoral site was the most frequently colonized insertion site in all types of catheters Objective : To document the effect of gingival and dental plaque antiseptic decontamination on the rate of nosocomial bacteremias and respiratory infections acquired in the intensive care unit ( ICU ) . Design : Prospect i ve , multicenter , double-blind , placebo-controlled efficacy study . Setting : Six ICUs : three in university hospitals and three in general hospitals . Patients : A total of 228 nonedentulous patients requiring endotracheal intubation and mechanical ventilation , with an anticipated length of stay ≥5 days . Interventions : Antiseptic decontamination of gingival and dental plaque with a 0.2 % chlorhexidine gel or a placebo gel , three times a day , during the entire ICU stay . Measurements and Main Results : Demographic and clinical characteristics , organ function data ( Logistic Organ Dysfunction score ) , severity of condition ( Simplified Acute Physiologic Score ) , and dental plaque status were assessed at baseline and until 28 days . Bacteriologic sampling of dental plaque and saliva was done every 5 days , and blood , tracheal aspirate , and bronchoalveolar lavage cultures were performed when appropriate . The primary efficacy end point was the incidence of bacteremia , bronchitis , and ventilator-associated pneumonia , expressed as a percentage and per 1000 ICU days . All baseline characteristics were similar between the treated and the placebo groups . The incidence of nosocomial infections was 17.5 % ( 13.2 per 1000 ICU days ) in the placebo group and 18.4 % ( 13.3 per 1000 ICU days ) in the plaque antiseptic decontamination group ( not significant ) . No difference was observed in the incidence of ventilator-associated pneumonia per ventilator or intubation days , mortality , length of stay , and care loads ( secondary end points ) . On day 10 , the number of positive dental plaque cultures was significantly lower in the treated group ( 29 % vs. 66 % ; p < .05 ) . Highly resistant Pseudomonas , Acinetobacter , and Enterobacter species identified in late-onset ventilator-associated pneumonia and previously cultured from dental plaque were not eradicated by the antiseptic decontamination . No side effect was reported . Conclusions : Gingival and dental plaque antiseptic decontamination significantly decreased the oropharyngeal colonization by aerobic pathogens in ventilated patients . However , its efficacy was insufficient to reduce the incidence of respiratory infections due to multiresistant bacteria BACKGROUND Selective digestive tract decontamination ( SDD ) and selective oropharyngeal decontamination ( SOD ) are infection-prevention measures used in the treatment of some patients in intensive care , but reported effects on patient outcome are conflicting . METHODS We evaluated the effectiveness of SDD and SOD in a crossover study using cluster r and omization in 13 intensive care units ( ICUs ) , all in The Netherl and s. Patients with an expected duration of intubation of more than 48 hours or an expected ICU stay of more than 72 hours were eligible . In each ICU , three regimens ( SDD , SOD , and st and ard care ) were applied in r and om order over the course of 6 months . Mortality at day 28 was the primary end point . SDD consisted of 4 days of intravenous cefotaxime and topical application of tobramycin , colistin , and amphotericin B in the oropharynx and stomach . SOD consisted of oropharyngeal application only of the same antibiotics . Monthly point-prevalence studies were performed to analyze antibiotic resistance . RESULTS A total of 5939 patients were enrolled in the study , with 1990 assigned to st and ard care , 1904 to SOD , and 2045 to SDD ; crude mortality in the groups at day 28 was 27.5 % , 26.6 % , and 26.9 % , respectively . In a r and om-effects logistic-regression model with age , sex , Acute Physiology and Chronic Health Evaluation ( APACHE II ) score , intubation status , and medical specialty used as covariates , odds ratios for death at day 28 in the SOD and SDD groups , as compared with the st and ard-care group , were 0.86 ( 95 % confidence interval [ CI ] , 0.74 to 0.99 ) and 0.83 ( 95 % CI , 0.72 to 0.97 ) , respectively . CONCLUSIONS In an ICU population in which the mortality rate associated with st and ard care was 27.5 % at day 28 , the rate was reduced by an estimated 3.5 percentage points with SDD and by 2.9 percentage points with SOD . ( Controlled Clinical Trials number , IS RCT N35176830 . BACKGROUND Infectious complications and associated mortality are a major concern in acute pancreatitis . Enteral administration of probiotics could prevent infectious complications , but convincing evidence is scarce . Our aim was to assess the effects of probiotic prophylaxis in patients with predicted severe acute pancreatitis . METHODS In this multicenter r and omized , double-blind , placebo-controlled trial , 298 patients with predicted severe acute pancreatitis ( Acute Physiology and Chronic Health Evaluation [ APACHE II ] score ≥8 , Imrie score ≥3 , or C-reactive protein > 150 mg/L ) were r and omly assigned within 72 h of onset of symptoms to receive a multispecies probiotic preparation ( n = 153 ) or placebo ( n = 145 ) , administered enterally twice daily for 28 days . The primary endpoint was the composite of infectious complications-i.e . , infected pancreatic necrosis , bacteremia , pneumonia , urosepsis , or infected ascites-during admission and 90-day follow-up . Analyses were by intention to treat . This study is registered , number IS RCT N38327949 . FINDINGS One person in each group was excluded from analyses because of incorrect diagnoses of pancreatitis ; thus , 152 individuals in the probiotics group and 144 in the placebo group were analysed . Groups were much the same at baseline in terms of patients ' characteristics and disease severity . Infectious complications occurred in 46 ( 30 % ) patients in the probiotics group and 41 ( 28 % ) of those in the placebo group ( relative risk 1.06 , 95 % CI 0.75 - 1.51 ) . 24 ( 16 % ) patients in the probiotics group died , compared with nine ( 6 % ) in the placebo group ( relative risk 2.53 , 95 % CI 1.22 - 5.25 ) . Nine patients in the probiotics group developed bowel ischaemia ( eight with fatal outcome ) , compared with none in the placebo group ( p = 0.004 ) . INTERPRETATION In patients with predicted severe acute pancreatitis , probiotic prophylaxis with this combination of probiotic strains did not reduce the risk of infectious complications and was associated with an increased risk of mortality . Probiotic prophylaxis should therefore not be administered in this category of patients . ( Lancet . 2008;371(9613):651 - 659 ) MGH Besselink , HC van Santvoort , E Buskens , et al , for the Dutch Acute Pancreatitis Study Group Introduction Preventing carriage of potentially pathogenic micro-organisms from the aerodigestive tract is an infection control strategy used to reduce the occurrence of ventilator-associated pneumonia in intensive care units . However , antibiotic use in selective decontamination protocol s is controversial . The purpose of this study was to investigate the effect of oral administration of a probiotic , namely Lactobacillus , on gastric and respiratory tract colonization/infection with Pseudomonas aeruginosa strains . Our hypothesis was that an indigenous flora should exhibit a protective effect against secondary colonization . Methods We conducted a prospect i ve , r and omized , double-blind , placebo-controlled pilot study between March 2003 and October 2004 in a 17-bed intensive care unit of a teaching hospital in Clermont-Ferr and , France . Consecutive patients with a unit stay of longer than 48 hours were included , 106 in the placebo group and 102 in the probiotic group . Through a nasogastric feeding tube , patients received either 109 colony-forming units unity forming colony of Lactobacillus casei rhamnosus or placebo twice daily , from the third day after admission to discharge . Digestive tract carriage of P. aeruginosa was monitored by cultures of gastric aspirates at admission , once a week thereafter and on discharge . In addition , bacteriological analyses of respiratory tract specimens were conducted to determine patient infectious status . Results The occurrence of P. aeruginosa respiratory colonization and /or infection was significantly delayed in the probiotic group , with a difference in median delay to acquisition of 11 days versus 50 days ( P = 0.01 ) , and a nonacquisition expectancy mean of 69 days versus 77 days ( P = 0.01 ) . The occurrence of ventilator-associated pneumonia due to P. aeruginosa in the patients receiving the probiotic was less frequent , although not significantly reduced , in patients in the probiotic group ( 2.9 % ) compared with those in the placebo group ( 7.5 % ) . After multivariate Cox proportional hazards modelling , the absence of probiotic treatment increased the risk for P. aeruginosa colonization in respiratory tract ( adjusted hazard ratio = 3.2 , 95 % confidence interval – 1.1 to 9.1 ) . Conclusion In this pilot study , oral administration of a probiotic delayed respiratory tract colonization/infection by P. aeruginosa . Trial registration The trial registration number for this study is NCT00604110 Objective : To compare a strategy of combination therapy with a strategy of monotherapy with broad-spectrum antibiotics for suspected late ventilator-associated pneumonia . Design : R and omized trial . Setting : Twenty-eight intensive care units in Canada and the United States . Patients : The study included 740 mechanically ventilated patients who developed suspected ventilator-associated pneumonia after 96 hrs in the intensive care unit . Patients known to be colonized or infected with Pseudomonas or methicillin-resistant Staphylococcus aureus or who were immunocompromised were excluded from the study . Interventions : As initial unblinded therapy , patients were allocated to receive meropenem ( 1 g every 8 hrs ) and ciprofloxacin ( 400 mg every 12 hrs ) or meropenem alone . Before starting antibiotics , patients were also r and omized to bronchoalveolar lavage with quantitative cultures or endotracheal aspirates . When culture results were available , physicians were encouraged to adjust antibiotics . Adequacy of antibiotics was defined as the organism present in the enrollment culture having in vitro susceptibility to one or more of the study antibiotics . Measurements and Main Results : Baseline characteristics and etiologies of ventilator-associated pneumonia were similar in the two groups . There was no difference in 28-day mortality between the combination and monotherapy groups ( relative risk = 1.05 , 95 % confidence interval 0.78–1.42 , p = .74 ) . Duration of intensive care unit and hospital stay , clinical and microbiological treatment response , emergence of antibiotic-resistant bacteria , isolation of Clostridium difficile in stool , and fungal colonization were also similar in the two groups . In a subgroup of patients who had infection due to Pseudomonas species , Acinetobacter species , and multidrug-resistant Gram-negative bacilli at enrollment ( n = 56 ) , the adequacy of initial antibiotics ( 84.2 % vs. 18.8 % , p < .001 ) and microbiological eradication of infecting organisms ( 64.1 % vs. 29.4 % , p = .05 ) was higher in the combination group compared with the monotherapy group , but there were no differences in clinical outcomes . Conclusions : For critically ill patients who have suspected late ventilator-associated pneumonia and who are at low risk for difficult-to-treat Gram-negative bacteria , monotherapy is associated with similar outcomes compared with combination therapy . For those patients at high risk of difficult-to-treat Gram-negative bacteria , combination therapy is safe and may be associated with better microbiological and clinical outcomes AIM To determine the effect of aminoglycoside cycling in six tertiary intensive care units ( ICU ) on the rates of sepsis , aminoglycoside resistance patterns , antibiotic consumption , and costs . METHODS This was a prospect i ve longitudinal interventional study that measured the effect of change from first-line gentamicin usage ( February 2002-February 2003 ) to amikacin usage ( February 2003-February 2004 ) on the aminoglycoside resistance patterns , number of patients with gram-negative bacteremia , consumption of antibiotics , and the cost of antimicrobial drugs in 6 tertiary care ICUs in Zagreb , Croatia . RESULTS The change from first-line gentamicin to amikacin usage led to a decrease in the overall gentamicin resistance of gram-negative bacteria ( GNB ) from 42 % to 26 % ( P<0.001 ; z-test of proportions ) and netilmicin resistance from 33 % to 20 % ( P<0.001 ) , but amikacin resistance did not change significantly ( P=0.462 ) , except for Acinetobacter baumanni ( P=0.014 ) . Sepsis rate in ICUs was reduced from 3.6 % to 2.2 % ( P<0.001 ; chi(2 ) test ) , with a decline in the number of nosocomial bloodstream infections from 55/100 patient-days to 26/100 patient-days ( P=0.001 , chi(2 ) test ) . Furthermore , amikacin use led to a 16 % decrease in the overall antibiotic consumption and 0.1 euro/patient/d cost reduction . CONCLUSION Exclusive use of amikacin significantly reduced the resistance of GNB isolates to gentamicin and netilmicin , the number of GNB nosocomial bacteremias , and the cost of total antibiotic usage in ICUs BACKGROUND Both targeted decolonization and universal decolonization of patients in intensive care units ( ICUs ) are c and i date strategies to prevent health care-associated infections , particularly those caused by methicillin-resistant Staphylococcus aureus ( MRSA ) . METHODS We conducted a pragmatic , cluster-r and omized trial . Hospitals were r and omly assigned to one of three strategies , with all adult ICUs in a given hospital assigned to the same strategy . Group 1 implemented MRSA screening and isolation ; group 2 , targeted decolonization ( i.e. , screening , isolation , and decolonization of MRSA carriers ) ; and group 3 , universal decolonization ( i.e. , no screening , and decolonization of all patients ) . Proportional-hazards models were used to assess differences in infection reductions across the study groups , with clustering according to hospital . RESULTS A total of 43 hospitals ( including 74 ICUs and 74,256 patients during the intervention period ) underwent r and omization . In the intervention period versus the baseline period , modeled hazard ratios for MRSA clinical isolates were 0.92 for screening and isolation ( crude rate , 3.2 vs. 3.4 isolates per 1000 days ) , 0.75 for targeted decolonization ( 3.2 vs. 4.3 isolates per 1000 days ) , and 0.63 for universal decolonization ( 2.1 vs. 3.4 isolates per 1000 days ) ( P=0.01 for test of all groups being equal ) . In the intervention versus baseline periods , hazard ratios for bloodstream infection with any pathogen in the three groups were 0.99 ( crude rate , 4.1 vs. 4.2 infections per 1000 days ) , 0.78 ( 3.7 vs. 4.8 infections per 1000 days ) , and 0.56 ( 3.6 vs. 6.1 infections per 1000 days ) , respectively ( P<0.001 for test of all groups being equal ) . Universal decolonization result ed in a significantly greater reduction in the rate of all bloodstream infections than either targeted decolonization or screening and isolation . One bloodstream infection was prevented per 54 patients who underwent decolonization . The reductions in rates of MRSA bloodstream infection were similar to those of all bloodstream infections , but the difference was not significant . Adverse events , which occurred in 7 patients , were mild and related to chlorhexidine . CONCLUSIONS In routine ICU practice , universal decolonization was more effective than targeted decolonization or screening and isolation in reducing rates of MRSA clinical isolates and bloodstream infection from any pathogen . ( Funded by the Agency for Healthcare Research and the Centers for Disease Control and Prevention ; REDUCE MRSA Clinical Trials.gov number , NCT00980980 ) The aim of this study was to compare the effect of closed versus open endotracheal suction systems on the development of ventilator-associated pneumonia ( VAP ) . A prospect i ve , r and omized , controlled trial was performed in a medical intensive care unit ( MICU ) of a university hospital in patients who received mechanical ventilation for more than 48 h. Patients were r and omized to receive endotracheal suction with either closed catheters ( closed suction group ; N-41 ) or single-use catheters ( open suction group ; N=37 ) . Cultures were taken from the ventilator tubing of 42 patients to determine the rate of colonization . There was no difference between the groups in terms of the frequency of development of VAP , mortality in the MICU , length of MICU stay and duration of mechanical ventilation . Thirteen patients in the open suction group and 16 patients in the closed suction group became colonized ( P=0.14 ) . The colonization rates by Acinetobacter spp . and Pseudomonas aeruginosa were more frequent in the closed suction group than in the open suction group ( P<0.01 and P=0.04 , respectively ) . In conclusion , closed endotracheal suction result ed in increased colonization rates of ventilator tubing with multi drug-resistant micro-organisms but did not increase the development of VAP and MICU outcome compared with open endotracheal suction BACKGROUND Selective decontamination of the digestive tract ( SDD ) is an infection-prevention regimen used in critically ill patients . We assessed the effects of SDD on intensive-care-unit ( ICU ) and hospital mortality , and on the acquisition of resistant bacteria in adult patients admitted to intensive care . METHODS We did a prospect i ve , controlled , r and omised , unblinded clinical trial . 934 patients admitted to a surgical and medical ICU were r and omly assigned oral and enteral polymyxin E , tobramycin , and amphotericin B combined with an initial 4-day course of intravenous cefotaxime ( SDD group n=466 ) , or st and ard treatment ( controls n=468 ) . Primary endpoints were ICU and hospital mortality and the acquisition of resistant bacteria . FINDINGS In the SDD group 69 ( 15 % ) patients died in the ICU compared with 107 ( 23 % ) in the control group ( p=0.002 ) . Hospital mortality was lower in the SDD groups than in the control group ( 113 [ 24 % ] vs 146 [ 31 % ] , p=0.02 ) . During their stay in intensive care , colonisation with gram-negative bacteria resistant to ceftazidime , ciprofloxacin , imipenem , polymyxin E , or tobramycin occurred in 61 ( 16 % ) of 378 SDD patients and in 104 ( 26 % ) of 395 patients in the control group ( p=0.001 ) . Colonisation with vancomycin-resistant enterococcus occurred in five ( 1 % ) SDD patients and in four ( 1 % ) controls ( p=1.0 ) . No patient in either group was colonised with meticillin-resistant Staphylococcus aureus . INTERPRETATION In a setting with low prevalence of vancomycin-resistant enterococcus and meticillin-resistant S aureus , SDD can decrease ICU and hospital mortality and colonisation with resistant gram-negative aerobic bacteria Objective : To compare a mixing vs. a cycling strategy of use of anti-Pseudomonas antibiotics on the acquisition of resistant Gram-negative bacilli in the critical care setting . Design : Prospect i ve , open , comparative study of two strategies of antibiotic use . Setting : Two medical intensive care units of a university hospital . Patients : A total of 346 patients admitted for ≥48 hrs to two separate medical intensive care units during an 8-month period . Interventions : Patients , who according to the attending physician ’s judgment required an anti-Pseudomonas regimen , were assigned to receive cefepime/ceftazidime , ciprofloxacin , a carbapemen , or piperacillin-tazobactam in this order . “ Cycling ” was accomplished by prescribing one of these antibiotics during 1 month each . “ Mixing ” was accomplished by using the same order of antibiotic administration on consecutive patients . Interventions were carried out during two successive 4-month periods , starting with mixing in one unit and cycling in the other . Measurements and Main Results : Swabbing of nares , pharynx , and rectum and culture of respiratory secretions were obtained thrice weekly . The main outcome variable was the proportion of patients acquiring enteric or nonfermentative Gram-negative bacilli resistant to the antibiotics under intervention . The scheduled cycling of antibiotics was only partially successful . Although the expected antibiotic was the most prevalent anti-Pseudomonas agent used within the corresponding period , it never accounted for > 45 % of all anti-Pseudomonas antimicrobials administered . During mixing , a significantly higher proportion of patients acquired a strain of Pseudomonas aeruginosa resistant to cefepime ( 9 % vs. 3 % , p = .01 ) , and there was a trend toward a more frequent acquisition of resistance to ceftazidime ( p = .06 ) , imipenem ( p = .06 ) , and meropenem ( p = .07 ) . No differences in the rate of acquisition of potentially resistant Gram-negative bacilli or incidence of intensive care unit-acquired infections and infections due to particular organisms were observed . Conclusions : In critically ill medical patients , a strategy of monthly rotation of anti-Pseudomonas & bgr;-lactams and ciprofloxacin may perform better than a strategy of mixing in the acquisition of P. aeruginosa resistant to selected & bgr;-lactams OBJECTIVE To assess the effectiveness of selective digestive decontamination ( SDD ) for eradicating carbapenem-resistant Klebsiella pneumoniae ( CRKP ) oropharyngeal and gastrointestinal carriage . DESIGN A r and omized , double-blind , placebo-controlled trial with 7 weeks of follow-up per patient . SETTING A 1,000-bed tertiary-care university hospital . PATIENTS Adults with CRKP-positive rectal swab cultures . METHODS Patients were blindly r and omized ( 1 :1 ) over a 20-month period . The SDD arm received oral gentamicin and polymyxin E gel ( 0.5 g 4 times per day ) and oral solutions of gentamicin ( 80 mg 4 times per day ) and polymyxin E ( 1 x 10(6 ) units 4 times per day for 7 days ) . The placebo arm received oral placebo gel 4 times per day and 2 placebo oral solutions 4 times per day for 7 days . Strict contact pre caution s were applied . Sample s obtained from the throat , groin , and urine were also cultured . RESULTS Forty patients ( mean age ± st and ard deviation , 71 ± 16 years ; 65 % male ) were included . At screening , greater than or equal to 30 % of oropharyngeal , greater than or equal to 60 % of skin , and greater than or equal to 35 % of urine cultures yielded CRKP isolates . All throat cultures became negative in the SDD arm after 3 days ( P < .0001 ) . The percentages of rectal cultures that were positive for CRKP were significantly reduced at 2 weeks . At that time , 16.1 % of rectal cultures in the placebo arm and 61.1 % in the SDD arm were negative ( odds ratio , 0.13 ; 95 % confidence interval , 0.02 - 0.74 ; P < .0016 ) . A difference between the percentages in the 2 arms was still maintained at 6 weeks ( 33.3 % vs 58.5 % ) . Groin colonization prevalence did not change in either arm , and the prevalence of urine colonization increased in the placebo arm . CONCLUSIONS This SDD regimen could be a suitable decolonization therapy for selected patients colonized with CRKP , such as transplant recipients or immunocompromised patients pending chemotherapy and patients who require major intestinal or oropharyngeal surgery . Moreover , in outbreaks caused by CRKP infections that are uncontrolled by routine infection control measures , SDD could provide additional infection containment CONTEXT Use of a chlorhexidine gluconate-impregnated sponge ( CHGIS ) in intravascular catheter dressings may reduce catheter-related infections ( CRIs ) . Changing catheter dressings every 3 days may be more frequent than necessary . OBJECTIVE To assess superiority of CHGIS dressings regarding the rate of major CRIs ( clinical sepsis with or without bloodstream infection ) and noninferiority ( less than 3 % colonization-rate increase ) of 7-day vs 3-day dressing changes . DESIGN , SETTING , AND PATIENTS Assessor-blind , 2 x 2 factorial , r and omized controlled trial conducted from December 2006 through June 2008 and recruiting patients from 7 intensive care units in 3 university and 2 general hospitals in France . Patients were adults ( > 18 years ) expected to require an arterial catheter , central -vein catheter , or both inserted for 48 hours or longer . INTERVENTIONS Use of CHGIS vs st and ard dressings ( controls ) . Scheduled change of unsoiled adherent dressings every 3 vs every 7 days , with immediate change of any soiled or leaking dressings . MAIN OUTCOME MEASURES Major CRIs for comparison of CHGIS vs control dressings ; colonization rate for comparison of 3- vs 7-day dressing changes . RESULTS Of 2095 eligible patients , 1636 ( 3778 catheters , 28,931 catheter-days ) could be evaluated . The median duration of catheter insertion was 6 ( interquartile range [ IQR ] , 4 - 10 ) days . There was no interaction between the interventions . Use of CHGIS dressings decreased the rates of major CRIs ( 10/1953 [ 0.5 % ] , 0.6 per 1000 catheter-days vs 19/1825 [ 1.1 % ] , 1.4 per 1000 catheter-days ; hazard ratio [ HR ] , 0.39 [ 95 % confidence interval { CI } , 0.17 - 0.93 ] ; P = .03 ) and catheter-related bloodstream infections ( 6/1953 catheters , 0.40 per 1000 catheter-days vs 17/1825 catheters , 1.3 per 1000 catheter-days ; HR , 0.24 [ 95 % CI , 0.09 - 0.65 ] ) . Use of CHGIS dressings was not associated with greater resistance of bacteria in skin sample s at catheter removal . Severe CHGIS-associated contact dermatitis occurred in 8 patients ( 5.3 per 1000 catheters ) . Use of CHGIS dressings prevented 1 major CRI per 117 catheters . Catheter colonization rates were 142 of 1657 catheters ( 7.8 % ) in the 3-day group ( 10.4 per 1000 catheter-days ) and 168 of 1828 catheters ( 8.6 % ) in the 7-day group ( 11.0 per 1000 catheter-days ) , a mean absolute difference of 0.8 % ( 95 % CI , -1.78 % to 2.15 % ) ( HR , 0.99 ; 95 % CI , 0.77 - 1.28 ) , indicating noninferiority of 7-day changes . The median number of dressing changes per catheter was 4 ( IQR , 3 - 6 ) in the 3-day group and 3 ( IQR , 2 - 5 ) in the 7-day group ( P < .001 ) . CONCLUSIONS Use of CHGIS dressings with intravascular catheters in the intensive care unit reduced risk of infection even when background infection rates were low . Reducing the frequency of changing unsoiled adherent dressings from every 3 days to every 7 days modestly reduces the total number of dressing changes and appears safe . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00417235 OBJECTIVE To evaluate whether enteral prophylaxis with probiotics in patients with predicted severe acute pancreatitis prevents infectious complications . DESIGN Multicentre , r and omised , double-blind , placebo-controlled trial . METHOD A total of 296 patients with predicted severe acute pancreatitis ( APACHE II score > or = 8 , Imrie score > or = 3 or C-reactive protein concentration > 150 mg/l ) were included and r and omised to one of two groups . Within 72 hours after symptom onset , patients received a multispecies preparation of probiotics or placebo given twice daily via a jejunal catheter for 28 days . The primary endpoint was the occurrence of one of the following infections during admission and go-day follow-up : infected pancreatic necrosis , bacteraemia , pneumonia , urosepsis or infected ascites . Secondary endpoints were mortality and adverse reactions . The study registration number is IS RCT N38327949 . RESULTS Treatment groups were similar at baseline with regard to patient characteristics and disease severity . Infections occurred in 30 % of patients in the probiotics group ( 46 of 152 patients ) and 28 % of those in the placebo group ( 41 of 144 patients ; relative risk ( RR ) : 1.1 ; 95 % CI : 0.8 - 1.5 ) . The mortality rate was 16 % in the probiotics group ( 24 of 152 patients ) and 6 % ( 9 of 144 patients ) in the placebo group ( RR : 2.5 ; 95 % CI : 1.2 - 5.3 ) . In the probiotics group , 9 patients developed bowel ischaemia ( of whom 8 patients died ) , compared with none in the placebo group ( p = 0.004 ) . CONCLUSION In patients with predicted severe acute pancreatitis , use of this combination of probiotic strains did not reduce the risk of infections . Probiotic prophylaxis was associated with a more than two-fold increase in mortality and should therefore not be administered in this category of patients The aim of this prospect i ve observational study was to determine the accuracy of American Thoracic Society (ATS)/Infectious Diseases Society of America ( IDSA ) criteria in predicting infection or colonization related to multidrug-resistant ( MDR ) bacteria at intensive-care unit ( ICU ) admission . MDR bacteria were defined as methicillin-resistant Staphylococcus aureus , ceftazidime-resistant or imipenem-resistant Pseudomonas aeruginosa , Acinetobacter baumannii , Stenotrophomonas maltophilia , and extended-spectrum β-lactamase-producing Gram-negative bacilli . Screening for MDR bacteria ( using nasal and rectal swabs and tracheal aspirates from intubated patients ) was performed at ICU admission . Risk factors for infection or colonization with MDR bacteria at ICU admission were determined using univariate and multivariate analyses . The accuracy of ATS/IDSA criteria in predicting infection or colonization with these bacteria at ICU admission was calculated . Eighty-three ( 13 % ) of 625 patients were infected or colonized with MDR bacteria at ICU admission . Multivariate analysis allowed identification of prior antimicrobial treatment ( OR 2.3 , 95 % CI 1.2 - 4.3 ; p 0.008 ) , residence in a nursing home ( OR 2 , 95 % CI 1.1 - 3.7 ; p < 0.001 ) , and prior hospitalization ( OR 3.9 , 95 % CI 1.7 - 8.8 ; p < 0.001 ) as independent predictors of infection or colonization with MDR bacteria at ICU admission . Although sensitivity ( 89 % ) and negative predictive values ( 96 % ) were high , low specificity ( 39 % ) and a positive predictive value ( 18 % ) were found when ATS/IDSA criteria were used in predicting infection or colonization with MDR bacteria at ICU admission . In patients with pneumonia , adherence to guidelines was associated with increased rates of appropriate initial antibiotic treatment and de-escalation . ATS/IDSA criteria had an excellent negative predictive value and a low positive predictive value concerning infection or colonization with MDR bacteria at ICU admission BACKGROUND Previously , we assessed selective digestive tract decontamination ( SDD ) and selective oropharyngeal decontamination ( SOD ) on survival and prevention of bacteraemia in patients in intensive-care units . In this analysis , we aim ed to assess effectiveness of these interventions for prevention of respiratory tract colonisation and bacteraemia with highly resistant microorganisms acquired in intensive-care units . METHODS We did an open-label , clustered group-r and omised , crossover study in 13 intensive-care units in the Netherl and s between May , 2004 , and July , 2006 . Participants admitted to intensive-care units with an expected duration of mechanical ventilation of more than 48 h or an expected stay of more than 72 h received SOD ( topical tobramycin , colistin , and amphotericin B in the oropharynx ) , SDD ( SOD antibiotics in the oropharynx and stomach plus 4 days ' intravenous cefotaxime ) , or st and ard care . The computer-r and omised order of study regimens was applied by an independent clinical pharmacist who was masked to intensive-care-unit identity . We calculated crude odds ratios ( 95 % CI ) for rates of bacteraemia or respiratory tract colonisation with highly resistant microorganisms in patients who stayed in intensive-care units for more than 3 days ( ie , acquired infection ) . This trial is registered at http://is rct n.org , number IS RCT N35176830 . FINDINGS Data were available for 5927 ( > 99 % ) of 5939 patients , of whom 5463 ( 92 % ) were in intensive-care units for more than 3 days . 239 ( 13 % ) of 1837 patients in st and ard care acquired bacteraemia after 3 days , compared with 158 ( 9 % ) of 1758 in SOD ( odds ratio 0·66 , 95 % CI 0·53 - 0·82 ) , and 124 ( 7 % ) of 1868 in SDD ( 0·48 , 0·38 - 0·60 ) . Eight patients acquired bacteraemia with highly resistant microorganisms during SDD , compared with 18 patients ( with 19 episodes ) during st and ard care ( 0·41 , 0·18 - 0·94 ; rate reduction [ RR ] 59 % , absolute risk reduction [ ARR ] 0·6 % ) and 20 during SOD ( 0·37 , 0·16 - 0·85 ; RR 63 % , ARR 0·7 % ) . Of the patients staying in intensive-care units for more than 3 days , we obtained endotracheal aspirate cultures for 881 ( 49 % ) patients receiving st and ard care , 886 ( 50 % ) receiving SOD , and 828 ( 44 % ) receiving SDD . 128 ( 15 % ) patients acquired respiratory tract colonisation with highly resistant microorganisms during st and ard care , compared with 74 ( 8 % ) during SDD ( 0·58 , 0·43 - 0·78 ; RR 38 % , ARR 5·5 % ) and 88 ( 10 % ) during SOD ( 0·65 , 0·49 - 0·87 ; RR 32 % , ARR 4·6 % ) . Acquired respiratory tract colonisation with Gram-negative bacteria or cefotaxime-resistant and colistin-resistant pathogens was lowest during SDD . INTERPRETATION Widespread use of SDD and SOD in intensive-care units with low levels of antibiotic resistance is justified . FUNDING None |
14,089 | 27,566,002 | Conjunction analysis revealed shared activation for both types of moral judgement in the left middle temporal gyrus , cingulate gyrus , and medial frontal gyrus .
Contrast analyses found no significant clusters of increased activation for the moral evaluations-moral response decisions contrast , but found that moral response decisions additionally activated the left and right middle temporal gyrus and the right precuneus .
Making one 's own moral decisions involves different brain areas compared to judging the moral actions of others , implying that these judgements may involve different processes | The aims of this systematic review were to determine : ( a ) which brain areas are consistently more active when making ( i ) moral response decisions , defined as choosing a response to a moral dilemma , or deciding whether to accept a proposed solution , or ( ii ) moral evaluations , defined as judging the appropriateness of another 's actions in a moral dilemma , rating moral statements as right or wrong , or identifying important moral issues ; and ( b ) shared and significantly different activation patterns for these two types of moral judgements . | Humans are endowed with a natural sense of fairness that permeates social perceptions and interactions . This moral stance is so ubiquitous that we may not notice it as a fundamental component of daily decision making and in the workings of many legal , political , and social systems . Emotion plays a pivotal role in moral experience by assigning human values to events , objects , and actions . Although the brain correlates of basic emotions have been explored , the neural organization of “ moral emotions ” in the human brain remains poorly understood . Using functional magnetic resonance imaging and a passive visual task , we show that both basic and moral emotions activate the amygdala , thalamus , and upper midbrain . The orbital and medial prefrontal cortex and the superior temporal sulcus are also recruited by viewing scenes evocative of moral emotions . Our results indicate that the orbital and medial sectors of the prefrontal cortex and the superior temporal sulcus region , which are critical regions for social behavior and perception , play a central role in moral appraisal s. We suggest that the automatic tagging of ordinary social events with moral values may be an important mechanism for implicit social behaviors in humans Cortical systems engaged during executive and volitional functions receive and integrate input from multiple systems . However , these integration processes are not well understood . In particular , it is not known whether these input pathways converge or remain segregated at the executive levels of cortical information processing . If unilateral information streams are conserved within structures that serve high-level executive functions , then the functional organization within these structures would predictably be similarly organized . If , however , unilateral input information streams are integrated within executive-related structures , then activity patterns will not necessarily reflect lower organizations . In this study , subjects were imaged during the performance of a perceptual go/nogo task for which instructions were based on spatial ( where ) , temporal ( when ) , or object ( what ) stimulus features known to engage unilateral processing streams , and the expected hemispheric biases were observed for early processing areas . For example , activity within the inferior and middle occipital gyri , and the middle temporal gyrus , during the what and when tasks , was biased toward the left hemisphere , and toward the right hemisphere during the where task . We discover a similar lateralization within the medial frontal gyrus , a region associated with high-level executive functions and decision-related processes . This lateralization was observed regardless of whether the response was executed or imagined , and was demonstrated in multiple sensory modalities . Although active during the go/no-go task , the cingulate gyrus did not show a similar lateralization . These findings further differentiate the organizations and functions of the medial frontal and cingulate executive regions , and suggest that the executive mechanisms operative within the medial frontal gyrus preserve fundamental aspects of input processing streams Moral decision-making is central to everyday social life because the evaluation of the actions of another agent or our own actions made with respect to the norms and values guides our behavior in a community . There is previous evidence that the presence of bodily harm -- even if irrelevant for a decision -- may affect the decision-making process . While recent neuroimaging studies found a common neural substrate of moral decision-making , the role of bodily harm has not been systematic ally studied so far . Here we used event-related functional magnetic resonance imaging ( fMRI ) to investigate how behavioral and neural correlates of semantic and moral decision-making processes are modulated by the presence of direct bodily harm or violence in the stimuli . Twelve participants made moral and semantic decisions about sentences describing actions of agents that either contained bodily harm or not and that could easily be judged as being good or bad or correct/incorrect , respectively . During moral and semantic decision-making , the presence of bodily harm result ed in faster response times ( RT ) and weaker activity in the temporal poles relative to trials devoid of bodily harm/violence , indicating a processing advantage and reduced processing depth for violence-related linguistic stimuli . Notably , there was no increase in activity in the amygdala and the posterior cingulate cortex ( PCC ) in response to trials containing bodily harm . These findings might be a correlate of limited generation of the semantic and emotional context in the anterior temporal poles during the evaluation of actions of another agent related to violence that is made with respect to the norms and values guiding our behavior in a community Language dominance and factors that influence language lateralization were investigated in right-h and ed , neurologically normal subjects ( n = 100 ) and right-h and ed epilepsy patients ( n = 50 ) using functional MRI . Increases in blood oxygenation-dependent signal during a semantic language activation task relative to a non-linguistic , auditory discrimination task provided an index of language system lateralization . As expected , the majority of both groups showed left hemisphere dominance , although a continuum of activation asymmetry was evident , with nearly all subjects showing some degree of right hemisphere activation . Using a categorical dominance classification , 94 % of the normal subjects were considered left hemisphere dominant and 6 % had bilateral , roughly symmetric language representation . None of the normal subjects had rightward dominance . There was greater variability of language dominance in the epilepsy group , with 78 % showing left hemisphere dominance , 16 % showing a symmetric pattern and 6 % showing right hemisphere dominance . Atypical language dominance in the epilepsy group was associated with an earlier age of brain injury and with weaker right h and dominance . Language lateralization in the normal group was weakly related to age , but was not significantly related to sex , education , task performance or familial left-h and edness |
14,090 | 17,291,929 | Early and mid-term follow-up of diabetic patients after revascularization indicates that the incidence of myocardial infa rct ion and repeat revascularization are reduced in surgically treated patients compared with those treated by balloon angioplasty alone .
Percutaneous coronary intervention ( PCI ) with bare metal stents has reduced the surgical advantage ( for reintervention ) in the early-mid-term ; however , repeat revascularization in diabetic patients continues to be substantially higher after PCI . | Although diabetic patients represent approximately one-quarter of all those undergoing revascularization , their outcomes after revascularization are usually worse compared with non-diabetic patients .
We examined the recent advances in percutaneous and surgical revascularization that are relevant to the treatment of diabetic patients . | Background —This investigation compares the results of contemporary percutaneous coronary intervention ( PCI ) with st and ard balloon angioplasty among patients with multivessel coronary disease . Patients having balloon angioplasty in the Bypass Angioplasty Revascularization Investigation ( BARI ) and those within the Dynamic Registry meeting BARI eligibility criteria were studied . Methods and Results — Clinical features and in-hospital and 1-year outcomes of 857 BARI-eligible patients in the Dynamic Registry ( contemporary PCI ) were compared with the 904 r and omized patients who underwent percutaneous transluminal coronary angioplasty in BARI . Compared with BARI patients , Registry patients had fewer lesions attempted ( 1.53 versus 2.56 , P = 0.001 ) , more frequent single-vessel PCI ( 76 % versus 33 % , P < 0.001 ) , greater use of intracoronary stents ( 76 % versus 1 % , P < 0.001 ) , and GP IIb/IIIa receptor antagonist ( 24 % versus 0 % , P < 0.001 ) . Angiographic success was achieved more often among Registry patients ( 91 % versus 72 % , P < 0.001 ) , whereas abrupt closure ( 1.5 % versus 9.5 % , P < 0.001 ) and in-hospital coronary artery bypass graft ( CABG ) ( 1.9 % versus 10.2 % , P < 0.001 ) and myocardial infa rct ion ( 0.8 % versus 2.1 % , P = 0.025 ) were less common . No differences were observed in either in-hospital or 1-year death , but 1-year death/myocardial infa rct ion was lower in the Registry . Registry patients had lower 1-year rates of subsequent CABG ( 8.6 % versus 22.7 % , P < 0.001 ) and PCI ( 12.4 % versus 22.5 % , P < 0.001 ) . By multivariate analysis , contemporary PCI was independently associated with reduced risk for in-hospital CABG , 1-year CABG , and 1-year PCI . Conclusions —Among patients with multivessel disease , contemporary PCI result ed in safer and more durable revascularization . These results support the role of PCI for selected patients with multivessel coronary artery disease Background —Few studies have compared long-term status of bypass grafts between patients with and without diabetes , and uncertainty exists as to whether diabetes independently predicts poor clinical outcome after CABG . Methods and Results —Among 1526 patients in BARI who underwent CABG as initial revascularization , 99 of 292 ( 34 % ) with treated diabetes mellitus ( TDM ) ( those on insulin or oral hypoglycemic agents ) and 469 of 1234 ( 38 % ) without TDM had follow-up angiography . Angiograms with the longest interval from initial surgery and before any percutaneous graft intervention ( mean 3.9 years ) were review ed . An average of 3.0 grafts were placed at initial CABG for patients with TDM ( n=297 ; internal mammary artery [ IMA ] , 33 % ) and 2.9 grafts for patients without TDM ( n=1347 ; IMA , 34 % ) . Patients with TDM were more likely than those without to have small ( < 1.5 mm ) grafted distal vessels ( 29 % versus 22 % ) and vessels of poor quality ( 9 % versus 6 % ) . On follow-up angiography , 89 % of IMA grafts were free of stenoses ≥50 % among patients with TDM versus 85 % among patients without TDM ( P = 0.23 ) . For vein grafts , the corresponding percentages were 71 % versus 75 % ( P = 0.40 ) . After statistical adjustment , TDM was unrelated to having a graft stenosis ≥50 % ( adjusted odds ratio , 0.87 ; 95 % CI , 0.58 to 1.32 ) . Conclusions —Despite diabetic patients ’ having smaller distal vessels and vessels judged to be of poorer quality , diabetes does not appear to adversely affect patency of IMA or vein grafts over an average of 4-year follow-up . Previously observed differences in survival between CABG-treated patients with and without diabetes may be largely a result of differential risk of mortality from noncardiac causes BACKGROUND The impact of percutaneous transluminal coronary angioplasty ( PTCA ) and coronary artery bypass grafting ( CABG ) on long-term mortality rates in the presence of various demographic , clinical , and angiographic factors is uncertain in the population of patients suitable for both procedures . METHODS AND RESULTS In the Bypass Angioplasty Revascularization Investigation ( BARI ) r and omized trial and registry , 3610 patients who were eligible to receive PTCA and CABG were revascularized between 1989 and 1992 . Multivariate Cox models were used to identify factors associated with 5-year mortality and cardiac mortality , with particular attention to factors that interact with treatment . Diabetic patients receiving insulin had higher mortality and cardiac mortality rates with PTCA compared with CABG ( relative risk [ RR ] 1.78 and 2.63 , respectively , P<0.001 ) , and patients with ST elevation had higher cardiac mortality rates with CABG than with PTCA ( RR 4.08 , P<0.001 ) . Factors most strongly associated with high overall mortality rates were insulin-treated diabetes , congestive heart failure , kidney failure , and older age . Black race was also associated with higher mortality rates ( RR 1.49 , P=0.019 ) . CONCLUSIONS A set of variables was identified that could be used to help select a revascularization procedure and to evaluate risk of long-term mortality in the population of patients considering revascularization OBJECTIVES We sought to investigate the impact of body mass index ( BMI ) on short- and long-term outcomes after initial revascularization with percutaneous transluminal coronary angioplasty ( PTCA ) or coronary artery bypass graft surgery ( CABG ) . BACKGROUND Equivocal results exist on the impact of BMI on the risk of in-hospital complications after PTCA or CABG , and no long-term mortality data exist from a large series of revascularized patients . METHODS From the r and omized series and observational registry of the Bypass Angioplasty Revascularization Investigation ( BARI ) , 2,108 patients who had PTCA and 1,526 patients who had CABG were evaluated by taking their BMI at study entry . They were classified as follows : low ( < 20 kg/m(2 ) ) , normal ( 20 to 24.9 kg/m(2 ) ) , overweight ( 25 to 29.9 kg/m(2 ) ) , class I obese ( 30 to 34.9 kg/m(2 ) ) and class II/III obese ( greater-than-or-equal 35 kg/m(2 ) ) . In-hospital complications and short- and long-term mortalities were compared between levels of BMI within each mode of initial revascularization . RESULTS Among patients who had PTCA , each unit increase in BMI was associated with a 5.5 % lower adjusted risk of a major in-hospital event ( death , myocardial infa rct ion , stroke , coma ) ; among patients who had CABG , no difference in the in-hospital outcome was observed according to BMI . In contrast , BMI was not associated with five-year mortality in the PTCA group ; among the CABG group , adjusted relative risks of five-year cardiac mortality according to levels of BMI were 0.0 ( low ) , 1.0 ( normal ) , 2.02 ( overweight ) , 3.16 ( class I obese ) and 4.85 ( class II/III obese ) ( linear p < 0.001 ) . CONCLUSIONS Body mass index appears to have a differential impact on short- and long-term outcomes after coronary revascularization . These results underscore the need for further research to identify factors responsible for the apparent short-term protective effect of a higher BMI in patients undergoing PTCA and to study the impact of weight reduction on the long-term survival of obese patients undergoing CABG Background —Our aims were to compare coronary artery bypass grafting ( CABG ) and stenting for the treatment of diabetic patients with multivessel coronary disease enrolled in the Arterial Revascularization Therapy Study ( ARTS ) trial and to determine the costs of these 2 treatment strategies . Methods and Results — Patients ( n=1205 ) were r and omly assigned to stent implantation ( n=600 ; diabetic , 112 ) or CABG ( n=605 ; diabetic , 96 ) . Costs per patient were calculated as the product of each patient ’s use of re sources and the corresponding unit costs . Baseline characteristics were similar between the groups . At 1 year , diabetic patients treated with stenting had the lowest event-free survival rate ( 63.4 % ) because of a higher incidence of repeat revascularization compared with both diabetic patients treated with CABG ( 84.4 % , P < 0.001 ) and nondiabetic patients treated with stents ( 76.2 % , P = 0.04 ) . Conversely , diabetic and nondiabetic patients experienced similar 1-year event-free survival rates when treated with CABG ( 84.4 % and 88.4 % ) . The total 1-year costs for stenting and CABG in diabetic patients were $ 12 855 and $ 16 585 ( P < 0.001 ) and in the nondiabetic groups , $ 10 164 for stenting and $ 13 082 for surgery . Conclusions —Multivessel diabetic patients treated with stenting had a worse 1-year outcome than patients assigned to CABG or nondiabetics treated with stenting . The strategy of stenting was less costly than CABG , however , regardless of diabetic status Background — Outcomes after percutaneous coronary interventions in diabetic patients are shadowed by the increased rate of recurrence compared with nondiabetic patients . Methods and Results — We conducted a multicenter , r and omized trial to demonstrate the efficacy of sirolimus-eluting stents compared with st and ard stents to prevent restenosis in diabetic patients with de novo lesions in native coronary arteries . The primary end point of the trial was in-segment late lumen loss as assessed by quantitative coronary angiography at 9-month follow-up . The trial was stratified by diabetes treatment status . One hundred sixty patients were r and omized to sirolimus-eluting stents ( 80 patients ; 111 lesions ) or st and ard stent implantation ( 80 patients ; 110 lesions ) . On average , reference diameter was 2.34±0.6 mm , lesion length was 15.0±8 mm , and 13.1 % of lesions were chronic total occlusions . In-segment late lumen loss was reduced from 0.47±0.5 mm for st and ard stents to 0.06±0.4 mm for sirolimus stents ( P<0.001 ) . Target-lesion revascularization and major adverse cardiac event rates were significantly lower in the sirolimus group ( 31.3 % versus 7.3 % and 36.3 % versus 11.3 % , respectively ; both P<0.001 ) . Non – insulin- and insulin-requiring patients demonstrated similar reductions in angiographic and clinical parameters of restenosis after sirolimus-eluting stent implantation . During the 9-month follow-up , stent thrombosis occurred in 2 patients after st and ard stent implantation . Conversely , this phenomenon was not seen in the sirolimus stent group . Conclusions — This r and omized trial demonstrated that sirolimus stent implantation is safe and efficacious in reducing both angiographic and clinical parameters of restenosis compared with st and ard stents in diabetic patients with de novo coronary stenoses Background —The platelet glycoprotein IIb/IIIa receptor inhibitor abciximab , a monoclonal antibody , has been shown to improve early and late outcomes among diabetic patients undergoing percutaneous coronary intervention ( PCI ) . It is unknown whether small-molecule agents confer similar benefits . Methods and Results —In 18 countries , 4809 patients undergoing PCI with stent implantation were r and omized to tirofiban or abciximab . At the time of enrollment , patients were stratified according to diabetes status . As compared with non-diabetic patients , patients with diabetes ( n=1117 ) showed similar 30-day ischemic outcomes , an increased incidence of any target vessel revascularization ( TVR ) at 6 months ( 10.3 % versus 7.8%;P = 0.008 ) , and a trend toward higher 1-year mortality ( 2.5 % versus 1.6%;P = 0.056 ) . Among diabetic patients r and omized to tirofiban ( n=560 ) , the incidence of death , myocardial infa rct ion ( MI ) , or urgent TVR at 30 days was 6.2 % , and among those r and omized to abciximab ( n=557 ) it was 5.4 % ( hazard ratio [ HR ] 1.16;P = 0.540 ) . At 6 months , the composite of death , MI , or any TVR occurred in 15.7 % and in 16.9 % of tirofiban and abciximab patients , respectively ( HR 0.93;P = 0.610 ) . Any TVR occurred in 9.5 % and 11.1 % , respectively ( HR 0.84;P = 0.366 ) . The 1-year mortality was 2.1 % in the tirofiban group and 2.9 % in the abciximab group ( HR 0.74;P = 0.436 ) . Conclusions —Among diabetic patients undergoing PCI , tirofiban and abciximab were associated with comparable event rates , including similar rates of 6-month TVR and 1-year mortality . These findings suggest that the non-glycoprotein IIb/IIIa properties of abciximab do not translate into a discernible long-term clinical benefit among diabetic patients OBJECTIVES We examined the relationship between diabetes mellitus and outcomes after coronary artery bypass graft ( CABG ) surgery in patients with severe left ventricular ( LV ) dysfunction . BACKGROUND Although diabetes is associated with poor outcomes after CABG surgery among unselected patients , the relationship between diabetes and mortality after CABG surgery among patients with LV dysfunction is less certain . METHODS Using data from The CABG Patch Trial , a study of implantable cardiac defibrillator therapy , we analyzed 900 patients with ejection fraction < 0.36 who underwent CABG surgery from 1990 to 1996 . RESULTS Diabetics comprised 38 % of the patients , and 48 % of diabetics were prescribed insulin . Diabetes was associated with hypertension , peripheral vascular disease , history of stroke , clinical heart failure and rales on physical exam . Diabetics were at higher risk for postoperative superficial sternal wound infection and renal failure . With an average follow-up time of 32 + /-16 months , actuarial all-cause mortality 48 months after CABG surgery was 26 % in diabetics and 24 % in nondiabetics ( p = 0.66 , log-rank test ) . Diabetes was not associated with long-term mortality in Cox multiple regression analyses . Actuarial re-hospitalization rates 48 months after CABG surgery were 85 % in diabetics and 69 % in nondiabetics ( p = 0.0001 , log-rank test ) . Diabetics had a 44 % higher risk of re-hospitalization for any cause ( p = 0.0001 ) and a 24 % higher risk of re-admission for cardiac causes ( p < 0.05 ) . Unexpectedly , fewer arrhythmic events were found in diabetics . CONCLUSIONS Diabetes was not a predictor of mortality after CABG surgery among patients with LV dysfunction despite associated comorbidities . However , diabetes was associated with increased postoperative complications and re-hospitalization OBJECTIVES The purpose of the present study is to report the five-year follow-up results of the ERACI II trial . BACKGROUND Immediate and one-year follow-up results of the ERACI II study showed a prognosis advantage of percutaneous coronary intervention ( PCI ) with stents over coronary artery bypass grafting ( CABG ) . METHODS A total of 450 patients were r and omly assigned to undergo either PCI ( n = 225 ) ; or CABG ( n = 225 ) . Only patients with multi-vessel disease were enrolled . Clinical follow-up during five years was obtained in 92 % of the total population after hospital discharge . The primary end point of the study was to compare freedom from major adverse cardiovascular events ( MACE ) at 30 days , 1 year , 3 years , and 5 years of follow-up . RESULTS At five years of follow-up , patients initially treated with PCI had similar survival and freedom from non-fatal acute myocardial infa rct ion than those initially treated with CABG ( 92.8 % vs. 88.4 % and 97.3 % vs. 94 % respectively , p = 0.16 ) . Freedom from repeat revascularization procedures ( PCI/CABG ) was significantly lower with PCI compared with CABG ( 71.5 % vs. 92.4 % , p = 0.0002 ) . Freedom from MACE was also significantly lower with PCI compared with CABG ( 65.3 % vs. 76.4 % ; p = 0.013 ) . At five years similar numbers of patients r and omized to each revascularization procedure were asymptomatic or with class I angina . CONCLUSIONS At five years of follow-up , in the ERACI II study , there were no survival benefits from any revascularization procedure ; however patients initially treated with CABG had better freedom from repeat revascularization procedures and from MACE CONTEXT Inflammation and ischemia-reperfusion injury during coronary artery bypass graft ( CABG ) surgery requiring cardiopulmonary bypass are associated with postoperative myocardial infa rct ion ( MI ) and mortality . OBJECTIVE To determine the efficacy and safety of pexelizumab , a C5 complement inhibitor , in reducing perioperative MI and mortality in CABG surgery . DESIGN , SETTING , AND PARTICIPANTS A r and omized , double-blind , placebo-controlled trial , including 3099 patients ( > or = 18 years ) undergoing CABG surgery with or without valve surgery at 205 hospitals in North America and Western Europe from January 2002 to February 2003 . INTERVENTIONS Patients were r and omly assigned to receive intravenous pexelizumab ( 2.0 mg/kg bolus plus 0.05 mg/kg per hour for 24 hours ; n = 1553 ) or placebo ( n = 1546 ) 10 minutes before undergoing the procedure . MAIN OUTCOME MEASURES The primary composite end point was the incidence of death or MI within 30 days of r and omization in those undergoing CABG surgery only ( n = 2746 ) . Secondary analyses included the intent-to-treat analyses of death or MI composite at days 4 and 30 in all 3099 study patients . RESULTS After 30 days , 134 ( 9.8 % ) of 1373 of patients receiving pexelizumab vs 161 ( 11.8 % ) of 1359 of patients receiving placebo ( relative risk , 0.82 ; 95 % confidence interval , 0.66 - 1.02 ; P = .07 ) died or experienced MI in the CABG surgery only population . In the intent-to-treat analyses , 178 ( 11.5 % ) of 1547 patients receiving pexelizumab vs 215 ( 14.0 % ) of 1535 receiving placebo died or experienced MI ( relative risk , 0.82 ; 95 % confidence interval , 0.68 - 0.99 ; P = .03 ) . The trial was not powered to detect a reduction in mortality alone . CONCLUSIONS Compared with placebo , pexelizumab was not associated with a significant reduction in the risk of the composite end point of death or MI in 2746 patients who had undergone CABG surgery only but was associated with a statistically significant risk reduction 30 days after the procedure among all 3099 patients undergoing CABG with or without valve surgery Background — Data are absent that compare midterm angiographic outcome between patients with and without diabetes after initial percutaneous transluminal coronary angioplasty ( PTCA ) and coronary artery bypass graft surgery ( CABG ) . Importantly , diabetes mellitus may differentially influence long-term survival after PTCA or CABG . Methods and Results — Patients with multivessel coronary disease who were previously enrolled in the Bypass Angiopathy Revascularization Investigation to compare initial PTCA versus CABG ( n=1829 ) and who had a reduction in jeopardized myocardium after initial revascularization and at least 1 angiogram during 5-year follow-up were analyzed ( n=897 ) . This included 369 CABG-treated patients ( 16 % with diabetes ) and 528 PTCA-treated patients ( 18 % with diabetes ) . The influence of diabetes on angiographic increase in percentage of jeopardized myocardium after initial revascularization with either PTCA or CABG was investigated . Among PTCA patients , the mean percentage increase in total jeopardized myocardium was significantly greater in those with diabetes than in those without at 1-year protocol -directed angiography ( 42 % versus 24 % , P = 0.05 ) and on the first clinical ly performed ( unscheduled ) angiogram within 30 months ( 63 % versus 50 % , P = 0.01 ) but not at 5-year protocol -directed angiography ( 34 % versus 26 % , P = 0.33 ) . This excess midterm risk associated with diabetes persisted after statistical adjustment . In contrast , among CABG patients , diabetes was not associated with percentage increase in jeopardized myocardium at any angiographic follow-up interval . Conclusions —Presence of diabetes differentially influences worsening of jeopardized myocardium after initial PTCA compared with CABG . This differential effect occurs irrespective of whether follow-up angiography is undertaken for clinical or non clinical purpose Background —Diabetes portends an adverse prognosis in patients undergoing percutaneous coronary intervention ( PCI ) . Whether improvements in current clinical practice ( stents , IIb/IIIa antagonists ) have result ed in substantial improvement of these outcomes remains an issue . The aim of this study was to determine the influence of diabetes on 9-month outcomes of patients undergoing PCI in the current era . Methods and Results —The 11 482 patients enrolled in the Prevention of REStenosis with Tranilast and its Outcomes ( PRESTO ) Trial were stratified according to the presence ( n=2694 ) or absence ( n=8798 ) of diabetes . Diabetic patients were older ; were more likely to be female ; had a higher proportion of congestive failure , hypertension , prior CABG , and unstable angina ; and had higher body mass index and lower ejection fraction than nondiabetic patients ( P < 0.01 for all comparisons ) . The degree of multivessel disease was similar between the two groups . American College of Cardiology/American Heart Association type C lesions were more common in diabetic patients ( 17 % versus 15 % , P < 0.01 ) . Angiographic and procedural success rates and in-hospital events were similar between the two groups . The primary end point of death , myocardial infa rct ion , or target vessel revascularization ( TVR ) was analyzed as time-to-first event within 9 months of the index PCI . After adjusting for certain baseline characteristics , diabetes was independently associated with death at 9 months ( relative risk [ RR ] , 1.87 ; 95 % CI , 1.31 to 2.68 , P < 0.01 ) and with an increased likelihood of TVR ( RR , 1.27 ; 95 % CI , 1.14 to 1.42 , P < 0.01 ) , as well as the composite end point of death/myocardial infa rct ion/TVR ( RR , 1.26 ; 95 % CI , 1.13 to 1.40 , P < 0.01 ) . Conclusions —Despite advances in interventional techniques , diabetes remains a significant independent predictor of adverse events in the intermediate term after PCI OBJECTIVES This study compared survival after percutaneous coronary intervention ( PCI ) with survival after coronary artery bypass graft surgery ( CABG ) among diabetics in the Veterans Affairs AWESOME ( Angina With Extremely Serious Operative Mortality Evaluation ) study r and omized trial and registry of high-risk patients . BACKGROUND Previous studies indicate that CABG may be superior to PCI for diabetics , but no comparisons have been made for diabetics at high risk for surgery . METHODS Over five years ( 1995 to 2000 ) , 2,431 patients with medically refractory myocardial ischemia and at least one of five risk factors ( prior CABG , myocardial infa rct ion within seven days , left ventricular ejection fraction < 0.35 , age > 70 years , or an intra-aortic balloon being required to stabilize ) were identified . A total of 781 were acceptable for CABG and PCI , and 454 consented to be r and omized . The 1,650 patients not acceptable for both CABG and PCI constitute the physician-directed registry , and the 327 who were acceptable but refused to be r and omized constitute the patient-choice registry . Diabetes prevalence was 32 % ( 144 ) among r and omized patients , 27 % ( 89 ) in the patient-choice registry , and 32 % ( 525 ) in the physician-directed registry . The CABG and PCI survival rates were compared using Kaplan-Meier curves and log-rank tests . RESULTS The respective CABG and PCI 36-month survival rates for diabetic patients were 72 % and 81 % for r and omized patients , 85 % and 89 % for patient-choice registry patients , and 73 % and 71 % for the physician-directed registry patients . None of the differences was statistically significant . CONCLUSIONS We conclude that PCI is a relatively safe alternative to CABG for diabetic patients with medically refractory unstable angina who are at high risk for CABG Background —Diabetic patients are at increased risk of adverse outcomes after percutaneous coronary interventions . Although subset analyses suggest particular benefit from the administration of abciximab in diabetic patients , no dedicated large r and omized trials have been performed in diabetic patients undergoing percutaneous coronary intervention , and certainly not after pretreatment with a high loading dose of clopidogrel . Methods and Results —This study ( Intracoronary Stenting and Antithrombotic Regimen : Is Abciximab a Superior Way to Eliminate Elevated Thrombotic Risk in Diabetics [ ISAR-SWEET ] Study ) enrolled 701 diabetic patients with coronary artery disease who underwent an elective percutaneous coronary intervention after pretreatment with a 600-mg dose of clopidogrel > 2 hours before the procedure : 351 patients were r and omly assigned to abciximab and 350 patients to placebo . The primary end point of the trial was the composite incidence of death and myocardial infa rct ion at 1 year . The frequency of angiographic restenosis ( diameter stenosis ≥50 % ) was the secondary end point . The incidence of death or myocardial infa rct ion was 8.3 % in the abciximab group and 8.6 % in the placebo group ( P=0.91 ) , with a relative risk of 0.97 ( 95 % CI , 0.58 to 1.62 ) . The incidence of angiographic restenosis was 28.9 % in the abciximab group and 37.8 % in the placebo group ( P=0.01 ) , with a relative risk of 0.76 ( 95 % CI , 0.62 to 0.94 ) . The incidence of target lesion revascularization was 23.2 % in the abciximab group and 30.4 % in the placebo group ( P=0.03 ) . Conclusions —The findings of this study do not support a significant impact of abciximab on the risk of death and myocardial infa rct ion in diabetic patients undergoing percutaneous coronary interventions after pretreatment with a 600-mg loading dose of clopidogrel at least 2 hours before the procedure . The present findings suggest , however , that abciximab reduces the risk of restenosis in diabetic patients receiving coronary bare metal stents OBJECTIVES Coronary angiograms obtained five years following revascularization were examined to assess the extent of compromise in myocardial perfusion due to failure of revascularization versus progression of native disease . BACKGROUND The Bypass Angioplasty Revascularization Investigation ( BARI ) r and omized revascularization c and i date s between bypass surgery and angioplasty . Entry and five-year angiograms from 407 of 519 ( 78 % ) patients at four centers were analyzed . METHODS Analysis of the distribution of coronary vessels and stenoses provided a measure of myocardial jeopardy that correlates with presence of angina . The extent to which initial benefits of revascularization were undone by failed revascularization versus native disease progression was assessed . RESULTS Myocardial jeopardy fell following initial revascularization , from 60 % to 17 % for percutaneous coronary intervention (PCI)-treated patients compared with 60 % to 7 % for coronary artery bypass graft ( CABG ) surgery patients ( p < 0.001 ) , rebounding at five years to 25 % for PCI and 20 % for surgery patients ( p = 0.01 ) . Correspondingly , angina prevalence was higher at five years in PCI-treated patients than in surgery-treated patients ( 28 % vs. 18 % ; p = 0.03 ) . However , myocardial jeopardy at five years , and not initial treatment ( PCI vs. surgery ) , was independently associated with late angina . Increased myocardial jeopardy from entry to five-year angiogram occurred in 42 % of PCI-treated patients and 51 % of CABG-treated patients ( p = 0.06 ) . Among the increases in myocardial jeopardy , two-thirds occurred in previously untreated arteries . CONCLUSIONS Native coronary disease progression occurred more often than failed revascularization in both PCI- and CABG-treated patients as a cause of jeopardized myocardium and angina recurrence . These results support intensive postrevascularization risk-factor modification This report presents baseline clinical and angiographic data from the Bypass Angioplasty Revascularization Investigation ( BARI ) , a multicenter international trial assessing the relative efficacy of percutaneous transluminal coronary angioplasty ( PTCA ) versus coronary artery bypass graft surgery ( CABG ) in selected patients with multivessel coronary artery disease . PTCA is commonly performed in patients with multivessel coronary artery disease , yet its long-term efficacy in comparison to CABG is unknown . From August 1988 through August 1991 , 1,829 qualifying patients with multivessel disease suitable for either procedure were r and omized to PTCA or CABG ; sample size estimates were based on anticipated 5-year mortality . Two registry population s were also defined for follow-up : ( 1 ) 2,013 patients eligible for r and omization but not r and omized ; and ( 2 ) 422 patients considered by angiography as unsuitable for r and omization . Patients r and omized in BARI were at relatively high risk for subsequent cardiac events : 39 % were > or = 65 years old , 55 % had prior myocardial infa rct ion , 69 % presented with unstable angina or non-Q wave myocardial infa rct ion , and 43 % had 3-vessel coronary artery disease . Patients r and omized to PTCA and CABG were equally matched in all the important baseline variables . The r and omized and the eligible but not r and omized groups were similar in most respects . However , the nonr and omized group had a higher proportion with college education ; fewer with a history of myocardial infa rct ion , heart failure , diabetes , and smoking ; and a somewhat better average ejection fraction . At the 3-month follow-up , PTCA had been performed more commonly in the nonr and omized eligible patients , especially those with 2-vessel disease . ( ABSTRACT TRUNCATED AT 250 WORDS Background —R and omized clinical trials have shown that a sirolimus-eluting stent significantly reduces restenosis after percutaneous coronary revascularization . Diabetic patients are known to have a higher risk of restenosis compared with nondiabetic patients . The purpose of this analysis was to determine the impact of sirolimus-eluting stents on outcomes of diabetic compared with nondiabetic patients . Methods and Results —The SIRIUS ( SIRolImUS-coated Bx Velocity balloon-exp and able stent in the treatment of patients with de novo coronary artery lesions ) trial is a r and omized , double-blind study that compared sirolimus-eluting and bare metal stent implantation in 1058 patients with de novo native coronary artery lesions . Diabetes mellitus was present in 279 ( 26 % ) patients ( diabetes mellitus group , 131 patients received sirolimus-eluting stents and 148 patients received bare metal stents ) and was absent in 778 patients ( no – diabetes mellitus group , 402 patients received sirolimus-eluting stents and 376 patients received bare metal stents ) . At 270 days , target lesion revascularization was reduced in diabetic patients from 22.3 % with bare metal stents to 6.9 % with sirolimus-eluting stents ( P < 0.001 ) and in nondiabetic patients from 14.1 % to 2.99 % ( P < 0.001 ) , respectively . Major adverse cardiac events were reduced in diabetic patients from 25 % with bare metal stents to 9.2 % with sirolimus-eluting stents ( P < 0.001 ) and from 16.5 % to 6.5 % ( P < 0.001 ) in nondiabetic patients , respectively . Conclusions —Implantation of sirolimus-eluting stents compared with bare metal stents in de novo coronary lesions reduces major adverse cardiac events in patients with and without diabetes mellitus . However , among patients receiving sirolimus-eluting stents , there remains a trend toward a higher frequency of repeat intervention in diabetic patients compared with nondiabetic patients , particularly in the insulin-requiring patients OBJECTIVE Diabetes mellitus is a risk factor for death after coronary artery bypass grafting . Its relative risk may be related to the level of perioperative hyperglycemia . We hypothesized that strict glucose control with a continuous insulin infusion in the perioperative period would reduce hospital mortality . METHODS All patients with diabetes undergoing coronary artery bypass grafting ( n = 3554 ) were treated aggressively with either subcutaneous insulin ( 1987 - 1991 ) or with continuous insulin infusion ( 1992 - 2001 ) for hyperglycemia . Predicted and observed hospital mortalities were compared with both internal and external ( Society of Thoracic Surgeons 1996 ) multivariable risk models . RESULTS Observed mortality with continuous insulin infusion ( 2.5 % , n = 65/2612 ) was significantly lower than with subcutaneous insulin ( 5.3 % , n = 50/942 , P < .0001 ) . Likewise , glucose control was significantly better with continuous insulin infusion ( 177 + /- 30 mg/dL vs 213 + /- 41 mg/dL , P < .0001 ) . For internal comparison , multivariable analysis showed that continuous insulin infusion was independently protective against death ( odds ratio 0.43 , P = .001 ) . Conversely , cardiogenic shock , renal failure , reoperation , nonelective operative status , older age , concomitant peripheral or cerebral vascular disease , decreasing ejection fraction , unstable angina , and history of atrial fibrillation increased the risk of death . For external comparison , observed mortality with continuous insulin infusion was significantly less than that predicted by the model ( observed/expected ratio 0.63 , P < .001 ) . Multivariable analysis revealed that continuous insulin infusion added an independently protective effect against death ( odds ratio 0.50 , P = .005 ) to the constellation of risk factors in the Society of Thoracic Surgeons risk model . CONCLUSION Continuous insulin infusion eliminates the incremental increase in in-hospital mortality after coronary artery bypass grafting associated with diabetes . The protective effect of continuous insulin infusion may stem from the effective metabolic use of excess glucose to favorably alter pathways of myocardial adenosine triphosphate production . Continuous insulin infusion should become the st and ard of care for glycometabolic control in patients with diabetes undergoing coronary artery bypass grafting OBJECTIVES To evaluate the long-term outcome of patients r and omized to coronary bypass surgery or coronary angioplasty . BACKGROUND The Emory Angioplasty versus Surgery Trial ( EAST ) is a single center r and omized comparison of a strategy of initial coronary angioplasty ( n = 198 ) or coronary bypass surgery ( n = 194 ) for patients with multivessel coronary artery disease . The primary end point ( death , myocardial infa rct ion or a large ischemic defect at 3 years ) was not different , and repeat revascularization was significantly greater in the angioplasty group . Subsequently , the National Heart , Lung and Blood Institute supported a five-year extension of the trial . METHODS After the three year anniversary visit , annual question naires , telephone contact and examination of medical records were accomplished until death or the eight year anniversary in 100 % of the patients surviving at 3 years . RESULTS Survival at 8 years is 79.3 % in the angioplasty group and 82.7 % in the surgical group ( p = 0.40 ) . Patients with proximal left anterior descending stenosis and those with diabetes tended to have better late survival with surgical intervention although not reaching statistical significance . After the first 3 years , repeat interventions remained relatively equal for both treatment groups . CONCLUSIONS Long-term survival is not significantly different between angioplasty and surgery , and late ( three to eight year ) revascularization procedures were infrequent . Patients without treated diabetes had similar survival in both groups Background : It is widely assumed that decline in cognition after coronary artery bypass grafting ( CABG ) is related to use of the cardiopulmonary bypass pump . Because most studies have not included comparable control groups , it remains unclear whether postoperative cognitive changes are specific to cardiopulmonary bypass , general aspects of surgery , or vascular pathologies of the aging brain . Methods : This nonr and omized study included four groups : CABG patients ( n = 140 ) ; off-pump coronary surgery ( n = 72 ) ; nonsurgical cardiac controls ( NSCC ) with diagnosed coronary artery disease but no surgery ( n = 99 ) ; and heart healthy controls ( HHC ) with no cardiac risk factors ( n = 69 ) . Subjects were evaluated at baseline ( preoperatively ) , 3 months , and 12 months . Eight cognitive domains and a global cognitive score , as well as depressive and subjective symptoms were analyzed . Results : At baseline , patients with coronary artery disease ( CABG , off-pump , and NSCC ) had lower performance than the HHC group in several cognitive domains . By 3 months , all groups had improved . From 3 to 12 months , there were minimal intrasubject changes for all groups . No consistent differences between the CABG and off-pump patients were observed . Conclusions : Compared with heart healthy controls ( HHC ) , the groups with coronary artery disease had lower cognitive test scores at baseline . There was no evidence that the cognitive test performance of coronary artery bypass grafting ( CABG ) patients differed from that of control groups with coronary artery disease over a 1-year period . This study emphasizes the need for appropriate control groups for interpreting longitudinal changes in cognitive performance after CABG BACKGROUND Patients with diabetes mellitus have increased morbidity and mortality after coronary revascularization . The Bypass Angioplasty Revascularization Investigation ( BARI ) , a trial of percutaneous transluminal coronary angioplasty ( PTCA ) versus coronary artery bypass graft surgery ( CABG ) in patients with multivessel disease , reported a 5-year survival advantage of CABG over PTCA in patients with treated diabetes mellitus ( TDM ) . This report examines these findings in more detail . METHODS AND RESULTS Eighteen clinical centers r and omly assigned 1829 patients with multivessel coronary disease to undergo initial CABG or PTCA . Patients were followed an average of 5.4 years . TDM was defined as a history of diabetes with use of oral hypoglycemic agents or insulin at study entry . Nineteen percent of the r and omized population ( 353 patients ) met these criteria . TDM patients had more unfavorable baseline characteristics than other patients , but among TDM patients , these characteristics were similar between the CABG and PTCA groups . Better average 5.4-year survival with CABG was due to reduced cardiac mortality ( 5.8 % versus 20.6 % , P=.0003 ) , which was confined to those receiving at least one internal mammary artery graft . CONCLUSIONS Patients with TDM assigned to an initial strategy of CABG have a striking reduction in cardiac mortality compared with PTCA . Long-term internal mammary artery graft patency may contribute to this improved outcome by reducing the fatality of follow-up myocardial infa rct ion BACKGROUND In patients with acute myocardial infa rct ion ( MI ) , increased plasma glucose levels at hospital admission are associated with worse outcome . We aim ed to assess the predictive value of admission glucose concentrations on short- and long-term mortality in patients with acute MI undergoing primary or rescue percutaneous coronary intervention ( PCI ) . METHODS We analyzed the 30-day and long-term ( mean follow-up 3.7 years ) outcome of 978 patients prospect ively included in a single-center registry of patients with acute MI treated with PCI within 24 hours after onset of symptoms . Patients were classified according to plasma glucose levels at admission : < 7.8 mmol/L ( group I , n = 322 ) , 7.8 to 11 mmol/L ( group II , n = 348 ) , and > 11.0 mmol/L ( group III , n = 308 ) . RESULTS Mortality at 30 days was 1.2 % in group I , 6.3 % in group II , and 16.6 % in group III ( P < .001 ) . After multivariate adjustment for age , the presence of cardiogenic shock , and TIMI 3 flow after PCI , the association of mortality with glucose classification remained significant ( P value for trend = .003 ) . The relative risk of death at 30 days for group III versus group I was 3.9 ( 95 % CI 1.2 - 13.2 ) . During long-term follow-up , mortality was similar in groups I and II . However , in group III adjusted mortality remained significantly increased compared with group I ( relative risk 1.76 , CI 1.01 - 3.08 ) . CONCLUSIONS In patients undergoing emergency PCI for acute MI , glucose levels at hospital admission are predictive for short- and long-term survival . Knowledge of admission glucose levels may improve initial bedside risk stratification BACKGROUND Sirolimus-eluting stents and paclitaxel-eluting stents , as compared with bare-metal stents , reduce the risk of restenosis . It is unclear whether there are differences in safety and efficacy between the two types of drug-eluting stents . METHODS We conducted a r and omized , controlled , single-blind trial comparing sirolimus-eluting stents with paclitaxel-eluting stents in 1012 patients undergoing percutaneous coronary intervention . The primary end point was a composite of major adverse cardiac events ( death from cardiac causes , myocardial infa rct ion , and ischemia-driven revascularization of the target lesion ) by nine months . Follow-up angiography was completed in 540 of 1012 patients ( 53.4 percent ) . RESULTS The two groups had similar baseline clinical and angiographic characteristics . The rate of major adverse cardiac events at nine months was 6.2 percent in the sirolimus-stent group and 10.8 percent in the paclitaxel-stent group ( hazard ratio , 0.56 ; 95 percent confidence interval , 0.36 to 0.86 ; P=0.009 ) . The difference was driven by a lower rate of target-lesion revascularization in the sirolimus-stent group than in the paclitaxel-stent group ( 4.8 percent vs. 8.3 percent ; hazard ratio , 0.56 ; 95 percent confidence interval , 0.34 to 0.93 ; P=0.03 ) . Rates of death from cardiac causes were 0.6 percent in the sirolimus-stent group and 1.6 percent in the paclitaxel-stent group ( P=0.15 ) ; the rates of myocardial infa rct ion were 2.8 percent and 3.5 percent , respectively ( P=0.49 ) ; and the rates of angiographic restenosis were 6.6 percent and 11.7 percent , respectively ( P=0.02 ) . CONCLUSIONS As compared with paclitaxel-eluting stents , the use of sirolimus-eluting stents results in fewer major adverse cardiac events , primarily by decreasing the rates of clinical and angiographic restenosis OBJECTIVE The purpose of this study was to compare percutaneous transluminal coronary revascularization ( PTCR ) employing stent implantation to conventional coronary artery bypass graft surgery ( CABG ) in symptomatic patients with multivessel coronary artery disease . BACKGROUND Previous r and omized studies comparing balloon angioplasty versus CABG have demonstrated equivalent safety results . However , CABG was associated with significantly fewer repeat revascularization procedures . METHODS A total of 2,759 patients with coronary artery disease were screened at seven clinical sites , and 450 patients were r and omly assigned to undergo either PTCR ( 225 patients ) or CABG ( 225 patients ) . Only patients with multivessel disease and indication for revascularization were enrolled . RESULTS Both groups had similar clinical demographics : unstable angina in 92 % ; 38 % were older than 65 years , and 23 % had a history of peripheral vascular disease . During the first 30 days , PTCR patients had lower major adverse events ( death , myocardial infa rct ion , repeat revascularization procedures and stroke ) compared with CABG patients ( 3.6 % vs. 12.3 % , p = 0.002 ) . Death occurred in 0.9 % of PTCR patients versus 5.7 % in CABG patients , p < 0.013 , and Q myocardial infa rct ion ( MI ) occurred in 0.9 % PTCR versus 5.7 % of CABG patients , p < 0.013 . At follow-up ( mean 18.5 + /- 6.4 months ) , survival was 96.9 % in PTCR versus 92.5 % in CABG , p < 0.017 . Freedom from MI was also better in PTCR compared to CABG patients ( 97.7 % vs. 93.4 % , p < 0.017 ) . Requirements for new revascularization procedures were higher in PTCR than in CABG patients ( 16.8 % vs. 4.8 % , p < 0.002 ) . CONCLUSIONS In this selected high-risk group of patients with multivessel disease , PTCR with stent implantation showed better survival and freedom from MI than did conventional surgery . Repeat revascularization procedures were higher in the PTCR group BACKGROUND In the setting of percutaneous coronary revascularization , agents in the class known as platelet glycoprotein IIb/IIIa inhibitors have significantly reduced the incidence of death or nonfatal myocardial infa rct ion at 30 days . We assessed whether there are differences in safety or efficacy between two such inhibitors , tirofiban and abciximab . METHODS Using a double-blind , double-dummy design at 149 hospitals in 18 countries , we r and omly assigned patients to receive either tirofiban or abciximab before undergoing percutaneous coronary revascularization with the intent to perform stenting . The primary end point was a composite of death , nonfatal myocardial infa rct ion , or urgent target-vessel revascularization at 30 days . The trial was design ed and statistically powered to demonstrate the noninferiority of tirofiban as compared with abciximab . RESULTS The primary end point occurred more frequently among the 2398 patients in the tirofiban group than among the 2411 patients in the abciximab group ( 7.6 percent vs. 6.0 percent ; hazard ratio , 1.26 ; one-sided 95 percent confidence interval of 1.51 , demonstrating lack of equivalence , and two-sided 95 percent confidence interval of 1.01 to 1.57 , demonstrating the superiority of abciximab over tirofiban ; P=0.038 ) . The magnitude and the direction of the effect were similar for each component of the composite end point ( hazard ratio for death , 1.21 ; hazard ratio for myocardial infa rct ion , 1.27 ; and hazard ratio for urgent target-vessel revascularization , 1.26 ) , and the difference in the incidence of myocardial infa rct ion between the tirofiban group and the abciximab group was significant ( 6.9 percent and 5.4 percent , respectively ; P=0.04 ) . The relative benefit of abciximab was consistent regardless of age , sex , the presence or absence of diabetes , or the presence or absence of pretreatment with clopidogrel . There were no significant differences in the rates of major bleeding complications or transfusions , but tirofiban was associated with a lower rate of minor bleeding episodes and thrombocytopenia . CONCLUSIONS Although the trial was intended to assess the noninferiority of tirofiban as compared with abciximab , the findings demonstrated that tirofiban offered less protection from major ischemic events than did abciximab BACKGROUND Changes in the treatment of coronary artery disease both surgically and percutaneously have rendered the major r and omized trials historical . Furthermore , the restrictive criteria of previous trials excluded most patients treated in daily practice . Although coronary surgery is still considered the current , evidence -based , gold-st and ard treatment of left main ( LM ) and 3-vessel coronary disease , the added benefit of drug-eluting stents has further exp and ed the use of percutaneous coronary intervention ( PCI ) beyond less complex population s in daily practice . STUDY DESIGN The 1500-patient , prospect i ve , multicenter , multinational ( European and North American ) , r and omized SYNTAX study with nested registries will enroll " all-comers . " Consecutive patients with de novo 3-vessel disease ( 3VD ) and /or LM disease will be screened for eligibility by the Heart Team ( composed of an interventionalist , a cardiac surgeon , and the study coordinator ) at each site and then allocated to either ( 1 ) the r and omized cohort , if comparable revascularization can be achieved by either PCI or coronary artery bypass surgery ( CABG ) , or ( 2 ) to one of the nested registries for CABG-ineligible patients ( PCI registry ) or for PCI-ineligible patients ( CABG registry ) . R and omized patients will be stratified based on LM disease and diabetes by site . The primary end point for the r and omized comparison is noninferiority of major adverse cardiac and cerebral events between the 2 groups at 1 year . To adequately project the expected enrollment rate per site , a run-in phase was m and ated for each site interested in participating in the trial . Both cardiothoracic and interventional cardiology departments within the same institution were asked to complete a question naire regarding their frequency of treatment of LM and 3VD over a retrospective 3-month period . IMPLICATION S By replacing most traditional inclusion and exclusion criteria with the real-world decision between the cardiothoracic surgeon and the interventionalist , this study will define the roles of CABG and PCI using drug-eluting stents in the contemporary management of LM and 3VD . Results of the run-in phase were used by the steering committee to determine eligibility and to project enrollment for each site OBJECTIVES To compare seven-year survival in the Bypass Angioplasty Revascularization Investigation ( BARI ) patients r and omly assigned to percutaneous transluminal coronary angioplasty ( PTCA ) versus coronary artery bypass grafting ( CABG ) . BACKGROUND The primary results of BARI reported no significant difference in five-year survival between CABG and PTCA groups . However , among patients with treated diabetes mellitus , a subgroup not specified a priori , a striking difference was seen in favor of CABG . METHODS Symptomatic patients with multivessel disease ( n = 1,829 ) were r and omly assigned to initial treatment strategy of CABG or PTCA and followed for an average of 7.8 years . The intention-to-treat principle was used to extend the initial five-year BARI treatment comparisons . RESULTS Kaplan-Meier estimates of seven-year survival for the total population were 84.4 % for CABG and 80.9 % for PTCA ( p = 0.043 ) . This difference could be explained by the 353 patients with treated diabetes mellitus for whom estimates of seven year survival were 76.4 % CABG and 55.7 % PTCA ( p = 0.0011 ) . Among the remaining 1,476 patients without treated diabetes , survival was virtually identical by assigned treatment ( 86.4 % CABG , 86.8 % PTCA , p = 0.72 ) . The PTCA group had substantially higher subsequent revascularization rates than the CABG group ( 59.7 % vs. 13.1 % , p < 0.001 ) ; however , the changes between the five- and seven-year rates were similar for the two groups . CONCLUSIONS At seven years , there was a statistically significant survival advantage for patients r and omized to CABG compared with PTCA . Among patients with treated diabetes mellitus , the benefit of CABG over PTCA seen at five years was more pronounced at seven years ; among nondiabetic patients , there was essentially no treatment difference OBJECTIVES We sought to determine the safety and efficacy of polymer-regulated site-specific delivery of paclitaxel in patients with diabetes mellitus undergoing stent implantation . BACKGROUND Percutaneous coronary intervention in patients with diabetes is associated with high rates of restenosis and repeat revascularization due to excessive neointimal proliferation , a process that may be blunted with the site-specific delivery of paclitaxel . METHODS In the TAXUS-IV trial , 1,314 patients were prospect ively r and omized to the slow rate-release polymer-based paclitaxel-eluting TAXUS stent or the bare-metal EXPRESS stent ( Boston Scientific Corp. , Natick , Massachusetts ) . Medically treated diabetes was present in 318 patients ( 24 % ) , 105 of whom required insulin . RESULTS Among patients with diabetes , the TAXUS stent , compared to the bare-metal stent , reduced the rate of 9-month binary angiographic restenosis by 81 % ( 6.4 % vs. 34.5 % , p < 0.0001 ) , and reduced the 12-month rates of target lesion revascularization by 65 % ( 7.4 % vs. 20.9 % , p = 0.0008 ) , target vessel revascularization by 53 % ( 11.3 % vs. 24 % , p < 0.004 ) , and composite major adverse cardiac events by 44 % ( 15.6 % vs. 27.7 % , p = 0.01 ) . The one-year rates of cardiac death ( 1.9 % vs. 2.5 % ) , myocardial infa rct ion ( 3.2 % vs. 6.4 % ) , and subacute thrombosis ( 0.6 % vs. 1.2 % ) were comparable between the paclitaxel-eluting and control stents , respectively . In the insulin-requiring subgroup , the TAXUS stent reduced angiographic restenosis by 82 % ( 7.7 % vs. 42.9 % , p = 0.0065 ) , and reduced the one-year rate of target lesion revascularization by 68 % ( 6.2 % vs. 19.4 % , p = 0.07 ) , a relative reduction similar to patients without diabetes . CONCLUSIONS The site-specific delivery of paclitaxel after coronary stent implantation is highly effective in reducing clinical and angiographic restenosis in patients with diabetes mellitus The effect of body mass index ( BMI ) on outcomes after coronary artery revascularization remains controversial . We studied 1,203 patients who had multivessel coronary artery disease and underwent stenting ( n = 599 ) or coronary artery bypass grafting ( CABG ; n = 604 ) in the Arterial Revascularization Therapies Study . Patients were assigned to 1 of 3 groups according to BMI : < 25 , 25 to 30 , and > 30 kg/m(2 ) . At 3-year follow-up , the incidence of death , cerebrovascular events , or myocardial infa rct ion was similar for these BMI categories regardless of the revascularization technique used . Rates of repeat revascularization procedures were significantly higher among patients who had been r and omized to stenting but were similar across BMI groups . For patients who had been r and omized to undergo CABG , there was a significant decrease in repeat revascularization procedures in obese patients ( p = 0.03 ) . Among patients who underwent stenting , BMI had no effect on the 3-year combined end point of rate of major adverse cardiac or cerebrovascular events . Among patients who underwent CABG , major adverse cardiac or cerebrovascular event rates were significantly lower for patients who were obese ( 11 % ) or overweight ( 16 % ) compared with patients who had a normal BMI ( 24 % ; p = 0.008 ) . Thus , in a large cohort of patients who had multivessel coronary artery disease and underwent surgical or percutaneous revascularization , BMI had no effect on 3-year outcome of those who underwent stenting . Conversely , among patients who underwent CABG , those who were overweight or obese had a significantly better outcome than did those who had a normal BMI with regard to survival without major adverse cardiac or cerebrovascular events , mainly due to lower rates of repeat revascularization procedures OBJECTIVE Despite the popularity of coronary stenting in coronary artery disease ( CAD ) , restenosis remains a challenging clinical problem . This study evaluated the efficacy of rosiglitazone for preventing in-stent restenosis in type 2 diabetic patients . RESEARCH DESIGN AND METHODS We conducted a prospect i ve , r and omized , case-controlled trial involving 95 diabetic patients with CAD who were r and omly assigned to either the control or rosiglitazone group ( 48 and 47 patients , respectively ) . Quantitative coronary angiography ( QCA ) was performed at study entry and again at 6-month follow-up . The primary end point was the restenosis rate , which was determined by QCA . RESULTS Eighty-three patients ( 45 patients with 55 lesions in the control group and 38 patients with 51 lesions in the rosiglitazone group ) completed follow-up angiography . Rosiglitazone treatment for 6 months reduced fasting insulin concentration . The high-sensitivity C-reactive protein concentration was significantly reduced in the rosiglitazone group compared with that in the control group ( from 2.92 + /- 1.98 to 0.62 + /- 0.44 mg/l , P < 0.001 vs. from 2.01 + /- 1.33 to 1.79 + /- 1.22 mg/l , P = NS ) . However , the baseline and follow-up glucose and lipid concentrations were not different between two groups . The rate of in-stent restenosis was significantly reduced in the rosiglitazone group compared with the control group ( for stent lesions : 17.6 vs. 38.2 % , P = 0.030 ) . The rosiglitazone group had a significantly lower degree of diameter stenosis ( 23.0 + /- 23.4 % vs. 40.9 + /- 31.9 % , P = 0.004 ) compared with the control group . CONCLUSIONS We demonstrated that treatment with rosiglitazone significantly reduces in-stent restenosis in diabetic patients with CAD who underwent coronary stent implantation BACKGROUND Preliminary reports of studies involving simple coronary lesions indicate that a sirolimus-eluting stent significantly reduces the risk of restenosis after percutaneous coronary revascularization . METHODS We conducted a r and omized , double-blind trial comparing a sirolimus-eluting stent with a st and ard stent in 1058 patients at 53 centers in the United States who had a newly diagnosed lesion in a native coronary artery . The coronary disease in these patients was complex because of the frequent presence of diabetes ( in 26 percent of patients ) , the high percentage of patients with longer lesions ( mean , 14.4 mm ) , and small vessels ( mean , 2.80 mm ) . The primary end point was failure of the target vessel ( a composite of death from cardiac causes , myocardial infa rct ion , and repeated percutaneous or surgical revascularization of the target vessel ) within 270 days . RESULTS The rate of failure of the target vessel was reduced from 21.0 percent with a st and ard stent to 8.6 percent with a sirolimus-eluting stent (P<0.001)--a reduction that was driven largely by a decrease in the frequency of the need for revascularization of the target lesion ( 16.6 percent in the st and ard-stent group vs. 4.1 percent in the sirolimus-stent group , P<0.001 ) . The frequency of neointimal hyperplasia within the stent was also decreased in the group that received sirolimus-eluting stents , as assessed by both angiography and intravascular ultrasonography . Subgroup analyses revealed a reduction in the rates of angiographic restenosis and target-lesion revascularization in all subgroups examined . CONCLUSIONS In this r and omized clinical trial involving patients with complex coronary lesions , the use of a sirolimus-eluting stent had a consistent treatment effect , reducing the rates of restenosis and associated clinical events in all subgroups analyzed BACKGROUND Drug-eluting stents are highly effective in reducing the rate of in-stent restenosis . It is not known whether there are differences in the effectiveness of currently approved drug-eluting stents in the high-risk subgroup of patients with diabetes mellitus . METHODS We enrolled 250 patients with diabetes and coronary artery disease : 125 were r and omly assigned to receive paclitaxel-eluting stents , and 125 to receive sirolimus-eluting stents . The primary end point was in-segment late luminal loss . Secondary end points were angiographic restenosis ( defined as in-segment stenosis of at least 50 percent at follow-up angiography ) and the need for revascularization of the target lesion during a nine-month follow-up period . The study was design ed to show noninferiority of the paclitaxel stent as compared with the sirolimus stent , defined as a difference in the extent of in-segment late luminal loss of no more than 0.16 mm . RESULTS The extent of in-segment late luminal loss was 0.24 mm ( 95 percent confidence interval , 0.09 to 0.39 ) greater in the paclitaxel-stent group than in the sirolimus-stent group ( P=0.002 ) . In-segment restenosis was identified on follow-up angiography in 16.5 percent of the patients in the paclitaxel-stent group and 6.9 percent of the patients in the sirolimus-stent group ( P=0.03 ) . Target-lesion revascularization was performed in 12.0 percent of the patients in the paclitaxel-stent group and 6.4 percent of the patients in the sirolimus-stent group ( P=0.13 ) . CONCLUSIONS In patients with diabetes mellitus and coronary artery disease , use of the sirolimus-eluting stent is associated with a decrease in the extent of late luminal loss , as compared with use of the paclitaxel-eluting stent , suggesting a reduced risk of restenosis PURPOSE Patients who develop recurrent myocardial ischemia after coronary artery bypass graft ( CABG ) surgery are often referred for percutaneous coronary interventions . The objective of this study was to evaluate the changing demographic and clinical characteristics , and procedural and long-term outcomes , in patients with prior CABG referred for percutaneous coronary interventions during a 20-year period . METHODS We prospect ively collected data on patients who underwent coronary interventional procedures following CABG surgery . We compared angiographic and procedural success , and long-term event-free survival , among patients who had procedures from 1979 to 1989 ( n = 393 ) , from 1990 to 1994 ( n = 811 ) , and from 1995 to 1998 ( n = 937 ) . RESULTS Patients in the 1995 to 1998 cohort were older , had a lower mean left ventricular ejection fraction , and were more likely to have diabetes , hypertension , and hyperlipidemia , but less likely to smoke . They were more likely to have treatment of complex lesions , including vein graft lesions , and had more prior CABG surgeries . More patients received intracoronary stents in 1995 to 1998 . Both angiographic success rates ( 78 % from 1979 to 1989 , 88 % from 1990 to 1994 , and 91 % from 1995 to 1998 , P < 0.0001 ) and procedural success rates ( 78 % , 86 % , and 91 % , P < 0.0001 ) improved with time . Long-term mortality was greater in the pre-1990 group ( relative risk = 1.8 , 95 % confidence interval : 1.3 to 2.4 ) and 1990 to 1994 group ( relative risk = 1.7 , 95 % confidence interval : 1.3 to 2.2 ) compared with the 1995 to 1998 group , as were the likelihoods of repeat revascularization and recurrent severe angina . CONCLUSION Although the demographic and clinical characteristics of patients who underwent percutaneous intervention following CABG surgery indicate that they are at increasingly greater risk of adverse cardiac events , success rates and long-term survival have improved with time . The rates of recurrent severe angina as well as of subsequent revascularization have also decreased , probably as a result of improvements in technique and greater use of stents and adjunctive medications OBJECTIVES The long-term ( five-year ) comparative results of treatment of multivessel coronary artery disease with stenting or coronary artery bypass grafting ( CABG ) is at present unknown . BACKGROUND The Arterial Revascularization Therapies Study ( ARTS ) was design ed to compare CABG and stenting in patients with multivessel disease . METHODS A total of 1,205 patients with the potential for equivalent revascularization were r and omly assigned to CABG ( n = 605 ) or stent implantation ( n = 600 ) . The primary clinical end point was freedom from major adverse cardiac and cerebrovascular events ( MACCE ) at one year ; MACCE at five-year follow-up constituted the final secondary end point . RESULTS At five years , there were 48 and 46 deaths in the stent and CABG groups , respectively ( 8.0 % vs. 7.6 % ; p = 0.83 ; relative risk [ RR ] , 1.05 ; 95 % confidence interval [ CI ] , 0.71 to 1.55 ) . Among 208 diabetic patients , mortality was 13.4 % in the stent group and 8.3 % in the CABG group ( p = 0.27 ; RR , 1.61 ; 95 % CI , 0.71 to 3.63 ) . Overall freedom from death , stroke , or myocardial infa rct ion was not significantly different between groups ( 18.2 % in the stent group vs. 14.9 % in the surgical group ; p = 0.14 ; RR , 1.22 ; 95 % CI , 0.95 to 1.58 ) . The incidence of repeat revascularization was significantly higher in the stent group ( 30.3 % ) than in the CABG group ( 8.8 % ; p < 0.001 ; RR , 3.46 ; 95 % CI , 2.61 to 4.60 ) . The composite event-free survival rate was 58.3 % in the stent group and 78.2 % in the CABG group ( p < 0.0001 ; RR , 1.91 ; 95 % CI , 1.60 to 2.28 ) . CONCLUSIONS At five years there was no difference in mortality between stenting and surgery for multivessel disease . Furthermore , the incidence of stroke or myocardial infa rct ion was not significantly different between the two groups . However , overall MACCE was higher in the stent group , driven by the increased need for repeat revascularization BACKGROUND Patients with treated diabetes in the r and omized-trial segment of the Bypass Angioplasty Revascularization Investigation ( BARI ) who were r and omized to initial revascularization with PTCA had significantly worse 5-year survival than patients assigned to CABG . This treatment difference was not seen among diabetic patients eligible for BARI who opted to select their mode of revascularization . We hypothesized that differences in patient characteristics , assessed and unmeasured , together with the treatment selection in the registry , at least partially account for this discrepancy . METHODS AND RESULTS Among diabetics taking insulin or oral hypoglycemic drugs at entry , angiographic and clinical presentations were comparable between r and omized and registry patients . However , more registry patients were white , and registry diabetics tended to be more educated and more physically active and to report better quality of life . Procedural characteristics and in-hospital complications were comparable . The 5-year all-cause mortality rate was 34.5 % in r and omized diabetic patients assigned to PTCA versus 19.4 % in CABG patients ( P=0.0024 ; relative risk [RR]=1.87 ) ; corresponding cardiac mortality rates were 23.4 % and 8.2 % , respectively ( P=0.0002 ; RR=3.10 ) . The CABG benefit was more apparent among patients requiring insulin . In the registry , all-cause mortality was 14.4 % for PTCA versus 14.9 % for CABG ( P=0.86 , RR=1.10 ) , with corresponding cardiac mortality rates of 7.5 % and 6 . 0 % , respectively ( P=0.73 ; RR=1.07 ) . These RRs in the registry increased to 1.29 and 1.41 , respectively , after adjustment for all known differences between treatment groups . CONCLUSIONS BARI registry results are not inconsistent with the finding in the r and omized trial that initial CABG is associated with better long-term survival than PTCA in treated diabetic patients with multivessel coronary disease suitable for either surgical or catheter-based revascularization BACKGROUND Patients with diabetes have an increased incidence and severity of ischemic heart disease , which leads to an increased requirement for coronary revascularization . Comparative information regarding mode of revascularization -- coronary artery bypass graft surgery surgery ( CABG ) or percutaneous coronary intervention (PCI)--is limited , mainly confined to a sub analysis of the Bypass Angioplasty Revascularization ( BARI ) trial , suggesting a mortality benefit of CABG over PCI . No prospect i ve trial has specifically compared these modes of revascularization in patients with diabetes . OBJECTIVE The Coronary Artery Revascularisation in Diabetes ( CARDia ) trial is design ed to address the hypothesis that optimal PCI is not inferior to modern CABG as a revascularization strategy for diabetics with multivessel or complex single-vessel coronary disease . The primary end point is a composite of death , nonfatal myocardial infa rct ion , and cerebrovascular accident at 1 year . METHOD A total of 600 patients with diabetes are to be r and omized to either PCI or CABG , with few protocol restrictions on operative techniques or use of new technology . This gives a power of 80 % to detect non-inferiority of PCI assuming that the PCI 1-year event rate is 9 % . A cardiac surgeon and a cardiologist must agree that a patient is suitable for revascularization by either technique prior to recruitment into the study . Twenty-one centers in the United Kingdom and Irel and are recruiting patients . Data on cost effectiveness , quality of life , and neurocognitive function are being collected . Long-term ( 3 - 5 year ) follow-up data will also be collected Objective To describe mortality , mode of death , risk indicators for death and symptoms of angina pectoris among survivors during 5 years after coronary artery bypass grafting ( CABG ) among patients with and without a history of diabetes mellitus . Methods All patients in western Sweden who underwent CABG without concomitant valve surgery and who had no previous CABG between June 1988 and June 1991 were entered prospect ively in this study . After 5 years , information on deaths that had occurred was obtained for the analysis . Results In all , 1998 patients were included in the analysis ; 242 ( 12 % ) had a history of diabetes . Among the non‐diabetic patients , 5‐year mortality was 12.5 % ; the corresponding relative risk for diabetic patients was 2.1 ( 95 % confidence interval 1.6 to 2.9 ) . A history of diabetes was an independent risk indicator of death ; there was no significant interaction between any other risk indicator and diabetes . Independent risk indicators for death among diabetic patients were : current smoking , renal dysfunction and left ventricular ejection fraction < 0.40 . Compared with non‐diabetic patients , those with diabetes more frequently died in hospital , died a cardiac death , or had death associated with the development of acute myocardial infa rct ion and with symptoms of congestive heart failure . Among survivors , diabetic patients tended to have more angina pectoris 5 years after CABG than did those without diabetes . Conclusion During a period of 5 years after CABG , diabetic patients had a mortality twice that of non‐diabetic patients . The increased risk included death in hospital , cardiac death and death associated with development of acute myocardial infa rct ion and with symptoms of congestive heart failure BACKGROUND The platelet glycoprotein IIb/IIIa inhibitors , although effective in reducing ischaemic complications of percutaneous coronary intervention , are used in few coronary stent implantation procedures . ESPRIT ( Enhanced Suppression of the Platelet IIb/IIIa Receptor with Integrilin Therapy ) is a r and omised , placebo-controlled trial to assess whether a novel , double-bolus dose of eptifibatide could improve outcomes of patients undergoing coronary stenting . METHODS We recruited 2064 patients undergoing stent implantation in a native coronary artery . Immediately before percutaneous coronary intervention , patients were r and omly allocated to receive eptifibatide , given as two 180 microg/kg boluses 10 min apart and a continuous infusion of 2.0 microg/kg/min for 18 - 24 h , or placebo , in addition to aspirin , heparin , and a thienopyridine . The primary endpoint was the composite of death , myocardial infa rct ion , urgent target vessel revascularisation , and thrombotic bailout glycoprotein IIb/IIIa inhibitor therapy within 48 h after r and omisation . The key secondary endpoint was the composite of death , myocardial infa rct ion , or urgent target vessel revascularisation at 30 days . FINDINGS The trial was terminated early for efficacy . The primary endpoint was reduced from 10.5 % ( 108 of 1024 patients on placebo [ 95 % CI 8.7 - 12.4 % ] ) to 6.6 % ( 69 of 1040 [ 5.1 - 8.1 % ] ) with treatment ( p=0.0015 ) . The key 30 day secondary endpoint was also reduced , from 10.5 % ( 107 of 1024 patients on placebo [ 8.6 - 12.3 % ] ) to 6.8 % ( 71 of 1040 [ 5.3 - 8.4 % ] ; p=0.0034 ) . There was consistency in reduction of events across all components of the composite endpoint and among the major subgroups . Major bleeding was infrequent but arose more often with eptifibatide than placebo ( 1.3 % , 13 of 1040 [ 0.7 - 2.1 % ] ) vs 0.4 % , 4 of 1024 [ 0.1 - 1.0 % ] ; p=0.027 ) . INTERPRETATION Routine glycoprotein IIb/IIIa inhibitor pretreatment with eptifibatide substantially reduces ischaemic complications in coronary stent intervention and is better than a strategy of reserving treatment to the bailout situation Background —Although it has been suggested that elevation of CK-MB after percutaneous coronary intervention is associated with adverse clinical outcomes , limited data are available in the setting of coronary bypass grafting . The aim of the present study was to determine the incidence , predictors , and prognostic significance of CK-MB elevation following multivessel coronary bypass grafting ( CABG ) . Methods and Results —The population comprises 496 patients with multivessel coronary disease assigned to CABG in the Arterial Revascularization Therapies Study ( ARTS ) . CK-MB was prospect ively measured at 6 , 12 , and 18 hours after the procedure . Thirty-day and 1-year clinical follow-up were performed . Abnormal CK-MB elevation occurred in 61.9 % of the patients . Patients with increased cardiac-enzyme levels after CABG were at increased risk of both death and repeat myocardial infa rct ion within the first 30 days ( P = 0.001 ) . CK-MB elevation was also independently related to late adverse outcome ( P = 0.009 , OR=0.64 ) . Conclusions —Increased concentrations of CK-MB , which are often dismissed as inconsequential in the setting of multivessel CABG , appear to occur very frequently and are associated with a significant increase in both repeat myocardial infa rct ion and death beyond the immediate perioperative period |
14,091 | 29,754,705 | The TNF superfamily and inflammatory cytokines may have a relationship with the neuroprogression of the disease .
This study suggests that TNF and ILs could play a role in neuroprogression .
However , longitudinal studies are needed to clarify the relationship between factors associated with neuroprogression | BACKGROUND Previous studies suggest that inflammatory molecules play an important role in the pathophysiology of Bipolar Disorder ( BD ) .
The evidence suggests that BD may present a progressive course .
Therefore there are theories that postulate the relationship between progression and stages of the disease with distinct peripheral biomarkers .
OBJECTIVE The aim of this study was to carry out a systematic review of the literature of studies about the association between peripheral inflammatory markers and clinical variables related with staging in BD patients . | OBJECTIVE To determine if the repeated occurrence of manic episodes in bipolar I disorder ( BD-I ) patients is associated with reduced cognitive performance , which could in turn imply a worsening in the disorder 's evolution . METHOD Cognitive performance in euthymic patients was assessed using attention , memory , and executive function tests on 24 BD-I patients who had experienced only 1 manic episode , on 27 BD-I patients with 2 manic episodes , on 47 BD-I patients with 3 or more manic episodes , and on 66 healthy control subjects . RESULTS In BD-I patients , number of manic episodes was positively associated with poorer performance on neurocognitive tests , an association that was not accounted for by depression , disease chronicity , onset , or medication . Significant differences in attention and executive function were found between patients and controls and in those patients who had had just 1 manic episode compared to those who had 3 or more . CONCLUSION The number of manic episodes predicted poor cognitive performance , suggesting that the recurrence of mania may have a long-term neuropsychological impact . Prospect i ve follow-up studies need to be completed to explore this effect further as better treatment adherence may have a protective effect on neurocognitive function OBJECTIVES Individuals with bipolar disorder have high rates of other medical comorbidity , which is associated with higher mortality rates and worse course of illness . The present study examined common predictors of medical comorbidity . METHODS The Clinical and Health Outcomes Initiative in Comparative Effectiveness for Bipolar Disorder study ( Bipolar CHOICE ) enrolled 482 participants with bipolar I or bipolar II disorder in a six-month , r and omized comparative effectiveness trial . Baseline assessment s included current and lifetime DSM-IV-TR diagnoses , demographic information , psychiatric and medical history , severity of psychiatric symptoms , level of functioning , and a fasting blood draw . Medical comorbidities were categorized into two groups : cardiometabolic ( e.g. , diabetes , hyperlipidemia , and metabolic syndrome ) and non-cardiovascular ( e.g. , seizures , asthma , and cancer ) . Additionally , we looked at comorbid substance use ( e.g. , smoking and drug dependence ) . RESULTS We found that 96.3 % of participants had at least one other medical comorbidity . Older age predicted a greater likelihood of having a cardiometabolic condition . Early age of onset of bipolar symptoms was associated with a lower chance of having a cardiometabolic condition , but a greater chance of having other types of medical comorbidity . Additional predictors of other medical comorbidities in bipolar disorder included more time spent depressed , less time spent manic/hypomanic , and longer duration of illness . Medications associated with weight gain were associated with low high-density lipoprotein and abnormal triglycerides . CONCLUSIONS There appears to be a substantial medical burden associated with bipolar disorder , highlighting the need for collaborative care among psychiatric and general medical providers to address both psychiatric and other medical needs concomitantly in this group of patients Neuropsychological assessment of older individuals with dementing illnesses has suffered from a lack of appropriately design ed test instruments . The Repeatable Battery for the Assessment of Neuropsychological Status ( RBANS ) was developed for the dual purpose s of identifying and characterizing abnormal cognitive decline in the older adult and as a neuropsychological screening battery for younger patients . The entire battery takes less than 30 minutes to administer , and yields scaled scores for five cognitive domains . The current study reports preliminary clinical validity results with the RBANS , comparing very mildly demented patients with a diagnosis of probable Alzheimer 's disease ( n = 20 ) to patients with Huntington 's disease ( n = 20 ) and normal controls ( n = 40 ) . Although the patient groups had essentially identical total scores on the RBANS , they exhibited opposite profiles , differing significantly on four of the five subsections . The AD patients performed most poorly on Language , and Delayed Memory subsections , while the HD patients obtained their lowest scaled scores on the Attention and the Visuospatial/Constructional subsections . These results are consistent with the neuropsychological profiles of these dementing disorders derived from lengthier st and ardized tests and experimental investigations . In addition , even those patients who performed above the suggested cut-off points on the MMSE and the Dementia Rating Scale scored significantly below their controls on the RBANS . These data suggest that the RBANS is effective at both detecting and characterizing dementia of different etiologies |
14,092 | 26,305,058 | The reported effect of rotation-correction can not be reliably verified | Objective The femoral neck-shaft angle ( NSA ) is an important measure for the assessment of the anatomy of the hip and planning of operations .
Despite its common use , there remains disagreement concerning the method of measurement and the correction of hip rotation and femoral version of the projected NSA on conventional radiographs .
We addressed the following questions : ( 1 ) What are the reported values for NSA in normal adult subjects and in osteoarthritis ? (
2 ) Is there a difference between non-corrected and rotation-corrected measurements ? (
3 ) Which methods are used for measuring the NSA on plain radiographs ? (
4 ) What could be learned from an analysis of the intra- and interobserver reliability ? | Objective To evaluate if pelvic or hip width predisposed women to developing greater trochanteric pain syndrome ( GTPS ) . Design Prospect i ve case control study . Participants Four groups were included in the study : those gluteal tendon reconstructions ( n=31 , GTR ) , those with conservatively managed GTPS ( n=29 ) , those with hip osteoarthritis ( n=20 , OA ) and 22 asymptomatic participants ( ASC ) . Methods Anterior-posterior pelvic x-rays were evaluated for femoral neck shaft angle ; acetabular index , and width at the lateral acetabulum , and the superior and lateral aspects of the greater trochanter . Body mass index , and waist , hip and greater trochanter girth were measured . Data were analysed using a one-way analysis of variance ( ANOVA ; posthoc Scheffe analysis ) , then multivariate analysis . Results The GTR group had a lower femoral neck shaft angle than the other groups ( p=0.007 ) . The OR ( 95 % CI ) of having a neck shaft angle of less than 134 ° , relative to the ASC group : GTR=3.33 ( 1.26 to 8.85 ) ; GTPS=1.4 ( 0.52 to 3.75 ) ; OA=0.85 ( 0.28 to 2.61 ) . The OR of GTR relative to GTPS was 2.4 ( 1.01 to 5.6 ) . No group difference was found for acetabular or greater trochanter width . Greater trochanter girth produced the only anthropometric group difference ( mean ( 95 % CI ) in cm ) GTR=103.8 ( 100.3 to 107.3 ) , GTPS=105.9 ( 100.2 to 111.6 ) , OA=100.3 ( 97.7 to 103.9 ) , ASC=99.1 ( 94.7 to 103.5 ) , ( ANOVA : p=0.036 ) . Multivariate analysis confirmed adiposity is associated with GTPS . Conclusion A lower neck shaft angle is a risk factor for , and adiposity is associated with , GTPS in women Purpose Inadequate reconstruction of femoral offset after total hip arthroplasty ( THA ) is associated with unfavourable outcomes , but its importance following hemiarthroplasty for displaced femoral neck fracture is unknown . Methods Our study examined the correlation between reconstructed femoral offset and functional outcome 12 months after post traumatic hemiarthroplasty in 126 prospect ively enrolled elderly patients . Rotation-corrected femoral offset ( FORC ) , relative femoral offset ( FORL ) and contralateral femoral offset ( FOC ) were measured on anteroposterior radiographs . The Harris Hip Score ( HHS ) was the primary outcome measure ; the timed up and go ( TUG ) test and Lawton instrumental activities of daily living ( IADL ) score were secondary outcomes . Correlations were sought using the Spearman correlation coefficient ( r ) . Sample size was calculated using an Altman nomogram , with the power set at 80 % , the significance level of 0.05 and a st and ardised difference of 0.75 . Results The mean reconstructed FORC was 41 mm ( 17–67 mm ) and showed a linear relationship and excellent correlation with the FOC . At 12 months , we found a significant positive correlation between FORC and HHS ( r = 0.303 , p = 0.025 ) and IADL ( r = 0.325 , p = 0.013 ) , but not TUG ( r = −0.026 , p = 0.863 ) . These findings were confirmed by bivariate and multivariate correlation between FORL and functional outcome parameters . Conclusions We found a clinical ly relevant relationship between femoral offset and functional outcome after hemiarthroplasty in elderly patients , comparable with that of THA , for treating osteoarthritis We analysed the time-dependent mean changes in the femoral neck length , neck-shaft angle and hip offset in a r and omised study comprising 48 patients who were treated with the dynamic hip screw ( DHS ) or the proximal femoral nail ( PFN ) for an unstable intertrochanteric femoral fracture . As a consequence of fracture compression , the mean post-operative neck length was significantly shorter in patients treated with the DHS . During the first 6 weeks after the operation , a mean decrease of 4.6 ° was observed in the neck-shaft angle , but there was not a significant difference between the treatment groups . The radiographic measures remained virtually unaffected during the interval from 6 weeks to 4 months in both groups . When the operated hip was compared to the opposite hip , patients who had received the DHS showed significantly greater medialisation of the femoral shaft at 4 months than those treated with the PFN . We thus recommend that unstable intertrochanteric fractures should be initially reduced in a slight valgus position in order to achieve an outcome after healing that is as normal as possible . As a result of differences in operative technique and implant stability , the PFN may be superior to the DHS in retaining the anatomical relations in the hip region in unstable intertrochanteric fractures . RésuméNous avons analysé les modifications , en fonction du temps , des valeurs moyennes de la longueur du col fémoral , de l’angle cervico-diaphysaire et du bras de levier de la hanche dans une étude r and omisée qui comprenait 48 malades traités avec une Vis Dynamique ( DHS ) ou un Clou Fémoral Proximal ( PFN ) aprés une fracture intertrochantérienne instable . Par suite de la compression de la fracture , la longueur du col était nettement plus courte chez les malades traités avec une DHS . Pendant les premières six semaines après l’opération , une baisse moyenne de 4.6 ° de l’angle cervico-diaphysaire a été observée mais il n’y avait pas de différence notable entre les groupes de traitement . Les mesures radiographiques sont restées pratiquement non affectées pendant l’intervalle de six semaines à quatre mois dans les deux groupes . Comparé à la hanche opposée , les malades qui avaient reçu une DHS ont montré à 4 mois une nettement plus gr and e médialisation de la diaphyse que ceux traités avec le PFN . Nous recomm and ons que ces fractures intertrochantériennes instables soient réduites en léger valgus pour avoir une situation aussi normale que possible après consolidation . Par suite de différences dans la technique opératoire et dans la stabilité de l’implant , le PFN semble supérieur au DHS pour rétablir l’anatomie de la région de la hanche dans les fractures intertrochantériennes instables Purpose It is crucially important to optimise functional outcome after fixation of trochanteric femoral fractures . While a number of risk factors that predict a poor clinical course have been identified , the influence of pre-existing radiographic osteoarthritis ( OA ) of the hip is unclear . Methods The influence of pre-existing radiographic OA of the hip on short- to mid-term functional outcome was prospect ively analysed in a cohort of patients undergoing proximal femoral nailing for trochanteric fracture . OA was grade d according to Kellgren and Lawrence ; functional outcome was assessed at six and 12 months by the Harris hip score ( HHS ) , the timed up and go ( TUG ) test and the Barthel Index . Results Our cohort comprised 188 patients ( 58 were male and 130 female ) , with a mean age of 82 years . At six and 12 months postoperatively , the HHS ( p < 0.001 and p = 0.008 , respectively ) and Barthel Index ( p < 0.001 and p = 0.02 , respectively ) correlated significantly with the grade of pre-existing OA . After adjustment for confounding variables , there was a significant association between the grade of pre-existing OA and the HHS at six months ( p = 0.02 ) . Although we observed trends suggestive of other relationships , none reached statistical significance . Conclusions Pre-existing radiographic OA of the hip is an important determinant of clinical outcome in elderly patients with a trochanteric femoral fracture . Further studies will be needed to establish the most effective means of restoring hip function after trochanteric femoral fracture in patients with radiographic OA of the hip INTRODUCTION Several clinical and radiological techniques have been described to assess lower limb length and angle measurements . None of them has yet met the ideal criteria for a reliable , reproducible , safe , and inexpensive system . In this context , a new biplanar X-ray system ( EOS ™ , EOS imaging , Paris , France ) makes it possible to obtain a 3D reconstruction of the lower extremities from two 2D orthogonal radiographic images , with associated calculation of 3D measurements . The reliability of this technique has never been documented on adults . HYPOTHESIS Lower limb measurements produced by the 3D EOS ™ reconstruction system are reproducible regarding inter- and intraobserver assessment and more reliable with this 3D technique than when they are obtained from 2D measurements . MATERIAL S AND METHODS This study included 25 patients awaiting total hip arthroplasty ( 50 lower limbs ) . Two independent observers made all measurements twice , both on the 2D frontal radiograph and using 3D reconstructions ( femoral measurements of length , offset , neck shaft angle , neck length , and head diameter , as well as the tibia length , limb length , HKA and HKS ) . Reproducibility was estimated by intraclass correlation coefficients . RESULTS Both the inter- and intraobserver reproducibility of the EOS ™ measurements was excellent ; more specifically inter- and intraobserver reproducibility was 0.997 and 0.997 for femoral length , 0.996 and 0.995 for tibial length , 0.999 and 0.999 for limb length , 0.894 and 0.891 for HKS , 0.993 and 0.994 for HKA , 0.870 and 0.845 for femoral offset , and 0.765 and 0.851 for neck shaft angle . For most of the variables , the interobserver correlations were statistically better with the EOS ™ 3D reconstruction . DISCUSSION Our results show that the EOS ™ systems allow reproducible lower limb measurements . Furthermore , 3D EOS ™ reconstructions offer better reproducible measures for most of the parameters than radiographic 2D projection . Its use before deciding on surgery and during planning for lower limb arthroplasty appears essential to us . LEVEL OF EVIDENCE Level III : diagnostic prospect i ve study on consecutive patients Femoral stem version has a major influence on impingement and early post-operative stability after total hip arthroplasty ( THA ) . The main objective of this study was to evaluate the validity of a novel radiological method for measuring stem version . Anteroposterior ( AP ) radiographs and three-dimensional CT scans were obtained for 115 patients ( female/male 63/72 , mean age 62.5 years ( 50 to 75 ) ) who had undergone minimally invasive , cementless THA . Stem version was calculated from the AP hip radiograph by rotation-based change in the projected prosthetic neck-shaft ( NSA * ) angle using the mathematical formula ST = arcos [ tan ( NSA * ) / tan ( 135 ) ] . We used two independent observers who repeated the analysis after a six-week interval . Radiological measurements were compared with 3D-CT measurements by an independent , blinded external institute . We found a mean difference of 1.2 ° ( sd 6.2 ) between radiological and 3D-CT measurements of stem version . The correlation between the mean radiological and 3D-CT stem torsion was r = 0.88 ( p < 0.001 ) . The intra- ( intraclass correlation coefficient ≥ 0.94 ) and inter-observer agreement ( mean concordance correlation coefficient = 0.87 ) for the radiological measurements were excellent . We found that femoral tilt was associated with the mean radiological measurement error ( r = 0.22 , p = 0.02 ) . The projected neck-shaft angle is a reliable method for measuring stem version on AP radiographs of the hip after a THA . However , a highly st and ardised radiological technique is required for its precise measurement BACKGROUND Increased femoral anteversion and coxa valga are common in patients with cerebral palsy . The purpose of the present study was to determine the validity and reliability of the methods that are commonly used to measure the proximal femoral geometry in patients with cerebral palsy . METHODS Thirty-six consecutive patients ( mean age , eleven years ; range , five to twenty years ) with cerebral palsy were enrolled in the present study . The validity and the interobserver reliability of the physical examinations performed by three examiners were determined by comparing the results of a trochanteric prominence angle test , hip internal rotation measurements , and hip external rotation measurements ( all with the patient in the prone position ) with the amount of femoral anteversion on two-dimensional computed tomography . Validity and intraobserver and interobserver reliability were assessed by comparing the neck-shaft angle on the anteroposterior internal rotation radiograph of the hips with that on the multiplanar reformatted computed tomographic image . RESULTS The trochanteric prominence angle test showed excellent concurrent validity ( R = 0.862 , p < 0.001 ) and reliability ( intraclass correlation coefficient , 0.809 ) . Hip internal rotation also showed good concurrent validity ( R = 0.787 , p < 0.001 ) and excellent reliability ( intraclass correlation coefficient , 0.889 ) , whereas hip external rotation appeared to be unsuitable for predicting femoral anteversion . The neck-shaft angle on the anteroposterior internal rotation radiograph of the hips showed excellent concurrent validity ( R = 0.892 , p < 0.001 ) and reliability ( intraclass correlation coefficient , 0.912 ) . CONCLUSIONS A physical examination for determining femoral anteversion and the neck-shaft angle as measured on the internal rotation radiograph of the hips appear to be clinical ly relevant methods for evaluating the proximal femoral geometry and version in patients with cerebral palsy . Computed tomographic examination can probably be replaced by physical examination and an anteroposterior internal rotation radiograph of the hips for patients with stable hips who are able to walk |
14,093 | 27,207,960 | Based on a limited number of studies , high‐fat milk was directly associated with stroke risk .
No associations were found for yogurt , butter , or total dairy .
Conclusions Milk and cheese consumption were inversely associated with stroke risk . | Background A higher milk consumption may be associated with a lower stroke risk .
We conducted a comprehensive systematic review and dose – response meta‐ analysis of milk and other dairy products in relation to stroke risk . | BACKGROUND AND PURPOSE High intakes of calcium , potassium , and magnesium have been hypothesized to reduce risks of cardiovascular disease , but only a few prospect i ve studies have examined intakes of these cations in relation to risk of stroke . METHODS In 1980 , 85 764 women in the Nurses ' Health Study cohort , aged 34 to 59 years and free of diagnosed cardiovascular disease and cancer , completed dietary question naires from which we calculated intakes of calcium , potassium , and magnesium . By 1994 , after 1.16 million person-years of follow-up , 690 incident strokes ( 129 subarachnoid hemorrhages , 74 intraparenchymal hemorrhages , 386 ischemic strokes , and 101 strokes of undetermined type ) had been documented . RESULTS Intakes of calcium , potassium , and magnesium were each inversely associated with age- and smoking-adjusted relative risks of ischemic stroke , excluding embolic infa rct ion of nonatherogenic origin ( n=347 ) . Adjustment for other cardiovascular risk factors , including history of hypertension , attenuated these associations , particularly for magnesium intake . In a multivariate analysis , women in the highest quintile of calcium intake had an adjusted relative risk of ischemic stroke of 0.69 ( 95 % CI , 0.50 to 0.95 ; P for trend=0.03 ) compared with those in the lowest quintile ; for potassium intake the corresponding relative risk was 0.72 ( 95 % CI , 0.51 to 1.01 ; P for trend=0.10 ) . Further simultaneous adjustment for calcium and potassium intake suggested an independent association for calcium intake . The association of risk with calcium intake did not appear to be log linear ; the increase in risk was limited to the lowest quintile of intake , and intakes > approximately 600 mg/d did not appear to reduce risk of stroke further . The inverse association with calcium intake was stronger for dairy than for nondairy calcium intake . Intakes of calcium , potassium , and magnesium were not related to risk of other stroke subtypes . CONCLUSIONS Low calcium intake , and perhaps low potassium intake , may contribute to increased risk of ischemic stroke in middle-aged American women . It remains possible that women in the lowest quintile of calcium intake had unknown characteristics that made them susceptible to ischemic stroke The authors aim ed to evaluate the association of the traditional Mediterranean diet and major food groups with incidence of and mortality from cerebrovascular disease ( CBVD ) in a Mediterranean population . The study population was a cohort of 23,601 participants from the Greek segment of the EPIC Study ( European Prospect i ve Investigation into Cancer and Nutrition ) who were free of cardiovascular diseases and cancer at baseline ( 1994 - 1999 ) . Diet was assessed by means of a vali date d food frequency question naire . A 10-point scale integrating key Mediterranean diet characteristics was used to assess the participants ' degree of adherence to this diet . During a median follow-up period of 10.6 years ( 1994 - 2009 ) , 395 confirmed incident cases and 196 deaths from CBVD were recorded . Using Cox proportional hazards regression and adjusting for potential confounders , increased adherence to the Mediterranean diet , as measured by 2-point increments in score , was inversely associated with CBVD incidence ( adjusted hazard ratio = 0.85 , 95 % confidence interval : 0.74 , 0.96 ) and mortality ( adjusted hazard ratio = 0.88 , 95 % CI : 0.73 , 1.06 ) . These inverse trends were mostly evident among women and with respect to ischemic rather than hemorrhagic CBVD and were largely driven by consumption of vegetables , legumes , and olive oil . These data provide support for an inverse association of adherence to the Mediterranean diet with CBVD incidence and mortality Background and Purpose — Few dietary protein sources have been studied prospect ively in relation to stroke . We examined the relation between foods that are major protein sources and risk of stroke . Methods — We prospect ively followed 84 010 women aged 30 to 55 years at baseline and 43 150 men aged 40 to 75 years at baseline without diagnosed cancer , diabetes , or cardiovascular disease . Diet was assessed repeatedly by a st and ardized and vali date d question naire . We examined the association between protein sources and incidence of stroke using a proportional hazard model adjusted for stroke risk factors . Results — During 26 and 22 years of follow-up in women and men , respectively , we documented 2633 and 1397 strokes , respectively . In multivariable analyses , higher intake of red meat was associated with an elevated risk of stroke , whereas a higher intake of poultry was associated with a lower risk . In models estimating the effects of exchanging different protein sources , compared with 1 serving/day of red meat , 1 serving/day of poultry was associated with a 27 % ( 95 % CI , 12%–39 % ) lower risk of stroke , nuts with a 17 % ( 95 % CI . 4%–27 % ) lower risk , fish with a 17 % ( 95 % CI , 0%–30 % ) lower risk , low-fat dairy with an 11 % ( 95 % CI , 5%–17 % ) lower risk , and whole-fat dairy with a 10 % ( 95 % CI , 4%–16 % ) lower risk . We did not see significant associations with exchanging legumes or eggs for red meat . Conclusions — These data suggest that stroke risk may be reduced by replacing red meat with other dietary sources of protein Background and Purpose Epidemiological studies of the associations of low-fat dairy and specific dairy food consumption with risk of stroke are sparse . Our aim was to examine the association between consumption of total , low-fat , full-fat , and specific dairy foods and risk of stroke in a prospect i ve cohort study . Methods We followed 74 961 Swedish women and men who were free from cardiovascular disease and cancer and who completed a 96-item food frequency question naire in 1997 . Incident cases of stroke were ascertained from the Swedish Hospital Discharge Registry . Results During a mean follow-up of 10.2 years , we ascertained 4089 cases of stroke , including 3159 cerebral infa rct ions , 583 hemorrhagic strokes , and 347 unspecified strokes . Consumption of low-fat dairy foods was inversely associated with risk of total stroke ( P for trend=0.03 ) and cerebral infa rct ion ( P for trend=0.03 ) . The multivariable relative risks for the highest compared with the lowest quintile of low-fat dairy consumption were 0.88 ( 95 % CI , 0.80–0.97 ) for total stroke and 0.87 ( 95 % CI , 0.78–0.98 ) for cerebral infa rct ion . Consumption of total dairy , full-fat dairy , milk , sour milk/yogurt , cheese , and cream/crème fraiche was not associated with stroke risk . Conclusions These results suggest that low-fat dairy consumption is inversely associated with the risk of stroke STUDY OBJECTIVE To study the association between reported milk consumption and cardiovascular and all cause mortality . DESIGN A prospect i ve study of 5765 men aged 35–64 at the time of examination . SETTING Workplaces in the west of Scotl and between 1970 and 1973 . PARTICIPANTS Men who completed a health and lifestyle question naire , which asked about daily milk consumption , and who attended for a medical examination . MAIN RESULTS 150 ( 2.6 % ) men reported drinking more than one and a third pints a day , Some 2977 ( 51.6 % ) reported drinking between a third and one and a third pints a day and 2638 ( 45.8 % ) reported drinking less than a third of a pint a day . There were a total of 2350 deaths over the 25 year follow up period , of which 892 deaths were attributed to coronary heart disease . The relative risk , adjusted for socioeconomic position , health behaviours and health status for deaths from all causes for men who drank one third to one and a third pints a day versus those who drank less than a third of a pint was 0.90 ( 95 % CI 0.83 , 0.97 ) . The adjusted relative risk for deaths attributed to coronary heart disease for men who drank one third to one and a third pints a day versus those who drank less than one third of a pint was 0.92 ( 95 % CI 0.81 , 1.06 ) . CONCLUSIONS No evidence was found that men who consumed milk each day , at a time when most milk consumed was full fat milk , were at increased risk of death from all causes or death from coronary heart disease Objective : To test the hypothesis that milk drinking increases the risk of ischaemic heart disease ( IHD ) and ischaemic stroke in a prospect i ve study . Design : In the Caerphilly Cohort Study dietary data , including milk consumption , were collected by a semiquantitative food frequency question naire in 1979–1983 . The cohort has been followed for 20–24 y and incident IHD and stroke events identified . Subjects : A representative population sample in South Wales , of 2512 men , aged 45–59 y at recruitment . Main outcome measures : In total , 493 men had an IHD event and 185 an ischaemic stroke during follow-up . Results : After adjustment , the hazard ratio in men with a milk consumption of one pint ( 0.57 l ) or more per day , relative to men who stated that they consumed no milk , is 0.71 ( 0.40–1.26 ) for IHD and 0.66 ( 0.24–1.81 ) for ischaemic stroke . At baseline , 606 men had had clinical or ECG evidence of vascular disease , and in these the vascular risk was even lower ( 0.37 ; 0.15–0.90 ) . The hazard ratio for IHD and ischaemic stroke combined is 0.64 ( 0.39–1.06 ) in all men and 0.37 ( 0.15–0.90 ) in those who had had a prior vascular event . Conclusion : The data provide no convincing evidence that milk consumption is associated with an increase in vascular disease risk . Evidence from an overview of all published cohort studies on this topic should be informative . Sponsorship : The Medical Research Council , the University of Wales College of Medicine and Bristol University . Current support is from the Food St and ards Agency Cerebrovascular disease was a leading cause of death from 1955 to 1980 in Japan . The mortality rate from this disease has decreased sharply in recent decades . This downward trend seems to correspond to the dietary habits of Japanese . Data from a large prospect i ve cohort study were analyzed to examine the association between dietary habits and cerebrovascular disease mortality in Japan . The subjects for this analysis were 223,170 men and women aged 40 to 69 at baseline in December 1965 . There were 6,168 deaths in men and 4,862 deaths in women due to cerebrovascular disease ( ICD7 : 330 - 334 ) during the follow-up period from January 1966 to December 1981 . Rate ratio ( RR ) and 95 % confidence interval ( 95 % CI ) adjusted for sex , attained age , follow-up period , prefecture , cigarette smoking , alcohol drinking and occupation was used for comparison . In this study , the risk of mortality from cerebrovascular disease was inversely associated with dairy milk , meat and fish consumption . Therefore the joint effect of dairy milk , meat and fish ( DMF ) as animal fat and protein was of interest . In the binary analysis , DMF ( D , M , F ) means the combination of dairy milk ( 1 - 3 times/week or more ) , meat ( 1 - 3 times/week or more ) and fish ( 4 times/week or more ) . Thus DMF ( d , m , f ) was the reference group having dairy milk ( less than 1 time/week ) , meat ( less than 1 time/week ) and fish ( less than 4 times/week ) . For the disease , the RR of DMF ( D , M , F ) was 0.68 with 95 % CI of 0.63 to 0.74 , relative to the reference group . Furthermore the joint effect of DMF was more strongly associated with cerebral haemorrhage ( ICD7 : 331 , DMF ( D , M , F ) ; RR : 0.63 , 95 % CI : 0.55 - 0.70 ) than with cerebral embolism and thrombosis ( ICD7 : 332 , DMF ( D , M , F ) ; RR : 0.79 , 95 % CI : 0.70 - 0.89 ) . These findings suggest that the increasing intake of animal fat and /or protein may have played a key role in reducing cerebrovascular disease in Japan AIM This study aim ed to investigate the relationship between total dairy intake and dairy subtypes ( high-fat dairy , low-fat dairy , milk and milk products , cheese and fermented dairy ) with incident coronary heart disease ( CHD ) and stroke . METHODS EPIC-NL is a prospect i ve cohort study among 33,625 Dutch men and women . At baseline ( 1993 - 1997 ) , dairy intake was measured with a vali date d food frequency question naire ( FFQ ) . The incidence of both fatal and non-fatal CHD and stroke was obtained by linkage to the national registers . RESULTS During 13 years follow-up , 1648 cases of CHD and 531 cases of stroke were documented . Total dairy intake was not significantly associated with risk of CHD ( hazard ratio per st and ard deviation ( SD ) increase=0.99 ; 95%-CI : 0.94 - 1.05 ) or stroke ( 0.95 ; 0.85 - 1.05 ) adjusted for lifestyle and dietary factors . None of the dairy subtypes was to CHD , while only fermented dairy tended to be associated ( p=0.07 ) with a lower risk of stroke ( 0.92 ; 0.83 - 1.01 ) . Hypertension appeared to modify the association of total and low-fat dairy with CHD ( p interaction<0.02 ) . Among participants without hypertension , but not among hypertensive participants , total ( 0.92 ; 0.85 - 1.02 ) and low-fat ( 0.94 ; 0.87 - 1.02 ) dairy tended to be associated with a lower risk of CHD . CONCLUSION Our results provide no evidence that dairy products are associated with risk of CHD or stroke . High intakes of total and low-fat dairy may be associated with a lower risk of CHD among participants without hypertension , while fermented dairy could be associated with a reduced risk of stroke |
14,094 | 18,794,553 | Contribution This systematic review of comparative trials in adults with type 2 diabetes found that premixed insulin analogues and premixed human insulin provided similar glycemic control .
Premixed analogues provided tighter glycemic control and caused more hypoglycemia than long-acting insulin analogues and noninsulin antidiabetic agents .
Premixed insulin analogues may be a better alternative than premixed human insulin preparations for patients who wish to have a near-physiologic insulin administration regimen but want to avoid multiple daily insulin injections . | Context The relative effects of premixed insulin analogues , other insulin regimens , and noninsulin antidiabetic agents for adults with type 2 diabetes are unclear .
The Editors According to the National Health Interview Survey , 28 % of patients with type 2 diabetes are using insulin , either alone ( 16 % ) or in combination with oral antidiabetic agents ( 12 % ) ( 1 ) .
Premixed insulin analogues are derived from rapid-acting insulin analogues and consist of a mixture of a rapid-acting insulin analogue and its intermediate-acting protaminated form .
Given the increasing prevalence of type 2 diabetes ( 2 ) , the number of patients who use insulin for glycemic control ( 1 ) , and the importance of glycemic control in decreasing mortality and morbidity ( 3 ) , it is imperative to establish the weight of evidence for the safety and effectiveness of these relatively newer insulin preparations compared with traditional insulin preparations .
Therefore , the Agency for Healthcare Research and Quality commissioned a systematic review of published studies on the comparative effectiveness and safety of all the premixed insulin analogues that are approved by the U.S. Food and Drug Administration and are available in the United States . | OBJECTIVE The goal of this study was to compare the efficacy and safety profiles of biphasic insulin aspart 30 ( 30 % soluble insulin aspart and 70 % protaminated insulin aspart [ BIAsp 30 ] ) and biphasic insulin lispro 25 ( 25 % soluble insulin lispro and 75 % neutral protamine lispro [ Mix25 ] ) used in a BID injection regimen in patients with type 2 diabetes mellitus ( DM ) . Also assessed was patients ' preference for pen device -- the NovoMix 30 FlexPen /NovoLog Mix 70/30 FlexPen ( FlexPen ) versus the Humalog Mix25 Pen/Humalog Mix75/25 Pen ( Humalog Pen ) . METHODS Patients with type 2 DM receiving current insulin treatment were r and omized to a multinational , multicenter , open-label , 2-period , crossover comparison of BIAsp 30 and Mix25 . Efficacy ( by analyses of variance ) and safety profiles were assessed after 12 weeks of treatment . Patients ' preference for pen device was assessed by question naires . RESULTS A total of 137 patients were r and omized to treatment ; 4 were withdrawn during the 2-week run-in treatment with biphasic human insulin 30 . The mean ( SD ) characteristics of the remaining 133 patients ( 79 men , 54 women ) were as follows : age , 62.3 ( 9.2 ) years ; body mass index , 28.1 ( 3.9 ) kg/m(2 ) ; and glycosylated hemoglobin ( HbA(1c ) ) , 8.5 % ( 1.1 ) . Glycemic control was assessed by the measurement of HbA(1c ) after 12 weeks of treatment . Treatment with BIAsp 30 was noninferior to treatment with Mix25 ( upper limit of 90 % CI for estimated difference [ BIAsp 30 - Mix25 ] was < 0.4 % ) . Self-monitored blood glucose levels were comparable ( P = NS ) . Adverse-event profiles were similar between treatments , as was the incidence of hypoglycemic episodes ( 0.69 episode/mo with BIAsp 30 and 0.62 episode/mo with Mix25 , P = 0.292 ) . For all device features assessed , the FlexPen consistently received higher scores ( all P < 0.005 ) . A total of 9.0 % of patients experienced problems with the FlexPen , compared with 32.4 % with the Humalog Pen ( P < 0.001 ) . Furthermore , 74.6 % preferred to continue using the FlexPen , whereas 14.3 % preferred the Humalog Pen ( P < 0.001 ) . CONCLUSIONS In this study , glycemic control with BIAsp 30 and Mix25 was found to be comparable in these patients with type 2 DM . Safety profiles were similar for both regimens . Patients preferred and experienced fewer problems with the FlexPen than the Humalog Pen OBJECTIVE —Rapid-acting insulin analogs in basal-bolus regimens can reduce nocturnal hypoglycemia , so it is conceivable that twice-daily biphasic insulin analogs might reduce hypoglycemia in patients with insulin-treated type 2 diabetes . We used a continuous glucose monitoring system ( CGMS ) and self-reported episodes to investigate differences in the frequency of low glucose values in patients with type 2 diabetes , using either biphasic insulin aspart 30 ( BIAsp 30 ) or biphasic human insulin 30 ( BHI 30 ) . RESEARCH DESIGN AND METHODS —This was a double-blind , two-period , crossover trial involving 160 subjects . After 8 weeks ’ run-in , subjects were r and omized to the first of two 16-week treatment periods . RESULTS —No differences in overall incidence of low interstitial glucose ( IG ) were found . Twenty-four – hour plots of CGMS showed low IG was more frequent at night than during the day and was unrecognized by patients . At night , subjects spent significantly less time ( percentage of total CGMS recorded ) with IG < 3.5 and < 2.5 mmol/l during BIAsp 30 than during BHI 30 treatment , respectively ( < 3.5 mmol/l : 6.36 vs. 7.93 % [ mean ] , 0.67 vs. 2.43 % [ median ] , P = 0.018 ; < 2.5 mmol/l : 2.35 vs. 2.86 % [ mean ] , 0 vs. 0 % [ median ] , P = 0.0467 ) . No treatment difference in A1C was observed . CONCLUSIONS —Overall rates of low glucose over 24 h were not different but were twice as frequent at night than during the day in individuals with type 2 diabetes . Compared with BHI 30 , BIAsp 30 was associated with similar low IG readings over 24 h but with fewer nocturnal episodes and less self-reported nocturnal hypoglycemia OBJECTIVE Safety and efficacy of biphasic insulin aspart 70/30 ( BIAsp 70/30 , prebreakfast and presupper ) were compared with once-daily insulin glargine in type 2 diabetic subjects inadequately controlled on oral antidiabetic drugs ( OADs ) . RESEARCH DESIGN AND METHODS This 28-week parallel-group study r and omized 233 insulin-naive patients with HbA(1c ) values > /=8.0 % on > 1,000 mg/day metformin alone or in combination with other OADs . Metformin was adjusted up to 2,550 mg/day before insulin therapy was initiated with 5 - 6 units BIAsp 70/30 twice daily or 10 - 12 units glargine at bedtime and titrated to target blood glucose ( 80 - 110 mg/dl ) by algorithm-directed titration . RESULTS A total of 209 subjects completed the study . At study end , the mean HbA(1c ) value was lower in the BIAsp 70/30 group than in the glargine group ( 6.91 + /- 1.17 vs. 7.41 + /- 1.24 % , P < 0.01 ) . The HbA(1c ) reduction was greater in the BIAsp 70/30 group than in the glargine group ( -2.79 + /- 0.11 vs. -2.36 + /- 0.11 % , respectively ; P < 0.01 ) , especially for subjects with baseline HbA(1c ) > 8.5 % ( -3.13 + /- 1.63 vs. -2.60 + /- 1.50 % , respectively ; P < 0.05 ) . More BIAsp 70/30-treated subjects reached target HbA(1c ) values than glargine-treated subjects ( HbA(1c ) < /=6.5 % : 42 vs. 28 % , P < 0.05 ; HbA(1c ) < 7.0 % : 66 vs. 40 % , P < 0.001 ) . Minor hypoglycemia ( episodes/year ) was greater in the BIAsp 70/30 group than in the glargine group ( 3.4 + /- 6.6 and 0.7 + /- 2.0 , respectively ; P < 0.05 ) . Weight gain and daily insulin dose at study end were greater for BIAsp 70/30-treated subjects than for glargine-treated subjects ( weight gain : 5.4 + /- 4.8 vs. 3.5 + /- 4.5 kg , P < 0.01 ; insulin dose : 78.5 + /- 39.5 and 51.3 + /- 26.7 units/day , respectively ) . CONCLUSIONS In subjects with type 2 diabetes poorly controlled on OADs , initiating insulin therapy with twice-daily BIAsp 70/30 was more effective in achieving HbA(1c ) targets than once-daily glargine , especially in subjects with HbA(1c ) > 8.5 % BACKGROUND Humalog Mix75/25 ( Mix75/25 ) is a novel premixed insulin containing 75 % neutral protamine lispro ( an intermediate-acting insulin ) and 25 % insulin lispro . OBJECTIVE The purpose of this study was to compare glycemic control and hypoglycemia rates with Mix75/25 versus glyburide , and with prepr and ial versus postpr and ial Mix75/25 , in patients aged 60 to 80 years with type 2 diabetes mellitus and persistent hyperglycemia on sulfonylurea therapy . METHODS In this open-label , 16-week , parallel-group study , patients were r and omized to 1 of 2 treatments : glyburide 15 mg/d ( or up to the maximum daily dose ) or Mix75/25 . The Mix75/25 group was r and omly subdivided into prepr and ial ( immediately before breakfast and dinner ) and postpr and ial ( within 15 minutes after the start of breakfast and dinner ) injection subgroups . The primary outcomes were glycemic control and rate of hypoglycemia . RESULTS A total of 143 patients were r and omized ; 127 completed the study . The change in glycosylated hemoglobin ( HbA(1c ) ) from baseline to end point was significantly greater with Mix75/25 than with glyburide ( mean + /- SEM , -1.14 % + /- 0.18 % vs -0.36 % + /- 0.15 % , P = 0.001 ) . HbA(1c ) changes with prepr and ial and postpr and ial Mix75/25 were not significantly different ( -1.20 % + /- 0.26 % vs -1.08 % + /- 0.26 % , P = 0.748 ) . Fasting blood glucose ( BG ) , 2-hour postpr and ial BG , and mean daily BG reductions were greater with Mix75/25 than with glyburide ( P < 0.001 ) ; prepr and ial and postpr and ial Mix75/25 administration did not differ significantly with respect to any of these BG variables . The hypoglycemia rate increased with Mix75/25 by 0.17 + /- 0.02 episodes per patient per 30 days , but there was no change with glyburide ( P = 0.077 ) . Body weight increased by 1.02 + /- 0.35 kg with Mix75/25 and decreased by 0.85 + /- 0.18 kg with glyburide ( P < 0.001 ) . CONCLUSIONS Compared with glyburide , Mix75/25 significantly improved glycemic control in older patients with type 2 diabetes mellitus , could be administered after meals without compromising glycemic control , and was well tolerated OBJECTIVE The purpose of this study was to compare the pharmacokinetics and pharmacodynamics of the premixed insulin analogue biphasic insulin aspart ( BIAsp 30 ) with the equivalent premixed biphasic human insulin ( BHI 30 ) , administered twice daily , in patients with type 2 diabetes mellitus . METHODS In this r and omized , double-blind , crossover trial , 13 patients ( mean age , 64 years ; baseline mean glycosylated hemoglobin , 7.7 % ; mean body mass index , 28.1 kg/m2 ) received 2 weeks of treatment with BIAsp 30 and 2 weeks of BHI 30 administered immediately before dinner and breakfast . At the end of each 2-week treatment period , 24-hour serum insulin and glucose profiles were determined using specific 2-sided enzyme-linked immunosorbent assays . All pharmacodynamic and pharmacokinetic end points were analyzed using analysis of variance . RESULTS Total daily insulin exposure was similar between treatment periods . Mean area under the total insulin concentration-time profile during the 2 hours following administration of BIAsp 30 was 17 % greater than that of BHI 30 after dinner and 44 % greater after breakfast ; both differences were statistically significant . The maximum serum insulin aspart concentrations following BIAsp 30 were significantly higher after dinner ( 18 % ) and breakfast ( 35 % ) . Peak serum insulin concentration was reached 1 hour earlier after breakfast and 45 minutes earlier after dinner in the BIAsp 30 group ; differences were significant only after breakfast . The mean daily pr and ial glucose excursion was significantly lower for BIAsp 30 ( 16.2 mmol x h x L(-1 ) ) than BHI 30 ( 17.9 mmol x h x L(-1 ) ) . Postpr and ial 4-hour glucose excursions were significantly lower with BIAsp 30 than with BHI 30 after dinner and breakfast , but were significantly greater after lunch . Mean 24-hour and nocturnal serum glucose concentrations were similar , and both insulins were associated with < or = 7 minor and no major hypoglycemic events . CONCLUSIONS Premeal injection of BIAsp 30 in a twice-daily regimen significantly reduced overall postpr and ial glucose excursions . This effect may be of importance when improvement in postpr and ial glucose control is desired AIM To compare insulin lispro mixture ( 25 % insulin lispro and 75 % NPL ; Mix 25/75 ) twice-daily plus oral glucose-lowering medications ( metformin and /or sulphonylurea ) with once-daily insulin glargine plus oral agents with respect to postpr and ial glycaemic control and other glucose and lipid parameters in patients with Type 2 diabetes inadequately controlled with insulin and /or oral glucose-lowering agents . METHODS This was a r and omized , open-label , crossover study . Pre study oral agents were continued and patients not already on oral agents were treated with metformin . Mix 25/75 and insulin glargine were adjusted over 3 months to attain premeal plasma glucose ( PG ) < 6.0 mmol/l and were then given during a 24-h in-patient test meal period with frequent PG , serum triglyceride ( TG ) and free fatty acid ( FFA ) measurements . RESULTS Twenty patients ( 10 F/10 M ; mean + /-sd age 54.0 + /- 10.7 years , body mass index 37.0 + /- 8.6 kg/m2 , HbA1c 8.4 + /- 1.01 % ) participated . Mean doses were 23 U before the morning and 37 U before the evening meal for Mix 25/75 and 44 U for insulin glargine . The combined 2-h morning and evening meal postpr and ial plasma glucose ( PPG ) was not different between groups ( 9.2 + /- 2.04 vs. 9.9 + /- 1.66 mmol/l , P = 0.161 ) . Mix 25/75 was associated with a lower mean 2-h PPG for all meals combined ( 9.0 + /- 1.88 vs. 9.9 + /- 1.80 mmol/l , P < 0.05 ) and lower mean 24-h PG ( 6.7 + /- 1.00 vs. 7.5 + /- 1.32 mmol/l , P < 0.01 ) . Eight patients experienced mild hypoglycaemia ( PG < 3.5 mmol/l ) with Mix 25/75 and 3 with insulin glargine . The endpoint HbA1c was lower with Mix 25/75 ( 6.9 + /- 0.52 % vs. 7.3 + /- 0.81 % , P < 0.05 ) . CONCLUSIONS In a 24-h test-meal setting in 20 patients , Mix 25/75 insulin plus oral glucose-lowering agents was associated with lower mean PPG and 24-h PG , more mild hypoglycaemia and similar TG , FFA and fasting PG concentrations . HbA1c was lower with Mix 75/25 plus oral agents , although it may not have reached steady state due to ongoing dose adjustment Introduction Intensive insulin therapy ( IIT ) with tight glycemic control may reduce mortality and morbidity in critically ill patients and has been widely adopted in practice throughout the world . However , there is only one r and omized controlled trial showing unequivocal benefit to this approach and that study population was dominated by post-cardiac surgery patients . We aim ed to determine the association between IIT and mortality in a mixed population of critically ill patients . Methods We conducted a cohort study comparing three consecutive time periods before and after IIT protocol implementation in a Level 1 trauma center : period I ( no protocol ) ; period II , target glucose 80 to 130 mg/dL ; and period III , target glucose 80 to 110 mg/dL. Subjects were 10,456 patients admitted to intensive care units ( ICUs ) between 1 March 2001 and 28 February 2005 . The main study endpoints were ICU and hospital mortality , Sequential Organ Failure Assessment score , and occurrence of hypoglycemia . Multivariable regression analysis was used to evaluate mortality and organ dysfunction during periods II and III relative to period I. Results Insulin administration increased over time ( 9 % period I , 25 % period II , and 42 % period III ) . Nonetheless , patients in period III had a tendency toward higher adjusted hospital mortality ( odds ratio [ OR ] 1.15 , 95 % confidence interval [ CI ] 0.98 , 1.35 ) than patients in period I. Excess hospital mortality in period III was present primarily in patients with an ICU length of stay of 3 days or less ( OR 1.47 , 95 % CI 1.11 , 1.93 There was an approximately fourfold increase in the incidence of hypoglycemia from periods I to III . Conclusion A policy of IIT in a group of ICUs from a single institution was not associated with a decrease in hospital mortality . These results , combined with the findings from several recent r and omized trials , suggest that further study is needed prior to widespread implementation of IIT in critically ill patients OBJECTIVE —There is insufficient r and omized trial data to support evidence -based recommendations for tight control of fasting blood glucose ( FBG ) among diabetic subjects in primary stroke prevention . We explored the relationship between FBG among diabetic subjects and risk of ischemic stroke in a multiethnic prospect i ve cohort . RESEARCH DESIGN AND METHODS —Medical and social data and FBG values were collected for 3,298 stroke-free community residents : mean age ± SD was 69 ±10 years ; 63 % were women , 21 % were white , 24 % were black , and 53 % were Hispanic ; and follow-up was 6.5 years . Baseline FBG levels were categorized : 1 ) elevated FBG : history of diabetes and FBG ≥126 mg/dl ( 7.0 mmol/l ) ; 2 ) target FBG : history of diabetes and FBG < 126 mg/dl ( 7.0 mmol/l ) ; or 3 ) no diabetes/reference group . Cox models were used to calculate hazard ratios ( HRs ) and 95 % CI for ischemic stroke and vascular events . RESULTS —In the Northern Manhattan Study , 572 participants reported a history of diabetes and 59 % ( n = 338 ) had elevated FBG . Elevated FBG among diabetic subjects was associated with female sex ( P < 0.04 ) , Medicaid ( P = 0.01 ) , or no insurance ( P = 0.03 ) . We detected 190 ischemic strokes and 585 vascular events . Diabetic subjects with elevated FBG ( HR 2.7 [ 95 % CI 2.0–3.8 ] ) were at increased risk of stroke , but those with target FBG levels ( 1.2 [ 0.7–2.1 ] ) were not , even after adjustment . A similar relationship existed for vascular events : elevated FBG ( 2.0 [ 1.6–2.5 ] ) and target FBG ( 1.3 [ 0.9–1.8 ] . CONCLUSIONS —This prospect i ve cohort study provides evidence for the benefits of tighter glucose control for primary stroke prevention Aim : To compare pre‐meal injection of Humalog ® Mix50 ™ ( Mix50 ) and Humalog ® Mix25 ™ ( Humalog ® Mix75/25 ™ in the US ; Mix25 ) with respect to 2 h postpr and ial ( 2 h pp ) blood glucose ( BG ) control after a carbohydrate‐rich breakfast in patients with type 2 diabetes AIM This study compared glycaemic control achieved with biphasic insulin aspart 30 ( BIAsp 30 ) monotherapy , BIAsp 30 plus metformin and glibenclamide plus metformin in patients with type 2 diabetes not adequately controlled with metformin . METHODS In this multinational , open-labelled , parallel group , 16-week trial , 341 patients ( patients not adequately controlled with metformin for at least 1 month ) with type 2 diabetes were studied . Patients were r and omized to receive BIAsp 30 , twice daily ( n = 107 exposed to treatment ) , or BIAsp 30 , twice daily , plus metformin ( n = 108 ) or glibenclamide plus metformin ( n = 114 ) . The primary endpoint was HbA(1c ) at end of trial ; adverse events , hypoglycaemia episodes , blood lipids and weight were also monitored . RESULTS In the total population ( HbA(1c ) 7.5 - 13.0 % at screening ) , end-of-trial HbA(1c ) levels were lower in patients receiving BIAsp 30 plus metformin compared with those receiving BIAsp 30 only [ mean treatment difference ( + /-s.e.m ) , 0.39 + /- 0.15 % , p = 0.007 ] . In a sub population ( HbA(1c ) > or = 9.0 % at baseline , n = 193 ) , patients receiving BIAsp 30 plus metformin had significantly lower HbA(1c ) levels at the end of the trial compared with those receiving glibenclamide plus metformin ( treatment difference , 0.46 + /- 0.21 % , p = 0.027 ) . Mean body weight ( + /-s.d ) at the end of the trial was significantly lower in patients receiving glibenclamide plus metformin compared with those receiving BIAsp 30 only ( 84.3 + /- 13.3 kg vs. 88.9 + /- 16.9 kg , p < 0.001 ) . No major hypoglycaemic episodes were recorded during the trial , and incidence rates for minor and symptoms-only hypoglycaemia were low and similar between treatment groups ( 0.03 - 0.04 events/patient/week ) . CONCLUSION BIAsp 30 added to metformin could be an appropriate therapeutic option for achieving good glycaemic control , compared with the addition of a second oral agent , particularly where HbA(1c ) > or = 9 % AIM To evaluate the efficacy and safety of adding biphasic insulin aspart 30 ( BIAsp30 ; NovoMix 30 ) to existing oral antidiabetic agents ( OADs ) vs. optimizing OADs in a subgroup of Western Pacific patients with type 2 diabetes inadequately controlled on oral monotherapy or oral combination therapy . METHODS This 26-week , multi-centre , open-labelled , r and omized , two-arm parallel trial consisted of a 2-week screening period , followed by 24 weeks of treatment . Subjects r and omized to BIAsp30 treatment ( n = 129 ) received BIAsp30 once daily ( o.d . ) at dinnertime between Week 2 and Week 14 , and those not reaching treatment targets were switched to twice daily ( b.i.d . ) BIAsp30 at Week 14 ( n = 50 ) . Subjects r and omized to the OAD-only arm ( n = 63 ) continued with their previous OAD treatment and , in an attempt to reach treatment goals , the dose was optimized ( but OAD unchanged ) in accordance to local treatment practice and labelling . RESULTS Significantly greater reductions in HbA(1c ) over Weeks 0 - 13 with BIAsp30 ( o.d . ) vs. OAD-only treatment ( 1.16 vs. 0.58 % ; p < 0.001 ) , and over Weeks 0 - 26 , with BIAsp30 ( o.d . ) and BIAsp30 ( b.i.d . ) treatments vs. OAD-only treatment ( 1.24 vs. 1.34 vs. 0.67 % ; p < 0.01 ) . Hypoglycaemic episodes were reported in 54 % of the patients in BIAsp30 ( o.d . and b.i.d . pooled ) and 30 % of the patients in OAD-only group . All episodes were minor or symptomatic , except for one in each treatment group , which was major . CONCLUSIONS Initiating BIAsp30 treatment is a safe and more effective way to improve glycaemic control in Western Pacific patients with type 2 diabetes inadequately controlled with oral monotherapy or oral combination therapy compared with optimizing oral combination therapy alone . In patients not reaching treatment target on BIAsp30 ( o.d . ) , treatment with BIAsp30 ( b.i.d . ) should be considered BACKGROUND Adding insulin to oral therapy in type 2 diabetes mellitus is customary when glycemic control is suboptimal , though evidence supporting specific insulin regimens is limited . METHODS In an open-label , controlled , multicenter trial , we r and omly assigned 708 patients with a suboptimal glycated hemoglobin level ( 7.0 to 10.0 % ) who were receiving maximally tolerated doses of metformin and sulfonylurea to receive biphasic insulin aspart twice daily , pr and ial insulin aspart three times daily , or basal insulin detemir once daily ( twice if required ) . Outcome measures at 1 year were the mean glycated hemoglobin level , the proportion of patients with a glycated hemoglobin level of 6.5 % or less , the rate of hypoglycemia , and weight gain . RESULTS At 1 year , mean glycated hemoglobin levels were similar in the biphasic group ( 7.3 % ) and the pr and ial group ( 7.2 % ) ( P=0.08 ) but higher in the basal group ( 7.6 % , P<0.001 for both comparisons ) . The respective proportions of patients with a glycated hemoglobin level of 6.5 % or less were 17.0 % , 23.9 % , and 8.1 % ; respective mean numbers of hypoglycemic events per patient per year were 5.7 , 12.0 , and 2.3 ; and respective mean weight gains were 4.7 kg , 5.7 kg , and 1.9 kg . Rates of adverse events were similar among the three groups . CONCLUSIONS A single analogue-insulin formulation added to metformin and sulfonylurea result ed in a glycated hemoglobin level of 6.5 % or less in a minority of patients at 1 year . The addition of biphasic or pr and ial insulin aspart reduced levels more than the addition of basal insulin detemir but was associated with greater risks of hypoglycemia and weight gain . ( Current Controlled Trials number , IS RCT N51125379 [ controlled-trials.com ] . ) OBJECTIVE —The purpose of this study was to compare two analog insulin therapies ( pr and ial premixed therapy [ PPT ] versus basal/bolus therapy [ BBT ] ) in type 2 diabetic patients previously treated with insulin glargine ( ≥30 units/day ) plus oral agents , with the aim of demonstrating noninferiority of PPT to BBT . RESEARCH DESIGN AND METHODS — Patients were r and omly assigned to PPT ( lispro mix 50/50 : 50 % insulin lispro protamine suspension and 50 % lispro ; n = 187 ) t.i.d . with meals or BBT ( glargine at bedtime plus mealtime lispro ; n = 187 ) in a 24-week , multicenter , open-label , noninferiority trial . Investigators could replace lispro mix 50/50 with lispro mix 75/25 at the evening meal if the fasting plasma glucose target was unachievable . RESULTS —Baseline A1C was similar ( PPT 8.8 % ; BBT 8.9 % ; P = 0.598 ) . At week 24 , A1C was lower with BBT ( 6.78 vs. 6.95 % , P = 0.021 ) . A1C was reduced significantly from baseline for both therapies ( P < 0.0001 ) . The difference in A1C change from baseline to the end point ( BBT minus PPT ) was −0.22 % ( 90 % CI −0.38 to −0.07 ) . Noninferiority of PPT to BBT was not demonstrated based on the prespecified noninferiority margin of 0.3 % . The percentages of patients achieving target A1C < 7.0 % ( PPT versus BBT , respectively ) were 54 vs. 69 % ( P = 0.009 ) and for target ≤6.5 % were 35 vs. 50 % ( P = 0.01 ) but did not differ for target ≤6.0 % or < 7.5 % . Rates of hypoglycemia were similar for both groups . CONCLUSIONS —Although noninferiority of PPT to BBT was not demonstrated , findings for A1C reduction , percentage of patients achieving A1C targets , hypoglycemia , and number of required injections should be considered in the individual decision-making process of advancing insulin replacement to PPT versus BBT in type 2 diabetes OBJECTIVE Biphasic insulin aspart 30 ( BIAsp30 ) is a dual release formulation , containing 30 % soluble and 70 % protamine-crystallized insulin aspart . This study compared the glycaemic control and safety profiles achieved with either twice daily BIAsp30 or NPH insulin in patients with type 2 diabetes not optimally controlled by oral hypoglycaemic agents ( OHAs ) , NPH insulin or a combination of both . METHODS In this 16-week multinational , parallel-group , double-blind trial , 403 such patients were r and omized to receive either BIAsp30 or NPH insulin immediately before breakfast and evening meals . OHAs were discontinued at r and omization . Efficacy was assessed by glycosylated haemoglobin ( HbA1c ) and self-recorded daily 8-point blood glucose ( BG ) profiles . Hypoglycaemic and other adverse events were the chosen safety parameters . RESULTS HbA1c concentration decreased by > 0.6 % ( p < 0.0001 vs. baseline ) in both groups , with metabolic control continuing to improve throughout the trial without reaching a stable level . Patients who switched from once or twice daily NPH monotherapy to twice daily BIAsp30 achieved a significantly greater reduction in HbA1c ( 0.78 % ) than those r and omized to twice daily NPH insulin ( 0.58 % ; p = 0.03 ) . BIAsp30 decreased mean daily postpr and ial glycaemic exposure to a greater extent than NPH insulin ( mean difference = 0.69 mmol/l ; p < 0.0001 ) , reflecting greater decreases in the postbreakfast and postdinner increments ( of 1.26 and 1.33 mmol/l , respectively ) , although postlunch increment was relatively increased ( by 0.56 mmol/l ) . Despite the greater reduction in overall postpr and ial glycaemic exposure in the BIAsp30 group , the overall safety profile of BIAsp30 was equivalent to that of NPH insulin with < 2 % of patients experiencing major hypoglycaemia , and approximately 33 % reporting minor hypoglycaemic episodes , in both groups . CONCLUSION Twice daily BIAsp30 reduced postpr and ial glucose exposure to a significantly greater extent than NPH insulin and was at least as effective at reducing HbA1c in patients with type 2 diabetes . Both insulins were well tolerated . In patients poorly controlled on OHAs or NPH alone , glycaemic control can be improved by switching to twice daily BIAsp30 , without increasing hypoglycaemic risk To evaluate glycemic control using convenience-oriented biphasic insulin analog compared with intensified insulin therapy , we conducted a 6-month multicentric , open-label , r and omized trial in Japanese insulin-naive patients with type 2 diabetes mellitus . A total of 160 adult patients at 19 centers were r and omized into two groups : those who received twice-daily injections of biphasic insulin aspart 30 and those on three-times-daily injections of insulin aspart with or without NPH insulin ( multiple daily injections ) . At 6 months , mean HbA(1c ) decreased by approximately 2.5 % in both groups . Reduction of HbA(1c ) on both regimens was better in patients whose prior therapy before starting the study was only diet and exercise ( -5.0 % ) than in patients who were previously taking oral antidiabetic agents ( -1.0 % ) . No incidence of major hypoglycemia was observed in either regimen . These results suggest that convenience-oriented insulin therapy using biphasic insulin analog is as useful as intensified insulin therapy with insulin analog for the treatment of type 2 diabetes mellitus over 6 months . Furthermore , early induction of insulin therapy in individuals hitherto using only diet and exercise may provide good glycemic control . This study suggests that convenience-oriented biphasic insulin aspart 30 might be a useful option for the treatment of type 2 diabetes mellitus , especially for insulin-naive patients over 6 months , although it should be changed to another regimen when expected efficacy is not obtained AIMS To compare the glycaemic control of an insulin lispro mixture ( 25 % insulin lispro and 75 % NPL ) twice daily in combination with metformin to that of once-daily insulin glargine plus metformin in patients with Type 2 diabetes inadequately controlled with intermediate insulin , or insulin plus oral agent(s ) combination therapy . RESEARCH DESIGN AND METHODS Ninety-seven patients were r and omized in a multicentre , open-label , 32-week crossover study . Primary variables evaluated : haemoglobin A1c ( A1c ) , 2-h post-pr and ial blood glucose ( BG ) , hypoglycaemia rate ( episodes/patient/30 days ) , incidence ( % patients experiencing > or = 1 episode ) of overall and nocturnal hypoglycaemia . RESULTS At endpoint , A1c was lower with the insulin lispro mixture plus metformin compared with glargine plus metformin ( 7.54 % + /- 0.87 % vs. 8.14 % + /- 1.03 % , P < 0.001 ) . Change in A1c from baseline to endpoint was greater with the insulin lispro mixture plus metformin ( -1.00 % vs. -0.42 % ; P < 0.001 ) . Two-hour post-pr and ial BG was lower after morning , midday , and evening meals ( P < 0.001 ) during treatment with the insulin lispro mixture plus metformin . The fasting BG values were lower with glargine plus metformin ( P = 0.007 ) . Despite lower BG at 03.00 hours ( P < 0.01 ) , patients treated with the insulin lispro mixture plus metformin had a lower rate of nocturnal hypoglycaemia ( 0.14 + /- 0.49 vs. 0.34 + /- 0.85 episodes/patient/30 days ; P = 0.002 ) , although the overall hypoglycaemia rate was not different between treatments ( 0.61 + /- 1.41 vs. 0.44 + /- 1.07 episodes/patient/30 days ; P = 0.477 ) . CONCLUSION In patients with Type 2 diabetes and inadequate glucose control while on insulin or insulin and oral agent(s ) combination therapy , treatment with a twice-daily insulin lispro mixture plus metformin , which targets both post-pr and ial and pre-meal BG , provided clinical ly significant improvements in A1c , significantly reduced post-pr and ial BG after each meal , and reduced nocturnal hypoglycaemia as compared with once-daily glargine plus metformin , a treatment that targets fasting BG OBJECTIVE The rapid-acting insulin analogs aspart and lispro have now been developed in biphasic formulations . This trial compared the postpr and ial serum glucose control of biphasic insulin aspart 30 ( BIAsp 30 : 30 % aspart , 70 % protaminated aspart ) with that of biphasic insulin lispro 25 ( Mix25 : 25 % lispro , 75 % protaminated lispro ) and biphasic human insulin 30 ( BHI 30 : 30 % regular insulin , 70 % NPH insulin ) in insulin-treated subjects with type 2 diabetes . RESEARCH DESIGN AND METHODS This was an open-labeled , r and omized , single-dose , three-way crossover trial of 61 insulin-treated subjects with type 2 diabetes who had no significant late diabetic complications . BIAsp 30 and Mix25 were injected subcutaneously immediately before a test meal , and BHI 30 was injected 15 min before a test meal . The primary target of analysis was serum glucose excursion 0 - 5 h after a meal . RESULTS The postpr and ial glycemic control with BIAsp 30 , as assessed by the 5-h postmeal serum glucose excursion , was superior to that with both BHI 30 and Mix25 ( 16.6 + /- 4.5 vs. 20.1 + /- 4.9 and 18.9 + /- 6.1 mmol/l per hour , respectively ; P < 0.001 and P < 0.05 ) . For BIAsp 30 versus BHI 30 , this was supported by a reduced maximum glucose concentration [ C(max(SG ) ) ] ( -5 % ; P < 0.05 ) occurring earlier ( -13 min ; P < 0.01 ) . Furthermore , BIAsp 30 displayed a higher maximum serum insulin concentration ( + 101 % ; P < 0.001 ) occurring earlier ( -55 min ; P < 0.001 ) compared with BHI 30 . Compared with Mix25 , there was a shorter time to C(max(SG ) ) ( -11 min ; P < 0.05 ) after treatment with BIAsp 30 . CONCLUSIONS This trial demonstrates that BIAsp 30 improves postpr and ial glycemic control compared with both Mix25 and BHI 30 in subjects with type 2 diabetes PURPOSE To compare the effects of pr and ial insulin therapy focusing on postpr and ial glucose control vs. basal insulin therapy focusing on fasting glucose control in patients with type 2 diabetes . METHODS This was an open-label , r and omized , parallel , three-arm multicenter trial in patients with type 2 diabetes starting insulin treatment . Patients ( n=159 ) were r and omly assigned to 24-week treatment with 3x daily insulin lispro , 3x daily lispro mid mixture ( MidMix ; 50 % lispro , 50 % protaminated lispro ) , or 1x daily insulin glargine ; oral antihyperglycemic agents were discontinued . Primary end point was the postpr and ial glucose excursion 2 h after breakfast at the end of study . Secondary outcomes included HbA1c , self-monitored blood glucose profiles , hypoglycemic episodes , body weight , and patient satisfaction . RESULTS At the end of study , glucose excursions 2 h after breakfast were significantly lower with lispro and MidMix than with glargine ( P<.001 for each vs. glargine ) : lispro , -0.6+/-2.0 mmol/l ; MidMix , + 0.8+/-2.4 mmol/l ; glargine , + 2.5+/-2.4 mmol/l . Fasting glucose decreases were significantly greater with glargine ( -2.6+/-2.4 mmol/l ) than with lispro or MidMix ( -0.9+/-2.2 mmol/l ; + 0.9+/-1.8 mmol/l ) . Nevertheless , HbA1c decreased by 1.1 % ( lispro ) and 1.2 % ( MidMix ) , vs. 0.3 % with glargine . Hypoglycemic episodes were rare with 1 - 1.5 self-reported episodes per 100 patient-days . CONCLUSIONS In patients with type 2 diabetes starting insulin , 3x daily pr and ial treatment with a rapid-acting analog focusing on postpr and ial glucose values enabled better control of postpr and ial and circadian blood glucose profiles than once-daily glargine , in spite suboptimal fasting glucose levels , which targets fasting glucose values . These results support studies suggesting that control of postpr and ial hyperglycemia plays a key role in achieving HbA1c targets OBJECTIVE To compare insulin lispro Mix25 and human insulin 30/70 with regard to their effect on morning and evening postpr and ial glucose ( PPG ) control , and on average daily blood-glucose ( BG ) , in patients with Type 2 diabetes who wish to fast during Ramadan . METHOD Insulin lispro Mix25 and human insulin 30/70 were compared in an open-label , multicenter , r and omised , crossover study involving 151 patients . Each treatment period had a duration of 14 days during which the patients self-monitored their BG before and 2 h after the main meals on any 3 days within the last 5 days of each treatment period . RESULTS The 2 h PPG excursion following the main evening meal after sunset was significantly lower with insulin lispro Mix25 ( 3.4+/-2.9 mmol/l ) compared with human insulin 30/70 ( 4.0+/-3.2 mmol/l , P=0.007 ) . The evening pre-meal fasting BG values were also lower with insulin lispro Mix25 ( 7.1+/-2.2 mmol/l ) versus human insulin 30/70 ( 7.5+/-2.6 mmol/l , P=0.034 ) . The average daily BG concentration was 9.5+/-2.4 mmol/l during treatment with insulin lispro Mix25 versus 10.1+/-2.5 mmol/l with human insulin 30/70 given in identical doses ( P=0.004 ) . CONCLUSION When compared with human insulin 30/70 , treatment of insulin-requiring Type 2 patients with insulin lispro Mix25 during Ramadan result ed in better average daily glycaemia , and better BG control before and after the evening meal . Insulin lispro Mix25 should be considered as a therapeutic option during Ramadan Abstract .We investigated the use , in a short period , of Humalog Mix25 ( Mix25 ) in a twice-daily administration regimen compared to a twice-daily injection therapy with Humulin 30/70 ( 30/70 ) in diabetic patients with Italian dietary habits . We studied 33 type 2 diabetic patients aged 59.1±8.1 years , BMI 29.8±2.7 kg/m2 , duration of diabetes and insulin therapy of 14.4±9.8 and 4.2±4.6 years , respectively . After a 4-day leadin period of twice-daily human insulin 30/70 treatment , patients were r and omized to one of two treatment sequences : ( 1 ) a twice-daily regimen with Mix25 just 5 minutes before the morning and evening meals for 12 days , followed by a twicedaily therapy with human insulin 30/70 given 30 minutes before the morning and evening meals for an additional 12 days ; or ( 2 ) the alternate sequence . Each patient underwent a mixed meal test : Humulin 30/70 was administered 30 minutes before the meal , while Mix25 was given 5 minutes before . The 2-hour post-pr and ial glucose concentration after breakfast was significantly lower during treatment with Mix25 than with Humulin 30/70 ( 157±43.2 vs. 180±43.2 mg/dl , p<0.05 ) . The glycemic excursion after dinner on Mix25 treatment was significantly lower than with Humulin 30/70 ( 12.2±48.01 vs. 35.5±36.92 mg/dl , p<0.05 ) . AUCglucose after Mix25 was lower than after Humulin 30/70 . Glycemia after test meal was significantly lower with Mix25 than with Humulin 30/70 . Insulin and free insulin concentrations after the test meal were significantly higher with Mix25 in comparison to Humulin 30/70 . AUC serum insulin and free insulin curves after Mix25 were significantly higher than after Humulin 30/70 ( p=0.028 and p=0.005 , respectively ) . Twice-daily injections of Humalog Mix25 , compared to human insulin 30/70 in type 2 diabetic patients with Italian dietary habits , provide improved and lasting post-pr and ial glycemic control , with the great convenience of the injection just before the meal BACKGROUND Few large r and omized controlled trials have assessed the value of adding insulin to an oral antidiabetic drug regimen . OBJECTIVE This trial compared the efficacy and safety of biphasic insulin aspart 30/70 ( BIAsp 30 ) plus pioglitazone ( n = 93 ) , glibenclamide ( glyburide ) plus pioglitazone ( n = 91 ) , or BIAsp 30 monotherapy ( n = 97 ) . METHODS This 18-week , multinational , multicenter , r and omized , open-label , parallel-group trial involved 281 patients with type 2 diabetes ( 60 % male ; mean age , 56 years ; mean body mass index , 29.5 kg/m2 ) with inadequate glycemic control ( mean glycosylated hemoglobin [ HbA(1c ) ] , 9.5 % ; range , 7.4%-14.7 % ) on glibenclamide monotherapy or combination therapy . The primary objective was to compare end-of-trial HbA(1c ) among the 3 treatment groups . Fasting and mean 7- and 8-point blood glucose profiles , blood lipid levels , plasminogen activator inhibitor levels , adverse events , and hypoglycemia frequency were also compared . Patients using BIAsp 30 ( alone or with pioglitazone ) were injected twice daily ( immediately before breakfast and dinner ) . Pioglitazone ( 30 mg/d ) and glibenclamide ( 5 - 15 mg/d ) were taken orally once daily with or immediately after breakfast . RESULTS At the end of the trial , HbA(1c ) was significantly lower for the BIAsp 30 plus pioglitazone group than for the glibenclamide plus pioglitazone group ( mean [ SD ] , -0.64 % [ 0.23 % ] ; P = 0.005 ) and the BIAsp 30 monotherapy group ( -0.60 % [ 0.22 % ] ; P = 0.008 ) . Mean ( SD ) fasting blood glucose ( before breakfast ) was significantly lower for BIAsp 30 plus pioglitazone than for glibenclamide plus pioglitazone ( 153 [ 45 ] mg/dL vs 169 [ 65 ] mg/dL , respectively ; P = 0.012 ) . Each time point on the 8-point blood glucose profile was lower for BIAsp 30 plus pioglitazone than for glibenclamide plus pioglitazone ( P < 0.001 to P < 0.05 ) . No major hypoglycemic episodes were reported , and the absolute rate of hypoglycemic events was low ( < 1 event/patient-week ) in the BIAsp-only group . Edema was reported in < or = 9 % of patients in each treatment group , but no occurrence was classified as serious . Weight gain ( mean , 4.0 kg ) was more common in the BIAsp plus pioglitazone group ( 8 % ) ; however , this was consistent with improved glycemic control and is similar to that reported in other pioglitazone trials . CONCLUSIONS BIAsp 30 plus pioglitazone provided an efficacious and well-tolerated treatment alternative to glibenclamide plus pioglitazone or BIAsp 30 alone in this population of patients who previously were not well controlled on glibenclamide monotherapy or combination therapy BACKGROUND Type 2 diabetes patients insufficiently controlled with sulfonylurea ( SU ) are commonly treated by switching to twice-daily premix insulin replacing SU . The efficacy of glargine ( GL ) added on to SU compared with the premix therapy has not been analyzed in Japan . METHODS The open-label two-arm study was conducted in 30 type 2 diabetes patients poorly controlled [ hemoglobin A(1c ) ( HbA(1c ) ) > 7.5 % ] with SU with or without other oral hypoglycemic agents ( OHAs ) . The GL group injected once-daily GL in addition to the OHAs . The aspart 70/30 ( 70/30 ) group discontinued SU among the OHAs and injected twice-daily 70/30 . Patients were recommended either method in a block r and om method , and if twice-daily 70/30 was rejected , once-daily GL was selected only at the first time . The insulin dose was titrated to achieve a target fasting plasma glucose of < 120 mg/dL and /or HbA(1c ) of < 7 % . RESULTS Nineteen of 20 patients treated with GL and 11 of 14 patients treated with 70/30 completed the 6-month study . Mean HbA(1c ) improved from 8.45 % to 7.5 % in the GL group and from 9.13 % to 7.93 % in the 70/30 group . The mean HbA(1c ) decrease during 6 months was -0.95 % in the GL group and -1.20 % in the 70/30 group ( P = 0.49 ) . Mean insulin doses at 6 months were 12.0 units/day for the GL group and 26.7 units/day for the 70/30 group . Both therapies were well tolerated without severe hypoglycemia . CONCLUSION Once-daily GL injection added on to OHAs was equally safe and effective compared with twice-daily injection of aspart 70/30 premix replacing SU in type 2 patients insufficiently controlled with OHAs Summary Objective : To compare the plasma glucose ( PG ) response with a fixed mixture of 25 % insulin lispro and 75 % NPL ( Mix25 ) , prior to a meal and 3 h before exercise , to human insulin 30/70 ( 30/70 ) in patients with type 2 diabetes . Research design and methods : Thirty-seven patients were treated in a r and omized , open-label , 8-week , two-period crossover study . Mix25 was injected 5 min before breakfast and dinner throughout the study , as was 30/70 on inpatient test days and on outpatient dose titration days . Following the 4-week outpatient phase , patients were hospitalized , and exercised at a heart rate of 120 beats/min on a cycle ergometer two times for 30 min , separated by 30 min rest , starting 3 h after a 339 kcal breakfast . Results : The 2-h postpr and ial PG was significantly lower with Mix25 ( ( mean ± SEM ) 10.5 ± 0.4 mmol/lvs 11.6 ± 0.4 mmol/l ; p = 0.016 ) . Maximum decrease in PG from onset of exercise to end of exercise was significantly less with Mix25 ( -3.6 ± 0.29 mmol/l vs -4.7 ± 0.31 mmol/l ; p = 0.001 ) . The maximum decrease in PG over 6 h , after exercise onset , was significantly less with Mix25 ( -4.3 ± 0.4 mmol/l vs -5.9 ± 0.4 mmol/l ; p < 0.001 ) . The frequency of hypoglycemia ( blood glucose ( BG ) < 3 mmol/l or symptoms ) during the inpatient test was not different between treatments . During the outpatient phase , the frequency of patient-recorded hypoglycemia was significantly lower with Mix25 ( 0.7 ± 0.2 episodes/30d vs 1.2 ± 0.3 episodes/30 d ; p = 0.042 ) . Conclusions : Mix25 result ed in better postpr and ial PG control without an increase in exercise-induced hypoglycemia . The smaller decrease in PG during the postpr and ial phase after exercise may suggest a lower risk of exercise-induced hypoglycemia with Mix25 than with human insulin 30/70 , especially for patients in tight glycemic control BACKGROUND The incidence of type 2 diabetes mellitus ( DM ) is rapidly increasing worldwide . Results from large-scale studies show that tight blood glucose ( BG ) control improves the outcome of patients with type 2 DM . OBJECTIVE This trial assessed the short-term efficacy and tolerability of adding a thiazolidinedione ( rosiglitazone [ ROS ] ) to existing sulfonylurea ( SU ) therapy ( glibenclamide ) compared with switching to combination treatment with a premixed insulin ( biphasic insulin aspart 30 [ BIAsp 30 ] , a rapid-acting insulin analog ) and the thiazolidinedione in a select group of patients with type 2 DM whose metabolic control was inadequate with SU monotherapy . METHODS In this 6-week , multicenter , open-label , parallel-group trial , patients with type 2 DM whose BG level was not adequately controlled with glibenclamide monotherapy ( glycosylated hemoglobin [ HbA1c ] 8%-13 % ) were r and omized either to replace glibenclamide with BIAsp 30 ( individually titrated dosages starting with 6 - 8 U BID ) plus rosiglitazone ( 4 mg once daily ) ( BIAsp 30 + ROS group ) or to add rosiglitazone ( 4 mg once daily ) to their pretrial doses of glibenclamide ( GLIB + ROS group ) . Patients measured their BG levels immediately before each of the 3 main meals , 90 minutes after the start of each meal , and at bedtime , and mean BG levels were calculated at weeks 0 ( baseline ) , 1 , 2 , 4 , 6 , and at 2-week follow-up ( week 8) . The primary end point was change in mean daily BG level during treatment . Secondary end points included prepr and ial , postpr and ial , and bedtime BG levels , serum fructosamine level HbA , and fasting BG level , which were measured at each study visit . Tolerability was assessed using hematologic and biochemical parameters , vital signs , and physical examination . RESULTS Forty-nine patients ( 32 men , 17 women ; mean [ SD ] age , 59.1 [ 8.9 ] years ; mean [ SD ] body mass index , 27.7 [ 3.7 ] kg/m2 ) participated in the study . A significant difference was found between treatments in the change in mean daily BG level from baseline to week 6 ( P=0.01 ) . After the 6-week treatment period , change in mean serum fructosamine level was significantly greater for BIAsp 30 + ROS compared with GLIB + ROS ( P=0.02 ) . HbA1c decreased in both treatment groups from baseline to study end , but the difference between groups was nonsignificant . The changes in fasting BG from baseline to study end also were nonsignificant between groups . Both combinations were well tolerated . CONCLUSIONS This short-term study in patients with type 2 DM whose BG level was poorly controlled with glibenclamide monotherapy suggests that switching to a combination of BIAsp 30 + ROS was efficacious and well tolerated and provided an alternative to adding rosiglitazone to existing glibenclamide treatment . The study also suggests that BIAsp 30 may be associated with greater improvements in short-term metabolic control BACKGROUND Modern premixed insulins offer a flexible approach to the initiation of insulin therapy in patients with poorly controlled type 2 diabetes . A disadvantage of twice-daily regimens of biphasic insulin aspart 30 ( BIAsp 30 ) is that lunchtime control ( when no insulin is administered ) can be suboptimal . Therefore , it is possible that administering BIAsp 30 thrice daily might further optimize glycemic control and offer an option for patients in whom metformin ( MET ) is contraindicated . OBJECTIVE This study evaluated the efficacy and safety profiles of 2 different regimens of BIAsp 30 compared with a regimen consisting of oral antidiabetic drugs ( OADs ) alone . METHODS In this multicenter , r and omized , open-label , parallel-group trial , insulin-naive patients with poorly controlled type 2 diabetes ( baseline glycosylated hemoglobin [ HbA(1c ) > or = 8.0 % ) who were taking OADs ( a sulfonylurea or meglitinide with/without MET or MET only ) were r and omized to receive BIAsp 30 TID , BIAsp 30 BID + MET , or continuation of their current OAD therapy for 16 weeks . The primary end point was HbA(1c ) at the end of the study . Secondary end points included reductions in HbA(1c ) , mean blood glucose ( BG ) , pr and ial increment , mean 7-point self-monitored BG profile , weight changes , tolerability ( hypoglycemia , adverse events ) , and satisfaction/ quality of life ( derived from 2 question naires completed at weeks 0 , 8 , and 16 ) . RESULTS The study enrolled 308 insulin-naive patients with type 2 diabetes ( 78.9 % female ; mean age , 58.3 years ; body mass index , 29.4 kg/m(2 ) ; HbA(1c ) , 10.3 % ) . Both BIAsp 30 TID and BIAsp 30 BID + MET were associated with significantly greater mean ( SD ) reductions in HbA(1c ) relative to OADs alone ( absolute percent reduction : 2.9 % [ 1.5 % ] , 3.0 % [ 1.6 % ] , and 2.1 % [ 1.4 % ] , respectively ; P < 0.001 , both insulin groups vs OAD group ) and improved post-pr and ial glucose control ( reduction in mean post-pr and ial glucose:-6.32 [ 4.07 ] , -6.44 [ 4.70 ] , and -3.59 [ 4.22 ] mmol/L ; P < 0.001 , both insulin groups vs OAD group ) . The mean decrease in the pr and ial increment was -1.26 mmol/L for BIAsp 30 TID , -2.15 mmol/L for BIAsp 30 BID + MET , and -0.44 mmol/L for OAD . The differences in reduction in the pr and ial increment were statistically significant for BIAsp 30 TID versus OAD ( P = 0.047 ) , BIAsp 30 BID + MET versus OAD ( P < 0.001 ) , and BIAsp 30 TID versus BIAsp 30 BID + MET ( P = 0.042 ) . Mean body weight increased significantly from baseline with both BIAsp 30 TID and BIAsp 30 BID + MET ( + 1.71 and + 1.50 kg , respectively ; both , P < 0.001 ) , and decreased significantly in the OAD group ( -0.75 kg ; P = 0.003 ) . There were no major hypoglycemic events , and most hypoglycemic events were recorded as symptoms only ( 144/158 [ 91.1 % ] ) . There were no significant differences in the mean frequency of overall hypoglycemic episodes between BIAsp 30 TID and BIAsp 30 BID + MET ( 0.73 and 0.69 episodes per patient-year , respectively ) . CONCLUSIONS In these patients with type 2 diabetes that was poorly controlled by OADs , BIAsp 30 TID and BIAsp 30 BID plus MET were associated with significantly greater reductions in HbA(1c ) and postpr and ial BG compared with OADs alone . The insulin regimens were associated with significantly more weight gain than OADs alone . There were no differences in rates of hypoglycemia between the insulin regimens OBJECTIVE The aim of this study was to test the ability of human insulin 70/30 , insulin lispro mixture 75/25 ( 75 % neutral protamine lispro [ NPL ] , 25 % insulin lispro ) , and insulin lispro mixture 50/50 ( 50 % NPL , 50 % insulin lispro ) to control postpr and ial glucose ( PPG ) concentrations in patients with type 2 diabetes mellitus ( DM ) . METHODS This single-center , r and omized , double-blind , 3-way crossover study was conducted at the Diabetes and Gl and ular Disease Research Center , San Antonio , Texas . We measured serum glucose responses after a st and ardized breakfast test meal ( 500 kcal ; 50 % carbohydrate , 34 % fat , 16 % protein ) in patients with type 2 DM receiving a single prepr and ial dose of human insulin 70/30 , insulin lispro 75/25 , or insulin lispro 50/50 by SC injection . All patients previously used insulin for at least 1 month prior to the study . The glucose responses were compared with those of healthy , untreated subjects administered the identical meal . RESULTS A total of 33 patients were enrolled ( 23 with type 2 DM and 10 healthy controls ) . The baseline characteristics of the patients were as follows : sex ratio ( M : F ) , 17:6 ; mean ( SD ) age , 61.3 ( 10.0 ) years ; mean ( SD ) body weight , 98.5 ( 13.2 ) kg ; mean ( SD ) body mass index , 33.0 ( 3.8 ) kg/m(2 ) ; mean ( SD ) glycosylated hemoglobin , 8.1 % ( 1.6 % ) ; mean ( SD ) fasting serum glucose ( FSG ) , 158.7 ( 27.6 ) mg/dL ; and 56.5 % white , 8.7 % black , and 34.8 % Hispanic . The mean ( SD ) doses ( U/d ) of the fixed-mixture preparations were similar : human insulin 70/30 , 44.1 ( 18.2 ) ; insulin lispro 75/25 , 44.1 ( 18.2 ) ; and insulin lispro 50/50 , 43.8 ( 17.8 ) . FSG levels obtained before the test meal were not significantly different between treatments . Compared with those in healthy subjects , incremental glucose AUC values for the 4 hours after the meal ( AUCglucose 0 - 4 ) for patients with type 2 DM were 6.4-fold higher with human insulin 70/30 , 4.6-fold higher with insulin lispro 75/25 , and 3.0-fold higher with insulin lispro 50/50 . Each insulin regimen produced AUC(glucose ) 0 - 4 and 2-hour PPG values significantly different from all other regimens ( all , P < 0.05 ) . Mean ( SD ) 2-hour PPG values ( mg/dL ) were lower with mixtures containing insulin lispro than with human insulin 70/30 and decreased as the proportion of insulin lispro within the fixed mixtures increased : human insulin 70/30 , 212.6 ( 47.0 ) ; insulin lispro 75/25 , 198.0 ( 67.5 ) ; and insulin lispro 50/50 , 158.8 ( 52.3 ) . CONCLUSIONS In this small study in patients with type 2 DM and healthy controls , prepr and ial administration of a fixed mixture containing rapid-acting or regular insulin and intermediate-acting components was associated with attenuation of the rise in PPG in patients with type 2 DM administered a test meal . Mixtures containing insulin lispro were associated with greater decreases in PPG concentrations compared with human insulin 70/30 . Furthermore , greater amounts of rapid-acting insulin contained within the mixture were associated with better PPG control OBJECTIVE This double-blind study was design ed to compare the postpr and ial glucodynamic profile of Humalog Mix75/25 , a new premixed insulin analogue containing 75 % neutral protamine lispro and 25 % insulin lispro with that of human insulin 70/30 ( 70 % neutral protamine Hagedorn insulin and 30 % regular human insulin ) in patients with type 2 diabetes mellitus . BACKGROUND Insulin lispro Mix75/25 ( Mix75/25 ) is the first available insulin formulation in which both the rapid-acting and basal components are insulin analogues . METHODS This r and omized , multicenter , double-blind , crossover study monitored patients ' postpr and ial glucodynamic response to Mix75/25 and human insulin 70/30 ( 70/30 ) after a st and ard test meal . Eighty-four patients with type 2 diabetes participated in this study and were r and omly assigned to 1 of 2 treatment sequence groups . Patients received an identical test meal on 4 occasions , completing 2 test meals for each treatment . Equal doses of Mix75/25 or 70/30 were administered 5 minutes before each of the 2 test meals , with doses individualized for each patient . Blood sample s were collected for 4 hours after the meal for measurement of plasma glucose . From these plasma glucose measurements , fasting plasma glucose , 2-hour postpr and ial glucose ( 2pp ) , 2-hour postpr and ial glucose excursion ( 2pp(ex ) ) , maximum glucose excursion ( Gex(max ) ) , the area under the glucose concentration versus time curve from 0 to 4 hours ( AUC4 ) , and the area under the glucose excursion versus time curve from 0 to 4 hours ( AUCex4 ) were calculated . RESULTS Because of significant differences in the baseline fasting plasma glucose levels between Mix75/25 and 70/30 ( Mix75/25 : 8.9+/-2.2 mmol/L [ 160.2+/-39.6 mg/dL ] ; 70/30 : 8.6+/-1.9 mmol/L [ 154+/-34 mg/dL ) , analyses of the excursion parameters provide a truer comparison of the glucodynamic response between insulin formulations . Mix75/25 result ed in significantly lower values for 2pp(ex ) ( 3.35+/-2.28 vs 4.13+/-2.26 mmol/L ) , Gex(max ) ( 4.51+/-1.88 vs 5.19+/-1.98 mmol/L ) , and AUCex4 ( 8.01+/-7.02 vs 10.6+/-6.47 mmol x h/L ) compared with 70/30 . CONCLUSIONS In patients with type 2 diabetes mellitus , premeal injection of Mix75/25 result ed in better postpr and ial glycemic control than did premeal injection of 70/30 in the 4 hours after a st and ard meal . Mix75/25 is a valuable option for managing postpr and ial blood glucose in patients with type 2 diabetes mellitus who require insulin AIM To compare the efficacy and safety of two analog insulins as starting regimens in insulin-naïve Type 2 diabetes patients . METHODS In this r and omized , open-label parallel study , twice-daily biphasic insulin aspart 30 ( 30 % soluble and 70 % protaminated insulin aspart ; BIAsp 30 ) plus metformin ( met ) was compared with once-daily insulin glargine ( glarg ) plus glimepiride ( glim ) in 255 insulin-naïve patients ( 131 male ; mean+/-SD age , 61.2+/-9.1 years ) . Mean baseline HbA ( 1c ) ( + /-SD ) was 9.2+/-1.4 % and 8.9+/-1.3 % for BIAsp 30 plus met ( N=128 ) and glarg plus glim ( N=127 ) , respectively ( P=0.0747 ) . Primary endpoint was the difference in absolute change in HbA ( 1c ) between groups after 26 weeks of treatment . RESULTS HbA ( 1c ) change was significantly greater in the BIAsp 30 plus met group than the glarg plus glim group ( between-group difference : -0.5 % ( 95 % CI : -0.8 ; -0.2 ) ; P=0.0002 ) . Mean pr and ial plasma glucose increment was significantly lower for BIAsp 30 plus met compared with glarg plus glim : 1.4+/-1.4 mmol/l vs. 2.2+/-1.8 mmol/l ; P=0.0002 . During the maintenance phase ( weeks 6 - 26 ) , one major hypoglycemic episode occurred in each group ; 20.3 % and 9 % of patients experienced minor hypoglycemic episodes in the BIAsp 30 plus met and glarg plus glim groups , respectively ( P=0.0124 ) . At end-of-trial , mean daily insulin doses were 0.40 U/kg BIAsp 30 and 0.39 U/kg glarg . Glarg plus glim-treated patients experienced significant weight gain of 1.5 kg ( 95 % CI : 0.84 ; 2.19 ; P<0.0001 ) . Weight change with BIAsp 30 plus met of + 0.7 kg was not statistically significant ( 95 % CI : -0.07 ; 1.42 ; P=0.0762 ) . CONCLUSIONS Starting insulin in Type 2 diabetes patients with twice-daily BIAsp 30 plus met can reduce HbA ( 1c ) and mean pr and ial plasma glucose increment to a greater extent than once-daily glarg plus glim AIM To evaluate the clinical effects of switching from premixed human insulin to a premixed rapid-acting insulin analogue in type 2 diabetic patients . RESEARCH DESIGN AND METHODS Thirty patients , who were treated with a twice-daily injection of premixed human insulin , were enrolled and r and omized to ( i ) 50/50 premixed insulin lispro twice-daily at the same daily dose as premixed human insulin ( analogue mix group ) , or ( ii ) continued premixed human insulin ( control group ) . The doses of insulin were adjusted every month by registered diabetologists to achieve adequate blood glucose levels . At the beginning of the study , and again 4 months later , HbA1c and blood glucose levels were measured , and the amount of insulin required and BMI were recorded in both groups . Insulin therapy-related quality of life ( ITR-QOL ) and the diabetes treatment satisfaction question naire ( DTSQ ) were also assessed in the analogue mix group at the beginning of the study and again 4 months later . RESULTS Although HbA1c levels did not change significantly over the duration of the study in the control group ( 7.33 + /- 0.58 vs 7.29 + /- 0.65 % ) , HbA1c did improve significantly in the analogue mix group ( 7.59 + /- 0.44 vs 7.24 + /- 0.49 % ; p<0.05 ) . The dose of insulin required in the analogue mix group did not change significantly ( 0.37 + /- 0.11 vs 0.38 + /- 0.14 U/kg/day ) , but increased in the control group from 0.34 + /- 0.15 to 0.37 + /- 0.16 U/kg/day ( p<0.05 ) . The switch to the premixed insulin analogue did not affect ITR-QOL and DTSQ scores . CONCLUSIONS This study showed that switching from premixed human insulin to 50/50 premixed insulin lispro improved blood glucose control without compromising QOL . This finding suggests that a premixed rapid-acting insulin analogue is more effective than human insulin for Japanese type 2 diabetic patients OBJECTIVE This study aim ed to assess glycemic response to a mixture of 75 % insulin lispro protamine suspension and 25 % insulin lispro ( Mix 75/25 ) BID plus metformin versus insulin glargine QD plus metformin in patients with type 2 diabetes mellitus ( DM ) . METHODS Adults new to insulin therapy were enrolled in a multicenter , r and omized , prospect i ve , open-label , crossover study with 16 weeks on each treatment . Variables included glycosylated hemoglobin ( HbA(1c ) ) , hypoglycemia rate , fasting blood glucose ( FBG ) , 2-hour postpr and ial blood glucose ( ppBG ) , and rise in blood glucose after meals . RESULTS One hundred five patients ( mean age , 55 years ) were r and omized . There was no difference in baseline mean values for either treatment sequence group for body mass index , duration of DM , or HbA(1c ) . Ninety-five patients completed the study and 67 were included in the efficacy analysis . Mix 75/25 was associated with lower mean ( SD ) HbA(1c ) at end point ( 7.4 % [ 1.1 % ] vs 7.8 % [ 1.1 % ] ; P = 0.002 ) . More patients using Mix 75/25 achieved target HbA(1c ) < or = 7.0 % ( 42 % [ 30/71 ] vs 18 % [ 13/71 ] ; P < 0.001 ) . With Mix 75/25 , the mean ( SD ) 2-hour ppBG was similar after lunch but lower after breakfast ( 156.4 [ 43.6 ] vs 171.1 [ 44.9 ] mg/dL ; P = 0.012 ) and dinner ( 164.8 [ 42.5 ] mg/dL vs 193.8 [ 51.0 ] mg/dL ; P < 0.001 ) , although FBG was higher ( 139.3 [ 36.6 ] mg/dL vs 123.9 [ 34.9 ] mg/dL ; P < 0.001 ) . Rise in ppBG was lower with Mix 75/25 after breakfast ( 16.9 [ 47.0 ] mg/dL vs 47.4 [ 34.8 ] mg/dL ; P < 0.001 ) and dinner ( 14.2 [ 44.1 ] mg/dL vs 45.9 [ 41.3 ] mg/dL ; P < 0.001 ) . Gain in mean ( SD ) body weight was greater with Mix 75/25 than insulin glargine ( 2.3 [ 4.0 ] kg vs 1.6 [ 4.0 ] kg ; P = 0.006 ) . For all r and omized patients , mean ( SD ) hypoglycemia rates were lower with insulin glargine ( 0.68 [ 1.38 ] vs 0.39 [ 1.24 ] episodes/patient per 30 days ; P = 0.041 ) , although nocturnal hypoglycemia was similar . CONCLUSION In this study population , Mix 75/25 plus metformin was associated with lower HbA(1c ) than insulin glargine plus metformin , smaller rise in ppBG after breakfast and dinner , and higher proportion of patients achieving HbA(1c ) < or = 7.0 % , with a slight increase in overall ( but not nocturnal ) hypoglycemia The objective of this 6-month , open-label , r and omized , two-period crossover study was to compare glycemic control when patients were treated with ( 1 ) 2 manufactured premixed insulin formulations containing insulin lispro and a novel insulin lispro-protamine formulation , neutral protamine lispro ( NPL ) , and ( 2 ) 2 manufactured premixed human insulin formulations , human insulin 50/50 and human insulin 30/70 . One hundred individuals , 37 with type 1 diabetes mellitus ( 12 females , 25 males ; mean age , 39.4 years ; mean body mass index [ BMI ] , 24.8 ; mean duration of diabetes , 12.9 years ) and 63 with type 2 diabetes mellitus ( 33 females , 30 males ; mean age , 59.0 years ; mean BMI , 28.4 ; mean duration of diabetes , 12.6 years ) , were treated with insulin lispro mixtures . Insulin lispro Mix50 ( 50 % insulin lispro/50 % NPL ) and human insulin 50/50 ( 50 % regular insulin/50 % neutral protamine Hagedorn [ NPH ] insulin ) were administered before breakfast ; insulin lispro Mix25 ( 25 % insulin lispro/75 % NPL ) and human insulin 30/70 ( 30 % regular insulin/70 % NPH ) were administered before dinner . Blood glucose ( BG ) , hypoglycemic episodes ( hypoglycemic signs or symptoms or BG < 3.0 mmol/L ) , insulin dose and timing of dose before meals , and hemoglobin A1c were measured . Mean doses of insulin lispro and human insulin mixtures were similar overall and for both diabetes subgroups . However , compared with human insulin mixtures , twice-daily administration of insulin lispro mixtures result ed in improved postpr and ial glycemic control , similar overall glycemic control , and less nocturnal hypoglycemia , as well as offering the convenience of dosing closer to meals OBJECTIVE To compare the effects of Humalog Mix25 ( Humalog Mix75/25 in the USA ) ( Mix25 ) and human insulin 30/70 ( 30/70 ) on the 24-hour inpatient plasma glucose ( PG ) profile in patients with type 2 diabetes mellitus ( T2DM ) . DESIGN A r and omised , open-label , 8-week crossover study . Study insulins were injected twice daily , 5 minutes before breakfast and dinner . SETTING Four-week outpatient ( dose-adjustment ) treatment phase , and 3-day inpatient ( test ) phase . PATIENTS Twenty-five insulin-treated patients with T2DM ( ages 40 - 66 years ) , mean ( + /- st and ard error of the mean ) ( SEM ) HbA1c 7.7 % + /- 0.23 % , and body mass index ( BMI ) 29.3 + /- 0.83 kg/m2 . OUTCOME MEASURES 24-hour PG profiles , PG excursions after meals , PG area under the curve ( AUC ) , and 30-day hypoglycaemia rate . RESULTS The 2-hour PG excursions following breakfast ( 5.5 + /- 0.34 v. 7.2 + /- 0.34 mmol/l , p = 0.002 ) and dinner ( 2.4 + /- 0.27 v. 3.4 + /- 0.27 mmol/l , p = 0.018 ) were smaller with Mix25 than with 30/70 . PG AUC between breakfast and lunch was smaller with Mix25 than with 30/70 ( 77.6 + /- 3.8 v. 89.5 + /- 4.3 mmol/h/ml , p = 0.001 ) . PG AUC between lunch and dinner , dinner and bedtime , and bedtime and breakfast did not differ between treatments . Pre-meal and nocturnal PG were comparable . The postpr and ial insulin requirement for lunch meals was supplied equally by the two insulin treatments . The thirty-day hypoglycaemia rate was low ( Mix25 0.049 + /- 0.018 v. 30/70 0.100 + /- 0.018 episodes/patient/30 days , p = 0.586 ) for both treatments . CONCLUSION In patients with T2DM , Mix25 improved the 24-hour PG profile with lower postpr and ial PG excursions than with human insulin 30/70 BACKGROUND : In this study , we sought to compare the long-term safety and efficacy of biphasic insulin aspart 30 ( BIAsp30 ) with that of biphasic human insulin 30 ( BHI30 ) over a period of 24 months in patients with type 2 diabetes . METHODS : Patients with type 2 diabetes ( n=125 ) were assigned to twice-daily BIAsp30 or BHI30 and participated in both a 3-month initial period and a 21-month extension of a r and omized , controlled , multinational trial . RESULTS : No significant difference was found in mean HbA(1c ) after 24 months [ BIAsp30 , 8.35+/-0.20 % ; BHI30 8.13+/-0.16 % ; adjusted mean difference ( BIAsp30-BHI30 ) 0.03 ( 90 % CI -0.29 to 0.34)% , P=0.89 ] . The proportion of patients experiencing major hypoglycaemia was also similar during the first year ( BIAsp30 , 5 % ; BHI30 , 8 % ; P=0.72 ) , but it was significantly lower with BIAsp30 than with BHI30 during the second year ( BIAsp30 , 0 % ; BHI30 , 10 % ; P=0.04 ) . The proportion experiencing minor hypoglycaemia was not significantly different . No significant difference was recorded in changes in nonspecific insulin antibody levels after 24 months ( BIAsp30 , 4.87+/-1.92 % ; BHI30 ; 1.00+/-1.66 % ; P=0.13 ) . Body weight change was 0.05+/-0.81 kg in the BIAsp30 group and 2.00+/-0.69 kg in the BHI30 group ( P=0.07 ) . CONCLUSIONS : Reduced major hypoglycaemia compared with BHI30 during the second year of treatment and comparable HbA(1c ) levels after 24 months appear to support the hypothesis that the improved pharmacokinetic profile of BIAsp30 may favourably affect the balance between hypoglycaemia and hyperglycaemia in insulin-treated type 2 diabetes AIM In patients with type 2 diabetes , insulin therapy is commonly initiated with either a single dose of basal insulin or twice-daily premixed ( basal plus pr and ial ) insulin despite no widely accepted recommendation . We compared the glycaemic control , as measured by a change in HbA1c , of intensive mixture therapy ( IMT ) , a basal plus pr and ial regimen using insulin lispro mixture 50/50 ( 50 % lispro and 50 % NPL ) before breakfast and lunch and insulin lispro mixture 25/75 ( 25 % lispro and 75 % NPL ) before dinner , vs. once-daily insulin glargine therapy , while continuing patients on oral antidiabetes medications . METHODS Following inadequate glycaemic control ( HbA1c 1.2 - 2.0 times the upper limit of normal ) and at least 2 months of two or more oral antidiabetes agent therapy , 60 insulin-naïve patients with type 2 diabetes were r and omized to one of the insulin regimens for 4 months with crossover to the alternative regimen for an additional 4 months . Glycaemic goals were prepr and ial blood glucose < 120 mg/dl ( 6.7 mmol/l ) and 2-h postpr and ial blood glucose < 180 mg/dl ( 10.0 mmol/l ) . The insulin dose was optimized by investigators without forced titration . RESULTS Mean pre study ( baseline ) HbA1c for all patients was 9.21 + /- 1.33 % ( + /-s.d . ) . IMT compared to glargine result ed in both a lower endpoint in HbA1c ( 7.08 + /- 0.11 % vs. 7.34 + /- 0.11 % ; p = 0.003 ) and a greater change in HbA1c from pretherapy ( -1.01 + /- 0.10 % vs. -0.75 + /- 0.10 % ; p = 0.0068 ) . Forty-four per cent of patients receiving IMT and 31 % of patients receiving insulin glargine achieved HbA1c < or = 7 % . Two-hour postpr and ial glucose values ( for all three meals ) and predinner glucose values were significantly less with IMT than with insulin glargine ( p = 0.0034 , 0.0001 , 0.0066 and 0.0205 ) . Overall hypoglycaemia throughout the complete treatment period was infrequent ( IMT vs. Glargine : 3.98 + /- 4.74 vs. 2.57 + /- 3.22 episodes/patient/30 days , p = 0.0013 ) , and no severe hypoglycaemia was observed during the study with either therapy . There was no difference in nocturnal hypoglycaemia between the two therapies . The mean insulin dose at the end of therapy was greater for IMT than for once-daily insulin glargine ( 0.353 + /- 0.256 vs. 0.276 + /- 0.207 IU/kg , p = 0.0107 ) . CONCLUSIONS In combination with oral antidiabetes agents , multiple daily injections of a basal plus pr and ial insulin IMT regimen ( using premixed insulin lispro formulations ) result ed in greater improvements and a lower endpoint in HbA1c compared with a basal-only insulin regimen . IMT also result ed in improved postpr and ial blood glucose control at each meal and enabled administration of a greater daily dose of insulin , which most likely contributed to these lower HbA1c measures . This greater reduction in HbA1c with IMT is accompanied by a small increased occurrence of mild hypoglycaemia but without any severe hypoglycaemia . Greater consideration should be given to initiating insulin as a basal plus pr and ial regimen rather than a basal-only regimen BACKGROUND Humalog Mix 25 ( Mix 25 ) is a premixed insulin mixture of 25 % lispro and 75 % neutral protamine lispro . Insulin lispro is an analog of human insulin . It is created when the amino acids at positions 28 and 29 of the B-chain of insulin are reversed . The natural sequence in human insulin at this position is proline at B28 and lysine at B29 . The pharmacokinetic and pharmacodynamic profiles of insulin lispro indicate that it is more rapid acting , and therefore more physiological mealtime insulin than regular human insulin . OBJECTIVE Primary objective of this study was to compare twice daily treatment with insulin lispro low mixture ( Mix 25 ) to oral treatment with glibenclamide in patients with type 2 diabetes , with respect to the mean 2-hour postpr and ial blood glucose excursions after breakfast and dinner . SECONDARY OBJECTIVES to compare the two treatments with regard to the following : hemoglobin A1c , fasting blood glucose , pre-dinner blood glucose , frequency of hypoglycemia , body weight , treatment satisfaction ( by question naire ) . METHODS The study described is a r and omized , open-label , parallel group comparison of two treatment regimens in patients with type 2 diabetes . The study included two periods . The lead-in period lasted 10 + /- 7 days , all patients were taking glibenclamide . The treatment period lasted 16 weeks . Patients were r and omized to receive either glibenclamide 15 mg daily or switch to Mix 25 before breakfast and dinner . Study design is illustrated in Fig. 1 . Glycemic control was assessed by glycosylated hemoglobin ( HbA1c ) measurements , 4-point self monitoring blood glucose profiles , and patient reported hypoglycemia . One treatment satisfaction question naire ( Appendix 1 ) was completed by each participant . RESULTS 175 patients were included from the two participating countries ( Romania--100 patients and Russia--75 patients ) . 85 were r and omized to receive Mix 25 and 90 to glibenclamide arm . 172 patients were included in the efficacy analysis . Baseline patient characteristics did not show any differences between treatment groups for any of the demographic ( age , gender , height , body weight , body mass index ) or efficacy parameters ( HbA1c or self monitored BG values ) . The mean age was 59.5 + /- 8.2 years , and 35.5 % ( 61/172 ) were men . The mean body mass index was 27.2 kg/m2 . The mean duration of type 2 diabetes was 10.2 + /- 6.6 years , and the mean duration of sulfonylurea treatment was 5.8 + /- 5.9 years . The mean HbA1c and fasting blood glucose levels were 10.07 + /- 1.4 % and 11.6 + /- 2.8 mmol/L , respectively , in the glibenclamide group and 9.85 + /- 1.2 % and 12.2 + /- 2.9 mmol/L , respectively , in the Mix 25 group . At the end point , all efficacy parameters were better improved in Mix 25 group ( HbA1c , fasting blood glucose , 2-hour postpr and ial blood glucose ) . Mean HbA1c was significantly lower in the Mix 25 group than in the GB group ( Mix 25 , 8.5 % + /- 1.3 % ; GB , 9.4 + /- 1.8 % ; P = 0.001 ) . For all self-monitored blood glucose values ( Fig. 2 ) a larger decrease from baseline was observed in the Mix 25 group : -1.4 % versus -0.7 % for HbA1c , ( P = 0.004 ) ; -2.8 mmol/L versus -1.1 mmol/L for fasting blood glucose , ( P < 0.01 ) ; -5.1 mmol/L versus -1.7 mmol/L for the morning 2-hour postpr and ial blood glucose , ( P < 0.001 ) ; -2.2 mmol/L versus -0.8 mmol/L for the evening prepr and ial blood glucose , ( P < 0.05 ) ; and 4.4 mmol/L versus -1.5 mmol/L for the evening 2-hour postpr and ial blood glucose , ( P < 0.001 ) . Percentage of patients experiencing at least 1 episode of hypoglycemia was -- as predicted -- higher in the Mix 25 group ( 44.7 % versus 10.3 % ; P = 0.01 ) . Patients expressed more satisfaction with Mix 25 than with GB , as measured by the weighted combined score on a treatment satisfaction question naire ( 2.0 + /- 1.3 vs 0.7 + /- 1.3 ) . CONCLUSIONS When glycemic control can no longer be achieved by oral antidiabetic agents , treatment with insulin should be considered as the next therapeutic option . Mix 25 provided good overall glycemic control , as well as patient treatment satisfaction OBJECTIVE To assess relationships of diabetes and asymptomatic hyperglycemia at baseline to the risk of cardiovascular disease ( CVD ) and all-cause ( ALL ) mortality in employed , white and black middle-aged men . RESEARCH DESIGN AND METHODS A prospect i ve cohort study of 11,554 white men and 666 black men between the ages 35 and 64 from 1967 to 1973 was conducted using data from the Chicago Heart Association ( CHA ) Detection Project in Industry 22-year mortality follow-up . cox proportional hazards models , adjusted fro age and other CVD risk factors , were used to estimate the relative risk ( RR ) and the 95 % CI of mortality associated with baseline glycemic status . RESULTS Age-adjusted baseline prevalence of clinical diabetes was similar in white ( 3.7 % ) and black ( 4.3 % ) men ; asymptomatic hyperglycemia ( glucose post–50-g load ≥ 11.1 mmol/l ) was present in 11.1 % of whites and 7.8 % of blacks . After controlling for age , lifestyle , and other CVD risk factors , mortality risk was increased among white men with clinical diabetes ( CVD : RR 2.51 , CI 2.08−3.02 ; ALL : RR 1.88 , CI 1.63−2.17 ) and asymptomatic hyperglycemia ( CVD : RR 1.18 , CI 1.01−1.37 ; ALL : RR 1.24 , CI 1.11−1.37 ) , compared with men with postload glucose < 8.9 mmol/l . Risks were similarly , though nonsignificantly ( owing to low statistical power ) , increased among black men with clinical diabetes ( CVD : RR 1.60 , CI 0.60−4.29 ; ALL : RR 1.78 , CI 0.97−3.25 ) and asymptomatic hyperglycemia ( CVD : RR 1.29 , CI 0.61−2.72 ; ALL : RR 1.37 , CI 0.85−2.20 ) . CONCLUSIONS Asymptomatic hyperglycemia and clinical diabetes appear to confer increased mortality risk in both white and black men . In addition , mortality risk is increased with increased severity of glycemia . These findings indicate the importance of applying efforts to reduce risk factors and prevent diabetes in both blacks and whites OBJECTIVE Major advantages of modern insulin regimens containing premixed insulin analogues in comparison to traditional insulin regimens have not been evaluated yet . The aim of the present study was to investigate whether meal-related ( breakfast , lunch , dinner ) application of biphasic insulin aspart 30 ( BIAsp 30 ) provides better glycaemic control than administration of biphasic human insulin 30 ( BHI 30 ) twice per day . RESEARCH DESIGN AND METHODS In a multi-centre , r and omized , open-label parallel trial , a total of 177 patients with type 2 diabetes mellitus were exposed to the two different insulin regimens described above over a study period of 24 weeks . HbA1c and glycemic exposure parameters were measured at predefined intervals . RESULTS The mean difference between treatment groups in HbA1c after 24 weeks of treatment was 0.08 % ( p = 0.6419 ) . Analysing the 7-point blood-glucose ( BG ) profiles , significant differences in BG levels were observed after lunch ( 156 vs. 176 mg/dl , p = 0.0289 ) , before dinner ( 142 vs. 166 mg/dl p = 0.006 ) and after dinner ( 154 vs. 182 mg/dl p = 0.002 ) in favour of BIAsp 30 insulin . Pr and ial BG increment was lower in the BIAsp 30 group at breakfast ( p = 0.057 ) and lunch ( p < 0.0005 ) . No difference was found regarding safety parameters in the two treatment groups . CONCLUSIONS This study demonstrates that meal-related BIAsp 30-insulin maintains postpr and ial BG control more effectively than traditional BHI 30 insulin twice per day in type 2 diabetic patients OBJECTIVE Humalog Mix25 is a manufactured premixed insulin formulation containing insulin lispro and a novel insulin lispro-protamine formulation ( NPL ) in a ratio of 25:75 % . The objective of this study was to compare Humalog Mix25 to human insulin 30/70 ( 30 % regular insulin/70 % NPH ) with respect to glycemic control . RESEARCH DESIGN AND METHODS Humalog Mix25 was compared with human insulin 30/70 in 89 individuals with type 2 diabetes during a 6-month r and omized open-label two-period crossover study . Each insulin was administered twice daily , before the morning and evening meals . Information regarding self-monitored blood glucose ( BG ) , hypoglycemic episodes ( hypoglycemic signs or symptoms or BG < or = 3.0 mmol/l ) , insulin dose , and HbA1c was collected . RESULTS Treatment with Humalog Mix25 result ed in better postpr and ial glycemic control after the morning and evening meals compared with treatment with human insulin 30/70 . Overall glycemic control and the incidence of hypoglycemia were comparable between the treatments . CONCLUSIONS In comparison to treatment with human insulin 30/70 , twice daily administration of Humalog Mix25 result ed in improved postpr and ial glycemic control , similar overall glycemic control , and the convenience of dosing immediately before meals BACKGROUND Newer insulin analogues viz . , premix insulin analogue ( biphasic insulin aspart ) and insulin glargine are now available in India . A multicenter all-India study was done to document the patient profile and responses to these analogues in routine clinical practice . METHODS The study was conducted prospect ively at 4 diabetes care clinics in different regions of India and collected data on the use of either of the two regimens A. Premix insulin analogue given twice-daily B. Basal-bolus analogue regimen ( insulin aspart with every meal and insulin glargine once-a-day at bedtime ) . The centers collected all data at 3 time-points -- baseline , 4 weeks later and end of 12 weeks . The study measures were FPG ( fasting plasma glucose ) , PPPG ( postpr and ial plasma glucose ) , HbA1c and insulin dose . FPG and PPPG were recorded at each of the three time points . HbA1c was recorded at baseline and end of study . Safety was assessed based on reported adverse drug reactions and occurrence of hypoglycaemias . RESULTS Data of 145 patients was available for analysis ( n=114 on premix insulin analogue and n=31 on basal-bolus analogue regimen ) . Baseline demography was comparable in the two groups . Both the regimens lowered all blood glucose parameters including HbA1c significantly as compared to baseline . However , the premix insulin analogue fared better than the basal-bolus regimen in lowering HbA1c ( 1.58 vs. 1.16 % respectively ; p<0.05 ) . Also 41 % more patients in the premix group could achieve target HbA1c of < 7 % at the end of study . The mean insulin dose was lower with the premix analogue group at the end of 12 weeks . There was no significant difference between the two groups in terms of change in body weight . No major hypoglycaemias were reported and the percentage of patients experiencing a minor episode was lower with the premix analogue than the basal-bolus regimen both at 4 and 12 weeks ( 11.4 vs. 35.48 % ; 16.7 vs. 58.06 % respectively ) . No adverse drug reactions were reported throughout the study . CONCLUSION We conclude that both premix analogue administered twice a day and four times a day basal bolus regimen appear to be a convenient , safe and effective way of initiating insulin therapy in people with type-2 diabetes . The premix analogues achieves target better than the basal bolus regimen as has better compliance Transitioning safely to insulin therapy when oral antidiabetic agents fail to provide adequate glycemic control is a critical aspect of care for the patient with type 2 diabetes mellitus ( T2DM ) . We evaluated the clinical effectiveness of starting patients on a relatively simple regimen of once-daily injections of either biphasic insulin aspart 70/30 ( 10 min before dinner ) , NPH insulin ( at 10 p.m. ) , or biphasic human insulin 70/30 ( 30 min before dinner ) in combination with metformin . Enrolled patients had T2DM and inadequate glycemic control ( AlC>/=7.5 % ) on a previous regimen of metformin as monotherapy or in combination with a sulphonylurea . One hundred and forty ( 140 ) patients received metformin monotherapy for 4 weeks followed by 12 weeks of combination treatment with metformin and once-daily insulin injections . AlC levels decreased from baseline by 1.1 - 1.3 % for patients in each of the three treatment groups . Overall , FPG values decreased from baseline by 31 % ( biphasic insulin aspart ) , 37 % ( NPH insulin ) , and 28 % ( biphasic human insulin ) . Subjects whose final FPG level was < 126 mg/dl experienced the largest decreases in AlC values ( -2.3 % , -1.9 % , -1.8 % , respectively ) . All three treatment regimens were well tolerated . The results indicate that patients with T2DM can safely and effectively begin insulin therapy using once-daily injections of biphasic insulin aspart 70/30 , biphasic human insulin 70/30 , or NPH insulin in combination with metformin AIM to compare the glycemic response to an insulin lispro mixture ( 25 % insulin lispro and 75 % NPL ) twice daily plus metformin ( Mix25+M ) with glibenclamide plus metformin ( G+M ) , in patients with type 2 diabetes inadequately controlled with a single oral agent . METHODS 597 patients treated in a r and omized , open-label , 16-week parallel study . Variables evaluated : hemoglobin A1C ( A1C ) , patient symptoms , hypoglycemia rate ( episodes/patient/30 days ) , and incidence ( % patients experiencing > or = 1 episode ) . For a subset of patients ( N=120 ) , fasting , 1-h , and 2-h postpr and ial plasma glucose ( FPG , 1-h ppPG , 2-h ppPG ) in response to a st and ardized test meal ( STM ) and self-monitored blood glucose ( BG ) profiles were measured . RESULTS improved A1C at endpoint for both groups , and A1C changes from baseline to endpoint were not significantly different between treatments ( Mix25+M , -1.87+/-1.35 % vs. G+M , -1.98+/-1.28 % ; p=0.288 ) . Among patients completing STM ; endpoint 2-h ppPG was significantly lower with Mix25+M ( 9.05+/-3.32 mmol/l vs. 12.31+/-3.65 mmol/l ; p<0.001 ) , as was 2-h ppPG excursion ( 2-h ppPGex)(0.38+/-3.23 mmol/l vs. 2.88+/-1.98 mmol/l ; p<0.001 ) . Percentage of patients achieving postpr and ial BG targets ( < 10 mmol/l ) at endpoint was significantly greater with Mix25+M ( 80 % vs. 48 % ; p<0.001 ) . Although , overall hypoglycemia rates were similar , percentage of patients experiencing and rate of nocturnal hypoglycemia was less with Mix25+M ( 1 % vs. 5 % ; p<0.01 , and 0.01 vs. 0.08 episodes/pt/30 d ; p=0.007 ) . Patients reported less polyuria with Mix25+M ( p<0.001 ) . CONCLUSION in patients with type 2 diabetes failing on metformin or a sulfonylurea , Mix25+M provided similar overall glycemic control , lower ppPG , reduced nocturnal hypoglycemia , and fewer hyperglycemic symptoms compared to Long-term beta blockade for perhaps a year or so following discharge after an MI is now of proven value , and for many such patients mortality reductions of about 25 % can be achieved . No important differences are clearly apparent among the benefits of different beta blockers , although some are more convenient than others ( or have slightly fewer side effects ) , and it appears that those with appreciable intrinsic sympathomimetic activity may confer less benefit . If monitored , the side effects of long-term therapy are not a major problem , as when they occur they are easily reversible by changing the beta blocker or by discontinuation of treatment . By contrast , although very early IV short-term beta blockade can definitely limit infa rct size , more reliable information about the effects of such treatment on mortality will not be available until a large trial ( ISIS ) reports later this year , with data on some thous and s of patients entered within less than 4 hours of the onset of pain . Our aim has been not only to review the 65-odd r and omized beta blocker trials but also to demonstrate that when many r and omized trials have all applied one general approach to treatment , it is often not appropriate to base inference on individual trial results . Although there will usually be important differences from one trial to another ( in eligibility , treatment , end-point assessment , and so on ) , physicians who wish to decide whether to adopt a particular treatment policy should try to make their decision in the light of an overview of all these related r and omized trials and not just a few particular trial results . Although most trials are too small to be individually reliable , this defect of size may be rectified by an overview of many trials , as long as appropriate statistical methods are used . Fortunately , robust statistical methods exist -- based on direct , unweighted summation of one O-E value from each trial -- that are simple for physicians to use and underst and yet provide full statistical sensitivity . These methods allow combination of information from different trials while avoiding the unjustified direct comparison of patients in one trial with patients in another . ( Moreover , they can be extended of such data that there is no real need for the introduction of any more complex statistical methods that might be more difficult for physicians to trust . ) Their robustness , sensitivity , and avoidance of unnecessary complexity make these particular methods an important tool in trial overviews Aims /hypothesisThe aim of this 52-week , open-label , non-inferiority trial was to compare the safety and efficacy of exenatide ( an incretin mimetic ) with that of biphasic insulin aspart . Material s and methods Patients on metformin and a sulfonylurea were r and omised to exenatide ( n = 253 ; 5 μg twice daily for 4 weeks , 10 μg thereafter ) or biphasic insulin aspart ( n = 248 ; twice-daily doses titrated for optimal glucose control ) , while continuing with metformin and sulfonylurea treatment . Results Glycaemic control achieved with exenatide was non-inferior to that achieved with biphasic insulin aspart ( mean±SEM , HbA1c change : exenatide −1.04 ± 0.07 % , biphasic insulin aspart −0.89 ± 0.06 % ; difference −0.15 [ 95 % CI −0.32 to 0.01]% ) . Exenatide-treated patients lost weight , while patients treated with biphasic insulin aspart gained weight [ between-group difference −5.4 ( 95 % CI −5.9 to −5.0 ) kg ] . Both treatments reduced fasting serum glucose ( exenatide −1.8 ± 0.2 mmol/l , p < 0.001 ; biphasic insulin aspart −1.7 ± 0.2 mmol/l , p < 0.001 ) . Greater reductions in postpr and ial glucose excursions following morning ( p < 0.001 ) , midday ( p = 0.002 ) and evening meals ( p < 0.001 ) were observed with exenatide . The withdrawal rate was 21.3 % ( 54/253 ) for exenatide and 10.1 % ( 25/248 ) for biphasic insulin aspart . Nausea ( 33 % incidence , 3.5 % discontinuation ) was the most common adverse event observed with exenatide . Conclusions /interpretationExenatide treatment result ed in HbA1c reduction similar to biphasic insulin aspart and provided better postpr and ial glycaemic control , making it a potential alternative for the treatment of type 2 diabetes . Treatment with biphasic insulin aspart was associated with weight gain and lower risk of adverse gastrointestinal events . Although the availability of glucose-lowering agents associated with weight reduction may be considered a therapeutic advance , the long-term implication s of progressive weight reduction observed with exenatide have yet to be defined BACKGROUND Epidemiologic studies have shown a relationship between glycated hemoglobin levels and cardiovascular events in patients with type 2 diabetes . We investigated whether intensive therapy to target normal glycated hemoglobin levels would reduce cardiovascular events in patients with type 2 diabetes who had either established cardiovascular disease or additional cardiovascular risk factors . METHODS In this r and omized study , 10,251 patients ( mean age , 62.2 years ) with a median glycated hemoglobin level of 8.1 % were assigned to receive intensive therapy ( targeting a glycated hemoglobin level below 6.0 % ) or st and ard therapy ( targeting a level from 7.0 to 7.9 % ) . Of these patients , 38 % were women , and 35 % had had a previous cardiovascular event . The primary outcome was a composite of nonfatal myocardial infa rct ion , nonfatal stroke , or death from cardiovascular causes . The finding of higher mortality in the intensive-therapy group led to a discontinuation of intensive therapy after a mean of 3.5 years of follow-up . RESULTS At 1 year , stable median glycated hemoglobin levels of 6.4 % and 7.5 % were achieved in the intensive-therapy group and the st and ard-therapy group , respectively . During follow-up , the primary outcome occurred in 352 patients in the intensive-therapy group , as compared with 371 in the st and ard-therapy group ( hazard ratio , 0.90 ; 95 % confidence interval [ CI ] , 0.78 to 1.04 ; P=0.16 ) . At the same time , 257 patients in the intensive-therapy group died , as compared with 203 patients in the st and ard-therapy group ( hazard ratio , 1.22 ; 95 % CI , 1.01 to 1.46 ; P=0.04 ) . Hypoglycemia requiring assistance and weight gain of more than 10 kg were more frequent in the intensive-therapy group ( P<0.001 ) . CONCLUSIONS As compared with st and ard therapy , the use of intensive therapy to target normal glycated hemoglobin levels for 3.5 years increased mortality and did not significantly reduce major cardiovascular events . These findings identify a previously unrecognized harm of intensive glucose lowering in high-risk patients with type 2 diabetes . ( Clinical Trials.gov number , NCT00000620 . |
14,095 | 29,963,686 | Therefore , a beneficial effect of antifibrinolytic therapy can currently only be assumed based on data from the people using VKAs | BACKGROUND Individuals on continuous treatment with vitamin K antagonists ( VKAs ) or direct oral anticoagulants ( DOACs ) are at increased risk of bleeding complications during and after oral or dental procedures .
Anticoagulant treatment is preferably continued at the same dose , since dose reduction or discontinuation of treatment is associated with an increased risk of thromboembolism .
The use of haemostatic measures during or after the procedure ( or both ) could enable continuation of the oral anticoagulant treatment . | Introduction Oral anticoagulants are widely prescribed drugs . Interruption of anticoagulant therapy prior to oral surgery has been an issue of great controversy . The purpose of this study was to evaluate the incidence of bleeding complications after dental extraction s in patients on anticoagulant therapy ( warfarin ) in whom different local hemostatic methods were used . Material and methods Patients using warfarin and requiring extraction s of at least two teeth were screened to participate in this prospect i ve , r and omized study . Extraction sites were considered as sampling units ( statistically representative sample size ) and were allocated to one of the three study groups ( G1—4.8 % tranexamic acid ; G2—fibrin sponge ; and G3—no local hemostatic agents ) . Results Eighty-four extraction sites were obtained from patients with mitral valve prolapse ( 47.4 % ) , prosthetic cardiac valve ( 23.7 % ) , venous thromboembolism ( 21.1 % ) , and pulmonary embolism ( 5.2 % ) . International normalized ratio ( INR ) values ranged between 2.1 and 3.1 ( mean 2.51 ± 0.1 ) . Postoperative bleeding was observed in four surgical sites ( p < 0.001 ) and was mainly in older patients ( p = 0.005 ) . Discussion The three local hemostatic protocol s were similarly effective in controlling postoperative bleeding in patients undergoing anticoagulant therapy with warfarin . The majority of teeth could be extracted with minimal problems in patients with cardiovascular diseases receiving treatment with anticoagulant therapy The optimal procedure for withdrawal of warfarin in patients with deep vein thrombosis ( DVT ) is still not defined . Rebound thrombin generation , which occurs after the withdrawal of warfarin , has been said to be associated with early recurrence of DVT . The aim of this study was to compare two procedures for warfarin withdrawal after the first episode of DVT with respect to rebound thrombin generation . Forty-one consecutive patients were r and omly assigned to abrupt withdrawal of warfarin ( group A ) , or to an additional month of warfarin , at the fixed dose of 1.25 mg/day ( group B ) . Plasma sample s were withdrawn for the assay of prothrombin fragment F1 + 2 ( F1 + 2 ) , protein C , factor VII and International Normalized Ratio ( INR ) , before any anticoagulant treatment ( I ) , during initial heparin ( II ) and full dose warfarin ( III ) , at the end of full dose warfarin ( IV ) and then 1 ( V ) , 4 ( VI ) , 5 ( VII ) and 9 ( VIII ) weeks after r and omization . The mean duration of full-dose warfarin treatment , the mean warfarin dose and the mean INR during full-dose warfarin treatment were similar in the two groups . A decrease in F1 + 2 was observed during heparin and warfarin treatment ( II , 1.7 nmol/ml ; III , 1.0 nmol/ml ; IV , 0.7 nmol/ml ; versus I , 3.5 nmol/ml ; P<0.01 ) . After the withdrawal of warfarin , an increase in F1 + 2 was observed in both groups , but without significant statistical differences ( group A : V , 1.2 nmol/ml ; VI , 1.5 nmol/ml ; VII , 1.6 nmol/ml ; VIII , 1.1 nmol/ml ; group B : V , 1.3 nmol/ml ; IV , 1.5 nmol/ml ; VII , 1.4 nmol/ml ; VIII , 1.4 nmol/ml ) . No significant difference between the two groups was observed in the recovery of protein C and factor VII . Four patients experienced a recurrence of DVT , three in group B and one in group A. Our findings confirm that rebound thrombin generation occurs in patients with DVT after the withdrawal of warfarin . Rebound thrombin generation is not reduced by a low , fixed dose of warfarin In a double-blind trial tranexamic acid ( AMCA , Cyclokapron ) , 1 g three times a day for five days , significantly reduced blood loss and transfusion requirements after dental extraction in patients with haemophilia and Christmas disease . No side effects were seen in either group of patients . Screening tests showed no toxic action of tranexamic acid on the liver , kidney , or heart A total of 124 patients on oral anticoagulation therapy with coumarin were treated by orosurgical procedures and entered into a study to determine the hemostatic efficiency of different methods . The therapeutic anticoagulation level was determined in accordance with the recommendations of the American Heart Association ( low risk : 2.0 < INR < 3.0 ; high risk : 2.5 < INR < 3.5 ) and maintained during treatment . In one group , the alveoli were treated with collagen , in a second group a mouthrinse regime with tranexamic acid was implemented . Twenty-three patients had to be excluded because anticoagulation levels differed from the recommended values . The group treated with collagen included 31 patients , the group with tranexamic acid mouthwashes , 32 patients . A third group was analyzed in which a controlled change in the anticoagulation level had been performed and all treated alveoli had been covered by mucosal flaps ( n = 38 ) ; they were compared to the other two groups . The surgical proceedings were outlined precisely . Patients treated with collagen had a bleeding rate of 19 % , patients with tranexamic acid mouthwash 6 % , and those treated with mucosal flaps 40 % . The data were not suited for statistical evaluation , they were objected to a descriptive analysis : the confidence intervals were determined by tables for binomial distributions . These did confirm the difference in the frequency of bleeding for the tranexamic acid and mucosal flap groups We carried out a placebo-controlled , double-blind , r and omized study of the hemostatic effect of tranexamic acid mouthwash after oral surgery in 39 patients receiving anticoagulant agents because of the presence of cardiac valvular stenosis , a prosthetic cardiac valve , or a vascular prosthesis . Surgery was performed with no change in the level of anticoagulant therapy , and treatment with the anticoagulant agent was continued after surgery . Before it was sutured , the operative field was irrigated in 19 patients with 10 ml of a 4.8 percent aqueous solution of tranexamic acid ( an inhibitor of fibrinolysis ) and in 20 patients with a placebo solution . For seven days thereafter , patients were instructed to rinse their mouths with 10 ml of the assigned solution for two minutes four times a day . There were no significant differences between the two treatment groups in base-line variables , including the level of anticoagulation at the time of surgery . Eight patients in the placebo group had a total of 10 postoperative bleeding episodes , whereas only 1 patient in the tranexamic acid group had a bleeding episode ( P = 0.01 ) . There were no systemic side effects . We conclude that local antifibrinolytic therapy is effective in preventing bleeding after oral surgery in patients who are being treated with anticoagulants PURPOSE This study assessed the risk associated with several schedules of perioperative treatment with coumadin in anticoagulated patients who underwent oral surgery . PATIENTS AND METHODS A prospect i ve , r and omized study compared bleeding complications with six perioperative schedules in 92 patients chronically treated with acenocoumarol . In three of the perioperative schedules , the dose was reduced before surgery and calcium heparin was added . In the other three , oral anticoagulation was not modified and heparin was not used . The groups also differed regarding the antifibrinolytic agents used and the postoperative measures applied . RESULTS Those schedules in which the oral anticoagulation was not modified preoperatively and an antifibrinolytic agent was applied locally both during and after surgery were not associated with a significantly higher odds ratio of bleeding complications than those in whom oral anticoagulation was reduced and calcium heparin was added preoperatively . CONCLUSIONS In orally anticoagulated patients who undergo oral surgery , schedules that maintain the oral anticoagulant regimen and use local tranexamic acid as an antifibrinolytic agent postoperatively for 2 days are safe , simple , and less troublesome The hemostatic effect of tranexamic acid solution ( 4.8 % ) used as a mouthwash was compared with a placebo solution in 93 patients on continuous , unchanged , oral anticoagulant treatment undergoing oral surgery . The investigation was a r and omized , double-blind , placebo-controlled , multicenter study . Before suturing , the surgically treated region was irrigated with 10 mL of tranexamic acid ( 46 patients ) or placebo ( 47 patients ) solution . The patients then performed mouthwash with 10 mL of the solution for 2 minutes four times daily for 7 days . The treatment groups were comparable regarding age , smoking habits , and surgery . Laboratory variables measuring vitamin K-dependent coagulation factors were within therapeutic ranges ( international normalized ratio 4.00 to 2.10 ) . One of the clinics used a different method for these measurements and therefore the levels of coagulation factor X in plasma obtained for the three clinics were compared . No significant difference in the range at which surgery was performed was found between clinics . In the placebo group , 10 patients developed bleeding requiring treatment , while none of the patients treated with tranexamic acid solution had bleeding . This difference was statistically significant ( P < .01 ) . The treatment with mouthwash was well tolerated . It was concluded that patients on oral anticoagulants can undergo oral surgery within the therapeutic range without reducing the dosage of anticoagulants , provided that local antifibrinolytic treatment with tranexamic acid solution is instituted PURPOSE The aim of this prospect i ve study was to compare the effectiveness of a 4.8 % tranexamic acid mouthwash versus an autologous fibrin glue preparation to control hemostasis in patients therapeutically anticoagulated with warfarin who required dental extraction s without interruption of their treatment . PATIENTS AND METHODS The 49 patients who underwent 152 dental extraction s were r and omly allocated to 2 groups : Group A were required to rinse with 10 mL of a 4.8 % tranexamic acid solution 4 times a day for 7 days postoperatively . Group B received autologous fibrin glue intraoperatively . The international normalized ratio was measured on the day of the procedure . All procedures were performed on an ambulatory basis by the same surgeon . RESULTS Of the 49 patients , 2 presented with postoperative bleeding ( 4 % ) . Both patients were from the autologous fibrin glue group and were found to have grossly elevated international normalized ratios on the day of the bleeding that was unaccounted for . CONCLUSIONS This study supports the consensus that dental extraction s can be performed without modification of oral anticoagulant treatment . Local hemostasis with an absorbable oxidized cellulose mesh , tranexamic acid , and sutures is the more cost efficient of the 2 methods compared ; however , autologous fibrin glue has an important role in patients unable to use a mouthwash effectively A double-blind r and omized study was carried out to evaluate the clinical hemostatic effect of tranexamic acid mouthwash after dental extraction in 30 patients who received anticoagulant agents . Surgery was performed with a reduction in the level of anticoagulant therapy in the control group and with no change in the level of anticoagulant therapy in the group who received the tranexamic acid . After the extraction the surgical field was irrigated with a 5 % solution of tranexamic acid in the group of 15 patients whose anticoagulant treatment had not been discontinued and with a placebo solution in the group of 15 patients for whom the anticoagulant therapy was reduced . Patients were instructed to rinse their mouths with 10 ml of the assigned solution for 2 minutes four times a day for 7 days . There was no significant difference between the two treatment groups in the bleeding incidence after oral surgery . We conclude that the anticoagulant treatment does not need to be withdrawn before oral surgery provided that local antifibrinolytic therapy is instituted |
14,096 | 20,824,837 | Acamprosate appears to be an effective and safe treatment strategy for supporting continuous abstinence after detoxification in alcohol dependent patients . | BACKGROUND Alcohol dependence is among the main leading health risk factors in most developed and developing countries .
Therapeutic success of psychosocial programs for relapse prevention is moderate , but could potentially be increased by an adjuvant treatment with the glutamate antagonist acamprosate .
OBJECTIVES To determine the effectiveness and tolerability of acamprosate in comparison to placebo and other pharmacological agents . | AIMS Acamprosate in combination with psychosocial treatment has been shown to be effective for the treatment of alcohol dependence . The goal of the present study was to determine whether the addition of psychosocial intervention to the medical prescription of acamprosate contributes to treatment outcome . METHODS Patients ( n = 248 ) meeting DSM-IV criteria for alcohol dependence or abuse were recruited in 14 outpatient treatment centres and r and omized into one of three treatment conditions : acamprosate ; acamprosate plus minimal intervention aim ed at motivational enhancement ( 3-weekly sessions of 20 min ) ; and acamprosate plus brief cognitive behavioural therapy ( 7-weekly sessions of 60 min ) . Acamprosate was prescribed for 28 weeks , medically monitored by a physician on six occasions lasting 10 min . Drinking behaviour , medication compliance and psychological distress were assessed throughout the treatment period . Follow-up assessment was undertaken 6 months after termination of pharmacological treatment . RESULTS Of 241 patients with intention to treat ( ITT ) , 114 ( 47.3 % ) remained in treatment for the full 28 weeks ; 169 of the ITT population ( 70.1 % ) were seen for follow-up . No statistically significant differences were found between treatment groups for any of the drinking outcomes either at the end of the 28 weeks of treatment or at 6-month follow-up . There were no statistically significant differences in medication compliance , drop-out rates , or psychological distress . However , a significant interaction effect was observed between treatment centre and treatment group , indicating that brief interventions were differentially effective in different treatment centres . CONCLUSIONS A clear supplemental value of minimal and brief psychosocial interventions to the prescription of acamprosate was not demonstrated . The widely held belief that pharmacotherapy for alcohol dependence should always be combined with psychosocial intervention is debatable and merits further research Recent empirical evidence supports the importance of adequate r and omization in controlled trials . Trials with inadequate allocation concealment have been associated with larger treatment effects compared with trials in which authors reported adequate allocation concealment . While that provides empirical evidence of bias being interjected into trials , trial investigators rarely document the sensitive details of subverting the intended purpose of r and omization . This article relates anonymous accounts run the gamut from simple to intricate operations , from transillumination of envelopes to search ing for code in the office files of the principal investigator . They indicate that deciphering is something more frequent than a rate occurrence . These accounts prompt some method ological recommendations to help prevent deciphering . R and omized controlled trials appear to annoy human nature -- if properly conducted , indeed they should AIMS To assess the effectiveness of pharmacotherapy with acamprosate in alcohol-dependent patients treated in a naturalistic setting in primary care in France . METHODS The ARES ( Acamprosate et Repercussions Economiques et Sociales ; Acamprosate and Economic and Social Repercussions ) study was performed by 149 general practitioners interested in treating alcohol use disorders in France who included patients fulfilling DSM-IV criteria for alcohol dependence . The only exclusion criteria concerned contra-indications to acamprosate , co-medication with naltrexone and multiple substance abuse . Eligible patients were r and omized to one of two treatment arms , either st and ard care alone or st and ard care with acamprosate , using an open-label design and followed up quarterly for a period of 1 year . The primary outcome variable was the change from baseline on the Alcohol-Related Problems Question naire . Secondary efficacy variables were abstinence , Clinical Global Impression , quality of life measured with the SF-36 and incidence of adverse events . An intent-to-treat population was used for outcome analysis . RESULTS 422 patients were included , of whom 348 ( 82 % ) completed the protocol as planned . At the end of the study , patients r and omized to the acamprosate group had significantly better outcomes in terms of total ARPQ score , change from baseline ( -2.61 vs -3.44 ) and number of subjects with no alcohol-related problem . On average , patients treated with acamprosate had one less alcohol-related problem than did the controls . The number needed to treat in order to save one additional patient from alcohol-related problems compared to st and ard care was 7.14 . Statistically significant differences in favour of the acamprosate group were observed for all secondary efficacy outcome measures including quality of life . CONCLUSIONS Adjunctive therapy with acamprosate in primary care is associated with significantly better functional outcome . Pragmatic trials in alcohol dependence are both feasible and informative AIMS A multi-centre , r and omized , double-blind , placebo-controlled trial was conducted to evaluate the efficacy and the safety of acamprosate over 8 weeks in Korean alcohol-dependent patients . METHODS One hundred and forty-two alcohol-dependent patients in 12 centres were r and omized to 8 weeks treatment with either acamprosate ( n = 72 ) or a placebo ( n = 70 ) in combination with out-patient psychosocial intervention . They were predominantly male ( 95.8 % ) , with a mean age of 44.3 + /- 8.3 years ; 76.1 % were married ; 59.9 % were employed ; 58.5 % had received previous alcoholism treatment ( previous mean number of admissions in alcoholism in-patient programmes 4.6 + /- 6.9 ) . At visits to the clinic ( weekly for 4 weeks , then biweekly for 4 weeks ) , a record was made of alcohol use ( Time-Line Follow-Back ) , alcohol craving using a Korean version of the Obsessive Compulsive Drinking Scale and a visual analogue scale , and adverse events . Serum aspartate aminotransferase , alanine aminotransferase , gamma-glutamyltransferase ( GGT ) , blood urea nitrogen and creatinine levels were measured on weeks 0 , 2 , 4 and 8 . RESULTS In the acamprosate group ( A ) , 71.4 % had had alcohol within the 2 days prior to starting medication , against 65.2 % of patients in the placebo group ( P ) ; ( P > 0.05 ) . One hundred and one subjects ( 71.1 % ) completed 8-weeks of treatment ( A , 73.6 % ; P , 68.6 % ; P > 0.05 ) . During the 8-week treatment period , 37 , ( A ) ( n = 72 ) and 32 % ( P ) ( n = 70 ) achieved continuous abstinence ( P > 0.05 ) , and 40 , ( A ) and 39 % ( P ) remained without relapse ( P > 0.05 ) ( defined as a day when a man consumed five or more drinks or a woman four or more drinks ) . The percentage of days abstinent during the 8-week treatment period was 81.2 , ( A ) and 78.5 % ( P ) ( P > 0.05 ) , and the percentage of days without heavy drinking 86.1 ( A ) and 84.9 % ( P ) ( P > 0.05 ) . The mean amount drunk per drinking occasion was 7.2 , ( A ) and 8.6 st and ard drinks ( P ) ( P > 0.05 ) . No statistically significant differences in changes in the serum GGT level or craving scores from baseline to the end-point of treatment were found between the two groups . Recency of drinking prior to commencing study drug predicted percentage of days abstinent in the first 2 weeks on treatment ; however , when ANOVAs were conducted using treatment outcomes as a dependent variable , medication condition as an independent variable and the period of abstinence prior to treatment as a covariate , a significant effect of medication condition was still not seen . CONCLUSIONS Acamprosate was ineffective in reducing drinking in this Korean sample . The result differs from that of most European acamprosate trials . This might be explained by our sample 's relatively severe alcohol dependence , and low social support , or the fact that many patients were still drinking near to their first medication . The variability of the psychosocial support , ethnicity ( which might also affect acamprosate pharmacokinetics ) and the Korean drinking style , which differs from that of Europeans , might have contributed to our negative result CONTEXT The Consoli date d St and ards for Reporting of Trials ( CONSORT ) statement was developed to help improve the quality of reports of r and omized controlled trials ( RCTs ) . To date , a paucity of data exists regarding whether it has achieved this goal . OBJECTIVE To determine whether use of the CONSORT statement is associated with improvement in the quality of reports of RCTs . DESIGN AND SETTING Comparative before- and -after evaluation in which reports of RCTs published in 1994 ( pre-CONSORT ) were compared with RCT reports from the same journals published in 1998 ( post-CONSORT ) . We included 211 reports from BMJ , JAMA , and The Lancet ( journals that adopted CONSORT ) as well as The New Engl and Journal of Medicine ( a journal that did not adopt CONSORT and was used as a comparator ) . MAIN OUTCOME MEASURES Number of CONSORT items included in a report , frequency of unclear reporting of allocation concealment , and overall trial quality score based on the Jadad scale , a 5-point quality assessment instrument . RESULTS Compared with 1994 , the number of CONSORT checklist items in reports of RCTs increased in all 4 journals in 1998 , and this increase was statistically significant for the 3 adopter journals ( pre-CONSORT , 23.4 ; mean change , 3.7 ; 95 % confidence interval [ CI ] , 2.1 - 5.3 ) . The frequency of unclear reporting of allocation concealment decreased for each of the 4 journals , and this change was statistically significant for adopters ( pre-CONSORT , 61 % ; mean change , -22 % ; 95 % CI , -38 % to -6 % ) . Similarly , 3 of the 4 journals showed an improvement in the quality score for reports of RCTs , and this increase was statistically significant for adopter journals overall ( pre-CONSORT , 2.7 ; mean change , 0.4 ; 95 % CI , 0.1 - 0.8 ) . CONCLUSION Use of the CONSORT statement is associated with improvements in the quality of reports of RCTs Background The heterogeneity statistic I2 , interpreted as the percentage of variability due to heterogeneity between studies rather than sampling error , depends on precision , that is , the size of the studies included . Methods Based on a real meta- analysis , we simulate artificially ' inflating ' the sample size under the r and om effects model . For a given inflation factor M = 1 , 2 , 3 , ... and for each trial i , we create a M-inflated trial by drawing a treatment effect estimate from the r and om effects model , using si2MathType@MTEF@5@5@+=feaagaart1ev2aaatCvAUfKttLearuWrP9MDH5MBPbIqV92AaeXatLxBI9gBaebbnrfifHhDYfgasaacPC6xNi = xH8viVGI8Gi = hEeeu0xXdbba9frFj0xb9qqpG0dXdb9aspeI8k8fiI+fsY = rqGqVepae9pg0db9vqaiVgFr0xfr = xfr = xc9adbaqaaeGaciGaaiaabeqaaeqabiWaaaGcbaGaem4Cam3aa0baaSqaaiabdMgaPbqaaiabikdaYaaaaaa@2FBE@/M as within-trial sampling variance . Results As precision increases , while estimates of the heterogeneity variance τ2 remain unchanged on average , estimates of I2 increase rapidly to nearly 100 % . A similar phenomenon is apparent in a sample of 157 meta-analyses . Conclusion When deciding whether or not to pool treatment estimates in a meta- analysis , the yard-stick should be the clinical relevance of any heterogeneity present . τ2 , rather than I2 , is the appropriate measure for this purpose BACKGROUND Naltrexone and acamprosate have been shown to be effective in relapse prevention of alcoholism via different pharmacologic mechanisms . Since it remains uncertain whether both substances are equally efficient and whether a combination of both drugs potentiates the efficacy , we conducted the first published controlled study comparing and combining both compounds . METHODS After detoxification , 160 patients with alcoholism participated in a r and omized , double-blind , placebo-controlled protocol . Patients received naltrexone , acamprosate , naltrexone plus acamprosate , or placebo for 12 weeks . Patients were assessed weekly by interview , self-report , question naires , and laboratory screening . Time to first drink , time to relapse , and the cumulative abstinence time were the primary outcome measures . RESULTS Naltrexone , acamprosate , and the combined medication were significantly more effective than placebo . Comparing the course of nonrelapse rates between naltrexone and acamprosate , the naltrexone group showed a tendency for a better outcome regarding time to first drink and time to relapse . The combined medication was most effective with significantly lower relapse rates than placebo and acamprosate but not naltrexone . CONCLUSIONS The results of this study support the efficacy of pharmacotherapeutic strategies in the relapse prevention of alcoholism . Naltrexone and acamprosate , especially in combination , considerably enhance the potential of relapse prevention AIMS To compare two levels of psychosocial intervention in combination with acamprosate medication for the treatment of alcohol dependence . METHODS Patients ( n = 70 ) were prescribed acamprosate and r and omized to Minimal Psychosocial Intervention ( MPI ) or Extended Psychosocial Intervention ( EPI ) . MPI patients met a psychiatrist for 20 - 30 min sessions on four occasions during a 6 month period . EPI patients were offered 10 - 15 sessions with a psychiatric nurse in addition to the visits to the psychiatrist . EPI patients were trained to use behavioural and cognitive coping skills to deal with high-risk situations in line with a manual developed for relapse prevention . Patients were assessed four times during the 24-week study by self-report and laboratory tests . RESULTS Patients on average reported a decline in days with heavy drinking and in cumulative number of drinking days . No significant differences between patients in MPI and EPI were found with respect to heavy drinking , cumulative number of drinking days , number of days to first drink , or biomarkers of alcohol consumption . Higher age and lower level of education were significant predictors of treatment success . CONCLUSIONS Adding more intensive individual treatments appears to add no extra improvement beyond that obtained by prescribing acamprosate and offering an infrequent consultation with a physician The objective of this study was to compare acamprosate with placebo in the treatment of alcohol-dependent patients during a 6-month post-detoxification treatment and a 3-month medication-free follow-up . Patients ( n = 330 ) were detoxified and r and omized to treatment with acamprosate ( 1998 mg/day ) or placebo within an out-patient programme including medical counselling , psychotherapy and self-help groups . The main outcome criterion was drinking behaviour as assessed by : abstinence/relapse ratio , cumulative abstinence duration ( CAD ) and the period of continued abstinence . Anxiety , depression and craving were also monitored . Intention to treat ( ITT ) statistical principles were followed . Twenty-five per cent of patients dropped out over the first 6 months . At the end of the treatment period , the abstinence rate was 57.9 % for acamprosate and 45.2 % for placebo ( P = 0.03 ) . The CAD was 110+/-77 days for acamprosate and 89+/-77 days for placebo ( P = 0.016 ) . Patients on acamprosate had a higher continuous abstinence rate and experienced less severe relapses . No differential effect was noted for anxiety , depression or craving . Treatment remained positive , but not significant , 3 months after termination of study medication . No significant difference in adverse events was noted between treatment groups . Acamprosate treatment over 180 days was consistently more effective than placebo to maintain abstinence and to diminish relapse severity AIMS To evaluate the efficacy of acamprosate in maintaining abstinence in weaned alcohol-dependent patients . DESIGN A multicentre , double-blind , r and omized control trial . Patients were individually r and omly allocated to active or placebo conditions . Abstinence was assessed during a 6-month treatment period and after a 6-month follow-up period . SETTING A community-based , outpatient alcohol rehabilitation programme . PARTICIPANTS Two hundred and forty-six alcohol-dependent patients between the ages of 18 and 65 years were recruited immediately following acute , inpatient withdrawal treatment . MEASUREMENTS The primary outcome measure was self-reported abstinence from alcohol since the previous sessions at 3 , 6 , 9 and 12 months following the start of treatment , with treatment taking place for a period of 6 months . FINDINGS A significantly higher proportion of patients in the acamprosate group were abstinent after 3 months and 6 months of treatment . The percentage of patients with continuous abstinence at the end of the treatment period was almost double for the acamprosate group than for the placebo group ( 40.7 % vs. 20.8 % , respectively ) . Acamprosate significantly increased the retention of patients in the treatment programme . Six months after drug treatment ceased , the criterion of abstinence since the previous visit was reached by significantly more patients from the acamprosate group ( 43.4 % ) than from the placebo group ( 29.8 % ) , but this difference was not statistically significant at the 3-month point after cessation of study medication . CONCLUSIONS Acamprosate may be a useful pharmacological compound for the long-term treatment of alcohol-dependence when applied in a community-based rehabilitation programme CONTEXT Alcohol dependence treatment may include medications , behavioral therapies , or both . It is unknown how combining these treatments may impact their effectiveness , especially in the context of primary care and other nonspecialty setting s. OBJECTIVES To evaluate the efficacy of medication , behavioral therapies , and their combinations for treatment of alcohol dependence and to evaluate placebo effect on overall outcome . DESIGN , SETTING , AND PARTICIPANTS R and omized controlled trial conducted January 2001-January 2004 among 1383 recently alcohol-abstinent volunteers ( median age , 44 years ) from 11 US academic sites with Diagnostic and Statistical Manual of Mental Disorders , Fourth Edition , diagnoses of primary alcohol dependence . INTERVENTIONS Eight groups of patients received medical management with 16 weeks of naltrexone ( 100 mg/d ) or acamprosate ( 3 g/d ) , both , and /or both placebos , with or without a combined behavioral intervention ( CBI ) . A ninth group received CBI only ( no pills ) . Patients were also evaluated for up to 1 year after treatment . MAIN OUTCOME MEASURES Percent days abstinent from alcohol and time to first heavy drinking day . RESULTS All groups showed substantial reduction in drinking . During treatment , patients receiving naltrexone plus medical management ( n = 302 ) , CBI plus medical management and placebos ( n = 305 ) , or both naltrexone and CBI plus medical management ( n = 309 ) had higher percent days abstinent ( 80.6 , 79.2 , and 77.1 , respectively ) than the 75.1 in those receiving placebos and medical management only ( n = 305 ) , a significant naltrexone x behavioral intervention interaction ( P = .009 ) . Naltrexone also reduced risk of a heavy drinking day ( hazard ratio , 0.72 ; 97.5 % CI , 0.53 - 0.98 ; P = .02 ) over time , most evident in those receiving medical management but not CBI . Acamprosate showed no significant effect on drinking vs placebo , either by itself or with any combination of naltrexone , CBI , or both . During treatment , those receiving CBI without pills or medical management ( n = 157 ) had lower percent days abstinent ( 66.6 ) than those receiving placebo plus medical management alone ( n = 153 ) or placebo plus medical management and CBI ( n = 156 ) ( 73.8 and 79.8 , respectively ; P<.001 ) . One year after treatment , these between-group effects were similar but no longer significant . CONCLUSIONS Patients receiving medical management with naltrexone , CBI , or both fared better on drinking outcomes , whereas acamprosate showed no evidence of efficacy , with or without CBI . No combination produced better efficacy than naltrexone or CBI alone in the presence of medical management . Placebo pills and meeting with a health care professional had a positive effect above that of CBI during treatment . Naltrexone with medical management could be delivered in health care setting s , thus serving alcohol-dependent patients who might otherwise not receive treatment . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00006206 OBJECTIVES This trial compared the efficacy of acamprosate , started at the beginning of detoxification , to acamprosate started at the completion of detoxification , in the treatment of alcohol dependence . METHODS This biphasic clinical trial consisted of a r and omized , double-blind , placebo-controlled Detoxification Phase ( DP ) , followed by a 10-week open-label Rehabilitation Phase ( RP ) . Forty alcohol dependent patients were r and omly assigned to receive either 1998 mg of acamprosate daily , or matching placebo , during the DP ( 5 - 14 days ) . After completing detoxification , all patients received open label acamprosate ( 1998 mg daily ) in the RP . Outcome measures during the DP included : treatment retention , alcohol withdrawal , alcohol consumption , and oxazepam used . Outcome measures during the RP included : treatment retention and alcohol consumption . RESULTS There were no significant outcome differences between acamprosate and placebo-treated patients during the DP . Patients given acamprosate , compared to placebo , during the DP drank more alcohol in the RP . CONCLUSIONS Starting acamprosate at the beginning of detoxification did not improve DP outcomes . Starting acamprosate after detoxification was completed was associated with better drinking outcomes during subsequent alcohol rehabilitation treatment OBJECTIVE This study sought to evaluate the effectiveness of compliance therapy in increasing adherence to pharmacological treatment for alcohol dependence . METHOD Forty subjects were r and omly allocated to receive usual medical care ( n = 20 ) or usual medical care plus compliance therapy ( n = 20 ) . All subjects were prescribed acamprosate ( Campral ) for 4 months . Subjects were volunteers treated at a hospital-based outpatient drug and alcohol treatment service , and were men and women who were 18 - 65 years old and with a Diagnostic and Statistical Manual of Mental Disorders , Fourth Edition , diagnosis of alcohol dependence . All subjects received usual medical care consisting of seven medical review s ( duration = 15 minutes ) over 4 months . Compliance therapy consisted of four to six individual sessions ( duration = 60 minutes ) in which beliefs about medication side effects , ambivalence , the benefits of treatment , treatment maintenance and relapse prevention were addressed and explored with motivational interviewing and cognitive behavior therapy techniques . RESULTS The outcome variables were number of days taking acamprosate , days to first drink , days to first relapse ( more than five drinks ) and days to first extended relapse ( greater than 2 consecutive days of more than five drinks ) . Intention-to-treat analyses showed little difference between the two groups in the outcome drinking measures . Nevertheless , the per- protocol analyses revealed that participation in three or more sessions of compliance therapy significantly increased adherence to acamprosate and improved overall treatment outcomes . CONCLUSIONS The present study highlights the need for psychological interventions to improve adherence to pharmacotherapy in the treatment of alcohol dependence and provides initial support for compliance therapy as an effective intervention CONTEXT Selective reporting of outcomes within published studies based on the nature or direction of their results has been widely suspected , but direct evidence of such bias is currently limited to case reports . OBJECTIVE To study empirically the extent and nature of outcome reporting bias in a cohort of r and omized trials . DESIGN Cohort study using protocol s and published reports of r and omized trials approved by the Scientific-Ethical Committees for Copenhagen and Frederiksberg , Denmark , in 1994 - 1995 . The number and characteristics of reported and unreported trial outcomes were recorded from protocol s , journal articles , and a survey of trialists . An outcome was considered incompletely reported if insufficient data were presented in the published articles for meta- analysis . Odds ratios relating the completeness of outcome reporting to statistical significance were calculated for each trial and then pooled to provide an overall estimate of bias . Protocol s and published articles were also compared to identify discrepancies in primary outcomes . MAIN OUTCOME MEASURES Completeness of reporting of efficacy and harm outcomes and of statistically significant vs nonsignificant outcomes ; consistency between primary outcomes defined in the most recent protocol s and those defined in published articles . RESULTS One hundred two trials with 122 published journal articles and 3736 outcomes were identified . Overall , 50 % of efficacy and 65 % of harm outcomes per trial were incompletely reported . Statistically significant outcomes had a higher odds of being fully reported compared with nonsignificant outcomes for both efficacy ( pooled odds ratio , 2.4 ; 95 % confidence interval [ CI ] , 1.4 - 4.0 ) and harm ( pooled odds ratio , 4.7 ; 95 % CI , 1.8 - 12.0 ) data . In comparing published articles with protocol s , 62 % of trials had at least 1 primary outcome that was changed , introduced , or omitted . Eighty-six percent of survey responders ( 42/49 ) denied the existence of unreported outcomes despite clear evidence to the contrary . CONCLUSIONS The reporting of trial outcomes is not only frequently incomplete but also biased and inconsistent with protocol s. Published articles , as well as review s that incorporate them , may therefore be unreliable and overestimate the benefits of an intervention . To ensure transparency , planned trials should be registered and protocol s should be made publicly available prior to trial completion 105 patients with severe alcohol dependence , who were treated in 13 centers in Switzerl and , took part in this open study . The abstinence rate achieved under treatment with Acamprosat , which was used within the framework of established psychotherapeutic intervention programmes in which the doctors could choose between five different procedures , was determined over a period of 24 weeks . In addition , a sociodemographic profile was drawn up , a physical examination was carried out and data were collected on the safety aspect of Acamprosat . It was also of interest to ascertain whether , and if so how , the patients ' quality of life changed under the treatment , and in what form they received psychosocial support . As supportive therapy almost two-thirds of the patients ( 63 % ) received individual psychotherapy , in 28 % the doctor decided on cognitive behavioural therapy , in 4 % a short intervention was carried out , in 4 % group therapy and in 2 % family therapy . In 85.7 % of the patients the doctor continued with the initial form of psychotherapy , while in the remaining patients it was changed once . Due to the very uneven distribution a comparison of the outcome in regard to the concomitant therapy was rather problematical . Psychiatric problems ( 21 % ) , polyneuritis ( 12 % ) and liver damage (10.6%)--all known complications of chronic alcohol abuse -- were the most frequent concomitant diagnoses . Of the 91 patients who had remained abstinent for the first two weeks after the start of the study , 12.9 % had a recurrence at the end of the study , 56 % did not have a recurrence ( they were abstinent , but did have a binge or a lapse ) and 31.8 % did not return for the control visits . When a recurrence did occur , however , significantly less alcohol was consumed than before the treatment . As a result of the combined intervention all the parameters relating to the quality of life that were documented in connection with the SF 36 showed improvement . With this study carried out in Switzerl and , which is part of an European study programme , it was again possible to demonstrate the beneficial effect of Acamprosat in patients with severe alcohol dependence . Acamprosat was well tolerated by all patients This study compares two methods for elicitation of treatment-emergent side effects . One is the open-ended general inquiry and the other is a specific inquiry that asks about a wide range of events thought to be treatment-related . The study goal was to determine the extent to which the specific inquiry method elicits clinical ly useful information over and above that elicited by the general inquiry method . The assessment instrument we used is SAFTEE , a structured interview schedule developed by the National Institute of Mental Health . We looked for differences between general and specific inquiry formats in terms of number of events elicited , type of event , severity , functional impairment , and clinician action taken . We found that both methods contributed to elicitation of events that , in the clinician 's opinion , required some change in management . However , events reported on the General Inquiry form were significantly more distressing , more often interfered with daily functioning , and elicited more extensive changes in clinical management . No medically serious events were elicited on the specific inquiry form alone . Based on these findings , and in view of the amount of time and effort required to administer and score it , we do not recommend the specific inquiry form of SAFTEE as a st and ard assessment tool for routine use in all clinical trials . We do consider it to be a useful method for comprehensive elicitation about treatment-emergent effects in targeted and specific research context s. We see the schedule as a comprehensive document or library of queries to be tailored to the needs of individual protocol A 6-month r and omized controlled study of acamprosate versus placebo in preventing relapse following withdrawal from alcohol was undertaken in 20 centres throughout the UK . Patients diagnosed as alcohol-dependent and detoxified within the preceding 5 weeks were r and omly assigned to treatment with either acamprosate ( A ) 666 mg three times/day or identical placebo ( P ) . A total of 664 patients were screened ; 581 were entered into the treatment phase . One-third were episodic drinkers , 84 % were male , 44 % were unmarried and 48 % were unemployed . Medication was first taken on average 24 days after the start of detoxification ; 32 % of patients had already relapsed by this time . The 6-month study period was completed by 35 % of patients ; adverse events led to withdrawal of a further 14 % ( A ) and 9 % ( P ) respectively . Compliance was poor in that , by the end of the second week , only 57 % of patients were judged to be taking at least 90 % of their tablets . The mean total of abstinent days achieved was 77 ( A ) and 81 ( P ) . Complete abstinence for 6 months was achieved by 12 % ( A ) and 11 % ( P ) ; drinking remained within controlled limits in a further 3 % ( A ) and 6 % ( P ) . An effect of acamprosate on consumption was not seen when subgroups , including those defined by the Lesch typology , were analysed separately . However , the mean percentage reduction in craving for alcohol measured on a visual analogue scale was greater in the acamprosate , than placebo , patients at week 2 and week 4 ( P<0.001 ) and the mean decrease in the Hamilton Anxiety score at the 4th week was greater in the acamprosate than placebo patients ( P = 0.017 ) . In comparison with other published trials of acamprosate , patients started study medication after a longer time following detoxification , had more often recommenced drinking before medication was started and had a higher drop-out rate , and this might have contributed to the lack of a treatment effect in this study INTRODUCTION Acamprosate and naltrexone have been shown to be effective in relapse prevention of alcoholism . It is hypothesized that naltrexone exerts its effects primarily on cue-induced craving and neuroendocrine cue reactivity , whereas acamprosate exerts its effect primarily on autonomic nervous system reactions to alcohol-related cues . EXPERIMENTAL PROCEDURES In a r and omized double-blind experiment , 131 abstinent alcoholics received either acamprosate ( n=56 ) , naltrexone ( n=52 ) or placebo ( n=23 ) for three weeks and participated in two cue-exposure sessions : the first the day before and the second at the last day of medication . RESULTS Consistent with the hypotheses , naltrexone reduced craving more than acamprosate , and acamprosate reduced heart rate more than naltrexone . No medication effect was found on cue-induced cortisol . DISCUSSION The findings provide some evidence for differential effects of naltrexone and acamprosate : naltrexone may exert its effect , at least partly , by the reduction of cue-induced craving , whereas acamprosate may exert its effect , at least partly , by the reduction of autonomic nervous system reactions to alcohol-related cues BACKGROUND About 50 % of alcoholic patients relapse within 3 months of treatment . Previous studies have suggested that acamprosate may help to prevent such relapse . The aim of our study was to assess the efficacy and safety of long-term acamprosate treatment in alcohol dependence . METHODS In this multicentre , double-blind , placebo-controlled study , we recruited 455 patients , aged 18 - 65 years , with chronic or episodic alcohol dependence . Patients were r and omly allocated treatment with acamprosate ( 1998 mg daily for bodyweight > 60 kg ; 1332 mg daily for < or = kg ) or placebo for 360 days . Patients were assessed on the day treatment started and on days 30 , 90 , 180 , 270 , and 360 by interview , self-report , question naire , and laboratory screening . Patients were classified as abstinent , relapsing , or non-attending . Time to first treatment failure ( relapse or non-attendance ) was the primary outcome measure . FINDINGS Seven patients were excluded from the intention-to-treat analysis because they did not attend on the first treatment day and therefore received no medication . The acamprosate ( n = 224 ) and placebo ( n = 224 ) groups were well matched in terms of baseline demographic and alcohol-related variables . 94 acamprosate-treated and 85 placebo-treated patients completed the treatment phase : of those withdrawn , 104 ( 52 in each group ) relapsed , 69 ( 33 vs 36 , respectively ) were lost to follow-up , 63 ( 31 vs 32 ) refused to continue treatment , 16 ( 15 vs 11 ) had concurrent illness , three ( two vs one ) died , ten ( six vs four ) had adverse side-effects , one ( acamprosate treated ) received the wrong medication , and three ( placebo treated ) were non-compliant . The proportion without treatment failure was higher in the acamprosate than in the placebo group throughout the treatment period ( p < 0.001 , Mantel-Cox ) . At the end of treatment , 41 ( 18.3 % ) acamprosate-treated and 16 ( 7.1 % ) placebo-treated patients had been continuously abstinent ( p = 0.007 ) . Mean cumulative abstinence duration was significantly greater in the acamprosate group than in the placebo group ( 138.8 [ SD 137.5 ] vs 103.8 [ 119.0 ] days ; p = 0.012 ) . 148 patients ( 79 acamprosate , 69 placebo ) completed 27 months follow-up : 27 ( 11.9 % ) acamprosate-treated and 11 ( 4.9 % ) placebo-treated patients remained continuously abstinent , and the mean cumulative abstinence duration was 230.8 days ( 259.1 ) and 183.0 days ( 235.2 ) , respectively . Apart from occasional diarrhoea , there was no difference in side-effects between groups . INTERPRETATION Acamprosate is an effective and well-tolerated pharmacological adjunct to psychosocial and behavioural treatment programmes for treatment of alcohol-dependent patients Abstract . Background : About 50 % of adult alcoholic patients relapse within 3 months of treatment . Previous studies have suggested that acamprosate may help to prevent such relapse . The aim of our study was to assess the efficacy and safety of long-term acamprosate treatment in alcohol dependence of adolescents . Methods : In this , double-blind , placebo-controlled study , we recruited 26 patients , aged 16–19 years , with chronic or episodic alcohol dependence . Patients were r and omly allocated treatment with acamprosate ( 1332 mg daily ) or placebo for 90 days . Patients were assessed on the day treatment started and on days 30 , and 90 by interview , self report , question naire , and laboratory screening . Findings : 13 acamprosate-treated and 13 placebo-treated patients completed the treatment phase : of those withdrawn , 11 ( 1 vs 6 ) relapsed , 5 ( 3 vs 2 ) refused to continue treatment , 3 ( 1 vs 2 ) had concurrent illness , and 2 ( 1 vs 1 ) had adverse side-effects . At the end of treatment , 7 acamprosate treated and 2 placebo-treated patients had been continuously abstinent ( p = 0.0076 ) . Mean cumulative abstinence duration was significantly greater in the acamprosate group than in the placebo group ( 79.8 [ SD 37.5 ] vs 32.8 [ 19.0 ] days ; p = 0.012 ) . Interpretation : Acamprosate is an effective and well-tolerated pharmacological adjunct to psychosocial treatment programmes CONTEXT The evaluation of the method ologic quality of r and omized controlled trials ( RCTs ) is central to evidence -based health care . Important method ologic detail may , however , be omitted from published reports , and the quality of reporting is therefore often used as a proxy measure for method ologic quality . We examined the relationship between reporting quality and method ologic quality of published RCTs . METHODS Study of 60 reports of placebo-controlled trials published in English- language journals from 1985 to 1997 . Reporting quality was measured using a 25-item scale based on the 1996 issue of the Consoli date d St and ards of Reporting Trials ( CONSORT ) . Concealment of allocation , appropriate blinding , and analysis according to the intention-to-treat principle were indicators of method ologic quality . Method ologic quality was compared between groups of trials defined by reporting quality scores of low , intermediate , and high . Reporting quality scores were compared between groups defined by high and low method ologic quality . RESULTS Among 23 trials of low reporting quality ( median score , 9 [ range , 3.5 - 10.5 ] ) , allocation concealment was unclear for all but 1 trial , but there were 16 trials ( 70 % ) with adequate blinding and 9 trials ( 39 % ) that had been analyzed according to the intention-to-treat principle . Among 18 trials of high reporting quality ( median score , 18 [ range 16.5 - 22.0 ] ) , there were 8 trials ( 44 % ) with adequate allocation concealment , 16 trials ( 89 % ) with adequate blinding , and 13 trials ( 72 % ) analyzed according to the intention-to-treat principle . The median reporting score was 15.0 for the 33 trials that were analyzed according to intention-to-treat principle and 14.5 for the 14 trials with on-treatment analyses ( P = .67 ) . CONCLUSIONS Similar quality of reporting may hide important differences in method ologic quality , and well-conducted trials may be reported badly . A clear distinction should be made between these 2 dimensions of the quality of RCTs BACKGROUND A multicenter , prospect i ve study was conducted in five European countries to observe outcome in alcohol misusers treated for 24 weeks with acamprosate and various psychosocial support techniques , within the setting of st and ard patient care . METHODS Patients diagnosed as alcohol dependent using DSM-III-R criteria were treated , for 24 weeks , with acamprosate and appropriate psychosocial support . Potential predictor variables were recorded at inclusion . Drinking behavior was monitored throughout ; the proportion of cumulative abstinence days was the principal outcome measure . The influence of baseline clinical and demographic variables on outcome was assessed using multiple regression analysis . Adverse events were recorded systematic ally . RESULTS A total of 1289 patients were recruited ; 1230 took at least one dose of the drug and provided at least one set of follow-up data ; 543 ( 42.1 % ) patients were observed for the full 24-week period . The overall proportion of cumulative abstinence days was 0.48 . Multiple physical and psychiatric comorbidities and a history of drug addiction were negatively correlated with outcome , as were , to a lesser extent , multiple previous episodes of detoxification , unemployment , and living alone . Older age and stable employment were positively associated with outcome . The difference in the unadjusted proportion of cumulative abstinence days between countries was significant ( < 0.001 ) but less so when adjusted for the predictive factors identified in the multivariate model ( < 0.019 ) . Overall , outcome was not influenced by the nature of the psychosocial support provided . Adverse events were generally mild , with gastrointestinal disorders , which occurred in 21.5 % of patients , being the most frequent . CONCLUSIONS This open-label study confirms the efficacy and safety of acamprosate in the treatment of alcohol dependence in the setting of st and ard patient care . Treatment benefit was observed irrespective of the nature of the psychosocial support provided . Predictors of the response to treatment were identified ; their heterogeneous distribution within the study population explained , at least in part , the differences in outcome between countries BACKGROUND The effectiveness of acamprosate ( calcium bisacetylhomotaurinate ) as a treatment to maintain abstinence in alcohol-dependent patients was assessed for 1 year . METHODS After short-term detoxification , 272 patients participated in a r and omized , double-blind , placebo-controlled study . Patients received routine counseling and either the study medication or placebo for 48 weeks ; they were followed up for another 48 weeks without medication . Statistical analysis was performed according to the intention-to-treat principle . RESULTS Patients who were receiving acamprosate showed a significantly higher continuous abstinence rate within the first 60 days of treatment compared with patients who were assigned to placebo treatment ( 67 % vs 50 % ) until completion of the treatment period ( 43 % vs 21 % , log rank P = .005 ) , and they had a significantly longer mean abstinence duration of 224 vs 163 days , or 62 % vs 45 % days abstinent ( P < .001 ) ; however , there was no difference in psychiatric symptoms . Of the patients who were receiving acamprosate , 41 % had dropped out , whereas 60 % of the placebo-treated patients dropped out of the study . Few side effects ( mainly diarrhea and headache ) were recorded . At the end of a further 48 weeks without receiving study medication , 39 % and 17 % of the acamprosate- and placebo-treated patients , respectively , had remained abstinent ( P = .003 ) . CONCLUSION Acamprosate proved to be a safe and effective aid in treating alcohol-dependent patients and in maintaining the abstinence of patients during 2 years AIMS In r and omized controlled trials with high internal validity , pharmacotherapy using acamprosate , naltrexone , and , to a somewhat lesser extent , disulfiram has proved effective in preventing relapse in patients with alcohol use disorders ( AUD ) . There remains , however , a paucity of studies with sufficient external validity in which the effectiveness of pharmacotherapy in clinical practice is investigated . This study aim ed to make a contribution to close this gap in research . METHODS In this naturalistic , prospect i ve study , a comparison on indices of substance use , psychiatric symptoms , and treatment service utilization was carried out using sample s of 92 patients who received pharmacotherapy and 323 patients who did not receive pharmacotherapy following discharge from 12 residential AUD programmes ( index stay ) . RESULTS Patients that received pharmacotherapy were more likely to use alcohol during the index stay and at the 1-year follow-up . Moreover , this patient group more readily utilized treatment services during a 2-year period prior to and a 1-year period following index stay than patients who were not given pharmacotherapy . Nevertheless , when pharmacotherapy was prescribed before first post-treatment alcohol use , it was associated with delay of alcohol use , fewer relapses , and a reduced need for inpatient treatment . In many cases , however , medication was not prescribed until alcohol use and relapse had occurred . The length of time to first alcohol use was longer , and the cumulative abstinence rate higher , for disulfiram than for acamprosate , the latter being generally prescribed for more severely alcohol-dependent patients . CONCLUSIONS There is a need for further studies to probe the reasons why medication for relapse prevention is not prescribed upon discharge from residential treatment and for less severely alcohol-dependent patients A prospect i ve placebo-controlled , r and omized double-blind study of Acamprosate at two dose levels in alcohol-dependent patients followed up for 12 months was performed . After detoxification , each of the 538 patients included was r and omly assigned to one of three groups : 177 patients received placebo , 188 received Acamprosate at 1.3 g/day ( low dose group ) and 173 received 2.0 g/day ( high dose group ) for 12 months . This was followed by a single blind 6 month period on placebo . The patients ' mean age was 43.2 + /- 8.6 years . Their mean daily alcohol intake was high ( nearly 200 g/day ) and of long duration ( 9.5 + /- 7.1 years ) . Abstinence figures followed the order high dose > low dose > placebo . The difference was significant at 6 months ( P < or = 0.02 ) but not at 12 months ( P = 0.096 ) . The number of days of continuous abstinence after detoxification was 153 + /- 197 for the high-dose group versus 102 + /- 165 for the placebo group ( P = 0.005 ) , with the lose-dose group reporting 135 + /- 189 days . Clinic attendance was significantly better in the Acamprosate groups than in the placebo group at 6 months ( P = 0.002 ) and 12 months ( P = 0.005 ) . During the 6-month post-treatment period , no increased relapse rate or residual drug effect was observed . The side effect profile for Acamprosate was good compared with controls with only diarrhoea being reported more frequently ( P < 0.01 ) . This study confirms the pharmacological efficacy of Acamprosate and its good acceptability . As an adjunct to psychotherapy , this study supports the inclusion of Acamprosate in a strategy for treating alcoholism OBJECTIVE On the basis of several controlled clinical investigations the cost-effectiveness of acamprosate as adjuvant therapy of alcohol-dependent patients has yet been evaluated . These optimal conditions can not be found in the daily ambulant practice and results in asking which of the alternatives , " st and ard plus acamprosate " or " st and ard without acamprosate " , is more cost-effective in maintaining abstinence in alcohol dependent patients under realistic conditions . PATIENTS AND METHODS In an open multi-centre study , medical care , costs and therapeutic outcome was prospect ively documented . Prior to enrolling , all patients were obliged to undergo a detoxification procedure . At a mean age of 45 years the patients suffered an average of ten years from alcohol dependence . 521 patients were documented in the acamprosate cohort and 265 patients in the cohort " other therapy " over one year . Two thirds of the participating patients were male . RESULTS At 33.6 % the rate of abstinence was remarkably higher in the acamprosate cohort in comparison to the cohort " other " at 21.1 % abstinent patients . The mean total costs per patient and year amounted to DM 3191 in the acamprosate-cohort and were significantly lower than in the cohort " other " with DM 4046 . Effectiveness-adjusted costs of DM 9500 per successfully treated patient in the acamprosate-cohort were superior to the cohort " other " , amounting to DM 19 148 per successfully treated patient . CONCLUSION The described economic benefits may be utilised under conditions of an adequate disease management To test acamprosate 's role as an aid in preventing relapse after detoxification , 296 alcohol-dependent patients entered a prospect i ve , multicentre , r and omized , double-blind , parallel comparison of acamprosate treatment consisting of two 333 mg tablets given three times daily for 180 days with matching placebo treatment . Unlike previous studies , acamprosate was prescribed from the start of alcohol withdrawal , rather than after the detoxification process . During the treatment period , 110 patients dropped out . The two treatment groups were balanced with regard to baseline values and reasons for discontinuation . There was no difference between the groups in the severity of withdrawal symptoms as measured by the CIWA-Ar ( Clinical Institute Withdrawal Assessment for Alcohol scale ) . Acamprosate given during withdrawal did not cause unwanted effects . The cumulative abstinence duration ( CAD , main end-point ) was 19 days longer in the acamprosate treatment group than the placebo treatment group ( analysis of variance on ranks , P = 0.0006 ) and the stable recovery duration , defined as the number of abstinent days between the last relapse into any drinking and the end of the trial , was 16 days longer in the acamprosate treatment group ( P = 0.021 ) . Continuous abstinence , estimated by survival analysis on time to first relapse , was achieved by 35 % of acamprosate-treated patients and 26 % of placebo-treated patients ( log rank P = 0.068 ) . The geometric mean of the ratio final/baseline values for serum carbohydrate-deficient transferrin was 0.802 ( placebo ) and 0.733 ( acamprosate ) ( P = 0.059 ) . The geometric mean of the ratio final/baseline values for serum gamma-glutamyltransferase was 0.496 ( placebo ) and 0.415 ( acamprosate ) ( P = 0.024 ) which corroborated the greater abstinence reported by the acamprosate group BACKGROUND Acamprosate is a newly registered drug that appears to reduce alcohol-drinking in both animal models and clinical conditions . METHOD In order to assess the efficacy and safety of the drug in the treatment of detoxified alcoholics , we performed a 90-day double-blind trial comparing two dosages of acamprosate ( 1332 mg/day and 1998 mg/day ) . RESULTS For all efficacy parameters , acamprosate appeared to be significantly superior to placebo , with a trend towards a better effect at the higher dosage . Furthermore , acamprosate appeared to be extremely safe . CONCLUSION This study confirms that acamprosate could be an interesting adjuvant for maintaining abstinence in detoxified alcoholics Acamprosate and naltrexone have each demonstrated safety and efficacy for alcohol dependence in placebo-controlled clinical trials . There is scientific and clinical interest in evaluating these drugs in combination , given their high tolerability , moderate effect sizes , different pharmacological profiles and potentially different effects on drinking outcomes . Thus , this is the first human pharmacokinetic and pharmacodynamic drug interaction study of acamprosate and naltrexone . Twenty-four normal , healthy adult volunteers participated in a double-blind , multiple dose , within subjects , r and omized , 3-way crossover drug interaction study of the st and ard therapeutic dose of acamprosate ( 2 g/d ) and the st and ard therapeutic dose of naltrexone ( 50 mg/d ) , given alone and in combination , with seven days per treatment condition and seven days washout between treatments . Blood sample s were collected on a st and ardized schedule for pharmacokinetic analysis of naltrexone , 6-β-naltrexol , and acamprosate . A computerized assessment system evaluated potential drug effects on cognitive functioning . Coadministration of acamprosate with naltrexone significantly increased the rate and extent of absorption of acamprosate , as indicated by an average 33 % increase in acamprosate maximum plasma concentration , 33 % reduction in time to maximum plasma concentration , and 25 % increase in area under the plasma concentration-time curve . Acamprosate did not affect the pharmacokinetic parameters of naltrexone or 6-β-naltrexol . A complete absence of negative interactions on measures of safety and cognitive function supports the absence of a contraindication to co-administration of acamprosate and naltrexone in clinical practice Five hundred and sixty-nine alcoholics were included in a double-blind placebo-controlled r and omized multicenter study of the effects of Acamprosate ( calcium acetylhomotaurinate ( CA ) , 1.3 g/day ) on indicators of alcoholic relapse after withdrawal . One hundred and eighty-one patients in the CA group versus 175 in the placebo group completed the three-month study . The major efficacy criterion was plasma gamma-glutamyl transpeptidase ( GGT ) , as an indicator of recent alcohol ingestion . This analysis was completed by criteria concordance analysis on a number of indicators of alcohol intake . Patients in both groups were similar initially . After 3 months of treatment , the patients in the CA group had significantly lower GGT ( 1.4 + /- 1.56 versus 2.0 + /- 3.19 times normal , P = 0.016 ) . All significant differences ( P less than 0.05 ) or trends ( 0.10 greater than P greater than 0.05 ) were in favor of a superior effect of CA over placebo . The major side-effect of CA was diarrhea ( present in 13 % of CA patients versus 7 % of placebo , P = 0.04 ) . CA proved superior to placebo on the evolution of markers of alcohol ingestion at three months , in this large-scale multicenter study . It could be a new modality in the drug therapy of alcoholism , not involving an antabuse effect , an antidepressant action , or conditioning Animal studies suggested that acamprosate modulates neuronal hyperexcitability of acute alcohol withdrawal , acting through the glutamatergic neurotransmission . In the present study , we further investigated whether treatment with acamprosate could attenuate the post-alcohol withdrawal hyperexcitability or hyperarousal in humans using brain magnetoencephalography mapping of spontaneous fields . A double-blind , r and omised , placebo-controlled study with a parallel group design comparing 2,000 mg/day of acamprosate versus placebo was conducted in alcohol-dependent subjects meeting DSM-IV criteria for alcohol dependence . Treatments were initiated 8 days before alcohol withdrawal and prolonged during the 15 following ( abstinence ) days . The study demonstrated that during alcohol withdrawal , acamprosate decreased the arousal level as reflected by alpha slow-wave index ( ASI ) measurement . This effect was mostly evidence d in left parietotemporal regions and , to a lesser extent , in the contiguous anterior , posterior and right-sided regions . In the placebo group , on the contrary , ASI measures increased between day 2 ( acute withdrawal ) and day 14 ( prolonged withdrawal ) . The present results suggest a sustained effect of acamprosate on the hyperexcitability state due to alcohol withdrawal in alcohol-dependent patients and that acamprosate may have a protective effect when administered 8 days before alcohol withdrawal This study presents the results of a multicenter investigation of the efficacy of acamprosate in the treatment of patients with chronic or episodic alcohol dependence . One hundred eighteen patients were r and omly assigned to either placebo or acamprosate , and both groups were stratified for concomitant voluntary use of disulfiram . Treatment lasted for 360 days , with an additional 360-day follow-up period . The primary efficacy parameters evaluated were : relapse rate and cumulative abstinence duration ( CAD ) . Results were analyzed according to Intention-To-Treat principles using chi2 , t , and multiple regression analyses where appropriate . After 30 days on study medication , 40 of 55 ( 73 % ) acamprosate-treated patients were abstinent , compared with 26 of 55 ( 43 % ) placebo-treated patients ( p = 0.019 ) . The treatment advantage remained throughout the study medication period and was statistically significant until day 270 ( p = 0.028 ) . Twenty-seven percent of patients on acamprosate and 53 % of patients on placebo had a first drink within the first 30 days of the study . The mean CAD was 137 days ( 40 % abstinent days ) for the patients treated with acamprosate and 75 days ( 21 % abstinent days ) for the placebo group ( p = 0.013 ) . No adverse interaction between acamprosate and disulfiram occurred , and the subgroup who received both medications had a better outcome on CAD than the those on only one or no medication . Acamprosate was well tolerated . Diarrhea was the only significant treatment-induced effect . It was concluded that acamprosate was a useful and safe pharmacotherapy in the long-term treatment of alcoholism . Concomitant administration of disulfiram improved the effectiveness of acamprosate BACKGROUND To compare topiramate versus naltrexone in the treatment of alcohol dependence . METHODS A 6-month naturalistic , r and omized and open-label , trial of topiramate versus naltrexone , with assessment s at enrollment and after 3 and 6 months of treatment . The setting was an outpatient alcohol clinic . One hundred and two alcohol-dependent patients who had been drinking heavily during the past month were included . Two r and omized groups were created . In one , naltrexone was used as the therapeutic agent and , in the other , topiramate was chosen as the therapeutic agent . Both groups received psychological relapse prevention therapy . Outcome was measured using tools that assessed alcohol intake , cravings , disability , and quality of life ; changes in biomarkers of alcohol intake were also used . With all the data , a secondary composite measure was created in order to assess each patient 's global alcohol intake and its consequences . RESULTS Both groups showed substantial reduction in their drinking . Naltrexone patients had higher nicotine consumption throughout the study . Topiramate was better at reducing alcohol-related cravings throughout the study . Both treatments had a similar mean cost throughout the study . CONCLUSIONS Both topiramate and naltrexone were efficacious in the treatment of alcohol dependence , and the treatment costs were similar . There is a trend for topiramate to be superior to naltrexone on critical measures of drinking ; however , the study did not have adequate statistical power to establish this fact At least three factors increase the probability that the results in a report of a clinical trial will be false positive : 1 ) Publication bias — the tendency for investigators to su bmi t and editors to accept selectively reports of trials that appear to give positive results ( 1 - 4 ) , some of which will occur by statistical chance . 2 ) The low probability that new treatments will lead to therapeutic advances ( 5 ) , implying a low prevalence of truepositive trials ( 6 ) . Just as a screening procedure ( e.g. , fecal occult blood test for colorectal cancer ) will give a high rate of false-positive results when applied to a population with low prevalence of a disease , so a clinical trial will have a high false-positive rate ( and a low false-negative rate ) if there is a low prevalence of true differences in outcome . This effect is illustrated by the following example , provided by Dr. M. Parmar ( personal communication ) . Suppose 200 trials are undertaken with a significance level of 5 % ( type I error of a = 0.05 ) and with a 0.9 power ( 1 0 [ type II error = 0.1 ] ) . If the prevalence of trials with a real difference is 10 % ( 20 trials ) . 18 ( 20 x 0.9 ) trials will be reported correctly as true positives ; in contrast , there will be nine ( 180 x 0.05 ) false positives or one in three ( i.e. , nine of 27 ) trials reported as positive . Overall , 173 of the 200 trials will be reported as negative ( 171 true negatives and two Table 1 . Characteristics of 32 reports of r and omized clinical OBJECTIVES This pilot study has been design ed to collect preliminary data on the use of a new antiepileptic drug in the management of alcoholic patients . Oxcarbazepine ( OXC ) blocks voltage-sensitive sodium channels . Its metabolite reduces high-voltage-activated calcium currents in striatal and cortical neurons , thus reducing glutamatergic transmission at corticostriatal synapses . This reduction is of interest in the treatment of alcohol dependence , as acamprosate ( ACP ) modulates NMDA receptors , result ing in an inhibition of glutamatergic transmission . Furthermore , OXC has revealed a mood-stabilizing effect in bipolar affective disorders . We have compared OXC with ACP in relapse prevention in recently withdrawn alcohol-dependent patients . METHODS We investigated the efficacy and safety of OXC ( vs ACP ) by conducting a 24-week r and omized , parallel-group , open-label , clinical trial on 30 acutely detoxified alcoholic patients . Survival analyses ( Kaplan-Meier ) were performed to look for evidence of a longer " survival " of patients receiving OXC . We assessed time to first severe relapse and additional secondary endpoints . RESULTS After withdrawal , time to severe relapse and time to first consumption of any ethanol by OXC patients were not longer than for ACP patients . Abstinent patients in both study groups showed a significantly lower obsessive compulsive drinking scale-German version ( OCDS-G ) than relapsed patients . No undesired effects occurred when OXC patients consumed alcohol . CONCLUSION Our findings indicate that it could be worthwhile to test relapse prevention using OXC in an adequate sample . While the current sample size clearly limits further conclusions from this pilot study , it is noteworthy that OXC is well tolerated , even when alcohol is on board . Thus , in medication-based relapse prevention , OXC could be a promising alternative for alcoholic patients unable to benefit from ACP or naltrexone or those who have affective liability . OXC certainly merits a larger placebo-controlled trial In a one-year double-blind-treatment study with acamprosat ( six months with and six months without substance ) the efficiency of this new medicament could be proved . The number of relapses in the treatment group was significantly lower during the first 30 days with a trend to further 150 days . The substance caused very few side effects OBJECTIVE This study was undertaken to evaluate the efficacy and safety of acamprosate in the treatment of alcohol dependence . METHOD The investigation was a double-blind , placebo-controlled , 24-week study carried out at the University of São Paulo , Brazil . The sample comprised 75 patients , 18 - 60 years of age , with an International Classification of Diseases ( ICD-10 ) diagnosis of alcohol dependence . After a 1-week detoxification period the patients were r and omly divided into two groups : the first received acamprosate ( 1.998 mg/day ) and the second received placebo . After the first 12 weeks , the patients continued follow-up for a similar length of time without medication . The main outcome measures were relapse rates , side effects and time to first relapse . RESULTS On an intention-to-treat basis , the Kaplan-Meier survival curve showed an advantage in relapse rates for acamprosate over placebo ( log-rank test , p = .02 ) , and acamprosate was well tolerated . CONCLUSIONS Acamprosate seems to be an effective treatment for alcohol dependence in a Brazilian population We examined kinetic and dynamic factors to determine the pharmacological and behavioral safety and tolerability of low versus high doses of an opiate antagonist , naltrexone ( 50 mg/day vs. 100 mg/day ) , and acamprosate ( 2 g/day vs. 3 g/day ) , a functional N-methyl-D-aspartate receptor antagonist , both independently and combined , among non-treatmentseeking , alcohol-dependent individuals . This double-blind , double-dummy , placebo-controlled , r and omized , 23-day , four-way crossover study involved 23 subjects assigned to one of four groups . Placebo washout ( phase I ) preceded phase II , where subjects received low-dose or high-dose naltrexone or acamprosate . In phases III and IV , the alternative medication type at its lower and higher doses , respectively , was administered with continuation of the phase II medication . Predetermined behavioral , performance , and pharmacological criteria determined significant pathological change from baseline ( phase I ) . Case records were review ed . Criterion-significant increases in symptoms from baseline with monotherapy included nervousness and fatigue with 3 g acamprosate and somnolence and headache with 50 mg and 100 mg naltrexone , respectively . Combined treatment at various doses evinced anger , depression , somnolence , nervousness , diarrhea , and headache . Notably , for all but one subject who dropped out , increased symptoms did not produce any remarkable clinical deterioration . Naltrexone administration significantly increased plasma acetylhomotaurine ( i.e. , acamprosate ) levels , presumably by prolonging gastric emptying . The level of neither plasma acetylhomotaurine nor plasma 6-β naltrexol ( i.e. , naltrexone ’s metabolite ) predicted adverse-event frequency . Naltrexone and acamprosate , both alone and in combination at the tested doses , were behaviorally and pharmacologically safe . Adverse events were infrequent , were of moderate intensity , and resolved with reassurance and symptomatic treatment . More side effects were noted with the combination of medications than with either medication alone . Naltrexone administration significantly increased plasma acamprosate levels AIM To compare the effects in alcohol-dependent patients of three pharmacotherapies , disulfiram ( DIS ) , naltrexone ( NTX ) , and acamprosate ( ACA ) , when used with a brief manual-based cognitive-behavioural intervention . METHOD We conducted a r and omized , open label , multicentre naturalistic study in two phases ; first , a 12-week continuously supervised medication , followed by targeted medication ( TM ) up to 52 weeks in addition to a 67-week follow-up period ; altogether 119 weeks ( 2.5 years ) , in 243 voluntary treatment-seeking alcohol-dependent adult out patients . Subjects were r and omized 1:1:1 to receive supervised NTX , ACA or DIS , 50 , 1998 , or 200 mg , respectively , per day , plus a brief manual-based cognitive-behavioural intervention . The patients were met in the second and sixth weeks , and then after 3 , 6 , and 12 months . The primary outcome measures were the time ( days ) to first heavy drinking day ( HDD ) , and time during the first 3 months to the first drinking day after medication started . Secondary variables were abstinent days/week ( 0 drinks/day ) , average weekly alcohol intake , Alcohol Use Disorder Identification Test ( AUDIT ) , Severity of Alcohol Dependence Data ( SADD ) , and quality of life ( QL ) measures . RESULTS All three study groups showed marked reduction in drinking , from baseline to the end of the study . During the continuous medication phase , treatment with DIS was more effective in reducing HDDs and average weekly alcohol consumption , and increasing time to the first drink , as well as the number of abstinent days . During the TM period , there were no significant differences between the groups in time to first HDD and days to first drinking , but the abstinence days were significantly more frequent in the DIS group than ACA and NTX . There were no differences between the NTX and ACA groups in either phase of the study of drinking outcomes . However , SADD scores improved more in the NTX group than the ACA group . CONCLUSIONS Patients allocated to ACA , NTX and DIS combined with brief manual-based cognitive behavioural intervention significantly reduce their alcohol consumption and report improved QL . Supervised DIS appeared superior , especially during the continuous medication period , to NTX and ACA After they had been weaned off alcohol in hospital 85 severe alcoholics ( above 200 g alcohol/day ) were included in a double-blind study of calcium bis acetyl homotaurine ( Ca AOTA , 25 mg/kg/day ) , a new gamma-aminobutyric acid agonist , versus placebo . Patients were treated as out patients during the 3-month study . The only other treatment that patients received was meprobamate , 800 to 1200 mg/day , in the first month . The criterion for success was abstinence at 3 months ( with normal gamma-glutamyl transpeptidase being one of the criteria ) . Of the 70 patients who completed the study , 33 received Ca AOTA and 37 placebo . 20 patients on Ca AOTA did not relapse , compared with 12 on placebo ( p less than 0.02 by X2 test ) . Side-effects were noted by 7 patients on Ca AOTA and 2 on placebo . The results suggest that Ca AOTA may be useful in helping severe alcoholics who have been weaned off alcohol not to relapse Abstract Objective : To determine abstinence rates and to obtain safety data during the use of integrated therapy with acamprosate and the main established psychotherapeutic intervention programmes in the treatment of alcohol dependence . Design : Non-blind , parallel-group , multicentre , phase IV study . Setting : Naturalistic setting reflecting the clinical use of acamprosate in out-patient treatment of alcoholics in Germany . Patients : 753 patients meeting the DSM-III-R criteria for alcohol dependence . At study entry , patients had to be abstinent for 1 to 4 weeks , and those who relapsed within the first 14 days of treatment were withdrawn from the study . Interventions : All patients received acamprosate 1332 to 1998 mg/day according to bodyweight and were assigned to one of the following treatment groups : individual psychotherapy , group psychotherapy , behavioural therapy , brief intervention or family therapy . The patients were followed for 24 weeks . Outcome measures : The principal outcome criterion was the time to the first drink . Secondary outcome measures were cumulative abstinence duration and craving . Adverse events were recorded systematic ally and classified according to World Health Organization adverse reaction terminology . Results : The mean time to first drink was 81.5 days . 236 ( 33.5 % ) patients were continuously abstinent during the study . The discontinuation rate in the study was 49 % , and the cumulative abstinence duration was 61 % . Abstinence and discontinuation rates in this study were similar to those found in placebo-controlled clinical trials . Craving fell to scores of less than 50 on the Lübecker Craving Scale within 2 weeks of treatment initiation . There were no significant differences between the different psychosocial support treatment arms concerning time to first relapse or abstinence rates . Linear regression analysis showed severity of alcohol dependence according to DSM-III-R criteria to be associated with treatment outcome ( p = 0.003 ) . The most common adverse clinical events during the first 2 weeks of treatment were diarrhoea ( 69 patients ) , pruritus ( 37 patients ) , headache ( 28 patients ) and fatigue ( 16 patients ) . Acamprosate was discontinued in nine patients ( 1 % ) because of severe adverse events ; only two cases were clearly linked to treatment ( diarrhoea and dermatitis ) . One death occurred during the study ( status asthmaticus ) . Conclusions : Abstinence rates with integrated acamprosate and psychosocial support in a naturalistic setting are similar whatever the psychosocial support used , and similar to those seen in placebo-controlled clinical trials of acamprosate . The safety profile of acamprosate was good BACKGROUND There is growing evidence that pharmacological treatment with two of the best vali date d anticraving drugs , acamprosate and naltrexone , is efficacious in promoting abstinence in recently detoxified alcohol-dependent subjects . OBJECTIVE The stability of effects after termination of treatment remains to be answered , especially when combining both the drugs . METHOD After detoxification , 160 alcohol-dependent subjects participated in a r and omized , double-blind , placebo-controlled trial . Patients received naltrexone or acamprosate or a combination of naltrexone and acamprosate or placebo for 12 weeks . Patients were assessed weekly by interview , self-report , question naires and laboratory screening . Additionally , follow-up evaluation based on telephone interview of participants , general practitioners and relatives was conducted 12 weeks after terminating the medication . RESULTS At week 12 , the proportion of subjects relapsing to heavy drinking was significantly lower in the group with combined medication compared with both placebo and acamprosate ( P < 0.05 ) . No difference was detectable between acamprosate and naltrexone , both of which were superior to placebo ( P < 0.05 ) . Relapse rates were 28 % ( combined medication ) , 35 % ( naltrexone ) , 50 % ( acamprosate ) and 75 % ( placebo ) . After follow-up ( week 24 ) , combined medication led to relapse rates significantly lower than placebo , but not lower than acamprosate . Again , both naltrexone and acamprosate were superior to placebo . Relapse rates were 80 % ( placebo ) , 54 % ( acamprosate ) , 53 % ( naltrexone ) and 34 % ( combined medication ) . CONCLUSIONS The results of this study highlight the stability of effects of pharmacotherapy on relapse prevention in alcohol dependence |
14,097 | 27,486,869 | The most promising results were noted with cediranib , nintedanib , and pazopanib . | The present systematic review summarizes current evidence regarding the mechanisms of action , the efficacy , and the adverse effects of tyrosine kinase inhibitors ( TKIs ) in ovarian cancer patients . | PURPOSE This trial evaluated the efficacy of maintenance erlotinib , an epidermal growth factor receptor ( EGFR ) tyrosine kinase inhibitor , after first-line chemotherapy . PATIENTS AND METHODS Eligible patients had high-risk International Federation of Gynecology and Obstetrics stage I or stage II to IV epithelial ovarian , primary peritoneal , or fallopian tube cancer and were not selected for EGFR expression . All patients underwent first-line platinum-based chemotherapy ( CT ) and showed no signs of progression at the end of CT . Patients were r and omly assigned to maintenance erlotinib 150 mg orally daily for 2 years or to observation . EGFR immunohistochemistry ( IHC ) , fluorescent in situ hybridization ( FISH ) , and mutation analyses were performed in 318 patients . RESULTS Between October 2005 and February 2008 , 835 patients were r and omly assigned ( median follow-up , 51 months ) . Twenty-six percent of the patients stopped erlotinib as a result of adverse effects ( of these , 67 % were due to rash ) . For erlotinib and observation , respectively , the median progression-free survival was 12.7 and 12.4 months ( hazard ratio [ HR ] , 1.05 ; 95 % CI , 0.90 to 1.23 ) , and the median overall survival was 50.8 and 59.1 months ( HR , 0.99 ; 95 % CI , 0.81 to 1.20 months ) , respectively . No subgroup could be identified with improved effect of erlotinib , based on IHC or FISH for EGFR , or mutations in genes related to the EGFR pathway , or on rash during erlotinib therapy . However , patients with a positive FISH EGFR score had a worse overall survival ( 46.1 months ) than those with a negative score ( 67.0 months ; HR , 1.56 ; 95 % CI , 1.01 to 2.40 ; P = .044 ) . Global health/ quality -of-life scores showed a significant difference during the first year ( P = .0102 ) in favor of the observation arm . CONCLUSION Maintenance erlotinib after first-line treatment in ovarian cancer did not improve progression-free or overall survival PURPOSE This phase II trial assessed the activity and tolerability of an oral dose of imatinib mesylate 400 mg twice daily in patients with recurrent or persistent epithelial ovarian or primary peritoneal carcinoma . The association between the expression of certain markers and clinical outcome was investigated . PATIENTS AND METHODS Primary measure of clinical efficacy was progression-free survival ( PFS ) at 6 months . Mutational analysis of KIT , immunohistochemistry ( IHC ) and enzyme-linked immunosorbent assay for markers ( KIT , platelet-derived growth factor [ PDGF ] receptor [ -R ] , AKT2 , phosphorylated AKT [ p-AKT ] , stem cell factor [ SCF ] , and PDGF ) were performed . RESULTS Fifty-six eligible patients were evaluated . Nine patients were progression free for at least 6 months including one complete responder . The median PFS and survival were 2 and 16 months , respectively . The most common grade 3 and 4 toxicities were neutropenia , GI , dermatologic effects , pain , and electrolyte disturbances . At least one target of imatinib ( KIT , PDGFR-alpha , or PDGFR-beta ) was expressed in all tumors , and most tumors expressed all three receptors . Higher expression of p-AKT and PDGFR-beta were associated with shorter PFS , and higher IHC scores ( % immunopositive cells x staining intensity ) of SCF and p-AKT were associated with decreased overall survival . No sequence mutations were detected in the KIT gene . Higher pretreatment plasma concentrations of PDGF-AB , PDGF-BB , and vascular endothelial growth factor ( VEGF ) were individually associated with shorter PFS and survival . CONCLUSION Imatinib mesylate was well tolerated but had minimal single-agent activity in patients with recurrent ovarian or primary peritoneal carcinoma . No marker was identified that would predict activity of imatinib ; however , tumor p-AKT and plasma VEGF levels were associated with poor outcome OBJECTIVES Approximately 50 % of ovarian cancers have elevated levels of epidermal growth factor receptor ( EGFR ) which correlates with a poor prognosis . Pre clinical evidence suggests that EGFR tyrosine kinase inhibitors ( TKIs ) , such as erlotinib ( OSI-774 ) , may potentiate the anti-tumour effects of cytotoxic agents , including carboplatin . Blocking EGFR could thus potentially reverse drug resistance . The primary objective of the study was to assess the response rate to the addition of erlotinib in patients with recurrent ovarian cancer who were receiving carboplatin . METHODS Patients enrolled on this study had either local or advanced recurrent ovarian cancer with measurable disease . They may have had up to 2 prior chemotherapy regimens , one of which must have contained platinum , and they must have responded to prior platinum therapy . Patients were stratified by platinum sensitivity and were treated with erlotinib 150 mg daily on a continuous dosing schedule , and carboplatin at an AUC of 5 every 21 days . RESULTS Fifty patients with recurrent ovarian cancer entered the study , 33 in the platinum-sensitive arm and 17 in the platinum-resistant arm . Of patients evaluable for response , there were 14 partial responses ( PR ) of 30 evaluable for response ( 57 % objective response rate ( ORR ) ) in the platinum-sensitive arm , and 1 PR of 14 evaluable for response ( 7 % ORR ) in the platinum-resistant arm . CONCLUSIONS The combination of erlotinib and carboplatin was active in patients with platinum-sensitive disease , but not in platinum-resistant disease . The toxicities seen were those expected with carboplatin and erlotinib BACKGROUND Inhibition of angiogenesis is a valuable treatment strategy for ovarian cancer . Pazopanib is an anti-angiogenic drug active in ovarian cancer . We assessed the effect of adding pazopanib to paclitaxel for patients with platinum-resistant or platinum-refractory advanced ovarian cancer . METHODS We did this open-label , r and omised phase 2 trial at 11 hospitals in Italy . We included patients with platinum-resistant or platinum-refractory ovarian cancer previously treated with a maximum of two lines of chemotherapy , Eastern Cooperative Oncology Group performance status 0 - 1 , and no residual peripheral neurotoxicity . Patients were r and omly assigned ( 1:1 ) to receive weekly paclitaxel 80 mg/m(2 ) with or without pazopanib 800 mg daily , and stratified by centre , number of previous lines of chemotherapy , and platinum-free interval status . The primary endpoint was progression-free survival , assessed in the modified intention-to-treat population . This trial is registered with Clinical Trials.gov , number NCT01644825 . This report is the final analysis ; the trial is completed . FINDINGS Between Dec 15 , 2010 , and Feb 8 , 2013 , we enrolled 74 patients : 37 were r and omly assigned to receive paclitaxel and pazopanib and 37 were r and omly assigned to receive paclitaxel only . One patient , in the paclitaxel only group , withdrew from the study and was excluded from analyses . Median follow-up was 16·1 months ( IQR 12·5 - 20·8 ) . Progression-free survival was significantly longer in the pazopanib plus paclitaxel group than in the paclitaxel only group ( median 6·35 months [ 95 % CI 5·36 - 11·02 ] vs 3·49 months [ 2·01 - 5·66 ] ; hazard ratio 0·42 [ 95 % CI 0·25 - 0·69 ] ; p=0·0002 ) . We recorded no unexpected toxic effects or deaths from toxic effects . Adverse events were more common in the pazopanib and paclitaxel group than in the paclitaxel only group . The most common grade 3 - 4 adverse events were neutropenia ( 11 [ 30 % ] in the pazopanib group vs one [ 3 % ] in the paclitaxel group ) , fatigue ( four [ 11 % ] vs two [ 6 % ] ) , leucopenia ( four [ 11 % ] vs one [ 3 % ] ) , hypertension ( three [ 8 % ] vs none [ 0 % ] ) , raised aspartate aminotransferase or alanine aminotransferase ( three [ 8 % ] vs none ) , and anaemia ( two [ 5 % ] vs five [ 14 % ] ) . One patient in the pazopanib group had ileal perforation . INTERPRETATION Our findings suggest that a phase 3 study of the combination of weekly paclitaxel plus pazopanib for patients with platinum-resistant or platinum-refractory advanced ovarian cancer is warranted . FUNDING National Cancer Institute of Napoli and GlaxoSmithKline BACKGROUND V and etanib is an oral tyrosine kinase inhibitor of VEGFR-2/3 , EGFR and RET , which has demonstrated clinical activity as a single agent and in combination with taxanes . We explored the efficacy , safety and toxicity of docetaxel and v and etanib in women with recurrent ovarian cancer ( OC ) . METHODS Women with refractory or progressive OC were r and omised 1:1 to docetaxel ( 75 mg/m(2 ) , IV)+v and etanib ( 100 mg daily , PO , D+V ) or docetaxel ( 75 mg/m(2 ) , D ) . Up to three additional cytotoxic regimens for recurrence and prior anti-angiogenic agents ( as primary therapy ) were allowed . The primary end-point was progression free survival ( PFS ) . The study had 84 % power to detect a PFS hazard ratio of 0.65 , using a one-sided P of 0.1 . This corresponds to an increase in median PFS from 3.6 months to 5.6 months . Patients progressing on D were allowed to receive single agent v and etanib ( D → V ) . RESULTS 131 Patients were enrolled ; two were excluded . 16 % had received prior anti-angiogenic therapy . The median PFS estimates were 3.0 mos ( D+V ) versus 3.5 ( D ) ; HR : 0.99 ( 80 % CI : 0.79 - 1.26 ) . 61 Patients on D+V were assessable for toxicity ; 20(33 % ) had treatment-related Grade ( G ) 4 events , primarily haematologic . Similarly , 17 ( 27 % ) of 64 patients receiving D had G4 events , primarily haematologic . 27 Evaluable patients crossed-over to V. 1/27(4 % ) experienced a G4 event . G3 diarrhoea was observed in 4 % D → V patients . Median OS was 14 mos ( D+V ) versus 18 mos ( D → V ) ; HR(OS ) : 1.25 ( 80 % CI : 0.93 - 1.68 ) . Crossover v and etanib response was 4 % ( 1/27 evaluable patients ) . High plasma IL-8 levels were associated with response to D+V. CONCLUSIONS Combination docetaxel+v and etanib did not prolong PFS relative to docetaxel alone in OC patients . No unexpected safety issues were identified OBJECTIVES Pre clinical data suggest an important role for the sarcoma proto-oncogene tyrosine kinase ( SRC ) in the oncogenesis of epithelial ovarian cancer ( EOC ) or primary peritoneal carcinoma ( PPC ) . The Gynecologic Oncology Group ( GOG ) conducted a Phase II trial to evaluate the efficacy and safety of dasatinib , an oral SRC-family inhibitor in EOC/PPC , and explored biomarkers for possible association with clinical outcome . METHODS Eligible women had measurable , recurrent or persistent EOC/PPC and had received one or two prior regimens which must have contained a platinum and a taxane . Patients were treated with 100 mg orally daily of dasatinib continuously until progression of disease or adverse effects prevented further treatment . Primary endpoints were progression-free survival (PFS)≥6months and response rate . Serial plasma sample s were assayed for multiple biomarkers . Circulating free DNA was quantified as were circulating tumor and endothelial cells . RESULTS Thirty-five ( 35 ) patients were enrolled in a two-stage sequential design . Of the 34 eligible and evaluable patients , 20.6 % ( 90 % confidence interval : 10.1 % , 35.2 % ) had a PFS≥6months ; there were no objective responses . Grade 3 - 4 toxicities were gastrointestinal ( mostly nausea and emesis ; n=4 ) , pulmonary ( dyspnea and /or pleural effusion ; n=4 ) and pain ( n=5 ) , and infrequent instances of anemia , malaise , insomnia , rash , and central nervous system hemorrhage . Lack of clinical activity limited any correlation of biomarkers with outcome . CONCLUSION Dasatinib has minimal activity as a single-agent in patients with recurrent EOC/PPC OBJECTIVES Vascular endothelial growth factors ( VEGF ) and their receptors have a critical role in stimulating the growth of ovarian cancer cells . Motesanib is a small molecule inhibitor of multiple receptor tyrosine kinases including VEGF receptors 1 - 3 , as well as c-KIT and platelet-derived growth factor which are related to the VEGF family . PATIENTS AND METHODS Twenty-two eligible patients with recurrent ovarian , fallopian tube or primary peritoneal carcinoma were treated with an oral daily dose of 125 mg of motesanib . Peripheral blood was analyzed for circulating tumor cells ( CTC ) and circulating endothelial cells/circulating endothelial progenitors ( CEC/CEP ) , VEGF levels and cell-free circulating DNA ( cfDNA ) . RESULTS The study was abruptly halted after four patients developed posterior reversible encephalopathy syndrome . One patient had a partial response and seven patients had stable disease at the time they were removed from study treatment . Twelve of the 22 patients ( 50 % ) had indeterminate responses at trial closure . Early closure without clinical efficacy data precludes meaningful correlative studies . CONCLUSIONS The serious central nervous system toxicity observed in patients with recurrent ovarian cancer precluded full examination of this agent in this population . There were no clear cut explanations for the high incidence of this known class effect in the study population compared with patients with other cancers BACKGROUND Olaparib is a poly(ADP-ribose ) polymerase inhibitor and cediranib is an anti-angiogenic agent with activity against VEGF receptor ( VEGFR ) 1 , VEGFR2 , and VEGFR3 . Both oral agents have antitumour activity in women with recurrent ovarian cancer , and their combination was active and had manageable toxicities in a phase 1 trial . We investigated whether this combination could improve progression-free survival ( PFS ) compared with olaparib monotherapy in women with recurrent platinum-sensitive ovarian cancer . METHODS In our r and omised , open-label , phase 2 study , we recruited women ( aged ≥18 years ) who had measurable platinum-sensitive , relapsed , high- grade serous or endometrioid ovarian , fallopian tube , or primary peritoneal cancer , or those with deleterious germline BRCA1/2 mutations from nine participating US academic medical centres . We r and omly allocated participants ( 1:1 ) according to permuted blocks , stratified by germline BRCA status and previous anti-angiogenic therapy , to receive olaparib capsules 400 mg twice daily or the combination at the recommended phase 2 dose of cediranib 30 mg daily and olaparib capsules 200 mg twice daily . The primary endpoint was progression-free survival analysed in the intention-to-treat population . The phase 2 trial is no longer accruing patients . An interim analysis was conducted in November , 2013 , after 50 % of expected events had occurred and efficacy results were unmasked . The primary analysis was performed on March 31 , 2014 , after 47 events ( 66 % of those expected ) . The trial is registered with Clinical Trials.gov , number NCT01116648 . FINDINGS Between Oct 26 , 2011 , and June 3 , 2013 , we r and omly allocated 46 women to receive olaparib alone and 44 to receive the combination of olaparib and cediranib . Median PFS was 17·7 months ( 95 % CI 14·7-not reached ) for the women treated with cediranib plus olaparib compared with 9·0 months ( 95 % CI 5·7 - 16·5 ) for those treated with olaparib monotherapy ( hazard ratio 0·42 , 95 % CI 0·23 - 0·76 ; p=0·005 ) . Grade 3 and 4 adverse events were more common with combination therapy than with monotherapy , including fatigue ( 12 patients in the cediranib plus olaparib group vs five patients in the olaparib monotherapy group ) , diarrhoea ( ten vs none ) , and hypertension ( 18 vs none ) . INTERPRETATION Cediranib plus olaparib seems to improve PFS in women with recurrent platinum-sensitive high- grade serous or endometrioid ovarian cancer , and warrants study in a phase 3 trial . The side-effect profile suggests such investigations should include assessment s of quality of life and patient-reported outcomes to underst and the effects of a continuing oral regimen with that of intermittent chemotherapy . FUNDING American Recovery and Reinvestment Act grant from the National Institutes of Health ( NIH ) ( 3 U01 CA062490 - 16S2 ) ; Intramural Program of the Center for Cancer Research ; and the Division of Cancer Treatment and Diagnosis , National Cancer Institute , NIH BACKGROUND Tamoxifen and gefitinib ( IRESSA ) combination therapy was studied in patients with ovarian cancer refractory or resistant to platinum- and taxane-based therapy . PATIENTS AND METHODS In this phase II study , 56 patients with epithelial ovarian carcinoma or cancer of the fallopian tube or peritoneum received oral tamoxifen 40 mg/day and gefitinib 500 mg/day until progression or unacceptable toxicity . RESULTS Seventeen patients ( mean age : 59.6 years ) had previously received first-line platinum/taxane treatment only , while 39 had received 2 - 8 ( median 2 ) prior chemotherapy regimens . Gefitinib dose reduction to 250 mg/day was performed in 10 patients ( 14.9 % ) , predominantly due to diarrhea ( 6 patients [ 10.7 % ] ) . Trial medication was discontinued in 6 patients ( 10.7 % ) due to adverse events ( AEs ) . The most frequent drug-related AEs were diarrhea and acne-like skin rash . There were no tumor responses , but 16 patients had stable disease . Median time-to-progression was 58 days ( 95 % CI , 55 - 71 days ) and median survival was 253 days ( 95 % CI , 137 - 355 days ) . CONCLUSION Gefitinib plus tamoxifen did not appear to be efficacious in the treatment of patients with refractory/resistant ovarian cancer . The addition of tamoxifen did not worsen the known side effects of gefitinib , or induce additional side effects PURPOSE Inhibiting angiogenesis is one of the most promising avenues for new therapies for ovarian cancer . We investigated the efficacy and safety of a novel agent , BIBF 1120 , a triple angiokinase inhibitor , after chemotherapy for relapsed disease . PATIENTS AND METHODS We conducted a r and omized , double-blind , controlled phase II trial in 83 patients who had just completed chemotherapy for relapsed ovarian cancer , with evidence of response , but at high risk of further early recurrence . The patients were r and omly assigned to receive maintenance therapy using BIBF 1120 250 mg or placebo , twice per day , continuously for 36 weeks . End points were progression-free survival ( PFS ) , toxicity , and overall survival . RESULTS Thirty-six-week PFS rates were 16.3 % and 5.0 % in the BIBF 1120 and placebo groups , respectively ( hazard ratio , 0.65 ; 95 % CI , 0.42 to 1.02 ; P = .06 ) . Four patients continued on BIBF 1120 , including two patients for another year or more . The proportion of patients with any grade 3 or 4 adverse events was similar between the groups ( 34.9 % for BIBF 1120 v 27.5 % for placebo ; P = .49 ; mostly grade 3 ) . However , more patients on BIBF 1120 experienced diarrhea , nausea , or vomiting ( mainly grade 1 or 2 and no grade 4 ) . There was a higher rate of grade 3 or 4 hepatotoxicity in patients on BIBF 1120 ( 51.2 % ) compared with patients on placebo ( 7.5 % ; P < .001 ) , but this was rarely of clinical significance , and patients continued with the trial treatment . A single-level dose reduction to 150 mg was made in 15 patients , all on active drug . CONCLUSION BIBF 1120 is well tolerated and associated with a potential improvement in PFS . The observed treatment effect is sufficient to justify further study within a large phase III trial Purpose Sorafenib is a novel oral anticancer agent targeting signal transduction and angiogenic pathways through inhibitory effects against MAP kinases and vascular endothelial growth factor receptor-2 . The objectives of this neoadjuvant phase II-trial in patients with advanced epithelial ovarian cancer were to assess the activity and tolerability of the combination therapy of carboplatin/paclitaxel with multi-target tyrosine kinase inhibitor sorafenib . Material s and methods Patients with histologically proven stage IIIC or IV disease and large volume ascites were eligible . Enrolled patients received 2 of 6 cycles carboplatin ( area under the curve 5 ) and paclitaxel ( 175 mg/m2 ) preoperatively and concomitant sorafenib 400 mg twice daily . After four cycles of postoperative chemotherapy , a maintenance phase of single agent oral sorafenib through 1 year was planned . This phase II- study was planned with a sample size of 102 patients and progression-free survival as primary study endpoint . Results Four patients were enrolled . After preoperative treatment and cytoreductive surgery , all patients were excluded from protocol due to severe toxicities . Three patients had life threatening events ( cardiac output failure , myocardial infa rct ion , anastomotic leak ) ; two patients had primary progressive disease . The study was terminated on the basis of the recommendation of an independent data safety monitoring board . Conclusion The addition of sorafenib to carboplatin/paclitaxel chemotherapy was not feasible within this neoadjuvant regimen in primary advanced ovarian cancer . Although the occurrence of serious adverse events might have emerged at r and om , a detrimental effect of preoperative study medication could not be denied . Further evaluations of sorafenib in ovarian cancer are warranted 5008 Background : Cabozantinib ( Cabo ) is an oral , potent inhibitor of MET and VEGFR2 . MET over-expression has been observed in advanced ovarian cancer ( OC ) . Anti-VEGF pathway agents have shown clinical benefit in pts w/ OC . Simultaneous targeting of the MET and VEGF signaling pathways with Cabo may therefore be a promising treatment strategy . METHODS Epithelial OC pts with progressive measurable disease ( mRECIST ) received Cabo at 100 mg qd PO over a 12 wk Lead-in stage . Up to 2 prior regimens are allowed for platinum-resistant ( R ) , and up to 3 prior regimens for platinum-sensitive ( S ) pts . Tumor response was assessed every 6 wks . Treatment ≥ wk 12 was based on response : pts with PR continued open-label Cabo , pts with SD were r and omized to Cabo vs placebo , and pts with PD discontinued . Primary endpoint was ORR per mRECIST in the Lead-in stage , and progression free survival ( PFS ) in the r and omized period . Accrual in any cohort could be halted for either high rates of ORR or PD . RESULTS Accrual was halted at 68 pts based on an observed high rate of clinical activity . The median number of prior systemic treatments was 2 . Most common related AEs ≥ Grade 3 were h and -foot syndrome ( 10 % ) , diarrhea ( 8 % ) and fatigue ( 4 % ) . Dose reductions and permanent discontinuations for AEs occurred in 43 % and 10 % of pts , respectively . Of 51 pts evaluable for mRECIST RR at 12 wks , 28 are R , 17 are S , and 6 have unknown status . mRECIST RR at 12 wks : overall = 12/51(24 % ) , R = 5/28(18 % ) ; S= 5/17(29 % ) . Five additional PRs await confirmation . The overall DCR ( PR+SD ) at wk 12 is 58 % ( 30/51 ) . After a median f/u of 4 mos ( range : 1 to 11 mos ) , the median duration of response and median PFS have not been reached . CA125 responses ( assessed by GCIG criteria ) in 40 pts with ≥1 post-baseline result : 7/40 ( 18 % ) . Median maximum increase in hemoglobin ( Hb ) in anemic pts ( Hb < 11 g/dL ) was 1.9 g/dL ( N=8 in pts w/ ≥ 6 wk f/u ; range , 1.1 - 3.2 g/dL ) . All maximum Hb changes occurred w/in the first 12 wks . R and omization in this cohort was halted & pts unblinded due to observed efficacy . CONCLUSIONS Cabo exhibits clinical activity in ovarian cancer pts with advanced disease , regardless of prior platinum status , as reflected by high rates of response Purpose : To evaluate clinical activity and target modulation of v and etanib in women with recurrent ovarian cancer . Experimental Design : A phase II trial of orally administered v and etanib 300 mg daily was design ed to include analyses of target inhibition through paired biopsies and dynamic imaging . Core 18-gauge needle biopsies and dynamic contrast-enhanced magnetic resonance imaging were obtained before initiation of therapy and 6 weeks into therapy . Biopsy sample s were subjected to reverse-phase protein lysate array endpoint analysis . Cytokine concentrations were measured by enzyme-linked immunosorbent assay in serially collected plasma sample s. Results : Twelve patients entered the study , and accrual was terminated in the first stage because of lack of response or disease stabilization beyond 6 months . Adverse events included rash , diarrhea , and prolonged QT interval corrected for heart rate , but not hypertension . Exploratory analyses showed that epidermal growth factor receptor ( EGFR ) phosphorylation was reduced in the eight paired biopsy sets obtained ; vascular endothelial growth factor ( VEGF ) receptor-2 phosphorylation was not consistently affected nor were dynamic contrast-enhanced MRI permeability and flow parameters . Serial plasma VEGF concentrations were variable and did not significantly change in the 11 patients assessed . Conclusions : V and etanib 300 mg daily monotherapy had no significant clinical benefit in this disease setting . Proteomic analysis of paired biopsies detected both phosphorylated-EGFR and phosphorylated-VEGF receptor-2 in ovarian tumor tissue , but only phosphorylated-EGFR was measurably inhibited by v and etanib . Clin Cancer Res ; 16(2 ) ; The primary objective of this study was to evaluate the biochemical effects of gefitinib on its target signal‐transduction pathways in patients with recurrent epithelial ovarian cancer ( EOC ) . The secondary objectives included assessing clinical activity and toxicity and determining the association between biochemical and clinical outcomes BACKGROUND The purpose of this study was to determine whether adding the anti-epidermal growth factor receptor ( EGFR ) tyrosine kinase inhibitor erlotinib to carboplatin/paclitaxel improved pathologic complete response ( pCR ) at re assessment surgery in epithelial ovarian , fallopian tube , or primary peritoneal cancers ( OFPC ) . METHODS Patients with stage III-IV OFPC initiated treatment within 12 weeks of initial cytoreductive surgery or , after histologic confirmation of diagnosis , neoadjuvantly . Treatment included paclitaxel ( 175 mg/m² ) and carboplatin ( AUC 6 ) every 3 weeks for up to 6 cycles , plus oral erlotinib 150 mg daily . The primary objective was to determine whether the pCR rate at re assessment surgery was at least 60 % after optimal cytoreduction at initial surgery ( < 1 cm residual disease ) , or at least 40 % after suboptimal cytoreduction ( at least 1 cm residual disease ) using a two-stage design ( alpha=0.10 , beta=0.10 ) . RESULTS The study population included 56 patients with stage III-IV OFPC . EGFR gene amplification was present in 15 % of the 20 tumors evaluated . Twenty-eight patients had protocol therapy after optimal cytoreduction ( stratum I ) , 23 had protocol therapy either after suboptimal cytoreduction ( stratum II ) , and 5 received neoadjuvant therapy prior to cytoreduction ( stratum III ) . Pathologic CR was confirmed in 8 patients ( 29 % ; 95 % confidence intervals 13 % , 49 % ) in stratum I and 3 patients ( 11 % , 95 % C.I. 2 % , 28 % ) in stratum II , which did not meet the prespecified efficacy endpoint in either stratum . CONCLUSIONS Among unselected patients , erlotinib plus carboplatin-paclitaxel did not improve pCR rates compared with historical experience with carboplatin-paclitaxel alone in patients with stage III-IV OFPC OBJECTIVES The objectives of this phase II trial were to assess the activity and tolerability of the combination of bevacizumab and erlotinib in patients with recurrent ovarian , primary peritoneal or fallopian tube cancer . METHODS This was a single arm , multicenter phase II trial with overall objective response as the primary endpoint . Eligible patients had two or fewer prior chemotherapy regimens for recurrent or refractory disease and no prior anti-VEGF or anti-EGFR agents . Bevacizumab , 15 mg/kg , was administered intravenously every 21 days and erlotinib , 150 mg orally , was given daily . RESULTS Between July and October 2005 , 13 patients were enrolled . There were two major objective responses , one complete response of 16 + month duration and one partial response of 11 month duration , for a response rate of 15 % ( 95 % CI 1.9 % to 45.4 % ) . Seven patients had a best response of stable disease . The most common grade 3 or 4 toxicities included anemia ( n=1 ) , nausea ( n=2 ) , vomiting ( n=1 ) , hypertension ( n=1 ) , and diarrhea ( n=2 ) . One patient with an ileostomy was removed from the study secondary to grade 3 diarrhea . Two patients had fatal gastrointestinal perforations . CONCLUSION There was no strong suggestion that this combination was superior to single agent bevacizumab , and the rate of gastrointestinal perforation was of concern . The study was therefore stopped . Identification of risk factors for gastrointestinal perforation will be of importance for the use of bevacizumab in the treatment of ovarian cancer Purpose : This phase II trial evaluated bevacizumab plus erlotinib in platinum-resistant ovarian cancer ; exploratory biomarker analyses , including that of tumor vascular endothelial growth factor A ( VEGF-A ) , were also done . Experimental Design : Forty heavily pretreated patients received erlotinib ( 150 mg/d orally ) and bevacizumab ( 10 mg/kg i.v . ) every 2 weeks until disease progression . Primary end points were objective response rate and response duration ; secondary end points included progression-free survival ( PFS ) , toxicity , and correlations between angiogenic protein levels , toxicity , and efficacy . Results : Grade 3 toxicities included skin rash ( n = 6 ) , diarrhea ( n = 5 ) , fatigue ( n = 4 ) , and hypertension ( n = 3 ) . Grade 4 toxicities were myocardial infa rct ion ( n = 1 ) and nasal septal perforation ( n = 1 ) . Only one grade 3 fistula and one grade 2 bowel perforation were observed . Nine ( 23.1 % ) of 39 evaluable patients had a response ( median duration , 36.1 + weeks ; one complete response ) , and 10 ( 25.6 % ) patients achieved stable disease , for a disease control rate of 49 % . Median PFS was 4 months , and 6-month PFS was 30.8 % . Biomarker analyses identified an association between tumor cell VEGF-A expression and progression ( P = 0.03 ) ; for every 100-unit increase in the VEGF-A score , there was a 3.7-fold increase in the odds of progression ( 95 % confidence interval , 1.1 - 16.6 ) . Conclusions : Bevacizumab plus erlotinib in heavily pretreated ovarian cancer patients was clinical ly active and well tolerated . Erlotinib did not seem to contribute to efficacy . Our study raises the intriguing possibility that high levels of tumor cell VEGF-A , capable of both autocrine and paracrine interactions , are associated with resistance to bevacizumab , emphasizing the complexity of the tumor microenvironment . Clin Cancer Res ; 16(21 ) ; 5320–8 . © 2010 AACR BACKGROUND Recurrent platinum-resistant ovarian cancer usually has a poor outcome with conventional chemotherapeutic therapy and new treatment modalities are warranted . This phase II study was conducted to evaluate sunitinib , an oral antiangiogenic multitargeted tyrosin kinase inhibitor , in this setting . MATERIAL AND METHODS The primary end point of this r and omized phase II trial was the objective response rate according to RECIST criteria and /or Gynecologic Cancer InterGroup CA125 response criteria to sunitinib in patients with recurrent platinum-resistant ovarian cancer who were pretreated with up to three chemotherapies . A selection design was employed to compare two schedules of sunitinib ( arm 1 : 50 mg sunitinib daily orally for 28 days followed by 14 days off drug ; and arm 2 : 37.5 mg sunitinib administered daily continuously ) . RESULTS Of 73 patients enrolled , 36 patients were r and omly allocated to the noncontinuous treatment arm ( arm 1 ) and 37 patients were r and omly allocated to the continuous treatment arm ( arm 2 ) . The mean age was 58.8 and 58.5 years , respectively . We observed six responders ( complete response + partial response ) in arm 1 ( 16.7 % ) and 2 responders in arm 2 ( 5.4 % ) . The median progression-free survival ( arm 1 : 4.8 [ 2.9 - 8.1 ] months ; arm 2 : 2.9 [ 2.9 - 5.1 ] months ) and the median overall survival ( arm 1 : 13.6 [ 7.0 - 23.2 ] months ; arm 2 : 13.7 [ 8.4 - 25.6 ] months ) revealed no significant difference . Adverse events included fatigue as well as cardiovascular , gastrointestinal and abdominal symptoms , hematologic and hepatic laboratory abnormalities . Pattern and frequency of adverse events revealed no substantial differences between both treatment groups . CONCLUSIONS Sunitinib treatment is feasible and moderately active in relapsed platinum-resistant ovarian cancer . The noncontinuous treatment schedule should be chosen for further studies in ovarian cancer PURPOSE Pazopanib is an oral , multikinase inhibitor of vascular endothelial growth factor receptor ( VEGFR ) -1/-2/-3 , platelet-derived growth factor receptor ( PDGFR ) -α/-β , and c-Kit . Pre clinical and clinical studies support VEGFR and PDGFR as targets for advanced ovarian cancer treatment . This study evaluated the role of pazopanib maintenance therapy in patients with ovarian cancer whose disease did not progress during first-line chemotherapy . PATIENTS AND METHODS Nine hundred forty patients with histologically confirmed cancer of the ovary , fallopian tube , or peritoneum , International Federation Gynecology Obstetrics ( FIGO ) stages II-IV , no evidence of progression after primary therapy consisting of surgery and at least five cycles of platinum-taxane chemotherapy were r and omized 1:1 to receive pazopanib 800 mg once per day or placebo for up to 24 months . The primary end point was progression-free survival by RECIST 1.0 assessed by the investigators . RESULTS Maintenance pazopanib prolonged progression-free survival compared with placebo ( hazard ratio [ HR ] , 0.77 ; 95 % CI , 0.64 to 0.91 ; P = .0021 ; median , 17.9 v 12.3 months , respectively ) . Interim survival analysis based on events in 35.6 % of the population did not show any significant difference . Grade 3 or 4 adverse events of hypertension ( 30.8 % ) , neutropenia ( 9.9 % ) , liver-related toxicity ( 9.4 % ) , diarrhea ( 8.2 % ) , fatigue ( 2.7 % ) , thrombocytopenia ( 2.5 % ) , and palmar-plantar erythrodysesthesia ( 1.9 % ) were significantly higher in the pazopanib arm . Treatment discontinuation related to adverse events was higher among patients treated with pazopanib ( 33.3 % ) compared with placebo ( 5.6 % ) . CONCLUSION Pazopanib maintenance therapy provided a median improvement of 5.6 months ( HR , 0.77 ) in progression-free survival in patients with advanced ovarian cancer who have not progressed after first-line chemotherapy . Overall survival data to this point did not suggest any benefit . Additional analysis should help to identify subgroups of patients in whom improved efficacy may balance toxicity ( NCT00866697 ) Objectives : Antiangiogenic strategies have demonstrated efficacy in epithelial ovarian cancer ( EOC ) . Sorafenib is a novel multitargeted kinase inhibitor with antiangiogenic activity . Gemcitabine has known activity against EOC . A phase 1 clinical trial of this combination suggested activity in ovarian cancer with no dose-limiting toxicity . This phase 2 study was design ed to examine the safety and efficacy of gemcitabine and sorafenib in patients with recurrent EOC . Methods : Patients with recurrent EOC after platinum-based chemotherapy and who had subsequently received up to 3 prior chemotherapy regimens were eligible . Gemcitabine ( 1000 mg/m2 intravenous [ IV ] ) was administered weekly for 7 of 8 weeks in the first cycle , then weekly for 3 weeks of each subsequent 4-week cycle . Sorafenib ( 400 mg p.o . bid ) was given continuously . The primary end point for this trial was objective response rate by the Response Evaluation Criteria in Solid Tumors . Secondary endpoints included Gynecologic Cancer Intergroup ( GCIG ) CA-125 response , time to progression , overall survival , and toxicity . Results : Forty-three patients were enrolled , and 33 completed at least 1 cycle . Two patients had a partial response ( Response Evaluation Criteria in Solid Tumors objective response rate = 4.7 % ) . Ten patients ( 23.3 % ) maintained response or stable disease for at least 6 months . GCIG CA-125 response was 27.9 % . The median time to progression was 5.4 months , and the median overall survival was 13.0 months . Hematologic toxicity was common but manageable . The most common nonhematologic adverse events were h and -foot syndrome , fatigue , hypokalemia , and diarrhea . Conclusion : This trial of gemcitabine and sorafenib in recurrent EOC did not meet its primary efficacy end point , but the combination was associated with encouraging rates of prolonged stable disease and CA-125 response Purpose : This phase II trial assessed the activity and tolerability of a daily oral dose of 500 mg gefitinib ( ZD1839 , Iressa ) in patients with recurrent or persistent epithelial ovarian or primary peritoneal carcinoma , and explored the clinical value of determining the status of the epidermal growth factor receptor ( EGFR ) . Experimental Design : Primary measure of efficacy was progression-free survival at 6 months . Mutations in exons 18 to 21 of EGFR and /or immunohistochemical expression of EGFR were evaluated in tumor specimens from patients enrolled in this trial as well as from patients not treated with gefitinib . Results : Twenty-seven of 30 ( 90 % ) patients were eligible and evaluable for analysis of gefitinib efficacy and toxicity . Of these , four survived progression-free > 6 months with one objective response ( 4 % ) . The most commonly observed grade 3 toxicities were dermatologic ( 15 % , 4 of 27 ) and diarrhea ( 30 % , 8 of 27 ) . Specimens from 26 of 26 or 25 of 26 patients were evaluable for immunohistochemical or mutation analysis , respectively . The response rate for patients with EGFR-positive tumors was 9 % ( 1 of 11 ) . EGFR expression was associated with longer progression-free survival ( P = 0.008 ) and possibly longer survival ( P = 0.082 ) . The patient with the only objective response had a mutation in the catalytic domain of the tumor 's EGFR ( P = 0.04 ) . Among 32 invasive tumors from patients not treated with gefitinib , one exhibited a catalytic domain mutation . Conclusions : Gefitinib was well tolerated but had minimal activity in unscreened patients with recurrent ovarian or primary peritoneal carcinoma . Prescreening patients for activating mutations in EGFR may improve response rate to gefitinib . This report is the first to document activating mutations in catalytic domain of EGFR in 3.5 % ( 2 of 57 ) of ovarian cancers OBJECTIVES Sorafenib , an oral multikinase inhibitor of the VEGFR/PDGFR/Raf/MEK/ERK pathway , has shown potential activity in patients with recurrent ovarian cancer ( OC ) . One strategy to prolong disease control and survival in patients with OC is maintenance therapy after achieving a complete response . A double-blind , r and omized , placebo-controlled , phase II study to assess the efficacy and safety of maintenance therapy with sorafenib in the treatment of OC is presented . METHODS Patients with epithelial OC or primary peritoneal cancer in complete remission were r and omized to sorafenib 400 mg BID or matching placebo . The primary endpoint was progression-free survival ( PFS ) . RESULTS Of 246 r and omized patients , 93 % had OC ; baseline characteristics were balanced between treatment arms . There was no significant difference between sorafenib and placebo arms for PFS ( median 12.7 vs 15.7 months ; hazard ratio 1.09 ; 95 % CI 0.72 - 1.63 ) , although there was a notable imbalance in early censoring . The most common ≥ grade 3 adverse events ( AEs ) were h and -foot skin reaction ( 39.0 % vs 0.8 % ) and rash ( 14.6 % vs 0 % ) . More patients receiving sorafenib versus placebo required dose reductions ( 67.5 % vs 30.1 % ) , result ing in a lower than planned median daily dose ( median 584.6 vs 800.0 mg ) . Treatment with sorafenib was of shorter duration ( median 17.6 vs 51.9 weeks ) with more frequent discontinuations due to AEs ( 37.4 % vs 6.5 % ) . CONCLUSIONS Sorafenib 400 mg BID can not be recommended as maintenance therapy for patients with OC in complete remission . Assessment of efficacy was limited by the high rate of dose reductions and early discontinuations PURPOSE To evaluate the antitumor activity and toxicity of two doses of CI-1033 in patients with platinum-refractory or recurrent ovarian cancer , and to determine baseline expression of epidermal growth factor receptor in tumor cells . PATIENTS AND METHODS This phase II , open-label clinical trial evaluated CI-1033 in patients with ovarian cancer who failed prior platinum-based therapy . Two oral doses of CI-1033 were evaluated -- a 50-mg and a 200 - -mg oral dose administered daily for 21 days in a 28-day cycle . Patients were evaluated for tumor response and toxicity ; in addition , archival baseline tumor sample s were analyzed by immunohistochemistry for erbB1 to erbB4 status . RESULTS One hundred five eligible patients were treated . Baseline demographic characteristics were balanced in this heavily pretreated patient population . The median number of prior chemotherapy regimens received was four . The most commonly encountered drug-related adverse events for both dose arms were gastrointestinal ( diarrhea , nausea , stomatitis ) toxicity , asthenia , and rash . No responses were observed . Stable disease was confirmed in 34 % and 26 % of patients in the 200-mg and 50-mg arms , respectively , and 1-year survival rates were 38.5 % and 37.7 % , respectively . Baseline erbB3 and erbB4 revealed the highest frequencies of expression , while erbB2 was the lowest . CONCLUSION CI-1033 did not show activity in unscreened patients with advanced ovarian cancer . At 50 mg/d , CI-1033 had a more favorable adverse events profile than at 200 mg/d . erbB3 and erbB4 receptors showed the highest expression in tumor sample s while erbB2 revealed the least . There appears to be no association between baseline erbB expression and disease stability OBJECTIVE Imatinib mesylate ( IM , Gleevec ) , a potent PDGF/PDGFR tyrosine kinase inhibitor , affects stroma and vascular endothelial cells . Our study sought to determine the safety and activity of paclitaxel with an intermittent schedule of IM . MATERIAL S AND METHODS rEOC patients previously treated with platinum/paclitaxel and ≤2 regimens for recurrence were enrolled . Paclitaxel 80 mg/m2 was given on days 3 , 10 , 17 every 28 days and oral IM 300 mg bid on days 1 - 4 , 8 - 11 , and 13 - 18 . RESULTS Between 2007 - 2009 , 14 patients enrolled , 12 were evaluable . Nine patients were on study at 12 weeks . Objective responses ( by RECIST and /or CA125 ) occurred in 4 patients . There were no grade 4 , and only four grade 3 toxic events : diarrhea , edema and 2 cases of neutropenia . Early study closure was due to sufficient safety information with preliminary encouraging efficacy results . CONCLUSION This weekly paclitaxel regimen with intermittent IM is tolerable with anti-tumor activity , making it suitable as part of future studies Platinum-resistant ovarian cancer continues to be a difficult therapeutic problem . Clearly , molecularly targeted agents should be evaluated in this patient population . Patients were eligible for this phase II study with stage III or IV ovarian cancer , whose tumor expressed Kit ( CD117 ) or platelet-derived growth factor receptor ( PDGFR ) and with relapse of measurable disease within 6 months of completing frontline , platinum- and taxane-based chemotherapy . Patients were treated daily with 400 mg of imatinib mesylate orally . It was assumed that the agent would be of no further interest if the population response rate was less than 10 % . A two-stage design was used for patient accrual . A total of 34 patients were registered to the study . Of these , 15 were found to be ineligible or not evaluable ( 8 because their tumor sample s were negative for both DC117 and PDGFR ) . Of 19 evaluable patients , 2 ( 11 % ) tested positively for c-Kit and 17 ( 89 % ) tested positively for PDGFR . There were no objective responders . Thirteen patients ( 68 % ) had increasing disease or symptomatic deterioration , and six ( 32 % ) went off protocol during the first month due to adverse events . Median progression-free survival was 2 months ( 95 % CI 1–3 months ) and median overall survival was 10 months ( 95 % CI 6–18 months ) . Eleven percent of patients experienced grade 4 hematologic/metabolic toxicity and 37 % experienced grade 3 nonhematologic toxicity . We conclude that imatinib mesylate as a single agent does not appear to have useful clinical activity in c-Kit and /or PDGFR positive , recurrent ovarian cancer in heavily pretreated patients with ovarian Ovarian tumors frequently express c‐Kit and /or platelet‐derived growth factor receptors ( PDGFRs ) . Imatinib mesylate blocks the growth of ovarian cancer cells in vitro and may enhance the activity of chemotherapy . This study was conducted to determine the activity of imatinib in combination with docetaxel in patients with recurrent , platinum‐resistant epithelial ovarian cancer ( EOC ) PURPOSE New agents are required for the patients with epithelial ovarian cancer ( EOC ) who progress after first and second line of the treatment . Tumor vasculature targeted agents are potentially active in EOC . We aim ed to assess the activity of sorafenib in patients with recurrent EOC who had received two prior therapies . PATIENTS AND METHODS A phase II non-r and omized , open-label , single-arm study aim ed to assess the efficacy , safety and tolerance of sorafenib monotherapy as a third line therapy in patients with EOC or primary peritoneal cancer ( PPC ) . Sorafenib was administered as 400 mg twice daily on days 1 - 28 of each 4-week cycle . The primary end point of the study was to demonstrate the progression free survival ( PFS ) . RESULTS Eleven patients were enrolled . The median number of cycles was two . Among the 11 patients eligible for efficacy analysis , no patients experienced a partial response or complete response or stable disease lasting longer than 6 months according to RECIST criteria . Thus , the trial stopped at the end of the first stage of study design . The median PFS was 2.00 months ( 95 % CI , 1,80 - 3,90 ) . The median OS was 11.78 months ( 95 % CI , 7.66 to 15.39 ) . There were no grade 4 toxicities and few grade 3 toxicities . CONCLUSION Sorafenib fails to achieve sufficient objective response or sustained disease stabilization as third-line treatment for EOC PURPOSE Cediranib is a potent multitargeted inhibitor of vascular endothelial growth factor receptor ( VEGFR ) 1 , 2 and 3 . The study was initiated to evaluate the activity of cediranib in patients ( pts ) with recurrent ovarian , peritoneal or fallopian tube cancer ( OC ) . METHODS Eligible pts had persistent/recurrent OC following one prior platinum-based chemotherapy with measurable disease or progression based on Gynecologic Cancer Inter Group CA-125 criteria . Because of toxicities observed in the first 23 pts , the initial starting dose of oral daily ( od ) cediranib was reduced from 45 mg to 30 mg . The primary endpoint was objective response rate at 16weeks . This study was stratified into two arms : platinum-sensitive ( PL-S ) and platinum-resistant ( PL-R ) . RESULTS 74 pts were enrolled ; 39 were PL-S and 35 PL-R , with a median age of 58years [ 31 - 87 ] . In PL-S group , 10 ( 26 % ) partial responses ( PR ) and 20 ( 51 % ) stable disease ( SD ) were confirmed while in the PL-R arm there were no confirmed PR and 23 pts ( 66 % ) had SD . The main grade 3/4 toxicities observed at the 30 mg starting dose were hypertension ( 27 % ) , fatigue ( 20 % ) and diarrhea ( 14 % ) . The median progression-free survival for all patients was 4.9months [ 3.9 - 7.0 ] , 7.2months [ 4.3 - 9 ] for PL-S and 3.7months [ 2.6 - 4.5 ] for PL-R groups . The median overall survival was 18.9months ( 95 % CI : 13.5 - 31.5 ) ; 27.7months [ 17.8 - 43.3 ] for PL-S and 11.9months [ 8.1 - 18.9 ] for PL-R groups . CONCLUSION Cediranib shows significant activity in recurrent platinum sensitive OC . The toxicities were expected and manageable at the dose of 30 mg od PURPOSE Sunitinib is a multitargeted receptor tyrosine kinase inhibitor . We conducted a two-stage phase II study to evaluate the objective response rate of oral sunitinib in recurrent epithelial ovarian cancer . PATIENTS AND METHODS Eligibility required measurable disease and one or two prior chemotherapies , at least one platinum based . Platinum-sensitive or -resistant disease was allowed . Initial dose schedule was sunitinib 50 mg daily , 4 of 6 weeks . Observation of fluid accumulations during off-treatment periods result ed in adoption of continuous 37.5 mg daily dosing in the second stage of accrual . RESULTS Of 30 eligible patients , most had serous histology ( 67 % ) , were platinum sensitive ( 73 % ) and had two prior chemotherapies ( 60 % ) . One partial response ( 3.3 % ) and three CA125 responses ( 10 % ) were observed , all in platinum-sensitive patients using intermittent dosing . Sixteen ( 53 % ) had stable disease . Five had > 30 % decrease in measurable disease . Overall median progression-free survival was 4.1 months . Common adverse events included fatigue , gastrointestinal symptoms , h and -foot syndrome and hypertension . No gastrointestinal perforation occurred . CONCLUSIONS Single-agent sunitinib has modest activity in recurrent platinum-sensitive ovarian cancer , but only at the 50 mg intermittent dose schedule , suggesting that dose and schedule may be vital considerations in further evaluation of sunitinib in this cancer setting BACKGROUND We investigated whether the Src inhibitor saracatinib ( AZD0530 ) improved efficacy of weekly paclitaxel in platinum-resistant ovarian cancer . PATIENTS AND METHODS Patients with platinum-resistant ovarian , fallopian tube or primary peritoneal cancer were r and omised 2 : 1 to receive 8-week cycles of weekly paclitaxel ( wPxl ; 80 mg/m(2)/week ×6 with 2-week break ) plus saracatinib ( S ; 175 mg o.d . ) or placebo ( P ) continuously , starting 1 week before wPxl , until disease progression . Patients were stratified by taxane-free interval ( < 6 versus ≥6 months/no prior taxane ) . The primary end point was progression-free survival ( PFS ) rate at 6 months . Secondary end points included overall survival ( OS ) and response rate ( RR ) . RESULTS A total of 107 patients , median age 63 years , were r and omised . Forty-three ( 40 % ) had received > 2 lines of prior chemotherapy . The 6-month PFS rate was 29 % ( wPxl + S ) versus 34 % ( wPxl + P ) ( P = 0.582 ) . Median PFS was 4.7 versus 5.3 months ( hazard ratio 1.00 , 95 % confidence interval 0.65 - 1.54 ; P = 0.99 ) . RR ( complete + partial ) was 29 % ( wPxl + S ) versus 43 % ( wPxl + P ) , P value = 0.158 . Grade 3/4 adverse events were 36 % versus 31 % ( P = 0.624 ) ; the most frequent G3/4 toxicities were vomiting ( 5.8 % saracatinib versus 8.6 % placebo ) , abdominal pain ( 5.8 % versus 0 % ) and diarrhoea ( 4.3 % versus 5.7 % ) . Febrile neutropenia was more common in the saracatinib arm ( 4.3 % ) than placebo ( 0 % ) . Response , PFS and OS were all significantly ( P < 0.05 ) better in patients with taxane interval ≥6 months/no prior taxane ( n = 85 ) than those < 6 months ( n = 22 ) , regardless of r and omisation . CONCLUSIONS Saracatinib does not improve activity of weekly paclitaxel in platinum-resistant ovarian cancer . Taxane-free interval of ≥6 months/no prior taxane was associated with better outcome in both groups . TRIALS REGISTRATION Clinical trials.gov NCT01196741 ; IS RCT N 32163062 The aim of this single-arm , phase II study was to estimate the tumor response rate and safety profile of erlotinib HCl ( erlotinib , Tarceva ™ , OSI-774 ) monotherapy in patients with refractory , recurrent , HER1/EGFR-positive epithelial ovarian tumors , who had failed prior taxane and /or platinum-based chemotherapy . Thirty-four patients received 150 mg erlotinib orally once daily for up to 48 weeks or until disease progression or dose-limiting toxicity . Two patients had partial responses , lasting 8 + and 17 weeks , giving an objective response rate of 6 % ( 95 % confidence interval [ CI ] , 0.7–19.7 % ) . Fifteen patients ( 44 % ) had stable disease , and 17 patients ( 50 % ) had progressive disease . Median overall survival was 8 months ( 95 % CI , 5.7–12.7 months ) , with a 1-year survival rate of 35.3 % ( 95 % CI , 19.8–53.5 % ) . Patients with rash survived significantly longer than those without ( P = 0.009 ) , correlating with rash grade . Erlotinib was generally well tolerated . The most frequent erlotinib-related adverse events were rash ( 68 % ) and diarrhea ( 38 % ) . Erlotinib had marginal activity but was generally well tolerated . The safety profile appears more favorable than typically experienced with st and ard chemotherapeutic agents , which is encouraging in these heavily pretreated patients . Combination of erlotinib with chemotherapy or other targeted agents should be considered OBJECTIVE The progression-free and median survival of patients with advanced ovarian cancer has not appreciably improved over the last decade . Novel targeted therapies , particularly antiangiogenic agents , may potentially improve clinical outcomes in patients with ovarian cancer . This phase II , open-label study evaluated oral pazopanib monotherapy in patients with low-volume recurrent ovarian cancer . METHODS Patients with recurrent epithelial ovarian , fallopian tube , or primary peritoneal carcinoma with complete CA-125 response to initial platinum-based chemotherapy and subsequent elevation of CA-125 to ≥ 42 U/mL ( > 2 × ULN ) were treated with pazopanib 800 mg once daily until PD or unacceptable toxicity . This Green-Dahlberg study required 2 CA-125 responses in stage I ( 20 patients ) to proceed to stage II ( 15 patients ) . The primary endpoint was CA-125 response ( ≥ 50 % decrease from baseline , confirmed ≥ 21 days after initial evaluation ) . RESULTS Eleven of 36 patients ( 31 % ) had a CA-125 response to pazopanib , with median time to response of 29 days and median response duration of 113 days . Overall response rate was 18 % in patients with measurable disease at baseline . The most common adverse events leading to discontinuation of study drug were grade 3 ALT ( 8 % ) and AST ( 8 % ) elevation . Only 1 grade 4 toxicity ( peripheral edema ) was reported . CONCLUSIONS Pazopanib monotherapy was relatively well tolerated , with toxicity similar to other small-molecule , oral angiogenesis inhibitors , and demonstrated promising single-agent activity in patients with recurrent ovarian cancer . Further studies evaluating the potential role of pazopanib in patients with ovarian cancer are ongoing OBJECTIVE Ovarian cancer is a highly angiogenic tumor and a model for antiangiogenic research . The tyrosine kinase receptor inhibitors target several receptors allowing for the pharmacological disruption of several independent pathways . Sunitinib malate is a multitargeted tyrosine kinase inhibitor . A phase II study utilizing a modified dosing schedule was conducted to assess the efficacy and safety of Sunitinib in recurrent ovarian , fallopian tube and peritoneal carcinoma . METHODS A nonr and omized phase II study was modeled as a two-stage Simon design initially enrolling 17 evaluable participants in stage one and 18 patients in stage two . Patients received the study drug at 37.5 mg every day over a 28 day treatment cycle until clinical or radiological evidence of progressive disease . Disease was evaluated radiographically and best overall response was defined using the RECIST 1.0 criteria . The primary objective of this study was to define the response rate ( defined as complete response and partial response ) while the secondary objectives included both the progression free rate as well as the safety of this agent in this patient population . RESULTS The response rate ( PR+CR ) was 8.3 % ( 95 % confidence interval : 1.8 % , 22.5 % ) . The 16-week and 24 week progression-free survival estimate was 36 % ( 95 % confidence interval and 19.2 % ) , respectively . The median progression-free survival estimate was 9.9 weeks . Hypertension and gastrointestional events were the most common toxicities noted . CONCLUSIONS A modest response rate of 8.3 % was achieved with Sunitinib malate . This phase II study adds to the body of literature of VEGFR inhibitors and further underscores the need of defining a genetic angiogenic signature Objective Lapatinib , a tyrosine kinase inhibitor targeting epidermal growth factor receptor ( EGFR ) and human epidermal growth factor receptor 2 ( HER2 ) , also inhibits breast cancer resistance protein ( BCRP ) involved in resistance to topotecan . The aim of this multicenter study was to assess the efficacy of the combination topotecan-lapatinib in epithelial ovarian cancer relapsing after a first line of chemotherapy . Methods Patients having relapsed within 6 months ( n = 20 ) or between 6 and 12 months ( n = 19 ) received weekly topotecan ( 3.2 mg/m2 given intravenously on days 1 , 8 , and 15 ) and daily oral lapatinib ( 1250 mg ) . Translational studies were performed on tumor and serum . Results An objective ( partial ) response was observed for 5 patients ( 14 % ) , all with late relapse . The rates of overall benefits , including responses and stabilizations , were 37 % and 62 % in patients having relapsed within or after 6 months , respectively . Corresponding median time to progression were 58 and 94 days . The most frequent toxicity was hematological , including grade 4 neutropenia ( 18 % ) and thrombocytopenia ( 3 % ) . None of the tumors overexpressed HER2 or EGFR , and no mutation was found . Two Kras mutations were identified . Positive expressions of BCRP and cyclin A ( median , 70 % and 40 % ) were not correlated to the response to treatment . Conclusions This study failed to demonstrate a clinical benefit of lapatinib-topotecan compared to previously described activity with topotecan alone in a context of low levels of EGFR and HER2 expressions , and no biomarkers could be identified . The absence of correlation between BCRP expression and clinical outcomes suggests that other mechanisms of resistance to topotecan could predominate OBJECTIVE This trial determined the efficacy and tolerability of sorafenib and weekly topotecan in patients with platinum-resistant ovarian cancer ( OC ) or primary peritoneal carcinomatosis ( PPC ) . METHODS Primary endpoints were maximum tolerated dose of sorafenib with weekly topotecan ( phase I ) and response rate ( phase II ) . Secondary endpoints were progression free survival ( PFS ) , overall survival ( OS ) , toxicity , and rate of clinical benefit . Eligibility included recurrent platinum-resistant OC or PPC , <3 prior regimens , normal end-organ function . 3 + 3 dose escalation was used for phase I , sorafenib being tested at 400 mg and 800 mg orally daily . Topotecan dose was reduced from 4 mg/m(2 ) to 3.5mg/m(2 ) IV weekly . The phase II regimen was sorafenib 400 mg daily and topotecan 3.5mg/m(2 ) weekly on days 1 , 8 , 15 of a 28 days cycle . RESULTS 16 patients were enrolled in phase I and 14 patients in phase II . Median age was 52.5 years ( range 35 - 79 ) , 27 patients had OC , and 3 PPC . Median number of cycles administered was 2.5 ( 0 - 15 ) . There were 5 partial responses ( PR ) ( 16.7 % ) , and 14 patients ( 46.7 % ) with stable disease ( SD ) . Four PRs were recorded during phase I and 1 during phase II . One of those PRs occurred in a patient with platinum-sensitive disease . Grade 3/4 toxicities included leukopenia/neutropenia ( 23 % ) , thrombocytopenia ( 17 % ) , anemia ( 10 % ) , fatigue , nausea , vomiting ( 7 % each ) . One case of grade 3 h and -foot syndrome was recorded . CONCLUSIONS The combination of sorafenib and topotecan causes significant toxicity , precluding administration of full doses and result ing in modest clinical efficacy in platinum resistant OC or PPC OBJECTIVE Activation and dimerization of the ERBB family play a role in the pathogenesis and progression of ovarian cancer . We conducted a phase II trial to evaluate the activity and tolerability of lapatinib in patients with recurrent or persistent epithelial ovarian cancer ( EOC ) and to explore the clinical value of expression levels of epidermal growth factor receptors ( EGFR ) , phosphorylated EGFR , HER-2/neu , and Ki-67 , and the presence of EGFR mutations . METHODS Eligible patients had recurrent or persistent EOC or primary peritoneal carcinoma , measurable disease , and up to 2 prior chemotherapy regimens for recurrent disease . Patients were treated with lapatinib 1500 mg/day . The primary endpoint of efficacy was 6-month progression free survival ( PFS ) . RESULTS Twenty-five of 28 patients were eligible and evaluable for analysis of efficacy and toxicity . Two ( 8.0 % ) were alive and progression-free at 6 months . No objective responses were observed . There were 1 grade 4 toxicity ( fatigue ) and few grade 3 toxicities . Associations between Ki-67 with prior platinum-free interval , PFS , and a polymorphism in EGFR were suggested . CONCLUSIONS Lapatinib has minimal activity in recurrent ovarian cancer . Ki-67 expression may be associated with prior PFS and a polymorphism in EGFR exon 20 ( 2361G > A , Q787Q ) OBJECTIVE This phase II investigated efficacy and tolerability of gefitinib in combination with paclitaxel ( P ) and carboplatin ( C ) for second-line treatment of patients ( pts ) with ovarian , tubal or peritoneal adenocarcinoma . PATIENTS AND METHODS Women ( > 18 years ) with platinum-resistant/refractory ( relapsed<6 months ) , or platinum-sensitive ( relapsed > 6 months ) disease after first-line platinum-based and P chemotherapy . Pts received 6 - 8 cycles of gefitinib ( 500 mg/day ) , P ( 175 mg/m(2 ) 3 h infusion ) and C ( AUC 5 ) every 3 weeks , followed by gefitinib alone . The primary endpoint was objective response rate ( ORR ) ( RECIST or Rustin criteria ) . RESULTS Sixty-eight patients ( 26 resistant/refractory and 42 sensitive ) were enrolled ( median age : 57 years ) . ORR and disease control rates were 19.2 % and 69.2 % for resistant/refractory , and 61.9 % and 81.0 % , for sensitive disease . Median time to progression and overall median survivals were 6.1 and 16.9 months for resistant/refractory and 9.2 and 25.7 months for sensitive disease . Grade 3/4 toxicities ( in > or = 10 % patients ) were neutropenia ( 59 % ) , diarrhea ( 25 % ) , leukopenia ( 22 % ) , anemia ( 13 % ) , and acne ( 13 % ) . Two secondary myelodysplastic syndromes ( MDS ) and one secondary acute leukemia occurred during treatment , and one MDS 34 months after treatment discontinuation . CONCLUSION Gefitinib , administered in combination with paclitaxel and carboplatin , provides a good clinical response but associated with an increased risk of hematologic disorders OBJECTIVE Resistance to chemotherapy is a major challenge in the treatment of ovarian/peritoneal cancer . One purported mechanism of topotecan resistance is the breast cancer resistance protein ( BCRP ) and P-glycoprotein ( Pgp ) . We design ed a phase II clinical trial evaluating the efficacy and adverse event profile of concomitant topotecan and lapatinib , a small molecule pan-erbB inhibitor that can block BCRP/Pgp efflux of topotecan . METHODS Patients with platinum-refractory or resistant epithelial ovarian/peritoneal cancer were treated with topotecan 3.2 mg/m² IV on Day 1 , 8 and 15 and lapatinib 1250 mg PO daily , continuously in 28 day cycles . The primary endpoint was response rate . For correlative studies , archived tissue was assessed for expression of EGFR , HER2 , HIF-1α , CD31 , and BCRP . RESULTS Eighteen patients were enrolled and treated . Four experienced evidence of clinical benefit : one partial response and three with stable disease . Using a two-stage Simon design , the trial was stopped after the first stage due to insufficient activity . Grade s 3 + and 4 + adverse events ( AE ) were experienced in 14 and 4 patients , respectively . The most common grade 3/4 AE were neutropenia ( 56 % ) , thrombocytopenia ( 28 % ) , and diarrhea ( 22 % ) . CONCLUSIONS The combination of lapatinib plus topotecan for the treatment of platinum refractory/resistant epithelial ovarian cancer lacks sufficient activity to warrant further investigation . In particular , hematologic adverse events were substantial . Expression of correlative study markers did not reveal patterns of predicted benefit or toxicity . Disruption of erbB signaling and BCRP/Pgp efflux with lapatinib was insufficient for overcoming topotecan resistance , suggesting alternative mechanisms of resistance are involved OBJECTIVE To evaluate the efficacy and tolerability of imatinib mesylate in patients with recurrent low- grade serous carcinoma ( LGSC ) of the ovary , peritoneum , or fallopian tube . METHODS This open-label , single-institution phase II trial enrolled patients with platinum-resistant LGSC who had measurable disease , had received up to 4 platinum- and /or taxane-containing chemotherapy regimens , and had been previously screened for at least one imatinib targeted biomarker ( c-kit , platelet-derived growth factor receptor [PDGFR]-β , or bcr-abl ) . Imatinib ( 600 mg ) was administered daily for one 6-week course and continued in the absence of toxicity and disease progression . RESULTS Thirteen patients were enrolled ; 12 were evaluable for toxicity , and 11 were evaluable for response . A total of 17 courses were administered ( median , 1 course ; range , 1 - 5 courses ) . Complete or partial responses were not observed . One patient had stable disease for 7.3 months . c-Kit , bcr-abl , or PDGFR-β were present in 48 % , 77 % , and 100 % of patients , respectively . No correlation between best response ( stable disease ) and the presence of imatinib-targeted biomarkers was observed . Adverse events included grade 3 skin rash in one patient leading to discontinuation of the drug , and grade 3 febrile neutropenia and grade 2 weight gain in two patients leading to dose reductions . The most common grade 1 or 2 toxicities were fatigue ( 66 % ) , nausea/vomiting ( 66 % ) , and diarrhea ( 41 % ) ; grade 3 toxicities included skin rash and granulocytopenia events . No grade 4 or 5 toxicities were observed . The median progression-free survival time was 1.3 months ( 95 % CI , 1.27 , 1.40 months ) , and the median overall survival time was 14.9 months ( 95 % CI , 11.0 , 18.9 months ) . CONCLUSION Imatinib is well-tolerated but has no activity in patients with platinum- and taxane-resistant LGSC or the ovary , peritoneum , or fallopian tube PURPOSE Sorafenib is a kinase inhibitor targeting Raf and other kinases ( ie , vascular endothelial growth factor receptor [ VEGFR ] , platelet-derived growth factor receptor [ PDGFR ] , Flt3 , and c-KIT ) . This study assessed its activity and tolerability in patients with recurrent ovarian cancer ( OC ) or primary peritoneal carcinomatosis ( PPC ) . METHODS This open-label , multi-institutional , phase II study used a two-stage design . Eligible patients had persistent or recurrent OC/PPC after one to two prior cytotoxic regimens , and they experienced progression within 12 months of platinum-based therapy . Treatment consisted of sorafenib 400 mg orally twice per day . Primary end points were progression-free survival ( PFS ) at 6 months and toxicity by National Cancer Institute criteria . Secondary end points were tumor response and duration of PFS and overall survival . Biomarker analyses included measurement of ERK and b-Raf expression in tumors and phosphorylation of ERK ( pERK ) in peripheral-blood lymphocytes ( PBLs ) before and after 1 month of treatment . Results Seventy-three patients were enrolled , of which 71 were eligible . Fifty-nine eligible patients ( 83 % ) had measurable disease , and 12 ( 17 % ) had detectable disease . Significant grade 3 or 4 toxicities included the following : rash ( n = 7 ) , h and -foot syndrome ( n = 9 ) , metabolic ( n = 10 ) , GI ( n = 3 ) , cardiovascular ( n = 2 ) , and pulmonary ( n = 2 ) . Only patients with measurable disease were used to assess efficacy . Fourteen survived progression free for at least 6 months ( 24 % ; 90 % CI , 15 % to 35 % ) . Two patients had partial responses ( 3.4 % ; 90 % CI , 1 % to 10 % ) ; 20 had stable disease ; 30 had progressive disease ; and seven could not have their tumor assessed . ERK and b-Raf were expressed in all tumors . Exploratory analyses indicated that pERK in post-treatment PBL specimens was associated with PFS . CONCLUSION Sorafenib has modest antitumor activity in patients with recurrent OC , but the activity was at the expense of substantial toxicity |
14,098 | 19,180,283 | Difficulties in accessing primary health care ( difficulties in setting appointments , longer waiting periods , and short business hours at the primary health care service ) were also associated with inappropriate ED use . | This systematic review aim ed to measure the prevalence of inappropriate emergency department ( ED ) use by adults and associated factors . | OBJECTIVES To study the morbidity patterns of non-urgent patients utilising accident and emergency services and compare these patients with ' true ' accident and emergency cases . To analyse the morbidity pattern of non-urgent cases over different time periods , and across different age groups . DESIGN A cross-sectional study completed over a 1-year period . SETTING Four accident and emergency departments in Hong Kong . PATIENTS Two thous and , four hundred and ten patients r and omly selected from four accident and emergency departments . MAIN OUTCOME MEASURES The morbidity patterns by body system , according to the International Classification of Primary Care , were tabulated and analysed for ' true ' accident and emergency cases versus non-urgent cases . The ten most frequent diagnoses for the ' true ' accident and emergency and non-urgent cases were also compared . Further analysis of accident and emergency service utilisation was conducted comparing different age groups , and also different time periods . RESULTS Significantly more cases presenting to the accident and emergency service with respiratory and digestive problems were found to be non-urgent , rather than appropriate accident and emergency cases . In contrast , significantly more cases presenting with circulatory and neurological problems were appropriate cases for accident and emergency department management . The morbidity pattern for the ten most frequent diagnoses seen in non-urgent cases was noted to be similar to the Hong Kong general practice morbidity pattern for self-limiting conditions . Utilisation of accident and emergency services for acute self-limiting conditions was more marked in the late evening , and also among children and the younger population in general . CONCLUSION The utilisation of accident and emergency services by patients requiring a general practice service only , reflects problems in the primary health care delivery system . These may be solved by appropriate interfacing between general practitioners and other service providers , with the aim of providing seamless health care . Without revision of primary health care services , accident and emergency departments will continue to be used inappropriately by patients as an alternative to general practice care CONTEXT Emergency department utilization by chronically ill older adults may be an important sentinel event signifying a breakdown in care coordination . A primary care group visit ( i.e. , several patients meeting together with the provider at the same time ) may reduce fragmentation of care and subsequent emergency department utilization . OBJECTIVE To determine whether primary care group visits reduce emergency department utilization in chronically ill older adults . DESIGN R and omized trial conducted over a 2-year period . SETTING Group-model HMO in Denver , Colorado . PATIENTS 295 older adults ( > or = 60 years of age ) with frequent utilization of outpatient services and one or more chronic illnesses . INTERVENTION Monthly group visits ( generally 8 to 12 patients ) with a primary care physician , nurse , and pharmacist held in 19 physician practice s. Visits emphasized self-management of chronic illness , peer support , and regular contact with the primary care team . MEASURES Emergency department visits , hospitalizations , and primary care visits . RESULTS On average , patients in the intervention group attended 10.6 group visits during the 2-year study period . These patients averaged fewer emergency department visits ( 0.65 vs. 1.08 visits ; P = 0.005 ) and were less likely to have any emergency department visits ( 34.9 % vs. 52.4 % ; P = 0.003 ) than controls . These differences remained statistically significant after controlling for demographic factors , comorbid conditions , functional status , and prior utilization . Adjusted mean difference in visits was -0.42 visits ( 95 % CI , -0.13 to -0.72 ) , and adjusted RR for any emergency department visit was 0.64 ( CI , 0.44 to 0.86 ) . CONCLUSION Monthly group visits reduce emergency department utilization for chronically ill older adults Accident and Emergency Departments ( A&E ) have been a popular source of primary care , and studies have shown that up to two thirds of patients attending A&E have problems that could be managed by general practitioners ( GPs ) . Although many studies have found that patients of lower socio-economic class with less social support have a higher utilization rate of A&E , some recent studies have revealed contrary evidence . In this study 2410 patients were r and omly selected from four A&E at different times . The gold st and ard in differentiating true emergency cases and GP cases was based on a retrospective record review conducted independently by a panel of emergency physicians . Two emergency physicians review ed each case independently , and if their independent ratings were in agreement , this became the gold st and ard . Patients classified as GP cases were given a telephone interview , and a sample was selected and matched with cases from general out patient clinics ( GOPC ) in the public sector by morbidity . Reasons for not attending a private GP included closure of clinic , deterioration of symptoms , GPs ' inability to diagnose properly , and patients ' wish to continue medical treatment in the same hospital . Reasons why non-urgent patients did not choose to attend the nearby public GOPC included affordability , closure of the GOPC , patients ' wish to continue treatment at the same hospital , GOPC too far away , no improvement shown after visits to GOPC doctors , and GOPC doctors ' inability to make proper diagnoses . The reasons for high level of utilization of A&E services are complex and reflect problems of delivery of GP services . There is an urgent need for GPs to set up a network system to provide out of hours services , and also for a better interfacing between primary and secondary care , and between public and private sectors , so that patients can be referred back to GPs . Interim clinical services provided to those non-urgent cases by nursing practitioners or by GPs working in A&E could also facilitate discharge of patients to primary care facilities STUDY OBJECTIVE To assess agreement among health professionals with regard to the need for urgent care among emergency department patients . METHODS We conducted a chart review of 266 ED patients in an urban teaching hospital . Eight health professionals ( four emergency nurses , two emergency physicians , two family physicians ) used identical criteria to retrospectively rate urgency . Agreement was measured for all review ers , as well as among health professionals of the same specialty . Agreement was also measured between one ED nurse 's retrospective assessment and the prospect i ve assessment s of the triage nurses who had seen the patients on presentation . RESULTS The percentage of patients rated as needing urgent care by the retrospective review ers ranged from 11 % to 63 % . Agreement among the retrospective review ers was fair ( kappa = .38 ; 95 % confidence interval , .30 to .46 ) and was no better among review ers of the same specialty . We found only slight agreement between the nurse review er 's retrospective assessment and the triage nurses ' prospect i ve assessment s ( kappa = 19 ; 95 % confidence interval , .07 to .31 ) . CONCLUSION Even when using the same criteria , health professionals frequently disagree about the urgency of care in ED patients . When retrospective review ers disagree with a prospect i ve assessment of urgency , the potential exists for denial of payment or even lawsuits . Because the subjectivity of urgency definitions may increase disagreement , the development of more objective and uniform definitions may help improve agreement BACKGROUND We evaluate the appropriateness of medical visits to the accident and emergency department ( A&ED ) of a university hospital using an instrument based on explicit and objective criteria , analyze the association between inappropriate visits and certain factors , and identify reasons for inappropriate use . METHODS This concurrent review of a r and om sample of 2,980 adult medical patients ' visits to the A&ED of the hospital of Elche uses the Hospital Urgencies Appropriateness Protocol , an instrument based on explicit criteria . We analyze the association between inappropriate use and specific factors , and provide a descriptive analysis of reasons for inappropriate use assigned by A&ED staff . RESULTS Of the total number , 882 ( 29.6 % ) of the visits were evaluated as inappropriate . Inappropriate use was associated with younger patients , use of own means of transportation , referral by the hospital , certain months of the year , and certain diagnostic groups of lesser severity . The most frequent reasons for inappropriate use were the patients ' greater trust in the hospital than primary care ( 451 [ 51.1 % ] ) , inappropriate use of services by patients ( 160 [ 18.1 % ] ) , and inappropriate referrals by primary care physicians ( 142 [ 16.1 % ] ) . CONCLUSION Inappropriate use represents an important percentage of use of the A&ED . Many reasons contribute to it , although foremost among them is patient preference ( and the convenience and accessibility ) of these services compared with primary care OBJECTIVE : To test the feasibility of creating a valid and reliable checklist with the following features : appropriate for assessing both r and omised and non-r and omised studies ; provision of both an overall score for study quality and a profile of scores not only for the quality of reporting , internal validity ( bias and confounding ) and power , but also for external validity . DESIGN : A pilot version was first developed , based on epidemiological principles , review s , and existing checklists for r and omised studies . Face and content validity were assessed by three experienced review ers and reliability was determined using two raters assessing 10 r and omised and 10 non-r and omised studies . Using different raters , the checklist was revised and tested for internal consistency ( Kuder-Richardson 20 ) , test-retest and inter-rater reliability ( Spearman correlation coefficient and sign rank test ; kappa statistics ) , criterion validity , and respondent burden . MAIN RESULTS : The performance of the checklist improved considerably after revision of a pilot version . The Quality Index had high internal consistency ( KR-20 : 0.89 ) as did the subscales apart from external validity ( KR-20 : 0.54 ) . Test-retest ( r 0.88 ) and inter-rater ( r 0.75 ) reliability of the Quality Index were good . Reliability of the subscales varied from good ( bias ) to poor ( external validity ) . The Quality Index correlated highly with an existing , established instrument for assessing r and omised studies ( r 0.90 ) . There was little difference between its performance with non-r and omised and with r and omised studies . Raters took about 20 minutes to assess each paper ( range 10 to 45 minutes ) . CONCLUSIONS : This study has shown that it is feasible to develop a checklist that can be used to assess the method ological quality not only of r and omised controlled trials but also non-r and omised studies . It has also shown that it is possible to produce a checklist that provides a profile of the paper , alerting review ers to its particular method ological strengths and weaknesses . Further work is required to improve the checklist and the training of raters in the assessment of external validity Abstract Objectives : To compare outcome and costs of general practitioners , senior house officers , and registrars treating patients who attended accident and emergency department with problems assessed at triage as being of primary care type . Design : Prospect i ve intervention study which was later costed . Setting : Inner city accident and emergency department in south east London . Subjects : 4641 patients presenting with primary care problems : 1702 were seen by general practitioners , 2382 by senior house officers , and 557 by registrars . Main outcome measures : Satisfaction and outcome assessed in sub sample of 565 patients 7 - 10 days after hospital attendance and aggregate costs of hospital care provided . Results : Most patients expressed high levels of satisfaction with clinical assessment ( 430/562 ( 77 % ) ) , treatment ( 418/557 ( 75 % ) ) , and consulting doctor 's manner ( 434/492 ( 88 % ) ) . Patients ' reported outcome and use of general practice in 7 - 10 days after attendance were similar : 206/241 ( 85 % ) , 224/263 ( 85 % ) , and 52/59 ( 88 % ) of those seen by general practitioners , senior house officers , and registrars respectively were fully recovered or improving ( χ2=0.35 , P=0.840 ) , while 48/240 ( 20 % ) , 48/268 ( 18 % ) , and 12/57 ( 21 % ) respectively consulted a general practitioner or practice nurse ( χ2=0.51 , P=0.774 ) . Excluding costs of admissions , the average costs per case were £ 19.30 , £ 17.97 , and £ 11.70 for senior house officers , registrars , and general practitioners respectively . With cost of admissions included , these costs were £ 58.25 , £ 44.68 , and £ 32.30 respectively . Conclusion : Management of patients with primary care needs in accident and emergency department by general practitioners reduced costs with no apparent detrimental effect on outcome . These results support new role for general practitioners . Key messages We compared the costs and outcomes of general practitioners and hospital doctors treating patients with primary care problems who attended an accident and emergency department There were no significant differences between the types of doctor in terms of patients ' satisfaction and clinical outcome General practitioners provided care more cheaply than did the hospital doctors , reflecting their less frequent requests for investigations and referrals Employing general practitioners in accident and emergency departments offers a potential means of reducing the costs of treating patients with primary care BACKGROUND In Brazil , there continues to be an excessive use of emergency services by patients with elective medical problems . Those patients who report having a primary care physician are less likely to utilize the emergency department for non-urgent consultations . OBJECTIVE The objective of this study was to compare patients who have a primary care physician with those who do not in relation to severity of their chief complaint at presentation in the emergency department . METHODS The study was carried out as a cross-sectional interview-based survey at the Conceição Hospital Emergency Service in Porto Alegre ( Brazil ) . The sample was 553 patients selected through a systematic r and om sampling , and the response rate was 88 % . The data entry and analysis were performed using the software Epi-info , EGRET and SPSS . The analysis included simple statistics to determine the prevalence of the conditions being investigated and the effect of independent variables ( regular doctor ) in relation to the dependent variable ( severity of disease ) through logistic regression . RESULTS The chief complaints were divided up as follows : 15 % emergency cases , 46 % urgent cases and 39 % elective . The chief complaint was defined as urgent or emergency if it exhibited a significantly statistical association with the following independent variables , after being analysed by a logistic regression model : patients who reported having a primary care physician [ odds ratio ( OR ) = 2.98 , 95 % confidence interval ( CI ) = 1.84 - 4.80 ] and patients who usually go to the emergency room by car ( OR = 2.67 , 95 % CI = 1.75 - 4.05 ) . CONCLUSION One strategy to reduce the number of non-urgent consultations at emergency rooms is to establish a close out-patient relationship between patients and physician . There is a need to optimize the health care of patients who have non-urgent problems but still seek the emergency department through strategies at the primary health care level-especially when continuous care is available- and where a comprehensive approach with an emphasis on prevention would stimulate better quality of care at a lower cost STUDY OBJECTIVE There are no studies in Portugal supporting a common cl aim that most emergency department visits are inappropriate . The aim of this study was to determine the prevalence of and to evaluate factors associated with an appropriate ED visit in a major public hospital . METHODS A cross-sectional prospect i ve study was performed at a public university hospital ED . Data for demographic variables , duration of complaint , transfer from other medical sources , and previous medical care for the same complaints were collected by interviewing all patients who arrived at the ED within a consecutive period of at least 24 hours . Data for diagnostic tests , treatment performed , and final patient destination were collected by triage records review . An appropriate ED visit was defined by explicit criteria : interhospital transfer , patient death at the ED , hospitalization , and diagnostic tests or treatments performed . RESULTS The study included 5,818 adult patients . The prevalence of an appropriate ED visit , by use of our criteria , was 68.7 % . Sex was an effect modifier . According to this study , determinants of an appropriate visit for men and women were age 60 years or older and complaints of 24 hours or less and in women but not in men , retired from work and with arrival between midnight and 8 AM . CONCLUSIONS In a university hospital in Oporto , the majority of ED visits were appropriate according to explicit criteria . Some variables may be associated with appropriateness of ED visits . A duration of the complaint 24 hours or less along with an arrival between midnight and 8 AM in women and age 60 years or older in men were the most important determinants Abstract Objective : To compare patient characteristics and consultation activities for attenders at accident and emergency departments assessed by nurse triage as presenting with “ primary care ” or “ accident and emergency ” type problems . Design : One year prospect i ve study . Setting : A busy , inner city accident and emergency department in south London . Subjects : Of the 5658 patients treated for new problems during a stratified r and om sample of 204 three hour sessions between 10 am and 9 pm during June 1989 to May 1990 , all “ primary care ” ( 2065 patients ) and a 10 % r and om sample of “ accident and emergency ” ( 291 patients ) were included in the analysis . Main outcome measures : Patient 's age , sex , duration of presenting problem , diagnosis , laboratory and radiographic investigations , treatments , and referrals . Results : 40.9 % of attenders with new problems were classified by triage as presenting with “ primary care ” problems ( 95 % confidence interval 39.6 % to 42.2 % ) . Primary care attenders were more likely than accident and emergency patients to be young adults , to have symptoms with a duration of longer than 24 hours , and to present problems not related to injury ( all P<0.001 ) . Accident and emergency patients were considerably more likely to be referred to on call teams and to be admitted . Even so , 9.7 % of primary care patients were referred to on call teams and a further 8.9 % were referred to the fracture clinic or advised to return to the accident and emergency department for follow up . Conclusion : Accident and emergency triage can be developed to identify patients with problems that are more likely to be of a primary care type , and these patients are less likely to receive an investigation , minor surgical procedure , or referral . Many patients in this category , however , receive interventions likely to support their decision to attend accident and emergency rather than general practice . This may reflect limitations in the sensitivity of triage practice or a clinical approach of junior medical staff that includes a propensity to intervene STUDY OBJECTIVE To determine whether nonemergency patients can be prospect ively identified by triage nurses and safely triaged out of the emergency department without treatment . METHODS All adult patients ( 16 years or older ) who presented to a university ED were provided an evaluation by a triage nurse . For a patient 's case to be defined as nonemergency , four criteria were required : vital signs within a specific range , presence of 1 of 50 potentially nonemergent chief complaints , absence of key indicators found on screening examination , and absence of chest pain , abdominal pain , any severe pain , and inability to walk . Between July 1988 and July 1993 , patients who satisfied these criteria were defined as nonemergency , refused care in the ED , and triaged out of the ED . Patients were referred to off-site clinics . The clinics had agreed to see patients in advance of the study , and the referral lists were frequently up date d. Outcome data were obtained by telephone surveys to both triaged individuals and other health care providers . RESULTS In this 5-year study , 176,074 adults presented to the ambulatory triage area in the ED , and 31,165 ( 18 % ) were defined as nonemergency , were not treated , and were referred elsewhere . Letters and telephone calls to all referral clinics , eight local EDs , and the coroner 's office identified no instances of gross mistriage and only a small number of insignificant adverse outcomes . Telephone follow-up to individuals triaged away was successful in 34 % of calls and showed that 39 % of persons received care elsewhere on the same day , 35 % received care within 3 days , and 26 % decided not to seek medical care . A group of 1.0 % sought care at other hospital EDs for minor complaints . CONCLUSION A subset of patients with nonemergency problems can be prospect ively identified and triaged out of the ED without significant adverse outcomes provided there is community support for follow-up care Abstract Objective : To compare the process and outcome of “ primary care ” consultations undertaken by senior house officers , registrars , and general practitioners in an accident and emergency department . Design : Prospect i ve , controlled intervention study . Setting : A busy , inner city accident and emergency department in south London . Subjects : Patients treated during a stratified r and om sample of 419 three hour sessions between June 1989 and May 1990 assessed at nurse triage as presenting with problems that could be treated in a primary care setting . 1702 of these patients were treated by sessionally employed local general practitioners , 2382 by senior house officers , and 557 by registrars . Main outcome measures : Process variables : laboratory and radiographic investigations , prescriptions , and referrals ; outcome variables : results of investigations . Results : Primary care consultations made by accident and emergency medical staff result ed in greater utilisation of investigative , outpatient , and specialist services than those made by general practitioners . For example , the odds ratios for patients receiving radiography were 2.78 ( 95 % confidence interval 2.32 to 3.34 ) for senior house officer v general practitioner consultations and 2.37 ( 1.84 to 3.06 ) for registrars v general practitioners . For referral to hospital specialist on call teams or outpatient departments v discharge to the community the odds ratios were 2.88 ( 2.39 to 3.47 ) for senior house officers v general practitioners and 2.57 ( 1.98 to 3.35 ) for registrars v general practitioners . Conclusion : Employing general practitioners in accident and emergency departments to manage patients with primary care needs seems to result in reduced rates of investigations , prescriptions , and referrals . This suggests important benefits in terms of re source utilisation , but the impact on patient outcome and satisfaction needs to be considered further |
14,099 | 11,279,776 | REVIEW ER 'S CONCLUSIONS Alarm interventions are an effective treatment for nocturnal bedwetting in children .
Desmopressin and tricyclics appeared as effective while on treatment , but this effect was not sustained after treatment stopped , and alarms may be more effective in the long term . | BACKGROUND Enuresis ( bedwetting ) is a socially disruptive and stressful condition which affects around 15 - 20 % of five year olds , and up to 2 % of young adults .
Although there is a high rate of spontaneous remission , the social , emotional and psychological costs to the children can be great .
OBJECTIVES To assess the effects of alarm interventions on nocturnal enuresis in children , and to compare alarms with other interventions . | To determine whether changes in attitude and behavior occur after treatment of nocturnal enuresis , we r and omly assigned 121 children aged 8 to 14 years to receive conditioning therapy ( n = 66 ) or a 3-month waiting period ( n = 55 ) . All children completed the Piers-Harris Self-Concept Scale ( P-H ) , the State-Trait Anxiety Scale ( STAIC ) , and the Nowicki-Strickl and Locus of Control test ( NSLC ) at entry and after treatment or delay . Parents completed the Achenbach Child Behavior Checklist ( CBCL ) . There were no significant group differences in background demographic variables . Significant improvements in the P-H Scale ( P = 0.04 ) and three of its subscales occurred in children in the treatment group compared with those in whom treatment was delayed . The changes were greatest for those who had the largest decreases in wetting frequency . Changes in CBCL , STAIC , and NSLC scores were not statistically significant . We conclude that there may be mental health benefits in children helped to master the symptom of enuresis , which in this age group is probably a chronic stressor This study assessed change in the frequency of primary nocturnal enuresis as produced by either behavioral conditioning with a urine alarm , pharmacotherapy with imipramine hydrochloride , or assignment to a clinical waiting list . The study also investigated the effect of treatment method and outcome on subjects ' level of emotional and behavioral adjustment . An attempt was made to identify pretreatment predictors of treatment outcome and premature withdrawal from the treatment program . The results indicated a significantly more effective outcome for the conditioning approach . Comparison of pre- and post-treatment measures of adjustment provided insufficient evidence to support the hypotheses that either change in the frequency of nighttime wetting or the method of treatment received would influence the subject 's level of emotional and behavioral adjustment . The enuresis tolerance scale was found to be a highly significant predictor of early termination from conditioning treatment Fifty children with primary nocturnal enuresis were r and omised for a study comparing desmopressin ( DDAVP ) and enuresis alarm . Forty six completed the trial , 24 of whom were treated with 20 micrograms intranasal desmopressin nightly and 22 with enuresis alarm for three months . Failures were crossed over and relapses were continued on the same treatment for a further three months . The improvement rate was 70 % in the group given desmopressin and 86 % in the group treated with alarm ; the difference was not significant . During the first week of treatment the group given desmopressin was significantly dryer , and at the end of the study 10 of these patients relapsed compared with one patient in the group given the alarm . No serious side effects were observed . This study confirms the role of conditioning treatment as preferable in long term treatment of nocturnal enuresis . When this fails or when a safe drug with rapid effect is needed , however , desmopressin is a useful alternative Abstract It has been suggested that intermittent reinforcement may be of value in reducing the rate of relapse in bedwetting conditioning therapy . An experiment was conducted with 30 enuretic boys to examine acquisition and extinction parameters of continuous ( 100 % ) , intermittent ( 70 % variable ratio ) , and “ placebo ” ( 0 % ) reinforcement schedules . Reinforced trials were administered as in the typical Mowrer conditioning procedure . Non-reinforced trials were achieved by means of a time delay with the subsequent alarm being activated in the parent 's room rather than in the child 's room . These procedures required the development of a new conditioning device which could be programmed to automatically administer the desired schedule of reinforcement . The results of the field investigation revealed that continuous reinforcement ( CR ) and intermittent reinforcement ( IR ) groups attained acquisition in approximately the same number of trials and with essentially the same success rate . Relapse rate was significantly greater in the CR group than in the IR group . The placebo group showed no improvement over the 6 weeks of treatment . The results of this study may be interpreted as supporting the tenet that relapse can be viewed and treated as an extinction of the acquired response The effect on nocturnal activity of the wire mesh element within the ' buzzer and pad ' enuresis alarm device was studied using healthy adult volunteers in a single or double cross-over design . On the nights when the mesh was in the bed there was less activity , supporting the finding of improved polygraphic sleep on the mesh and suggesting an unexpected therapeutic mechanism Forty four children with daytime wetting were included in a r and omly controlled trial of two alarm devices , a contingent one that sounded when wetting occurred and a non-contingent one that went off from time to time unrelated to wetting events . A quota allocation system ensured comparability between treatment groups . Two thirds responded to an alarm by becoming dry . The non-contingent alarm produced as good a response as the contingent one and is recommended for routine use in children with diurnal enuresis . Twenty three per cent of those who responded to treatment relapsed up to two years after completion of the trial BACKGROUND Previous studies have suggested changes in self-concept with successful treatment of primary nocturnal enuresis ( PNE ) , but behavioral changes have not been reported as a consistent associated finding . OBJECTIVE To determine if self-concept and behavior change after 6 months of treatment of monosymptomatic PNE by conditioning alarm or desmopressin acetate ( DDAVP ) . DESIGN R and omized , controlled trial in an inner-city hospital clinic . Subjects were 182 children referred or recruited through media publicity , r and omly assigned both to 1 of 8 pediatricians and 1 of 3 treatment groups ( alarm , DDAVP , or placebo ) . Included were children > 7 years old with PNE , no daytime symptoms , bladder capacity > 50 % expected , and wetting > 3 times a week . Excluded were children with central nervous system disorders or developmental delays , and those currently on DDAVP or alarm . Subjects completed the Piers-Harris Children 's Self-Concept Scale and Harter 's Perceived Competence Scale for Children ( PCSC ) at initial visit and after 6 months of treatment . Parents completed the Achenbach Child Behavior Checklist ( CBCL ) at the same times . RESULTS After 6 months of treatment the Piers-Harris total score showed a highly significant treatment by period interaction effect for DDAVP , a significant effect for alarm , and no effect for placebo . For children who achieved 75 % dryness the CBCL showed a treatment by improvement interaction effect that was highly significant for DDAVP and placebo with no effect for alarm . For the PCSC there were no treatment or outcome interaction effects . After 6 months of treatment there were significant changes over time unrelated to outcome or treatment in the Piers-Harris Subscales and in the CBCL Internalizing and Externalizing Scores , and the Social Thought and Attention Problems Subscales . The PCSC was more stable with no changes in total score , and positive changes over time in only 2 Subscales , Scholastic and Social . CONCLUSION Children 's self-concept improved with the type of treatment and amount of success . Parents ' perceptions of behavior improve with type of treatment and amount of success . Children rate their self-concept and some physical attributes better after treatment with any of DDAVP , alarm , or placebo regardless of outcome . Frequent follow-up with emotional support and encouragement appear to be important components of an efficacious intervention for children with nocturnal enuresis Abstract Sixty‐four enuretic children with a mean age of 8.4 years were assessed over an 8‐week study to observe their response to a number of commonly used methods of treatment for enuresis . This was a double‐blind study with patients being assigned to one of eight possible treatment conditions . Imipramine , an alarm device , r and om awakening , and placebo were compared . These treatments were also studied in combination . The most practical and efficacious treatment was the individual use of either alarm or imipramine . R and om awakening and r and om awakening plus placebo were indistinguishable from placebo and were not at all effective Abstract One hundred and fifteen enuretic children were assigned to five treatment groups . Three groups received Mowrer-type continuous signal ( C.S. ) , Twin-Signal ( T.S. ) or intermittent Twin Signal ( T.S.-I.R. ) conditioning treatment , and two groups were given “ placebo ” or “ arousal ” control treatments . Over a one-month period , there was no difference between conditioning and control procedures , and it was concluded that further research is needed to determine the basis of treatment response . There was no evidence in support of the escape training hypothesis , and the twin-signal modification to st and ard bell- and -pad treatment is not recommended . The investigation confirmed the success of conditioning treatment in bringing about the initial arrest of enuresis ( i.e. in 81.4 per cent of the cases ) but the relapse rate was high . The investigation provided tentative evidence that intermittent conditioning treatment offers one way of reducing the frequency of relapse . The problem of obtaining satisfactory parental co-operation in a badly housed working-class population was apparent , and ways of reducing the dem and s that treatment imposes on parents are indicated . The results are discussed with regard to theories of conditioning treatment of nocturnal enuresis , and possible improvements in this technique of treatment Arousal Training is a fast , simple , and effective form of bibliotherapy for nocturnal enuresis with non- clinical children between 6 and 12 years of age . The parents act as therapists . They reward the operant behavior-pattern following the urine alarm . The success rate is 98 % ( N = 41 ) , which is significantly high when compared to the control conditions ( 79 % , N = 86 ) . There was a response rate of 100 % and no drop-out from therapy . All parents ( N = 127 ) completed and returned the record . The results of a follow-up of this bibliotherapy ( N = 113 ) 2 1/2 years later are presented . The success rate of Arousal Training was still significantly higher ( 92 % continent ) when compared to the urine device with specific instructions ( 77 % ) and urine alarm only ( 72 % ) . Arousal Training is the treatment of choice for non- clinical enuretic children between 6 and 12 years of age The mode of action of the enuresis alarm is not clear . Earlier work suggested that the wire mesh itself may alter sleep and in this way affect nocturnal enuresis . Seven healthy males have been studied within a two-period cross-over design in which their nocturnal motility , on and off an enuresis wire mesh , was recorded using a motility bed . There were no order , treatment or day effects in any of the variables studied . However , the mean hourly motility for each subject averaged over the three nights shows a substantial trend towards increased motility on the mesh . This lends some support to the hypothesis and merits further study Abstract Bedwetting has been a major and unsolved problem for the severely retarded . To solve this problem , an intensive training program was design ed similar to a recently developed program for daytime toilet training of the retarded . Some distinctive features of the new procedure were frequent positive reinforcement for correct toileting , a negative reinforcer for accidents , positive practice in night time toileting , increased level of urination by forcing drinking , immediate detection of correct and incorrect toileting , and Positive Practice for accidents . Of twelve retarded adult bedwetters , the average bedwetter required only one night of intensive training . Several days of apparatus monitoring were used following the training but proved unnecessary for two-thirds of the trainees . Accidents were reduced by about 85 % during the first week after training , and almost entirely ( 95 % ) during the fifth week with no relapse during a 3 month follow-up . No reduction of accidents result ed when the same bedwetters were given a control procedure that provided no positive or negative reactions other than the sounding of an alarm upon bedwetting . The Dry-Bed procedure appears to be a very rapid solution to the problem of enuresis among the retarded and may be applicable to other difficult population s and also to normals Seventy‐one children with nocturnal enuresis were enrolled in a controlled trial . The children were allocated to two matched groups . Children in both groups used an enuresis alarm until the end of treatment . Children in the first group were treated with 40/^g of intranasal desmopressin ( Desmospray ) for up to 6 weeks at the start of treatment with the alarm . During the observation period before treatment there were 2.3 dry nights per week in both groups . At the end of treatment there was a significant difference in the mean number of dry nights per week between the two groups ( 6.3 in the alarm and desmopressin group and 4.8 in the alarm group ) and also in the number of children becoming reliably dry . The combination of desmopressin and alarm was particularly helpful for children with severe wetting and those with family and behavioural problems . Desmopressin , enuresis alarm , nocturnal Results 2 1/2 years after an enuresis nocturna training are presented , including rate of success , percentage and duration of relapse for 113 children ( mean age 11.6 year at the start of the training ) . The bibliotherapeutic treatment by parents did not require any intervention by a professional . Behaviour of parents in the event of a relapse differed between training conditions . Children in the Arousal condition recovered faster from a relapse , 90 % of their parents used the Arousal training again at relapse or did not intervene at all and none of them consulted a professional . Clearly they had confidence in the method of Arousal training : combining the alarm device with reinforcement for correct behaviour at the time the alarm goes off . Parents in control conditions did not use the alarm device as often as the parents in the Arousal condition , but tried other means with less success , including consulting professionals Predictors of premature withdrawal from a 12-week program of behavioral conditioning for childhood nocturnal enuresis were examined for 47 children treated at a university outpatient clinic . All children were administered the Piers-Harris Children 's Self-Concept Scale ; parents completed the 55-item Behavior Problem Checklist and the Tolerance Scale for Enuresis . Parents also reported the methods ( i.e. , r and om awakening , restriction of fluids , rewards , punishment , medication , other ) previously used to control their child 's wetting . A stepwise discriminant function analysis revealed that the function containing number of previous techniques used , presence of child behavior problems , and parent tolerance of enuresis was a significant predictor of early termination of treatment In this study the prevalence of nocturnal enuresis defined according to the DSM III criteria was determined in a r and om sample of 2070 children aged from 4 to 16 years . Nocturnal enuresis declines in prevalence with age and is more frequent in boys than in girls . Moreover , the decline in prevalence with age was found to take place earlier in girls than in boys . It is therefore argued that the DSM III age limit for enuresis should be raised to 8 years for boys ABSTRACT . Primary nocturnal enuresis ( PNE ) is a very common problem in pediatric and child psychiatric practice . Many treatments have been tried , but none has proved entirely successful . Uristop ® , a commercially available alarm device based on a theory somewhat different from those used in the common alarm devices , was tried in a prospect i ve r and omized double‐blind study . Of 134 enuretic children who were examined on an out‐patient ward , 53 were selected for inclusion in this study on the basis of certain criteria . The children were r and omized either in a treatment group with a functioning device , or in a control group with a nonfunctioning device . They used their devices for 6 weeks and were followed for an additional 12 weeks . The sex , age , history of previous urinary tract infection ( UTI ) or treatment of PNE and a family history of PNE were compared between the groups and no statistical differences were found . In the control group , however , there was significantly more often a history of up setting life events and previous child psychiatric contact . This difference was not considered as having any effect on the results . The results showed that the device had no effect on the study group as compared with the control group . However , both groups improved significantly as compared with the expected sponaneous cessation of bedwetting Patients with primary nocturnal enuresis were entered into 4 treatment groups : observation , imipramine , desmopressin acetate or alarm therapy . Patients were weaned from therapy 6 months after inclusion in the study and were evaluated for continence at 3 , 6 , 9 and 12 months after beginning the study protocol . Of the 50 patients under observation 6 % were continent at 6 months and 16 % were continent within 12 months . Of 44 patients treated with imipramine 36 % were continent at 6 months on medication ; however , only 16 % were continent at 12 months , off medication . Similarly , of the 88 patients treated with desmopressin acetate 68 % were continent at 6 months but only 10 % were continent at 12 months . Of the 79 patients treated with alarm therapy 63 % were continent at 6 months and 56 % were dry at 12 months . Although each form of therapy improved continence over observation alone ( p < 0.01 ) , only the bed-wetting alarm system demonstrated persistent effectiveness ( p < 0.001 ) UNLABELLED The aim of the present studies was to investigate background factors and treatment in children with monosymptomatic primary nocturnal enuresis . The study material comprised enuretics , former enuretics and controls from the municipal community of Falkenberg on the west coast of Sweden . Whenever possible all investigations were made with the children staying in their own home environment . Different background factors have been suspected as being causative : sleep disturbances , behavioural or psychological disturbances , small bladder capacity , increased night diuresis and an insufficient production of the antidiuretic hormone during sleep . These factors have been investigated in these studies . The treatment of enuresis has been dominated by the alarm and antidiuretic treatment with DDAVP . Primary nocturnal monosymptomatic enuresis is a common problem in childhood . In this study the prevalence among 392 seven year old children was 7.3 % . A prior history of enuresis was found in 65 % of families of the enuretics compared to 25 % in controls . The enuretic children showed no statistically significant differences in behavioural or psychological problems compared to non-enuretic children . Enuretic children were described as heavy sleepers by their parents and a wake-up test performed at home showed that they were statistically significantly harder to arouse than the controls . Children with nocturnal enuresis , former enuretics and controls did not differ in social or behavioural traits in an interview study . No signs of symptom substitution was found when enuresis was resolved . Enuretic children had a normal bladder capacity and no statistically significant difference was found compared to controls and former enuretics . The enuretic children showed a normal calcium-creatinine quota in the urine . Former enuretic children showed a significantly enhanced calcium/creatinine quota compared to enuretics and controls . Enuretic children had a statistically significant lower morning plasma level of the anti diuretic hormone vasopressin than non-enuretic children . Enuretic children were treated for 12 weeks with DDAVP or the alarm . DDAVP treated patients had a more rapid effect compared with alarm treated patients . Alarm treated children had a lower relapse frequency . Enuretic children were treated in a r and omised , double blind , double dummy , cross over , placebo-controlled study with DDAVP 20 micrograms intranasally by a single dose pipette or 200 micrograms orally as a tablet . Both methods were equally effective in controlling enuresis , but significantly superior to placebo . CONCLUSION Enuretic children are normal , well adjusted children with a normal bladder capacity , a high level of arousal threshold , and a low morning level of plasma vasopressin . The alarm and DDAVP are equally effective in treating enuresis . ( ABSTRACT TRUNCATED AT 400 WORDS Fifty six children aged from 6 - 16 years who wet their beds at night were entered into a controlled trial of two alarm devices : a traditional alarm using a wet sensor mat on the bed attached to an alarm bell out of reach of the child , and a mini alarm system incorporating a tiny perineal wet sensor attached to a small alarm worn on the child 's clothing . A quota allocation system ensured comparability between the two treatment groups . The children were encouraged to use the alarm for four months . Both alarms were equally effective in helping children to become dry . There was no significant difference between the number of children unable to comply with treatment or to be helped by each alarm . The rate of acquisition of dryness was similar for the two groups . The traditional st and ard alarm was sturdier , more dependable , and easier to maintain , but the mini alarm had some advantages , particularly for girls . Both types of alarm are recommended for general use SUMMARY A controlled trial of conditioning by alarm and of amphetamine for the treatment of enuresis was planned . The experimental group was to consist of 118 enuretic schoolchildren of 8 years and over , detected in a community survey , but only 37 could be enrolled for the trial ; 57 had remitted spontaneously or improved before appointments could be made , 15 defaulted , and 9 were rejected as unsuitable . The 37 cases were allocated at r and om to the two treatments . Assessment s were made six months later , by which time 4 further cases had been lost to the trial . Among 33 cases remaining , 16 on alarm and 17 on amphetamine , the results for the alarm were significantly better ; this was more so among the 23 cases whose treatment was considered adequate . Amphetamine had no greater effect than the natural remission-rate . The significance of this result to theories of conditioning and of the mechanism of enuresis is discussed . RESUME Un essai de traitement par conditionnement dans Venuresie nocturne Les auteurs projetaient de comparer l'effet du conditionnement par alarme et de l'amphetamine dans le traitement de l'enuresie . A cet effet , 118 ecoliers enuretiques âges de 8 ans et au-dessus ont ete depistes au cours d'une enquete ; ils devaient constituer le groupe experimental mais 37 seulement ont pu etre enroles pour l'essai . 57 se sont dedits spontanement ou ameliores avant qu'on ait pu les convoquer , 15 ont fait defaut et 9 ont ete rejetes comme impropres a l'essai . Parmi ces 33 restant , 16 traites par alarme et 17 par l'amphetamine , les result ats obtenus par Falarme ont ete nettement meilleurs . L'effet de l'amphetamine ne depassait pas le taux de remission naturel . Les auteurs discutent la signification de ces result ats pour la theorie du conditionnement et celle du mecanisme de l'enuresie Study participants were fifty 5- to 13-year-old children ( 33 boys and 17 girls ) with nocturnal enuresis of at least 3 months duration . All wet their beds at least twice per week , were of normal intelligence , and were without demonstrable organic cause for their enuresis . Each youngster 's pretreatment maximum functional bladder capacity ( MFBC ) was used to classify the child as having small or large MFBC based on available norms . Youngsters were then r and omly assigned to treatment with the urine alarm ( UA ) alone or with the urine alarm supplemented with retention control training ( UA plus RCT ) . Of the 40 youngsters who completed treatment , 37 ( 92.5 % ) achieved the treatment goal of 14 consecutive dry nights . Two additional children became dry during follow-up , leaving only one child who failed to stop wetting . Sixteen children ( 41 % ) subsequently relapsed , but all who reentered treatment became dry . Because treatment outcome was uniformly excellent across all groups , treatment progress was evaluated by analyzing wetting frequency and arising at night to use the bathroom during treatment , as well as prechange and postchange in MFBC For both wetting frequency and arising at night , there was a significant interaction between bladder capacity and treatment . Small MFBC children treated with the UA plus RCT and large MFBC youngsters treated with the UA alone had the fewest wetting episodes and got up at night to use the bathroom less often ; these youngsters took less time to be successfully treated . Prechanges and postchanges in MFBC indicated that RCT did not lead to consistent increases in bladder capacity in the sample studies . The 10 children who terminated treatment prematurely had lower self-esteem and more parent-reported conduct problems than the 40 children who completed treatment Abstract Enuresis has been treated with moderate effectiveness by the urine-alarm method which requires many weeks of training . The present procedure used a urine-alarm apparatus but added such features as training in inhibiting urination , positive reinforcement for correct urinations , training in rapid awakening , increased fluid intake , increased social motivation to be nonenuretic , self-correction of accidents , and practice in toileting . After one all-night training session , the 24 enuretic children averaged only two bedwettings before achieving fourteen consecutive dry nights and had no major relapses . Little or no reduction in bedwetting occurred within the first two weeks for matched-control enuretics who were given the st and ard urine-alarm training . The results of a control-procedure showed that the new procedure did not involve Pavlovian conditioning . The new method appears to be a more rapid , effective and different type of treatment for enuresis Two experiments examined the significance of patient-therapist contact in the treatment of childhood nocturnal enuresis by behavioural methods . The first involving 45 enuretic children compared the effectiveness of the st and ard urine-alarm conditioning procedure when it is closely supervised as opposed to not supervised after the initial description of training . Results showed that adequate patient-therapist contact is necessary for the effective use of the st and ard conditioning treatment . One hundred and twenty children took part in the second experiment which compared st and ard conditioning with Dry-Bed Training ( DBT ) ( Azrin et al , 1974 ) administered under four different conditions — by the child 's parents at home , by a professional trainer at home , by a professional trainer in hospital and by the child 's parents without the adjunct of a conventional bed-buzzer device . DBT was superior to st and ard conditioning in terms of the proportion of bedwetters successfully treated and in terms of the speed of treatment . DBT was equally effective under all conditions of administration except where it did not have the adjunct of a machine , in which case it was only marginally better than no treatment at all Despite long-st and ing cl aims that the conditioning method of treating enuresis is based on the classic conditioning paradigm , research explicitly investigating this cl aim has been limited . This study compares two conditioning methods of treating enuresis , both using the bell and pad , one in a classic conditioning paradigm and the other in an operant paradigm with an unconditioned stimulus delay of 3 minutes together with an operant reinforcement for wet or dry behavior . Sixty children were r and omly assigned to one of the 2 treatment groups or a control group . Using Dunn 's procedure , a planned comparison showed the control group and delay group did not differ significantly , but both differed significantly from the classic conditioning group ( p less than 0.05 ) . Fifty percent of the classic conditioning group reached criterion of 14 consecutive dry nights while 17 % of the delay group reached criterion . None of the control group reached criterion . Results suggest that the operant procedures are a much weaker form of treatment than the bell and pad . This study indicates that enuresis in children can be successfully managed with a short duration outpatient program Abstract Forty-five children with night wetting only ( NW ) and 30 children with day and night wetting ( DNW ) were r and omly assigned to 2 treatment groups : alarm only and alarm preceded by 4 weeks of retention control training ( R.C.T. ) . Fewer children became dry at night in the DNW group than the NW group and DNW children relapsed earlier following treatment . The enuresis alarm was far superior to R.C.T. in reducing night wetting in both enuretic groups . It also reduced day wetting in some of the DNW children . Children who became dry in the NW group did not show significant changes in functional bladder capacity . Although changes in functional bladder capacity were seen in the DNW children who became dry , changes were only noticeable once dryness had been achieved Summary A relapse rate of approximately one third following the conditioning treatment of childhood enuresis is commonly reported . A procedure of “ overlearning ” in which the child is instructed to drink two pints of liquid in the last hour before retiring is suggested as a means of strengthening the resistance of the learned response to extinction . Overlearning therapy was given to 61 cases r and omly allocated from a total sample of 144 patients at a special investigation clinic . It was found to significantly reduce the relapse rate without increasing the likelihood of patients terminating treatment prematurely . Ab and oning unsuccessful attempts at overlearning was not found to affect relapse , nor to increase the likelihood of termination The efficacy of alarm monotherapy ( 35 children ) was compared with the efficacy of alarm treatment in combination with 40 micrograms desmopressin ( Minirin , DDAVP ) nasal spray ( 36 children ) . At the end of the treatment period , children receiving combination therapy had more dry nights per week ( mean : 6.1 ) than children using an alarm alone ( mean : 4.8 ) . In addition , more children achieved an initial success ( 4 weeks of dryness ) following combination treatment ( 27 children [ 75 % ] ) compared with alarm monotherapy ( 16 children [ 46 % ] , P < 0.005 ) . This improvement with alarm plus desmopressin was particularly pronounced in children with severe wetting ( > or = 6 nights per week ) , family problems or behavioural problems . It may , therefore , be appropriate to manage children in these categories with an enuresis alarm supplemented with desmopressin to improve treatment outcome This r and omized experiment was undertaken to determine if any difference in success occurred between an audio versus a vibration alarm for nocturnal enuresis . Similar rates of success were achieved for 47 children , aged 6 to 12 years , who partially or totally completed the 3-month period of alarm use Three treatments for enuresis were evaluated : ( a ) immediate detection with a urine-sensing alarm with additional operant training procedures , ( b ) delayed detection with staff activating the alarm and conducting the procedures in the morning , and ( c ) yoked-schedule awakenings when the awakening times were determined by the performance of a r and omly matched participant from the immediate-detection group . Twenty seven people with mental retardation ( most profoundly or severely h and icapped ) , whose ages ranged from 13 to 29 years , participated . Nine of the participants were noncompliant with the linen changing and practice walks to the bathroom and thus did not receive consistent treatment . All 7 of the compliant members of the immediate-detection group improved , 2 of the delayed-detection group worsened while 2 improved , and 6 of 7 yoked awakenings participants improved . Improvement negatively correlated with the frequency of baseline bed-wetting . Several method ological issues are raised concerning enuresis treatment Sixty-two children with primary nocturnal enuresis were assigned r and omly to one of two groups . Group 1 was treated with imipramine hydrochloride , and group 2 received a course of treatment with the Mozes Detector . Seventeen children from group 1 and 18 from group 2 were tested with the age-appropriate form of the Cattell personality question naire on three occasions : at the time of entry into the study , 2 months later and at follow-up , an average of 16 months later . The patients in group 2 , who were older , had a higher rate of cure than did the patients in group 1 . They also had significantly higher levels of extroversion and significantly lower levels of neuroticism at follow-up than did those in group 1 . These findings indicate that better results are seen with the Mozes Detector than with imipramine in older children with primary nocturnal enuresis PURPOSE We evaluated the combination of alarm and desmopressin versus alarm monotherapy for the treatment of nocturnal enuresis . MATERIAL S AND METHODS A double-blind , placebo controlled study of alarm therapy combined with desmopressin for children with nocturnal enuresis is described . Of 93 patients 47 were r and omized to receive alarm therapy and 40 microg . intranasal desmopressin for 3 weeks followed by 20 microg . desmopressin for 3 weeks ( group 1 ) and 46 received alarm therapy and placebo ( group 2 ) . After 6 weeks on alarm therapy and medication or placebo , both groups received an additional 3 weeks of alarm monotherapy . A specialized nurse practitioner advised patients and families of the treatment to be given at home and in the outpatient department . Bed-wetting frequency was evaluated before during and 2 weeks and 6 months after treatment . RESULTS A significantly greater reduction in the number of wet nights was observed after the first 3 weeks of treatment in group 1 . However , after long-term followup no significant differences in bed-wetting frequency were noted . CONCLUSIONS There is a temporary , positive effect on enuresis using desmopressin combined with alarm therapy . However , both treatment modalities have a low long-term success rate of 36 % to 37 % Abstract Previous studies of the “ conditioning method ” of enuresis treatment have confounded the effects of conditioning with those of nonspecific psychotherapeutic aspects of the procedure . The present study compared three groups of enuretic children : ( 1 ) under the conventional bell-light conditioning procedure ; ( 2 ) under a similar procedure , but which involved a three-minute delay between wetting and alarm , and ( 3 ) under no-treatment conditions . Double-blind pre caution s were used . Results suggested that conditioning effects improvement over and above that effected by nonspecific influences . The findings are qualified by large variances in improvement , and by premature termination of the experiment A descriptive analysis is provided of a group of 94 enuretic school‐children between 8 and 10 years of age , and the results of a clinical trial of treatment are reported Abstract The results of a long term follow-up of enuretics treated by conditioning techniques are presented . A high relapse rate has occurred after treatment with a combination of the “ bell and pad ” and stimulant drugs . The frequency of relapse is particularly high in the group of patients to whom Dexedrine had been administered . The importance of the relapse rate associated with conditioning treatment is discussed , and explanations and further research are considered Two studies examined the effectiveness of the body-worn alarm in out-patient treatment of childhood nocturnal enuresis . The first involved 40 children , previously untreated by conditioning methods , treated with either the body-worn alarm or the traditional pad and bell alarm . The second study compared the body-worn alarm with modified dry-bed training with 48 children previously resistant to treatment . Results of both studies indicated the body-worn alarm was as effective as other methods in terms of the proportion of children successfully treated and was superior with respect to rapidity of response and consumer appeal . Such findings indicate that the body-worn alarm could become the treatment of choice for nocturnal enuresis |
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